Chapter 1- Literature Review

Chapter 1- Literature Review Part I

CHAPTER 1 Literature Review Part I - Asthma Management

1.0. Plan of chapter The literature review chapter will be addressing three issues (part I, II, and III) that cover the introduction to my research. Part I will investigate the pathology, diagnosis, classification of severity, prevalence, morbidity, mortality, cost of asthma, guidelines for asthma management, and drug delivery in asthma. Part II will cover inhaler technique and asthma management, inhaler technique and adherence, assessment of inhaler technique, and inhaler technique interventions. Part III will explore the role of community pharmacists in managing chronic conditions, specifically asthma, interventions in community pharmacies on inhaler technique, current role of the community pharmacist in delivering inhaler technique education to asthma patients, barriers preventing the pharmacists from delivering this role, anticipated solutions and questions raised. All of the three issues addressed will finally lead to the aims and objectives of this thesis. 1.1. Definition of asthma There is still a lack of understanding of the mechanisms involved in asthma, but with an appreciation of the importance of the underlying inflammation in asthma, a more complete definition can be sought.

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Asthma can be defined as “a chronic inflammatory disorder of the airways in which many inflammatory cells play a role in particular, mast cells, eosinophils, lymphocytes, macrophages,

neutrophils,

and

epithelial

cells.

In

susceptible

individuals,

this

inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. The episodes are usually associated with widespread but variable airflow obstruction that is often reversible spontaneously or with treatment." The inflammation also causes an increase in the existing bronchial hyper-responsiveness to a variety of stimuli. Moreover, recent evidence indicates that sub-basement membrane fibrosis may occur in some patients with asthma, and that these changes contribute to persistent abnormalities in lung function (National Asthma Education and Prevention Program - Expert Panel Report II 2002). The Global initiative for Asthma (GINA), which was initiated in 1993, has a main goal of producing recommendations for asthma management based on the best and latest scientific information available, and according to its latest report (updated in 2006), the definition of asthma is still the same (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). 1.2. Prevalence of asthma Asthma is estimated to affect some 300 million patients worldwide (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006), and contributes a large proportion of the burden of respiratory disease. Asthma accounts for about one percent of all disability-adjusted life years (DALYs) lost (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). International population-based studies using standard techniques showed that the prevalence of asthma in Australia is one of the highest in the world for all different age groups; In the European Community Respiratory Health Survey (ECRHS) which was conducted to assess the geographical variations of asthma in adults, conducted in 22 different countries, it was shown that Australia and New Zealand had higher prevalence

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than other English speaking countries of self-reported asthma in the 20 to 44 years age group (European Community Respiratory Health Survey (ECRHS) 1996). In Australia, 12% of people (2.2 million) have been reported to have asthma as a current and long term condition (11% male, 13% female), which has increased from 8% in 198990 and 11% in 1995 based on estimates from National Health Surveys (Australian Bureau of Statistics 2002). Data on the prevalence of asthma among adults in Australia show evidence of an increase since the early 1990s (from 8% in 1990 to 12.8% in 2001) (Wilson et al. 2003). Most recent data revealed that the prevalence has doubled in females (from 7.3% in 1990 to 14.6% in 2003), with a smaller increase in males (from 7.8% to 9.4%). Asthma also increased in all age groups, but the largest relative increase occurred in patients aged 55 years and older (Wilson et al. 2006). The prevalence of asthma has become stable however, over recent years (Australian Institute of Health and Welfare 2005). As for children, it was shown in an International Study of Asthma and Allergies in Childhood (ISAAC) (The International Study of Asthma and Allergies in Childhood (ISAAC) 1998) which was conducted in 38 countries across all continents, that Australia had the second highest prevalence rates of self-reported current wheeze (in previous 12 months: 24.6%), and second highest in self-reported current attacks (8.7%) among children aged 6-7 years. Self-reported symptoms of asthma in children aged 13-14 years showed that the prevalence of asthma was highest in the UK, New Zealand, Australia, Republic of Ireland, followed by most centres in North, Central and South America (The International Study of Asthma and Allergies in Childhood (ISAAC) 1998). In addition, the prevalence of asthma has been documented to be higher among Australian born children (Robertson et al. 1998) than among those born overseas (Magnus and Jaakkola 1997). Evidence from Australian studies have shown that between 9-11% of children have persistent asthma (Woolcock et al. 2001), with the prevalence of current wheeze in Australian school children increasing substantially (Robertson et al. 1991) at a rate of 1.24% (Peat et al. 1994) to 1.4% per year (Robertson et al. 1998). More recent data have 3


shown that this increase may have reached a plateau or even decreased (from 1993 to 2002) (Robertson et al. 2004), (Toelle et al. 2004). In Australia, boys were found to be more likely to have current asthma than girls aged 014 years (15% of boys, 12% of girls) (Australian Bureau of Statistics 2002). Prevalence of current asthma decreased with age for both men and women (Australian Bureau of Statistics 2002). The prevalence of asthma does not significantly differ from the national average, among the states, or between major cities in Australia (Australian Institute of Health and Welfare 2005). Indigenous asthma patients were more likely to report having asthma than non-indigenous patients (17% compared with 12% in 2001) (Australian Bureau of Statistics 2003). The prevalence of asthma among indigenous children followed a similar pattern to that of the non-Indigenous population (Australian Bureau of Statistics 2003). 1.3. Mortality

In Australia, since 1989, the death rate has decreased markedly, and in 2003, asthma was identified as the underlying cause of 314 deaths only (108 males, 206 females) (Australian Institute of Health and Welfare 2005). It has been reported that death attributed to asthma increase with age, with very few deaths in childhood. Hence despite the prevalence and hospital use, the death rate among children was less than one death per 100,000 persons in 2003. This rate remains low during early and middle adult life, then increases markedly after the age of 50 (Australian Institute of Health and Welfare 2005). Mortality rates across different countries were compared by the workshop report on asthma by the Global initiative for asthma (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2004) and showed that Australia had the highest mortality rate (asthma mortality rate per 100,000 in persons aged 5 to 34 in 1993 = 0.86).

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1.4. Morbidity Morbidity refers to the impact of asthma on patients' lives in terms of hospitalisations, doctor visits, emergency room visits etc, and the degree to which it impairs it, i.e. patients' quality of life, perceived control over exacerbations of asthma, days off work, impairment of daily activities and similar aspects (Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2004). Asthma, due to its nature, affects patients physically, emotionally and socially. Patients have been found to be limited in their day-to-day activities such as sports, work or school work, and participation in other activities with friends, (Rabe et al. 2000), (Juniper 1997). It has been documented that children all around the world are missing school because of asthma (Anderson et al. 1983), (Taylor and Newacheck 1992), (Juniper 1997). Taking days off work is also a burden affecting asthma patients all around the world (Thompson 1984) and in Australia (1.5 to 1.9 million days of loss of production per year) (National Asthma Campaign 1992). Morbidity is still increasing, with 30% of the population still suffering from asthmarelated sleep disturbances at least once a week, and with one third of the children and more than half of the adults experiencing daytime symptoms at least once a week (Rabe et al. 2000). Other studies have confirmed this disturbing fact, as 24% to 52% of patients have been reported to have sleep disturbance due to asthma (Janson et al. 1997). In Australia, the burden of asthma among children is high compared to many other countries. Recent data show that 14-16% of children report a diagnosis of asthma that remains a problem, with more than one-third of children with asthma having sleep disturbance due to the illness, and 60% having missed school and/or experienced other restrictions in their activities due to the disease (Poulos et al. 2005). Asthma is one of the most frequent reasons of hospitalisation among children aged 0-14 years (Australian Institute of Health and Welfare 2005). In New South Wales, it was reported that 58% of children aged 2–12 years with asthma were restricted in their normal activity. This resulted in an average 9.3 days of reduced activity in 2001 (Centre for epidemiology and research - New South Wales Department of Health 2002).

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As for adults, asthma is one of the major reasons for visiting the doctor in Australia; being the seventh most common problem managed by general practitioners in 2002-2003 (asthma was managed in 2.7% of general practice encounters in 2002-2003). Asthma was the principal diagnosis in 37,230 hospital separations in 2002-2003, with an average length of stay of 2.5 days (Australian Institute of Health and Welfare 2005). Furthermore, it was documented lately in Australia that for patients with other existing chronic conditions, the additional presence of asthma was associated with significant further impairment in quality of life in those aged > 35 years (Adams et al. 2006). The results of the 2003 survey of disability "Ageing and Carers", showed that about 8.2% of patients with asthma have a level of disability associated with asthma, equally reported by males and females (Australian Bureau of Statistics 2003). 1.5. Cost of Asthma The cost of asthma is estimated by looking at the direct costs, which are relatively easy to measure (medication, medical bills and documented episodes of health service utilisation, such as clinic visits and hospital admissions) as well as indirect costs which include the adverse economic impact of the disease on an individual, family and society (cost of premature mortality, missed work or school, and days with restricted activity at work) (Smith et al. 1997), (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Consequently, and as a reflection of the chronic nature of the disease, recent reports of the economic burden of asthma to patients, their families, and society from all around the world indicate that asthma is a costly disease to manage (Anderson et al. 1983), (Thompson 1984), (Weiss et al. 1992). Estimates of the cost of asthma vary, with one study estimating a cost of $300 to $1300 per patients per year (Sullivan et al. 1996). It was estimated in a study conducted in the US that the total cost of asthma was $5.8 billion (95% CI, $3.6 to $8 billion), where the estimated direct expenditures were $5.1 billion (95% CI, $3.3 to $7.0 billion), and indirect expenditures were valued at $673 million (95% CI, $271 to $1,076 million) (Smith et al. 1997). As for children, the cost of medical

6


treatment for asthma has been estimated to range from 5.5 to 14.5% of the total family income (Marion et al. 1985). Studies in several countries have reported that patients with more severe asthma incur more costs than those with mild asthma. It was found that 10% of the population with severe asthma are responsible for 50% of the costs of asthma, while 70% of patients classified with mild asthma, were found to be responsible for 20% of the total asthma cost (Sullivan et al. 1996). Others reported that more than 80% of the resources are used by 20% of the population (defined as 'high-cost patients') (Smith et al. 1997). The number of long-acting 2-agonist and oral corticosteroid prescriptions was also found to have a significant association with high asthma costs (Sapra et al. 2005). The cost of asthma to the Australian community has been estimated to be $693 million in 2001-2002 (Australian Institute of Health and Welfare 2005). Health system expenditure, with the prescribed and over the counter medications causing the largest expense, accounted for $370 million (53.4% of the total expenditure attributed to asthma). Hospital use (admitted and non admitted patients), accounted for the 24.5% of the total expenditure (Australian Institute of Health and Welfare 2005). In children, asthma represents a considerable cost burden for Australian families, as the mean annual cost to each Australian family for each child with asthma was estimated to be $212.48 and 13.4 hours of time. The cost of asthma varied with the severity of the child's asthma. Families whose child had been hospitalised for asthma spent $884.34 and 153 hours of time annually (Toelle et al. 1995). Recent data have shown however, that since the early 1990s, there has been a decline in both hospitalisation rates and general practitioner consultation rates for asthma among children (Poulos et al. 2005). 1.6. Diagnosis of asthma GINA (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006) recommends that in defining asthma, measurements of lung function (objective measurements of airflow limitation and its variability, mainly reversibility of lung function abnormalities), are important for

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diagnosis and assessment of asthma as defining asthma in terms of symptoms alone is too difficult. Patients with asthma have poor recognition of their symptoms especially when their asthma is severe and long standing (Killian et al. 1993). Lung function measurements that are important for the diagnosis of asthma (in patients over 5 years of age) include Forced Expiratory Volume in one second (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow (PEF), and airway hyper-responsiveness (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). These measurements depend on the concept of airflow limitation relating directly to the luminal size of the airways and the elastic properties of the surrounding lung tissue (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Diagnostic testing of asthma can be confirmed by demonstrating the presence of variable airway obstruction, with the most common tests used being Spirometry and Peak Expiratory Flow (PEF) measurements (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Spirometry is a helpful tool in the diagnosis of asthma, as a 12% improvement in FEV1 either spontaneously, after inhalation of a bronchodilator, or in response to glucocorticosteroid therapy use, suggests a diagnosis of asthma (American Thoracic Society 2006), Measurement of FEV1 and FVC is done using a spirometer during a forced expiratory manoeuvre (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Spirometry is also used in monitoring a patient's asthma, but primarily in a clinic health care setting due to the expense and bulk of the apparatus (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2004). PEF is another important aid, not just in the diagnosis of asthma, but also in the subsequent management of asthma. Diagnosis of asthma is based on at least a 15% improvement in PEF after inhalation of a bronchodilator or after the trial of a corticosteroid (Quanjer et al. 1997).

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Asthma is difficult to diagnose in children, but is commonly a cause of wheeze. For this reason, several studies have investigated the presence of wheeze among children as a diagnostic tool, for example in 1997, 27% of Australian children aged 0-14 years, were reported to have had wheeze in the past twelve months (Woolcock et al. 2001). However in children, both in asthma patients and those with acute respiratory infections, wheezing is a consequence of widespread airway obstruction. In addition, localised airway obstruction and inhaled foreign bodies could be a cause of wheezing, which must be considered during differential diagnosis (Mok and Piesowicz 1993), (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). In addition, in the epidemiologic surveys for asthma, especially in countries with inadequate facilities for health care, or where problems with the interpretation of the wheeze may exist, objective markers (skin prick tests, pulmonary function and bronchial challenge tests) have been shown to be important and useful (Saraclar et al. 2003). 1.7. Asthma severity The Global Initiative for Asthma, workshop report 2002, classifies asthma on the basis of etiology, severity and pattern of airflow limitation (Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Patterns of airflow limitation monitored by PEF measurements have therapeutic implications. From this, the terms intermittent asthma (presence of occasional episodes of respiratory symptoms and PEF reductions in the last year with normal airway responsiveness in between episodes), and persistent asthma (daytime and nocturnal PEF variability, frequent symptoms and airway hyper-responsiveness) result (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). The conventional assessment of asthma severity has combined assessments of symptoms, reliever use, and lung function. The level of airflow limitation and its variability categorises asthma by severity into four groups: intermittent, mild persistent, moderate persistent and severe persistent according to GINA guidelines (Global Initiative for

9


Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). In Australia, the National Asthma Council Handbook (National Asthma Council Australia 2002) classifies asthma as mild, moderate and severe. Assessment takes place when the patients' asthma is stable using a table that is simple to use by health care professionals, to determine the patients‟ asthma severity (Table 1.1). This table considers the duration, intensity and frequency of symptoms as was suggested by O‟Connor and Weiss (O'Connor and Weiss 1994). The patients are assigned to the most severe grade in which any feature occurs (National Asthma Council Australia 2002). Table 1.1. Asthma Severity Table (National Asthma Council Australia 2002). Symptoms/Indicators

Mild

Moderate

Severe

Occasional

Most days

Every day

Nocturnal symptoms

Absent

< Once/week

> Once/week

Asthma symptoms on wakening

Absent

< Once/week

> Once/week

Absent

Usually not

Usually

Absent

Usually not

Bronchodilator use

< Twice/week

Most days

> 3-4 day

FEV1 (% predicted)

> 80%

60-80%

< 60%

Morning peak flow on waking

> 90% recent best

80-90% best

< 80% best

Wheeze, tightness, cough, dyspnoea

Hospital admission or Emergency Department attendance in past year Previous life-threatening attack (ICU or ventilator)

May have a history

It was recently reported by the Australian Institute of Health and Welfare, that the distribution of patients among the different levels of asthma severity in Australia, did not change significantly between 1999 and 2002 (Henderson et al. 2004). In 2002, 5.5% of

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adults were classified as having severe asthma, 27.2% moderate, 31.4% mild, and 35.9% very mild (Australian Institute of Health and Welfare 2005). 1.8. Asthma control There is a clear relationship between asthma severity and asthma control. The underlying severity of asthma in patients can be modified by changes in the environment, such as reducing exposure to trigger factors or optimising the treatment. This change in environmental and treatment factors will impact on the patients' symptoms and hence, their ability to function. 'Asthma control' reflects the combined effect of underlying disease severity, environmental exposure and the effectiveness of asthma treatment (Australian Institute of Health and Welfare 2005). Markers of asthma control include increased frequency and severity of asthma symptoms, increased use of reliever medication, being woken up frequently at night due to asthma, reduced days of activity, restricted physical activity, reduced functioning ability, and days lost from school or work. The last four markers of asthma control overlap with the impact of asthma on the quality of life of patients living with the disease (Australian Institute of Health and Welfare 2005). Hence, these markers are important for the ongoing monitoring of asthma. 1.9. Monitoring of Asthma Asthma can be monitored by assessing respiratory symptoms (such as shortness of breath, wheezing, cough, night-time awakening, and bronchodilator need), or by performing measurements of peak expiratory flow (PEF), using a portable device (Peak Flow Meters) (Kendrick et al. 1993), (Chan-Yeung et al. 1996), (Gibson 2000). Symptom-based self monitoring and PEF-based self monitoring are both beneficial in monitoring asthma control (Cote et al. 1997), (Cowie et al. 1997), (Turner et al. 1998), (Lopez-Vina and del Castillo-Arevalo 2000). However some patients with asthma are poor perceivers and remain asymptomatic despite the deterioration of their lung function (Burdon et al. 1982), (Apter et al. 1997), (Teeter and Bleecker 1998), which could lead to

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their delay in taking action, and hence lead to fatal attacks of asthma (Kikuchi et al. 1994). PEF-based action plans were found to be effective in protecting patients with asthma against severe exacerbations of their disease, and in reducing emergency department visits (Cowie et al. 1997), whereas, symptom-based action plans were found to be less reliable (Rietveld 1998). Not just asthma patients, but also physicians were found to incorrectly estimate the degree of airflow obstruction at least 50% of the time (Kendrick et al. 1993). So since an accurate evaluation of airflow obstruction is essential for achieving optimal treatment of asthma, the use of PEF monitoring is a valuable tool to assess airflow obstruction and asthma control (Burge 1992), (Rivo and Malveaux 1992), (Ignacio-Garcia and Gonzalez-Santos 1995). 1.9.1. Peak Flow Meter (PFM) use in asthma control monitoring The introduction of the Wright PFM in 1959 (Wright and Mc 1959) changed lung function testing from measurements carried out by health care professionals in hospital laboratories on few patients to a measurement wildly used in the management of patients by general practitioners (Jones 1991). There are many recent portable PEF meters that are suitable for general use, these include the mini-Wright, Allersearch, Vitalograph, Breathtaker, fdE and personal best. PFM are inexpensive and easy for patients to use and understand (Charlton and Charlton 1990). The use of PFM by patients with asthma has been thoroughly validated as an accurate measure of PEF (the maximum velocity of expiration that can be generated by patients) (Perks et al. 1979). The use of PFM has been recommended as an important part of self-management plans by the Global Initiative for Asthma Guidelines (Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Beside its recommended use for severity assessment, it is also recommended for use in the detection of exacerbations, monitoring response to therapy, identification of trigger factors and to provide objective justification for therapy to the patients. PEF measurements and monitoring provide an objective measure of lung function, and an important index of asthma stability and severity (Rubinfeld and Pain 1976), (National Asthma Education and Prevention Program - Expert Panel Report II 2002). Previous 12


studies have found that patients are capable of reliably recording PEF readings (Hetzel et al. 1979), (Janson-Bjerklie and Shnell 1988), (Gibson et al. 1995), (Cowie et al. 1997). It is important, however, that all measurements are performed on the same PFM for the patient, as although portable PFMs give highly repeatable readings, there may be significant differences between them because of non-linearity in PFMs, and hence, measurements can vary considerably between instruments (Koyama et al. 1998), (National Asthma Council Australia 2002). PEF have been proven to correlate highly with pulmonary function and clinical outcomes for asthmatic patients (Banner et al. 1976), (Mitchell et al. 1986), (Connolly and Chan 1987), (Troyanov et al. 1994), (Sachs et al. 1995), (Paggiaro et al. 1998). PEF readings are useful for monitoring diurnal variability in adults. Results can be expressed as percent predicted, percent personal best or absolute values (Gibson 2000). Reddel et al (Reddel et al. 1995) investigated various indices of PFM measurements, as patients recorded PEF morning and evening, before and after reliever use (if used) for two weeks. It was found that diurnal variability (amplitude percent maximum) without bronchodilator was significantly less than diurnal variability with bronchodilator. Reddel et al (Reddel et al. 1995) recommended the minimum morning pre-bronchodilator PEF over a period (a week or a fortnight), expressed as a percentage of the recent best PEF measurement (or the predicted best), as the best PEF index of peak flow measurements. This index is calculated as the lowest morning peak flow over recent best peak flow, times a hundred (%). Charts and nomograms show the mean PEF for selected populations, based on age, sex and height. The PEF value from two or three attempts should be recorded and is ideally measured during a stable period of lung function and symptom control. When writing an asthma action plan or changing treatment, the person's best PEF value is used. Many different options are available in interpreting the PEF measurement records, including relating the recorded value to the patients' previous best PEF (Gibson 2000). Relating PEF measurements to patients' previous best value provides a good indication of the day to day control of asthma (Gibson et al. 1995), (Reddel et al. 1998), (Global Initiative for

13


Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Meyer et al (Meyer et al. 1999) have shown that the graphic display of values in a series of data have an advantage over tables, when the displayed information has structure and when prior knowledge about structure exists, being an efficient way to detect abnormal values easily. The Asthma Management Handbook (National Asthma Council Australia 2002) provides general recommendations using PEF measurements, for health care professionals, to determine management decisions in asthma based on these measurements (Table 1.2).

Table 1.2. General recommendations using PEF measurements to determine management decision (based on the National Asthma Campaign - Asthma Management Handbook 2002) (National Asthma Council Australia 2002). PEF PEF > 80% of usual best PEF 60-80% of usual best

PEF 40-60% of usual best PEF < 40% of usual best

Symptoms No change Increased or at onset of upper respiratory tract infection Nocturnal waking, frequent need for bronchodilators (3-4 hourly) or no response to increased treatment No relief with bronchodilators

Advice Continue usual treatment Go to maximum dose of preventer (as detailed on the Action Plan) Start/resume oral corticosteroid and contact your doctor as soon as possible. If your doctor is not available, go to your nearest hospital emergency department Call an ambulance (000) and continue use of reliever

1.9.2. Asthma control and asthma related quality of life Traditional measures of disease impact, such as prevalence and mortality are important, but are of limited use to understand the extent of the effect of asthma on patients' lives (Australian Institute of Health and Welfare 2005). 'Quality of life' is defined as a "holistic,

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self-determined evaluation of satisfaction of issues important to the person" (Curtis et al. 1997). The more restrictive term 'health related quality of life', assesses the quality of life affected by health in general, and by the health care given to patients (Curtis et al. 1997). Hence 'health related quality of life' is a term used to describe the patients' perception of how asthma affects their physical, physiological and social wellbeing (Australian Institute of Health and Welfare 2005). Asthma, due to its nature as a chronic disease, puts considerable restrictions on the physical, emotional, and social aspect of asthma on patients' lives. So it was important to find an objective measure of these restrictions. Originally, a lengthy general scale of quality of life was used for the assessment of asthma, with the sickness impact profile consisting of 136 items in 12 categories (Bergner et al. 1981). After that, the validated, comparatively short SF-36 Health Status Questionnaire, based on 36 items selected to represent nine health concepts (physical, social, and role functioning; mental health; health perceptions; energy or fatigue; pain; and general health), proved its reliability and became widely used (Bousquet et al. 1994), (Stewart et al. 1988). However, it was then argued that quality of life scales that are disease specific are more relevant to asthma patients and more sensitive to small changes, and hence are favourable over the generic scales (Bergner and Rothman 1987). Specific quality of life scales, which included questions targeted to asthma patients, were then validated and used in clinical trials (Hyland et al. 1991), (Juniper et al. 1992), (Marks et al. 1992). Marks et al Asthma-related quality of life questionnaire was the shortest with 20 items only (Marks et al. 1992). The scale was formulated to be self-administered, with a Likert scale, and was proven to be a valid, responsive and reliable instrument (Marks et al. 1993). Health related quality of life can be used now to measure asthma control, describe and predict health outcomes, and assess clinical management (Australian Institute of Health and Welfare 2005). Hence, among asthma patients, disease severity, the level of disease control and the impact of the disease on the quality of life are interrelated (Australian Institute of Health and Welfare 2005). During periods of poor asthma control, asthma patients reported

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poorer quality of life (Vollmer et al. 1999). So, patients with severe asthma can be expected to have worse asthma outcomes and poorer quality of life than patients with less severe asthma. 1.10. Asthma management Asthma has no cure; however appropriate management control of the disease can be achieved. According to the GINA workshop report (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006), the goals for successful management of asthma include: achievement and maintaining control of symptoms, preventing asthma exacerbations, maintaining pulmonary function as close to normal levels as possible, maintaining normal activity levels including exercise, avoiding adverse effects from asthma medications, preventing development of irreversible airflow limitation, and preventing asthma mortality. In Australia, the 'Asthma Management Plan' was developed by the Thoracic Society of Australia and New Zealand in 1989 (Woolcock et al. 1989). The Asthma Management Plan is a simple set of guidelines for the management of asthma aimed at achieving and maintaining control of the disease. The plan was designed to assist health care professionals to develop good asthma management practices based on the safe and effective use of medications, to prevent asthma symptoms and to treat exacerbations. The asthma management plan is a dynamic document that reflects changes in asthma management (e.g. The introduction of the CFC free agents, trends away from nebulised to inhaled therapy, and the use of written asthma management plans) (Comino and Henry 2001). The 'National Asthma Campaign' was launched in Australian in 1990, to promote new approaches to asthma management through the dissemination of the Asthma Management Plan. The Asthma Management Handbook, first published in 1990, and revised and updated most recently in 2002 (National Asthma Council Australia 2002), is an excellent reference for health care professionals on asthma management.

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The asthma management plans provide asthma patients with instructions on how to recognise and respond to worsening asthma. It is recommended that these instructions are given to patients in writing. This plan is based on either symptoms and/or PEF measurements, and is individualised according to the patient's asthma pattern (Australian Institute of Health and Welfare 2005). The individualised plan of management is formulated in accordance with the 6-step Asthma Management Plan. The 6-step plan includes the following: 1- Assess asthma severity when the patient is stable. 2- Achieve best lung function by treatment with intensive asthma therapy until the „best‟ lung function is achieved. Back titrate to lowest dose that maintains good symptom control and best lung function. 3- Maintain best lung function by identifying and avoiding trigger factors (review of trigger factors is in the following section), and inappropriate medication use. 4-Maintain best lung function with optimal medication, by treating with the least number of medications and using the minimum doses necessary; ensuring the patient understands the difference between 'preventer', 'reliever' and 'symptom controller' medications;

and

taking active steps to reduce the risk of adverse effects from medications. 5- Develop an Action Plan by discussing and writing an individualised plan for the management of exacerbations; detailing the increases in medication doses and including when and how to gain rapid access to medical care. 6- Educate and review regularly, mainly by ensuring patients and their families understand the disease, the rationale for treatment and how to implement an Action Plan; emphasising the need for regular review, even when asthma is well controlled; reviewing inhaler technique and adherence to therapy at each consultation. The 'Asthma 3+ Visit Plan', is a program that began in Australia in 2001. This Asthma 3+ Visit Plan - Practice Incentive Program, is funded by the Australian government, and is aimed at patients with moderate to severe asthma. This program entails the development 17


and ongoing review of the Asthma Management Plan, over at least three visits to the general practitioner (Australian Institute of Health and Welfare 2005). Just recently, at the end of 2006, the Asthma 3+ plan has been replaced with the Asthma Cycle of Care Plan. The Asthma Cycle of Care plan is also funded by the Australian government and is also aimed at patients with moderate to severe asthma. However, this program entails the ongoing review of the management plan over at least two asthma related consultations within 12 months (National Asthma Council Australia 2006). Aspects of the 4th step in the 6-step Asthma Management Plan will now be reviewed in detail. 1.10.1. Medications used for the management of asthma In order to gain full appreciation of the different medications used for the management of asthma, it is important to understand the underlying pathology of the disease first. In patients who have died of asthma, the lung has been found to be over-inflated macroscopically. Both large and small airways appear to be filled with plugs comprised of a mixture of mucus, serum proteins, inflammatory cells and cell debris. There is microscopically extensive infiltration of the airway lumen and wall with eosinophils and lymphocytes accompanied by vasodilatation, evidence of microvascular leakage and epithelial disruption. Trophic changes identified include smooth muscle hypertrophy, new vessel formation, increased numbers of epithelial goblet cells, and the deposition of interstitial collagens beneath the epithelium. Recent data also provide evidence that IgE responses are involved in inflammatory processes apart from allergy, including asthma. In the airways, IgE plays an important role in bronchial hyperactivity (Rolinck-Werninghaus et al. 2005). Thus, there is evidence of both acute and chronic inflammation that is irregularly distributed through out the airways, including the smallest airways. This wide distribution of inflammation has implications for delivery of inhaled medications to the appropriate areas of the lung (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006).

18


Accordingly, approaches to asthma therapy reflect the ongoing understanding of the pathogenesis. Going back in history of asthma treatment, adrenalin was first used for asthma as an inhaled preparation in 1929 (Sakula 1988). The development of the inhalation devices in 1956 by the American engineer Philip Maschberg, facilitated the improvement in therapy (Barnes 1989). The realisation that asthma is an inflammatory process, has led, in the last two decades to advances in the treatment of asthma, where regular anti-inflammatory therapy, mainly inhaled corticosteroid products, have become the major therapy rather than the short-acting relievers (Paterson et al. 1995). Currently, medications for asthma form three major groups, bronchodilator (also referred to as reliever) medication, anti-inflammatory (also referred to as preventer) medication, and long-acting 2-agonist (also known as symptom controller) medication (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention Revised Workshop Report 2006). Preventative therapy is regarded as the first line therapy in patients with asthma, and there is increasing evidence that preventative therapy should be used as early as possible for all patients with asthma (Agertoft and Pedersen 1994), (Haahtela et al. 1994). Preventative therapy is important in controlling asthma symptoms and preventing structural damage to the lungs from the effects of chronic inflammation (Redington and Howarth 1997). It has also been shown that anti-inflammatory medications are important for all asthma patients, as airway inflammation was found even in mild asthma patients (Ward et al. 2002), and as soon as the diagnosis of asthma has been confirmed (Laitinen et al. 1993). Inhaled corticosteroids have considerable advantages over oral medications, as the clinical efficacy in the lung is similar, but with lower absorption systemically and fewer side effects (Wilson et al. 1998). The inhaled non steroidal anti-inflammatory agents include two chemically distinct agents from corticosteroids and from each other: sodium cromoglycate and nedocromil sodium (National Asthma Council Australia 2002). Sodium cromoglycate is used for exercise induced asthma in adults and children, or as an initial preventative therapy for children and adults with mild asthma. Nedocromil sodium produces similar protective effects

19


against allergen and exercise as sodium cromoglycate, but of longer duration (National Asthma Council Australia 2002). The leukotriene receptor antagonists form another class of preventer medications eg montelukast sodium. Leukotrienes are synthesised largely by many inflammatory cells (mainly mast cells and eosinophils) and contribute to the airflow obstruction, hyperactivity and inflammatory exudates associated with asthma (Spector 1996). Montelukast sodium competes with leukotrienes for receptors, and thus blocks leukotriene activity, improving pulmonary function and reducing the symptoms of asthma (Spector 1996). Montelukast sodium is not a substitute for inhaled corticosteroids or longacting 2-agonist, although it may act as a 'sparing drug', which might help tapering of corticosteroids in some instances. It may have a role in exercise-induced asthma as well (Garcia-Marcos and Schuster 1999). Theophylline has a number of functions, including bronchodilatory activity and down regulation of inflammatory mediators; however the drug's popularity has decreased because of its narrow therapeutic index (McDonald and Lipp 1998). Theophylline still has a role as a third or fourth line agent in the management of chronic persistent asthma (McDonald and Lipp 1998). Anticholinergic medications have been accepted as an important treatment in chronic asthma

(Beakes

1997).

Ipratropium

bromide

is

a

short-acting

anticholinergic

bronchodilator with few systemic effects, but its use has been reduced recently because of the introduction of tiotropium bromide, a long-acting anticholinergic medication (Australian Institute of Health and Welfare 2005). The major role of these medications has been in the treatment of chronic obstructive pulmonary disease (McDonald and Lipp 1998). In asthma, a recent review has shown that anticholinergic agents have a demonstrated role in combination with long-acting 2-agonist, in the treatment of acute severe asthma, and may benefit asthma patients with chronic obstructive pulmonary disease-like inflammation (Kanazawa 2006). Moreover, these agents could be also beneficial in preventing airway remodelling in asthmatic airways (Kanazawa 2006). Treatment with inhaled tiotropium bromide was found to markedly inhibit the increase in

20


airway smooth muscle mass, myosin expression, and contractility in asthma (Kanazawa 2006). With the effective use of the inhaled corticosteroids, interval oral corticosteroid use has been restricted to occasional use for patients with severe asthma (McDonald and Lipp 1998). The dose of inhaled corticosteroid should be titrated against asthmatic symptoms, PEF and reliever use, with the safest dose of inhaled corticosteroids being the lowest effective maintenance dose which produces optimal long term control (Lipworth 1999). Reliever medications include short-acting 2-agonist agents, e.g. salbutamol and terbutaline. These are the main drugs for the acute relief of asthma symptoms. They effectively and rapidly relieve symptoms relating to muscle spasm, peaking after 30-90 minutes and lasting for 4-6 hours; but they have no (or little) effect on the inflammation of the airways (McDonald and Lipp 1998). Relievers should generally be used on "as needed" basis, rather than regularly. Inhalation using either a pressurised metered dose inhaler, a breath activated inhaler (Autohaler) or a dry powder inhaler (Turbuhaler) is the preferred method of delivery. The regular use of relievers has been associated with loss of symptom control and reduced protection against bronchoconstriction (Cockcroft and Swystun 1996), and hence current guidelines recommend their use for symptom relief only (National Asthma Council Australia 2002). Symptom controllers include the long-acting 2-agonists eg salmeterol and eformoterol. They do not treat the underlying airway inflammation and should only be used as an adjunct to regular inhaled corticosteroids (Barnes 1997). They produce bronchodilatation of up to 12 hours after administration, making them particularly useful for the treatment of nocturnal asthma (McDonald and Lipp 1998). For patients whose asthma is not adequately controlled with inhaled corticosteroid therapy alone, improvements in lung function are achieved with the addition of a long-acting 2-agonist to inhaled corticosteroid therapy (Woolcock et al. 1996), (Lotvall 2002). The long-acting 2-agonist can also be considered as beneficial additions to inhaled corticosteroid therapy for the management of moderate to severe asthma (Lipworth 1999), (Lotvall 2002).

21


None of the existing treatments for asthma are curative, and symptoms return soon after treatment is stopped (Barnes 1997). Even patients who are started on a regimen of an effective dose of an inhaled corticosteroid at the onset of asthma and who are successfully maintained on that regimen for 2 years, demonstrate a return in symptoms after withdrawal of treatment (Haahtela et al. 1994), hence continual medication use for proper asthma management is a must. 1.11. Drug delivery in asthma Asthma is characterised by local inflammation in the lung, and so it is logical to use the inhalation route for treatment. Patients with asthma have used the lung as a route of drug administration in the 19th and early 20th centuries, where they have smoked asthma cigarettes (stramonium powder mixed with tobacco), to treat the symptoms of asthma. Inhalation remains the principal route for drug administration (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). Local administration of the drug has certain advantages over systemic treatment. Asthma is a disease localised to the airways, inhalation therapy allows the medication to be delivered directly to the lung, allowing a localised effect (Newhouse and Dolovich 1986), (National Asthma Education and Prevention Program Expert Panel Report II 2002). Also, the inhalation route allows the medication to bypass the need for systemic absorption and thus hepatic metabolism, therefore a smaller dose of drug can be administered via the inhaled route to achieve the maximum effect, helping to reduce the systemic side effects of the medication (Newhouse and Dolovich 1986), (Global Initiative for Asthma (GINA) - Global Strategy for Asthma Management and Prevention - Revised Workshop Report 2006). There are currently several different inhalation devices used in the treatment of asthma. The most common ones include Nebulisers, Pressurised Metered Dose Inhalers (pMDI), and several different Dry Powder Inhalers (DPI). Nebulisers are devices which produce a respirable aerosol from a solution-containing drug. Oxygen, compressed air or ultrasonic power are used to break up solutions or suspensions of medication into droplets for inhalation, the aerosol formed is then 22


administered by a mask to the patients, and this has been found to have high patient acceptability (Shaw 1999). They are generally reserved for patients who have difficulty in using pMDI and DPI. They are more commonly used by patients under 5 years of age but can be used for all age groups (Muers 1997). They are used in acute severe asthma exacerbations in the hospital environment, when a high dose of long-acting 2-agonist therapy is required (Muers 1997), (Ward 1997). However there is a great variability in the lung deposition ranging between 2-13% in adults (Zainudin et al. 1990), (Thomas et al. 1991), and 3-11% in children (Chua et al. 1994), (Wildhaber et al. 1999). Output from Nebulisers is influenced by a wide range of technical, environmental and drug factors (Bisgaard 1997), (Boulet et al. 1999), which can lead to low output predictability. Nebulisers are also expensive, cumbersome, bulky, difficult to operate, not easily portable, require technical and hygienic maintenance, and there is no evidence to suggest that they are superior to other delivery devices for asthma (Brand 2000). Considerable improvement of asthma therapy has been accomplished with the introduction of propelled pMDIs in 1956, which contained the chlorofluorocarbons (CFCs) as a propellant.

Since 1987, newer CFC-free inhaler devices using

hydrofluoroalkanes (HFAs) have been developed, where the drug is dissolved or suspended in the propellant under pressure, which when activated, releases a metered volume of drug and propellent. The pMDIs, in general, are the most widely used inhalation devices in the treatment of asthma particularly with regards to the delivery of reliever medications (Guidry et al. 1992), (Erickson et al. 1998). They have the advantages of being less time consuming when compared to the Nebulisers, (Wildhaber et al. 1999), portable, efficient and cost effective (Walley et al. 1999), (Boulet et al. 1999). The lung dose achieved ranges between 7-21%, provided patients demonstrate correct technique. pMDIs are still the most popular devices for asthma in Australia (Australian Institute of Health and Welfare 2005). However, there is a significant amount of literature going back two decades ago, reporting on the fact that many patients could not demonstrate the correct use of the pMDIs (from 5 to 87%), and hence would not get the optimal benefit from the medication (Horsley and Bailie 1988), (Manzella et al. 1989), (Hilton 1990), (Dompeling et al.

23


1992), (Larsen et al. 1994), (Goodman et al. 1994), (van Beerendonk et al. 1998), (Pinto Pereira et al. 2001). Recent studies have revealed the persistency of this problem, as only 42% and 53% of patients' were found to use their pMDIs correctly (Loh et al. 2004), (Minai et al. 2004) respectively. Despite instructions by medical personnel on pMDI technique, about 50% of patients still did not use the pMDIs as instructed, with the main drawback being the problem in coordination between the release of the dose and inhalation (Crompton 1982). Crompton et al (Crompton 1990) concluded in a later review, that 50% or less of adult patients can be expected to use the pMDIs correctly after reading the instruction leaflets, and hence foretell of a limited future use of the pMDIs. The problem of coordination with the pMDI has also been found to result in a decrease in the mean percentage of the dose deposited in the lungs (from 22.8% to 7.2%) (Newman et al. 1991). A spacer was used as a solution to the pMDI technique problem. Asthma patients were found to be able to learn and maintain proper technique with the use of a spacer (Johnson and Robart 2000). The spacer holds the aerosol from the pMDI in a confined space, and allows subsequent inhalation of the medication without coordination. Studies with a radio-aerosol have shown that the deposition of drug in the lung increased from 7.8% to 21% when a spacer was added to a pMDI (Newman et al. 1984), (Kerem et al. 1993). However, the use of a pMDI with a spacer makes the whole device very cumbersome, and often patients with asthma prefer to use another inhaler. Other devices were then introduced, such as the breath actuated pMDIs (BA-pMDIs), the Autohaler, which incorporated the mechanism of activation during the patients' inhalation, triggering the pMDI. The Autohaler can be used as an alternative to the traditional pMDI, as it does not involve any user coordination, therefore can improve lung deposition in patients with poor pMDI technique (Newman et al. 1991). The newer devices developed over the last two decades have been the DPIs, which solved the problem of coordination with inhalation (Roche and Huchon 2000). These devices contain micronised powdered medication with a propellant in a small portable aerosol device that gets dispersed into particles by the inspiration as the inhaler gets activated via 24


inhalation by the patient. Several types of DPIs are available, some with single dose, capsule based inhalers such as the Rotahaler, Aeroliser, or Handihaler. Others are multidose inhalers, and they are the more popular types of DPIs. Some of these multi-dose inhalers are reservoir type inhalers, such as the Turbuhaler (200 doses), Clickhaler (190 doses), Easyhaler (200 doses) and Novolizer (100 doses), and some are based on prefilled blisters (60 doses), such as the Accuhaler (Diskus), or blister disks (4 doses) such as the Diskhaler. DPIs were developed for use in adults and schoolchildren with bronchial asthma, and have been shown to deliver drugs safely and effectively (Kemp et al. 1997), (Richter 2004). Many studies have shown that patients prefer DPIs over pMDIs, and can use them more effectively (Chapman et al. 1993), (Kesten et al. 1994). DPIs were found to be easier to use than the pMDIs (Crompton 1991). DPIs maximise drug deposition in the lung, as pMDIs were found to deliver about one third of the amount of medication to the lungs when compared to the DPIs (Thorsson et al. 1994), (Borgstrom et al. 1996), (Roche and Huchon 2000). A study comparing pMDIs and DPIs, reported an improvement of lung deposition of terbutaline from 8% with the pMDI to 22% with the DPI (Borgstrom et al. 1996). Another study documented the lung deposition of budesonide via Turbuhaler to be 2.2-fold higher than that of fluticasone via pMDI (Thorsson et al. 2001). The dose of salbutamol delivered by TH was also found to be twice than that delivered via pMDI, and maybe even 1.5 to 2-fold higher than that delivered via pMDI with spacer (Ekstrom et al. 1995). However, although all the DPI devices are breath activated, their performance was found to vary in terms of lung deposition, from 9% for the Rotahaler (Zainudin et al. 1990) to 11-15% for the Diskhaler (Newman et al. 1981), to 26-32% for the Turbuhaler (Thorsson et al. 1994). This means that variation within the performance of these DPIs exists as well. Studies have found however, that the most common and efficient of the DPIs are the Turbuhaler and the Accuhaler (van der Palen et al. 1998).

25


Many factors play a role in the overall performance of the Turbuhaler (TH) and Accuhaler (ACC), from its mechanical and aerodynamic properties, to its pharmaceutical formulation, physical and chemical properties, and on the way it is used by the patients. Being the most popular of the DPIs, the function and performance of the TH (AstraZeneca, Sweden) and ACC (GlaxoSmithKline, UK), will be further investigated. 1.11.1. The Turbuhaler (TH) The TH is a type of a multi-dose reservoir system (contains 200 doses), that contains a reservoir of micronised particles of the medication and a dose metering unit which gets charged as the patient breathes from the inhaler (Figure 1.1). Many clinical studies have shown that the medication is effectively delivered and well tolerated via the reservoir powder inhaler (Persson et al. 1988), (Chapman 1995), (Pauwels et al. 1996), (Wettengel et al. 2000). The active drug is blended with lactose particles of similar size to the drug particles. The particle blend turns into small agglomerates, which disintegrate into their primary particles during the inhalation process. Turning the grip of the inhaler rotates the dosing unit and drug is moved into dose metering holes. As the patient inhales, air passes throughout the powder bed, and lifts the dose. Particle deaggregation is caused by turbulence in the two spiral channels within the mouthpiece. The inhaler has a tightly screwed on cap, and an internal drying agent in the inhaler which protects the drug from humidity (Borgstrom et al. 2005) (Figure 1.1). The TH does not contain propellants, carriers and other drug additives, and hence may avoid the occurrence of side effects due to excipients (Kemp et al. 1997). The TH showed an increase in drug deposition in the lung (Borgstrom et al. 1996) and a lower drug dose is required to produce optimal asthma control when drug is delivered by the TH than when given by a pMDI (Roche and Huchon 2000), (Lotvall 2001). The TH had been claimed to be technically superior to many of the other inhalation devices available as well, because it has a lower inter-subject variability with lung deposition and results in lower oropharyngeal deposition (Newman 1995), (Roche and Huchon 2000). The TH was found to be associated with a greater efficacy (Jackson and Lipworth 1995), (Metzger et

26


al. 2002), suggesting that the increased deposition could be associated with increased drug efficacy (Cochrane et al. 2000). From the patient perspective, the TH was found to be preferred and require significantly less time to master than the pMDIs (Kesten et al. 1994), (Welch et al. 2004). The TH has also been compared to other inhalers, regarding ease of use and acceptability, and it was found that both children and parents expressed a preference for the TH over other inhalers (Brown et al. 1992), (van der Palen et al. 1998), (Serra-Batlles et al. 2002).

Figure 1.1. An image of a TH device (adopted from Wetterlin (Wetterlin 1988)).

Mouthpiece with insert

Bypass air inlet Inhalation channel Air inlet Desiccant store

Window for dose indicator Dose indicator Storage unit for drug Dosing unit Operating unit Turning grip

Loading the device is performed by rotating the dosing unit in the storage unit, toward a pressure plate beneath the dosing unit, by a simple twisting back and forth of the turning grip.

27


1.11.2. The Accuhaler (ACC) The ACC (Diskus) is another multi-dose powder inhaler containing 60 doses, in which the drug is contained within blisters on a foil strip (Figure 1.2). The doses of drug in the ACC are protected from moisture (Ganderton 1997). The ACC was formulated to deliver precise individual doses of drug to allow the average patient a month's therapy. It was designed to be simple to operate and contains a dose counter. The pharmaceutical assessment of the ACC has shown that the delivered dose of salmeterol and fluticasone propionate remains at approximately 90% of the labelled claim at a range of flow rates of 30-90 l-min-1. The fine particle mass of salmeterol delivered from the ACC is unaffected by humid conditions (30 degrees C / 75% relative humidity) (Fuller 1995), as opposed to the reservoir powder inhalers. On the foil strip, each blister contains a metered amount of small drug particles blended with larger lactose particles as a carrier. As the blister is moved towards the mouthpiece, the foil covering is removed from the blister before inhalation. Air is drawn through the inhaler, which lifts and aerosolises the powder. No active drying agent is found inside the inhaler or the blisters (Figure 1.2). The ACC was preferred over the pMDIs by the patients, because of the dose counter, presence of an attached cover, taste, instruction for use, attractiveness, ease of use, ease of holding, shape and comfortable mouthpiece (Oliver and Rees 1997), (Chrystyn 1999), (Liam et al. 2000), (Serra-Batlles et al. 2002), (Moore and Stone 2004).

28


Figure 1.2. An image of an ACC device (adopted from Chrystyn (Chrystyn 1999)).

Body

Contracting wheel

Dose indicator

Lever Dose indicator wheel Thumb grip

Strip lid peeled from packets

Loading the device is performed by sliding the lever back which unseals one blister and opens the mouthpiece

Outer case Packets containing drug

Drug exit port mouthpiece

Lever

Coiled strip

Manifold Index wheel Empty strip Base wheel

Mouthpiece

1.11.3. Comparing the TH and the ACC Since the TH and the ACC were found to be equally preferred by patients (van der Palen et al. 1998), it would be interesting to compare the features they possess and the clinical effects of their medications. Variability in lung deposition is an important factor that determines the clinical effectiveness of an inhaled medication. The overall delivery of the medication can be affected by many steps, such as device performance, handling and correct use of the device at inhalation, inhalation flow and patient's anatomy (Borgstrom et al. 2005). In an evaluation of the clinical effect of the drugs delivered by the TH and the ACC, no statistically significant difference between budesonide TH and fluticasone ACC was found, neither in the minimal effective dose or in secondary variables (PEF, FEV1, use of reliever, and asthma related night-time awakenings) (Kuna et al. 2003). A comparison between both inhalers has shown little difference in therapeutic efficacy (Crompton 1991), (Brown et al. 1992). Another study showed that the TH and the ACC resulted in

29


the same magnitude of systemic effects measured by cortisol suppression, even though the TH resulted in a three fold higher lung deposition than the ACC (Thorsson et al. 2001). The fact that both devices incorporate an integral dose counter, facilitates monitoring of therapy by both patients and health care professionals (Sharma et al. 1996), (Schlaeppi et al. 1996), (Serra-Batlles et al. 2002). Both inhalers were found to be equally acceptable in terms of ease of use and convenience to carry (Brown et al. 1992). Serra-Battles et al (Serra-Batlles et al. 2002) found no significant difference between the proportion of patients who were quite satisfied or very satisfied with being prescribed the TH (74%) or the ACC (76%). However 60% of patients in this study overall preferred the ACC over the TH, with perceived ease of use and ease of learning to use the device being a factor in their preference (Serra-Batlles et al. 2002). Other studies also supported the ACC being preferred more than the TH by patients, with the perceived ease of use, dose counter, shape, and feel of the powder being inhaled, being the main reasons (Schlaeppi et al. 1996), (Ronmark et al. 2005). The combination of salmetrol and fluticasone propionate in the ACC (Seretide®), and budesonide and formoterol fumarate in the TH (Symbicort®), reflects current asthma treatment guidelines. This may facilitate patient compliance, thereby improving asthma control (Chrystyn 1999). Many studies have reported on the benefits of the association of the use of both inhaled corticosteroids and long-acting 2-agonist (Kavuru et al. 2000), (Bateman et al. 2004). The combination means more cost effective and better adherence to therapy with the one inhaler (Zetterstrom et al. 2002). Hence, we can conclude that both the TH and the ACC can be expected to perform equally when it comes to patients' preference and clinical effect of the treatment they deliver.

30

Chapter 1- Literature Review Part III

Literature Review Part III - Pharmaceutical Care/Disease Management

1.18. Pharmaceutical Care In 1990, Hepler and Strand proposed the concept of pharmaceutical care that gave pharmacists new roles and responsibilities in the appropriate use of the medication to optimise patients‟ health outcomes (Hepler and Strand 1990). This was then adopted by the pharmaceutical organisations and became the philosophy of pharmacy practice (Hepler and Strand 1990). Pharmaceutical care was said to include the identification of potential and actual drug related problems and resolving and preventing potential drug related problems (Hepler and Strand 1990). 1.18.1. Providing patient care Over the years, community pharmacists have become more and more active in patient care and have been acknowledged for the benefits of their counselling on patient treatment (Kansanaho et al. 2002), (Jones et al. 2005). Community pharmacists have shown that they are able to provide independent medication advice within primary care, in an unhurried, private, and credible environment (Self and Nahata 1997).

31


In a review conducted over 25 years (1969-1994), looking at the effects of pharmacistpatient communication, results revealed that pharmacists can increase patients' knowledge and compliance with their medications (De Young 1996) and are effective in changing patients‟ behaviour through the different services they deliver (Beney et al. 2000). A survey conducted over 10 years (from 1985 to 1995), found that in 1985 (Vainio et al. 2004), physicians were considered as the main providers of drug information, while public health nurses (22%), books and magazines (21%), and pharmacists (20%) were rated equally. Ten years later, the main providers were found to be the pharmacists (55%), followed by the physicians (33%). The perceived importance of physicians as a provider of drug information did not change between 1985 and 1995 (78% vs. 76% considered very important), while the proportion of patients who considered pharmacists being "very important" almost doubled (from 40% to 71%). No major changes took place in the perceived importance of the other providers. Hence it is clear that a highly positive shift in the perceptions about the role of the pharmacist as a medication information provider had taken place (Vainio et al. 2004). Previous research has also shown that patients are willing to discuss their medications in detail with their pharmacists (Chen and Britten 2000). In Australia, patients have been found to perceive pharmacists as trustworthy and highly reliable advisors on medication use (Benrimoj and Frommer 2004). 1.18.2. Supporting health care providers As well as delivering services to patients, community pharmacists can also play a significant role in providing product related information to other health care professionals (Haynes et al. 1992), (Hamrosi et al. 2006). Studies examining pharmacist services targeted at health professionals showed that positive outcomes, such as a decrease in prescribing and medication costs result, when compared to health professionals not receiving these services (Beney et al. 2000). This movement towards effective pharmacy involvement not only improved the quality of patient care and/or physician education, but also resulted in reducing the cost of the treatment (Strong and Tsang 1993). Hence there

32


is great need for pharmacists to continue their role in delivering education to patients and physicians regarding drug therapy, particularly in chronic diseases (Beney et al. 2000). 1.18.3. Providing health promotion Health promotion is another area in which community pharmacists have provided a positive impact on public health (Boyle et al. 2004), (Sinclair et al. 2004), including asthma (Kritikos et al. 2005). The health promotion activities delivered by community pharmacists are referred to as “non-product related”, as they do not just focus on drug therapy, but on the patient's general well being (Beney et al. 2000). 1.18.4. Providing economic benefits Economic benefits have been reported from the pharmacist's involvement in the drug use process for different chronic conditions including hypertension, hypercholesterolemia, diabetes and/or asthma (Munroe et al. 1997). In Australia, pharmaceutical care services have been proven to be highly valuable in helping at risk patients to better manage their condition and medications, resulting in a cost benefit to the health system (March et al. 1999), (Armour et al. 2004), (Saini et al. 2004). It has been suggested that clinical interventions delivered through community pharmacies can be cost beneficial if pharmacists are provided with the appropriate education (Benrimoj et al. 2000), signifying that educating pharmacists before they deliver the service is the key to the success of these services. 1.18.5. Management of chronic diseases Studies directed at pharmacist‟s provision of services for chronic diseases have indicated improvement in patient outcomes when compared to patients not receiving the services (Singhal et al. 1999).

33


Many studies have investigated the role of the pharmacist as an educator in different programs for patients with chronic diseases, such as hypertension, cancer, diabetes, and asthma. Results have demonstrated highly beneficial outcomes for patients from these programs (Armour et al. 2004), (Saini et al. 2004), (Armour et al. 2007). In hypertension, pharmacists have been found to be fully aware of hypertensive patients‟ clinical and humanistic outcomes and hence can counsel and advance patients‟ drug therapy (Franic et al. 1999). Community pharmacists have also generated, through an intervention, benefits that were 10 times higher than costs (Cote et al. 2003). In palliative care, community pharmacists have been shown to intervene effectively to improve patient care (Needham et al. 2002). In diabetes, community pharmacists have been shown to improve health care outcomes for people with diabetes after providing a specialised service (Armour et al. 2004), (Krass et al. 2005). In coronary heart disease, a review by Blenkinsopp et al (Blenkinsopp et al. 2003) showed that many studies in community pharmacy have provided evidence of clinical and cost effective improvement of patient care, which can lead to reduced risk factors for coronary heart disease. In asthma, community pharmacists have been successful in improving asthma patients' clinical and humanistic outcomes (Saini et al. 2004), (Armour et al. 2007). 1.19. Community pharmacists delivering asthma clinical interventions It has been properly stated that “Successful asthma management is 10% medication and 90% education” (Fink and Rubin 2005), and much effort has been directed at conducting clinical

interventions

for

asthma

patients.

Many

pharmacist

delivered

clinical

interventions have also been developed, and these usually aim to optimise drug therapy, minimise drug related problems, improve self-management and improve the quality of life of patients with asthma (Narhi et al. 2001), (Saini et al. 2004). An examination of the various studies exploring the role of community pharmacy based clinical interventions, from across the globe, clearly show that community pharmacists can have a positive impact on the care of patients with asthma. Recent data from studies in the United States (Odedina et al. 2000), (Weinberger et al. 2002), Finland (Narhi et al. 2002), Sweden (Lisper and Nilsson 1996), Malta (Cordina et al. 2001), the Netherlands (Stuurman-Bieze

34


et al. 2005), Canada (Diamond and Chapman 2001), the United Kingdom (Barbanel et al. 2003), British Columbia (McLean et al. 2003), Denmark (Herborg et al. 2001), Germany (Schulz et al. 2001), and closer to home, from New Zealand (Emmerton et al. 2003) demonstrate an improvement in patients‟ clinical and humanistic outcomes following pharmacist's interventions. In Australia, the effects of community pharmacy based interventions on asthma management were found to be equally successful in improving patients' clinical and humanistic outcomes (Saini et al. 2004), (Armour et al. 2007) and in producing cost savings (March et al. 1999), (Saini et al. 2004). In fact, a survey conducted in the early 1990s in Australia (n= 368 pharmacies) showed that pharmacists wanted to learn more about asthma, were interested in receiving asthma information and were prepared to distribute information to customers (Comino et al. 1992). Given this level of willingness to add value to existing asthma services, the results of the recent studies which demonstrate positive outcomes from pharmacist delivered asthma clinical interventions is hardly surprising. Additionally, it was shown in the pharmacists' survey that at least half the pharmacists in the sample were being regularly asked for advice about asthma (Comino et al. 1992). Hence, pharmacists and community pharmacy venues provide an ideal opportunity for facilitating patient asthma education activities. Inhaler technique education was incorporated as one aspect in many of the extensive clinical interventions delivered on asthma management (Narhi et al. 2000), (Odedina et al. 2000), (Cordina et al. 2001), (Schulz et al. 2001), (Herborg et al. 2001), (Diamond and Chapman 2001), (Narhi et al. 2002), (Weinberger et al. 2002), (Emmerton et al. 2003), (Barbanel et al. 2003), (McLean et al. 2003), (Saini et al. 2004), (Mangiapane et al. 2005), (Stuurman-Bieze et al. 2005), (Armour et al. 2007). Many of these clinical interventions reported improvements in patients' inhaler technique as an outcome (Diamond and Chapman 2001), (Narhi et al. 2002), (Cordina et al. 2001), (Schulz et al. 2001), (Herborg et al. 2001), (Saini et al. 2004), (Mangiapane et al. 2005), (StuurmanBieze et al. 2005), (Armour et al. 2007). As well as improvements in patients‟ inhaler technique, these studies also reported improvements in asthma symptoms (e.g. daytime wheeze, night time wheeze, nocturnal awakening, and allergic symptoms) (Narhi et al.

35


2000), (Cordina et al. 2001), (Diamond and Chapman 2001), (Herborg et al. 2001), (Emmerton et al. 2003), (Barbanel et al. 2003), (McLean et al. 2003), (Mangiapane et al. 2005), (Stuurman-Bieze et al. 2005), (Armour et al. 2007), improved peak flow readings (Narhi et al. 2000), (Cordina et al. 2001), (Herborg et al. 2001), (Weinberger et al. 2002), (Emmerton et al. 2003), (McLean et al. 2003), (Saini et al. 2004), (Mangiapane et al. 2005), as well as improved FEV1 (Schulz et al. 2001), reduction in reliever medication use (Diamond and Chapman 2001), (McLean et al. 2003), (Saini et al. 2004), (Armour et al. 2007), reduction in emergency room and medical visits (McLean et al. 2003), fewer days of sickness (days off work or school) (Herborg et al. 2001), (McLean et al. 2003), lower use of health care services (Herborg et al. 2001), decrease in emergency room and medical visits (McLean et al. 2003), increase in asthma knowledge (Saini et al. 2004), (Armour et al. 2007), improvements in humanistic outcomes (reported as asthma related quality of life, improved state of empowerment, improved coping behaviour with pulmonary medications and perceived control over asthma) (Schulz et al. 2001), (Herborg et al. 2001), (McLean et al. 2003), (Emmerton et al. 2003), (Saini et al. 2004), (Stuurman-Bieze et al. 2005), (Armour et al. 2007), greater satisfaction with the pharmacist role (Weinberger et al. 2002), (Narhi et al. 2002), (Saini et al. 2004), and cost effectiveness (McLean et al. 2003), (Saini et al. 2004). Although all these community pharmacy interventions have been shown to deliver positive improvements in health outcomes for asthma patients, it is not possible within these studies to attribute improved asthma outcomes to an improvement in inhaler technique. Whilst the improved inhaler technique may have been a contributor to the improvements in asthma outcomes, other areas of focus within the clinical interventions that these studies developed and tested could well be equal contributors. Since the importance of inhaler technique counselling for asthma patients has been highlighted previously by many researchers in this field (De Tullio and Corson 1987), (Ekedahl 1996), (Cordina et al. 2001), (Schulz et al. 2001) as being "one of prerequisites for achieving positive outcomes of drug therapy" (Schulz et al. 2001), it is important to investigate the effect of inhaler technique on health outcomes for asthma patients.

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The above community pharmacy interventions were very extensive and complex and the training provided to pharmacists in order to ensure competence to deliver these interventions reflected this complexity. In these studies, the pharmacists training took from two evenings {Cordina, 2001 #45} to two weekend workshops (Emmerton et al. 2003). In a recent review by Mcleane and MacKeigan (McLean and MacKeigan 2005) which compared different studies conducted on asthma services, it was shown that comprehensive pharmacist training was developed and implemented in all cases (from 13 hours of training in therapeutics, communications and protocols (Schulz et al. 2001), to a weekend workshop on pharmaceutical care of asthma with pre-reading and 3 cases to be submitted after the workshop (total 25 hours) (McLean et al. 2003). As reported by many authors (Diamond and Chapman 2001), (Narhi et al. 2002), this length of training and commitment may not be available in routine practice. Considering the time it took the pharmacists to deliver these intervention services (57 minutes per patient at the first visit, with follow-up visits taking 21 minutes (Saini et al. 2004); 15-120 minutes a visit (Narhi et al. 2002), 40-60 minutes a visit (Emmerton et al. 2003), (Barbanel et al. 2003), with follow-up visits taking 15-20 minutes (Emmerton et al. 2003)) the practicality of the above studies must be questioned. Hence, even if community pharmacists had the knowledge and the will to deliver these interventions, time constraints may restrict them from doing so. Time limitation has been acknowledged as an important difficulty in community pharmacists' counselling provision (Odedina et al. 1995), (Osman et al. 1999), (Hibbert 2000). Therefore, there is a need for interventions that are realistic in terms of the time required. Inhaler technique education is a focussed intervention which is not likely to require extensive training programs to educate the pharmacists, or further lengthy interventions to be delivered to the patients. At this stage, it would be important to investigate interventions delivered by community pharmacists focussing on inhaler technique counselling.

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1.20. Inhaler technique counselling interventions in community pharmacies Many questions arise when the role of the community pharmacist in patients‟ inhaler technique counselling is focussed upon. For example, what is the extent of the role of the community pharmacist with regards to educating asthma patients on correct inhaler technique?; how willing are community pharmacists to deliver inhaler technique counselling to asthma patients?; and how much time and how frequently do community pharmacists need to deliver inhaler technique counselling to asthma patients? Using a patient centred approach, one also needs to examine whether asthma patients are prepared to be reviewed on their inhaler technique in the community pharmacy. What is the effect of inhaler technique counselling by community pharmacists on asthma patients' inhaler technique and clinical and humanistic outcomes, both short term and long term? A review of the literature reveals that very few studies have been conducted to primarily investigate inhaler technique counselling interventions in community pharmacies. One of these studies was an open counselling program run in community pharmacy settings in Sweden for one year (all pharmacies in Sweden participated in this campaign ((1992)The Asthma Year)). The goal of this program was to investigate whether patients were willing to demonstrate how they used their inhaler (TH) in the pharmacy setting, how often was the TH incorrectly handled by patients and whether this could be improved by education (Ekedahl 1996). In this study, pharmacy staff were requested to view a videotape on the topic, and this was followed by face to face training on how to initiate communication and counselling with inhaler users. A standard protocol was provided to, and followed by the pharmacy staff which enabled them to identify and rectify errors in the handling of a TH by patients over two 1-month periods (April 1992, n=287; April 1993, n= 419). A checklist of 6 steps (checklist not provided) was used to assess patients' inhaler technique. The study included all patients purchasing prescribed medication for personal use (except for first time users). Sixteen out of nineteen invited pharmacies participated in the study. Results of the study revealed that patients were quite willing to demonstrate how they handled their TH in the community pharmacy. A significant

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improvement in the proportion of patients demonstrating correct TH technique as a result of the intervention was shown (from 53% to 67%) (Ekedahl 1996). Another study conducted in community pharmacy focused on counselling asthma patients to generate the required inspiratory effort during inhalation from a TH device (Hawksworth et al. 2000). Patients with asthma (n=24 patients) exiting a community pharmacy after just having obtained their inhaled medication were invited to participate. Those that agreed to participate were assessed on their inhalation rate as they inhaled through a placebo TH. Patient assessments were completed twice, once after they read the inhalation instructions provided with the TH (for 10 minutes), and then again, after a personal education on their inspiratory manoeuvre (the importance of deep and fast comfortable inhalation from the TH was emphasised). Although this study was conducted in a community pharmacy setting, it was not clear whether patient education was performed by the pharmacist or the researcher. Positive results were reported as a result of the intervention, as twelve patients achieved an inhalation rate of more than 60 l-min-1, and a further four obtained more than 55 l-min-1 (Hawksworth et al. 2000), with the mean inhalation rate (l-min-1) improving from 48.0 to 54.7 for all patients. In 2002, Wilcock et al (Wilcock 2002) conducted a study investigating the community pharmacists‟ role in assessing and educating patients (n=257) on correct inhaler technique for different devices (MDI, ACC, TH, and Diskhaler- checklists not provided). All pharmacies in Cornwall (United Kingdom) were invited to participate. Participating pharmacists were provided „hands-on‟ training on the use of inhaler devices by an experienced asthma nurse. Patients were selected 'opportunistically' to participate in the study and inhaler technique assessed at baseline. Pharmacists provided interventions to upskill those patients who were identified as not using their inhaler medication appropriately. The pharmacists were expected to recheck the technique of the patients 4-5 months later. Results showed that only 23% of patients demonstrated correct technique at baseline. A significant improvement in the patient's inhaler technique was reported as a result of the intervention, as 79% of patients were able to demonstrate the correct use of their inhalers during the second assessment. This study revealed an interesting fact: the unwillingness of the community pharmacists to provide inhaler technique counselling to

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asthma patients (16 out of the 87 invited pharmacies were enrolled, and only 6 pharmacies completed the study). This was the case despite the provision of financial incentives to participating pharmacies. In addition, only 34% of patients came back for the second assessment, which is hardly surprising, given that pharmacists were not enthusiastic about delivering the education in the first place. Our team previously conducted a study aimed at comparing the effect of three counselling methods provided to asthma patients in community pharmacy settings (Basheti et al. 2005). Eight out of the thirty one pharmacies contacted agreed to participate in this study. Asthma patients were invited to take part in the study by their pharmacists, with the counselling being delivered by the researcher (who, in this case was also a community pharmacist). Patients' (n=26) TH technique was assessed using their own device (TH), using a checklist developed from published data. After assessment, patients were randomly allocated to receive one of three types of counselling (verbal information, augmented verbal

information,

augmented

verbal information

plus

a

physical

demonstration of the inhaler technique). Counselling for the first two groups took approximately 5 minutes, with 5-10 minutes for the last group. Patients‟ TH technique was once again assessed two weeks following the counselling. Results of the study showed that none of the patients had correct TH technique at baseline, and that 0/7 patients who received standard verbal counselling, 2/8 who received augmented verbal counselling, and 7/9 patients who received augmented verbal counselling plus physical demonstration were able to demonstrate correct technique at the second assessment (two weeks after education). The aforementioned studies point to answers for many of the questions regarding the role of community pharmacists in counselling asthma patients about their inhaler technique. It is evident that community pharmacists have a key role in optimising patients' inhaler technique, given that they are the last contact that asthma patients have with a health care professional before they use their inhalers (Hawksworth et al. 2000). Pharmacists have the capability to correct patients' inhaler technique, when properly trained to do so (Wilcock 2002). Inhaler technique counselling presents a feasible and non time consuming counselling service that can be easily delivered by community pharmacists

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(Basheti et al. 2005). Asthma patients were willing to demonstrate their inhaler technique in the community pharmacy, however showed reluctance in project participation (Wilcock 2002), (Basheti et al. 2005). This was not surprising, considering that community pharmacists themselves were reluctant to participate despite incentives to do so (Wilcock 2002), (Basheti et al. 2005). The short term impact on patients' inhaler technique as a result of the interventions delivered by community pharmacists was quite favourable (Hawksworth et al. 2000), (Wilcock 2002), (Basheti et al. 2005). However, none of the above studies measured the short or long term asthma related clinical or humanistic outcomes for patients receiving directed interventions from their community pharmacists on appropriate inhaled medication usage. Nor has the long term effect on patients' inhaler technique and the need for repeated review and education of technique been examined. The impact of the intervention delivery on the routine practice flow of the pharmacist and long term feasibility of such intervention programs has also not been examined in depth. It can be concluded that even though community pharmacists are in a pivotal position to deliver inhaler technique counselling to asthma patients, and are capable of correcting patients' inhaler technique once they have the required skills, their current role in this area may be quite limited because of their unwillingness to deliver this counselling. At this stage, it would be vital to explore further the current role of the community pharmacist in inhaler technique counselling provision to asthma patients. 1.21. Current role of community pharmacists in inhaler technique counselling provision Although community pharmacists are in a pivotal position to deliver inhaler technique education to asthma patients, inhaler technique counselling rates in the community pharmacy have been reported to be low (Mickle et al. 1990), (Liu et al. 1999), (Osman et al. 1999) and pharmacists in many studies, in different continents, seem to be doing very little to educate their patients on correct inhaler technique (Mickle et al. 1990), (Nimmo et al. 1993), (Liu et al. 1999).

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This seems to be true in Australian pharmacies too, as the results of a survey, posted to one thousand six hundred and ten pharmacists to assess asthma counselling practices, showed that a high proportion (about 30%) of pharmacists "seldom or never" checked patients' inhaler technique (Gattera et al. 1998). Looking at the patients' perspective, the same picture emerges. The results of a large survey, completed by six hundred and seventy eight asthma patients in the USA, showed that just over 54% of patients reported that they had received inhaler technique education in the community pharmacy (Kradjan et al. 1999). It was also stated that pharmacists relied heavily on printed materials to convey information about this topic (Kradjan et al. 1999). This was supported later by a similar survey which revealed that none of the participating patients had been shown how to use their inhalers by their pharmacists (Hibbert 2000). This was also true in Australia where, in an intervention study, only 8% of asthma patients in the study sample reported to have received inhaler technique education by their pharmacists (Basheti et al. 2005). More recent results indicate that this problem continues, as only 7% of patients in a survey conducted in Flanders (Belgium) were found to have been given instructions on how to use their inhalers by their pharmacists (Mehuys et al. 2006). It is important to note however, that the problem of patients not receiving advice on inhaler technique is not restricted to community pharmacists only, as other health care professionals share the same problem. Previous studies have shown that about 25% of patients in the study sample reported never having received instructions on inhaler technique from a health care professional at all (Nimmo et al. 1993), and in another similar study, 23% of sample patients reported not receiving any previous instructions despite having used their DPIs for years (Verver et al. 1996). Other studies have shown that only up to 50% of patients have received inhaler technique education from their GPs (Nimmo et al. 1993), (Narhi et al. 2002). Conversely, despite the minimal current role that community pharmacists play in inhaler technique education and the additional lack of involvement of health care professionals, pharmacists have identified their role in inhalation technique education to be one of the

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most important aspects of their asthma counselling (Vainio et al. 2001). In addition, in a qualitative study conducted by Hussein and Partridge (Hussein and Partridge 2002), all patients (n=60) felt that pharmacists gave useful information about how to use the inhalers. Thus, if community pharmacists are in an excellent position to deliver inhaler technique education to asthma patients and strongly believe that this service is one of the most important aspects of their asthma counselling (Vainio et al. 2001), and yet they are not doing so, it would be important to investigate the barriers hindering them from fulfilling this role. 1.22. Barriers to inhaler technique education in community pharmacy 1.22.1. Pharmacist barriers In examining the barriers hindering community pharmacists from fulfilling their role in educating asthma patients‟ on correct inhaler technique, it is most important to investigate how well equipped in terms of training, skills and infrastructure community pharmacists are in order to fulfil this role. A lack of knowledge and skills required by the pharmacists to educate patients on correct inhaler technique has been identified as one main barrier (Henry et al. 1993), (Kesten et al. 1993), (Pronk et al. 2002). It has been suggested that a lack of knowledge naturally decreases confidence, and prevents pharmacists from delivering education (Vainio et al. 2001). In addition, pharmacists have been found to be unaware of the importance of repetitive counselling on inhaler technique for asthma patients (Erickson SR 2000). Hence, they may only deliver inhaler technique education to their patients when they are first dispensed an inhaler (Wiederholt et al. 1992), (Schommer and Wiederholt 1994), (Hibbert 2000), (Basheti et al. 2005). Another related barrier is pharmacists' belief that not all patients are in need of inhaler technique education. They believe that older patients and younger children, patients prescribed with newly introduced inhalers, spacer devices and high dose corticosteroid inhalers need more help in inhaler education (Hibbert 2000).

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Therefore, pharmacists are aware of special needs groups, but do not understand the nature of the problem in the general asthma community. Pharmacists' lack of motivation to deliver inhaler technique education is another important issue and could be a clear barrier to patient counselling. One community pharmacy study shed light on the fact that community pharmacists are not willing to participate in inhaler technique educational interventions (Wilcock 2002). In addition, it has been acknowledged that the content and amount of information provided by pharmacists to their patients is directly dependent on their motivation to deliver that counselling (Mason and Svarstad 1984), (Vainio et al. 2001). Lack of inhaler placebos at the community pharmacies present another barrier, as pharmacists require placebos in order to be able to demonstrate to their patients correct inhaler technique (Osman et al. 1999). Other barriers hindering pharmacists from fulfilling their role in inhaler technique education may include business pressures, perceived high implementation costs, time constraints, lack of private counselling areas in the pharmacy, limited well trained support personnel, profit driven rather than patient-care oriented practice, pharmacists' belief that patients require product oriented image and fast service and the perception of the pharmacists that their advice may not be welcomed by their patients (Raisch 1993), (Odedina et al. 1995), (Osman et al. 1999), (Hibbert 2000), (Saini et al. 2001), (Pronk et al. 2002). Potential damage to the inter-professional relationship between pharmacists and physicians could also prevent the pharmacists from delivering this role, believing that delivering this type of service could lead to conflict (Hibbert 2000). 1.22.2. Patient barriers From the patients' standpoint, the main barrier is their lack of interest in learning correct inhaler technique due to their belief that they know enough about this topic (Thoonen et al. 2002). Patients believe that they have correct technique (up to 92% of patients), whereas in reality, data suggests otherwise (as discussed in Section II of this review) (Pinto Pereira et al. 2001), (Kamps et al. 2002). In addition, patients may not approach

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their pharmacists for advice because they are not aware of the different services a pharmacist can provide (Schommer and Wiederholt 1994), (Chewning and Schommer 1996). Patients may also believe that pharmacists are not allowed to give information other than what is written on the prescription and so do not ask for any (Hibbert 2000). Some patients' fear the possibility of embarrassment, given that they have been using their inhalers for some time (Chewning and Schommer 1996). The fact that some asthma patients who have mild to moderate asthma do not regard their condition as a chronic disease would also form a barrier, as these patients would be unwilling to receive continuous review and education (Osman 1997), (Jones et al. 2000). Language is another important barrier, as it can prevent ethnic populations in the society from receiving appropriate and accurate counselling on inhaler technique (Siganga and Huynh 1997). Exploring possible solutions to the barriers cited above is extremely important in order to assist the pharmacist to approach asthma patients and deliver inhaler technique education, thus achieving better use of treatment. 1.23. Solutions to overcome barriers to inhaler technique education by community pharmacists It has been found that with proper training, pharmacists' skills and knowledge regarding counselling asthma patients on correct inhaler technique can improve significantly (Cairns and Eveleigh 1999), (Cain et al. 2001). This in turn can lead to a higher proportion of patients receiving counselling (Vainio et al. 2001). Pharmacists have reported previously that their increased knowledge made them more willing and competent to discuss with their patients different issues during counselling (Vainio et al. 2001). Pharmacists who have additional asthma training were found to be more confident in advice giving and give advice more often (Osman et al. 1999). This suggests that increased knowledge increases confidence, leading the way to more interactive counselling delivery by pharmacists (Vainio et al. 2001). Hence, the importance of training and support of community pharmacists cannot be underestimated in order to allow them to deliver effective patient education (Cairns and Eveleigh 1999).

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Providing the pharmacists with a feasible and practical education service to deliver to asthma patients can eliminate many of the barriers identified above, such as business pressures and time constraints (Odedina et al. 1995). Pharmacists' motivation to deliver inhaler technique education to their patients is an important issue which can be addressed in the different educational tools, remuneration strategies, and training programs (Osman et al. 1999), (March et al. 1999), (Vainio et al. 2001), Increasing the awareness of the patient to the importance of correct inhalation technique for effective asthma management is a crucial first step towards improving asthma control (Crompton et al. 2006). Hence, many of the patient barriers identified above can be eliminated by illustrating, and thus informing the patients of the pharmacists' role with regards to inhaler technique education, and of the importance of having their technique reviewed on regular basis. 1.24. Conclusion In conclusion, the literature has shown that pharmacists have become increasingly active in patient care over the years, and can demonstrate a positive impact on the management of many chronic diseases including asthma. Many comprehensive intervention studies have been delivered to asthma patients through community pharmacies, resulting in clinical and/or humanistic improvements. Inhaler technique education was an element in the majority of these comprehensive intervention studies. However, it is not possible to link any effect of inhaler technique education conducted in these studies to the positive outcomes shown. Focussed studies investigating community pharmacists' role in educating patients on correct inhaler technique have provided little information on the capability of the pharmacist in taking on this role. In addition, these studies did not provide a measure of the impact of inhaler technique education on clinical and/or humanistic outcomes for patients with asthma.

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Currently, pharmacists are not fulfilling their responsibilities regarding educating patients on correct inhaler technique. Pharmacists have a positive attitude, but lack the knowledge and skills needed. The evidence suggests that inhaler technique education is not only essential given the poor performance of the majority of patients, but also that many patients would welcome such advice. No previous study has investigated thoroughly the feasibility and impact of a simple focussed intervention on inhaler technique education delivered by skilled community pharmacists. Also, no previous study has investigated the short or the long term effects of such an intervention on the clinical and humanistic health outcomes for patients with asthma. 1.25. Aim of the study The aims of this study were to determine the effect of a specialised counselling service delivered by community pharmacists to asthma patients on dry powder inhaler technique, and to assess patients‟ clinical and humanistic health outcomes. In addition, a subsequent aim was to develop a module for asthma educators to use in training pharmacists on correct inhaler technique, so that they could deliver education to their asthma patients. This module could then be used to sustain the service in community practice. To meet these aims, five different phases were planned for this PhD study (Figure 1.4).

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Figure 1.4. The PhD design.

Phase 1 Protocol development for the PhD study

Phase 2 Recruitment of pharmacists

Phase 3 Delivery of an educational workshop to pharmacists

Phase 4 Conducting the cluster randomised parallel group single blinded study, comparing the effect of a pharmacist intervention focusing on inhaler technique education vs. standard care, on clinical and humanistic outcomes for patients with asthma

Phase 5 Designing a continuing professional development module for community pharmacists

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1.26. Chapter outline Chapter Two Chapter Two outlines the development of the first part of the study, involving the recruitment and education of community pharmacists. A review of the methods used in the implementation of the workshop is presented. An evaluation of the educational training program delivered to the participating pharmacists in the workshop was carried out. Chapter Three Chapter Three outlines the development and implementation of the cluster randomised parallel group single blinded study. This study was designed to evaluate the effectiveness of the educational intervention delivered to community pharmacists, and by the pharmacists in turn to their asthma patients, on clinical and humanistic outcomes. In addition, a long term assessment of the pharmacists' inhaler technique is also provided. Chapter Four Chapter Four describes the development of an educational module that follows the 'train the trainer approach' to be used by asthma educators to train pharmacists on correct inhaler technique, and on how to transfer this knowledge to their patients, with the ultimate outcome of more effective use of treatment and improved health outcomes. Chapter Five Chapter Five brings together the findings of each phase of the PhD study. The chapter concludes with a section dedicated to implications of the results and future directions.

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Chapter 2- Training of Community Pharmacists

CHAPTER 2 Training Community Pharmacists On Correct PFM, Turbuhaler And Accuhaler Technique

2.1. Introduction As members of the health care team, pharmacists are in an excellent position to recognise patients whose asthma may not be well controlled due to poor inhalation technique (Ekedahl 1996), (Cordina et al. 2001), (Schulz et al. 2001). Pharmacists are the last link in the therapy chain prior to patients‟ administration of the inhalation therapy, and hence have the obligation to their patients to ensure that they are using their inhalers correctly. It has been strongly suggested that patients using inhalation therapies need careful instruction, including step by step demonstration and observation of their technique at the time of dispensing the medication (Cordina et al. 2001), (Basheti et al. 2005). Since inhaler technique tends to decline without routine review (Skaer et al. 1996), periodic follow-up and reinstruction is crucial. Once again, the role of the pharmacist is important here, as pharmacists, of all health care professionals, are available not just when the patients obtain their first inhaler, but also when they obtain their refill inhalers, giving them the sole opportunity to assess and educate their patients regarding correct inhaler technique. However, it has been shown that pharmacists themselves are another group of health care professionals who require further education to be able to confidently assess and demonstrate correct inhaler technique to their patients (Chopra et al. 2002).

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Several studies have shown that patients are rarely assessed or educated by community pharmacists on inhaler administration technique (Nimmo et al. 1993), (Hunter and Bryant 1994), (Liu et al. 1999), (Hibbert 2000), (Basheti et al. 2005). Pharmacists' lack of knowledge and skills in this area could be responsible for this, affecting their confidence and resulting in the lack of inhaler technique education (Henry et al. 1993), (Kesten et al. 1993), (Pronk et al. 2002). Hence optimising pharmacists' inhaler technique is crucial as a first step to correct patients' inhaler technique. Previous studies have investigated different methods of educating health care professionals on correct inhaler technique (O'Connell et al. 1992), (Verver et al. 1996), (Rebuck et al. 1996), (Jackevicius and Chapman 1999), (Cain et al. 2001), (Lee-Wong and Mayo 2003). The methods used include handouts, videotapes on correct inhaler technique and hands-on experience with placebo inhalers (O'Connell et al. 1992), others have involved brief instructional one-on-one training sessions on the proper use of the inhalers until optimal use was achieved (Rebuck et al. 1996), (Cain et al. 2001), (LeeWong and Mayo 2003). Of all the methods used, the latter method proved to be the most effective in optimising health care professionals' ability to demonstrate the correct use of asthma inhaler devices (Jackevicius and Chapman 1999), (Lee-Wong and Mayo 2003). Hence, in order to provide effective education to patients, community pharmacists need to be equipped with the appropriate skills and knowledge to do so. Consequently, the aim of this part of the study is to train pharmacists in the 'Active' group on device technique and lung function assessment, in order to be able to deliver an intervention targeting inhaler technique, and to train pharmacists in the 'Control' group in lung function assessment only, in order to deliver standard care. The training of the pharmacists is the first step of a larger blinded cluster randomised parallel group study, assessing the impact of pharmacist counselling (Active vs. Control) on asthma outcomes (Chapter 3).

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2.2. Methods 2.2.1. Research objectives and Hypothesis This workshop aims to fulfil the following objectives and test the following specific hypotheses:Primary objectives (Objectives 1 and 2) 1. To determine the effect of an educational workshop on pharmacists‟ TH technique score. Hypothesis 1: Following completion of the educational workshop (post-education), there will be a statistically significant improvement in the pharmacists' TH technique score. 2. To determine the effect of an educational workshop on pharmacists‟ ACC technique score. Hypothesis 2: Following completion of the educational workshop (post-education), there will be a statistically significant improvement in the pharmacists' ACC technique score.

Secondary objectives (objectives 3-6) 3. To evaluate the TH technique of pharmacists prior to attending the educational workshop (pre-education). Hypothesis 3: Pre-education, pharmacists' TH technique score will be significantly different from the maximum TH technique score (maximum TH technique score = 9). 4. To evaluate the ACC technique of pharmacists prior to attending the educational workshop (pre-education).

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Hypothesis 4: Pre-education, pharmacists' ACC technique score will be significantly different from the maximum ACC technique score (maximum ACC technique score = 9). 5. To Compare the PFM technique score for pharmacists in the Active and Control groups post-education. Hypothesis 5: There will be no statistically significant difference in pharmacists' PFM technique score between the Active and Control groups. 6. To compare the primary source of education on inhaler technique, the time of that education, years in practice as community pharmacists and location of pharmacy (in a shopping area, next to a surgery, next to a hospital or in a rural area) for pharmacists in the Active and Control groups. Hypothesis 6: There will be no statistically significant differences between the Active and the Control pharmacists with regards to: - Primary source of information on PFM, TH or ACC technique - Timing of inhaler technique education previously received - Years in practice - Location of pharmacy 2.2.2. Participants In order to avoid confusion when referring to participants who are pharmacists and participants who are patients, the terms "pharmacists" and "patients" will be used throughout this thesis. One hundred and twenty registered community pharmacists were identified from a convenient sample of community pharmacists in the Sydney Metropolitan area, and were contacted by telephone. Pharmacists were introduced to the study, and an explanation letter was then mailed to those that accepted to read more about the study. Pharmacists

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who returned an expression of interest to participate (by faxing back the acceptance form) were then invited to attend the workshop. Prior to attending the workshop, pharmacists were randomly divided into two groups, Active (pharmacistAc) and Control (pharmacistC). Randomisation was done according to a single pre-determined computer-generated allocation list, created using the random number generation function of Excel. Pharmacists' recruitment took place over a three months period, from January to March 2003. Each pharmacist attended one evening workshop (three hours for the pharmacistAc and two hours for the pharmacistC groups). 2.2.3. Inclusion and exclusion criteria Inclusion criteria for pharmacists included: to be practising at a pharmacy located within the Sydney Metropolitan area, with at least one pharmacist assistant present at all times, and not to be involved in any other clinical study. Pharmacists were excluded from the study if they were not able to attend the workshop or complete commit to the 6 months study period. 2.2.4. Sample size In order to detect an increase in percentage mean score of 22.6%18.7% and 38.4%19.6% for the TH and the ACC respectively (Cain et al. 2001), with 80% power, 5% risk of a type I error, and a 20% drop out rate, it was determined that 28 pharmacists in total would need to be recruited. 2.2.5. Informed consent In accordance with the relevant regulations, an informed consent agreement that explained the procedures of the study was administered and explained to potential pharmacists, and then signed by each pharmacist at the start of the workshop. Pharmacists were assured of the freedom to withdraw from the study at any stage (Appendix A and B). Pharmacists were also informed about the duration of the study, number of visits, the commitment required on their part, the voluntary basis of their participation and the confidentiality of all information gathered during the course of the study. Contact details

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of the study supervisors and the Human Ethics Committee were also provided. The process of obtaining informed consent was carried out by the researcher. 2.2.6. Ethical review The protocol for the study was reviewed and approved by the University of Sydney Human Ethics Committee on December 2002 (Appendix C). The approved protocol was valid for 5 years. This study took place between April 2003 and April 2004, with followup assessment of pharmacists in May 2005. 2.2.7. Blinding Randomised allocation to each group was completed for all pharmacists who had agreed to participate in the study, but was concealed from the pharmacists until midway through the relevant workshop. Pharmacists did not know whether they were allocated to pharmacistAc or pharmacistC, however they were advised that there were two groups. All pharmacists were advised that the study was comparing two different strategies for asthma management, and they were asked to avoid discussing the study with other pharmacists in order to maintain blinding. After the groups were separated, there was no contact between pharmacists from the two groups, with pharmacistAc leaving the building one hour after pharmacistC. 2.2.8. Plan of the workshop The educational workshop for pharmacists was developed based on the envisaged role of the pharmacists in this study. It was known that the pharmacists would be required to assess/evaluate and train asthma patients on inhaler technique (TH and ACC) and PFM technique (pharmacistAc), or only on PFM technique (pharmacistC), and pharmacists in both groups were also required to collect data. Complete details of the study are included in Chapter 3. All pharmacists received basic training (Figure 2.1). A variety of basic asthma topics was delivered by appropriate experts in a variety of formats (Table 2.1). All pharmacists self-completed a 'Pharmacists' Questionnaire' pre-education (appendix D).

55


Following completion of the basic training, pharmacists were assessed on their PFM, TH and ACC technique and separated into their pre-assigned groups (pharmacistAc and pharmacistC), then each group received education relevant to study design (Chapter 3). Pharmacists in the pharmacistC group received training on data form completion while pharmacists in the pharmacistAc group received training on data form completion plus inhaler technique education (Figure 2.2). Pharmacists in the pharmacistAc group were reassessed on their TH and ACC technique post-education. Each pharmacist was given instant feedback individually by the researcher on every incorrectly performed step (Figure 2.2). Pharmacists (pharmacistAc and pharmacistC) were assessed again on their PFM technique at their pharmacies prior to commencement of the study (Chapter 3). Figure 2.1. Overall workshop design. Randomisation

Basic asthma training for all pharmacists (asthma management and PFM use) (35 minutes) 'Pharmacists' Questionnaire' (10 minutes) PFM technique practice (15 minutes) PFM technique assessment (with immediate feedback) TH and ACC technique assessment (with no feedback) (20 minutes)

pharmacistAc specific training (One hour and 40 minutes)

pharmacistC specific training (40 minutes)

56


Table 2.1. Basic asthma training program. Time

Content

Format

6:30-6:50

Registration

6:50-7:10

Introductory talk on asthma management; importance of monitoring in asthma management; role of the community pharmacist in asthma management.

Lecture

7:10- 7:25

Introductory talk on PFM use in asthma management; training on PFM technique, use of PFM diary and Min%Max calculation (hands-on education).

Lecture + physical demonstration

7:25- 7:35

Pharmacists' Questionnaire (demographic data, previous PFM, TH, and ACC technique education, years in practice, and location of pharmacy).

Self-completed questionnaire

7:35-7:50

PFM technique practice (in pairs), practice of PFM diary use and Min%Max calculation.

Hands-on education of PFM technique and diary use.

7:50-8.10

Assessment of pharmacists' PFM, TH, and ACC technique. Assessment was completed privately (Figure 2.3). Pharmacists were served refreshments when their assessments were completed.

Technique assessment using placebos (PFM, TH and ACC), PFM and inhaler specific checklists #

#PFM technique checklist is shown in Appendix E; TH and ACC technique specific checklists are shown in Table 2.3.

57


Figure 2.2. Specific training for pharmacistAc and pharmacistC.

Pharmacist Ac

PharmacistC

- A lecture on the importance of DPI technique education, and clinical effect of each incorrectly performed step in the checklists (lung images to explain the consequences of incorrectly performing different steps in the inhalation technique checklists (Table 3) was used) (20 minutes). TH and ACC demonstration (5 minutes).

- Protocol training with complete pharmacist - patient demonstration. (40 minutes).

technique

- TH and ACC technique practice (hands-on education followed by peer assessment) (15 minutes). - Post-education TH and ACC technique assessment with immediate feedback (20 minutes). - Protocol training with complete pharmacist - patient demonstration. (40 minutes).

The research team discussed the workshop with the Pharmaceutical Society of Australia, a major national body, and all pharmacists attending the workshop were awarded Continuing Professional Development (CPD) points (three points for pharmacistAc and two for pharmacistC) (Appendix F). All pharmacists received Certificates for completion of the workshop (Appendix G). These Certificates were displayed in the pharmacy for the period of the study.

58


2.2.9. Preparing the rooms for the workshop The workshop was conducted in the Faculty of Pharmacy, University of Sydney (a central location for all pharmacists). The environment in which the educational activities took place was set to satisfy all of the requirements for a good learning environment (Caffarella 2002). The rooms had easy access, with few windows, comfortable chairs with good back support, good lighting, pastel shaded, average sized, square in structure, air-conditioned, quiet, with easy access to restrooms and well ventilated. The rooms were arranged with the chairs put in the "traditional classroom" style, a series of straight rows of chairs (Figure 2.3). This style was chosen to allow for pair grouping (for the PFM, TH and ACC technique practice and peer assessment). Private areas were set in the room for the PFM, TH and ACC technique assessments (Figure 2.3). Figure 2.3. The general plan of the room used in the workshop.

Refreshments area

Name Tags PFM assessment area

Power Point presentation

Door

ACC assessment area

TH assessment area

59


2.3. Data management 2.3.1. Data collection Table 2.2 summarises the data recorded/collected during the workshop, the method/tools used to collect the data and by whom (researcher or pharmacist). Table 2.2. Summary of data recorded/collected throughout the workshop, the method/tools used to collect the data and by whom (researcher or pharmacist). Data recorded/collected

By whom

Method/Tool

Pharmacist demography Pharmacist Source of previous PFM, TH and Pharmacist ACC technique education Time since previous PFM, TH Pharmacist and ACC technique education Location of pharmacy Pharmacist Years in practice Pharmacist

Self-completed questionnaire Self-completed questionnaire

Pre-education TH and ACC researcher technique score Post-education PFM technique researcher score Post-education TH and ACC researcher technique score

TH and ACC technique checklists

Self-completed questionnaire Self-completed questionnaire Self-completed questionnaire

PFM technique checklist TH and ACC technique checklists

Pharmacists' Questionnaire (Appendix D). Inhaler technique checklists (see section 2.3.3, Table 2.3). PFM technique checklist (Appendix E).

2.3.2. Pharmacists' Questionnaire Pharmacists were required to complete a questionnaire designed to collect data about their baseline demographic characteristics including age, gender, years in practice as community pharmacists, location of pharmacy, source of education and years since most recent education on the PFM, TH and ACC technique (Appendix D). Prior to administration, this questionnaire was pilot tested by 8 community pharmacists, and revised based on the feedback obtained.

60


2.3.3. Inhaler technique Inhaler technique was assessed in the same way for both TH and ACC, however using 9-step checklists specific for each of the two inhalers (Table 2.3). Each item in the checklists represented one step associated with drug administration. Certain steps in the checklists for the TH and ACC were identified as 'Essential Steps', based on previous literature (van der Palen et al. 1998), (Basheti et al. 2005) and described as steps, if incorrectly performed, little or no medication would reach the lung. Pharmacists were required to demonstrate (using placebo inhalers), how they would usually demonstrate to their patients their inhaler technique based on the following statement: "Show me how you would normally demonstrate the use of the TH/ACC to your patients, from the start to the finish. This TH/ACC does not contain any active medication". Pharmacists received one point for each item (step) performed correctly. Based on this, pharmacists received a score out of "9", which related to the number of steps they were able to perform correctly. 'Correct TH Technique' indicated a "score of 9/9". 'Correct ACC Technique' indicated a "score of 9/9". 'Correct TH Essential Technique' indicated a score of 4/4. 'Correct ACC Essential Technique' indicated a score of 3/3 (based on correctly performing the Essential Steps identified in the checklists as in Table 2.3). Table 2.3. Checklists for assessment of TH and ACC technique. *Checklist for Turbuhaler technique 1. Remove the cap from the inhaler 2. Keep inhaler upright 3. Rotate grip anti-clockwise then back until a click is heard 4. Exhale to residual volume 5. Exhale away from the mouth piece 6. Place mouth piece between teeth and lips 7. Inhale forcefully and deeply 8. Hold breath for 5 seconds 9. Exhale away from mouth piece

*Checklist for Accuhaler technique 1. 2. 3. 4. 5. 6. 7. 8. 9.

Open inhaler Push lever back completely Exhale to residual volume Exhale away from mouthpiece Mouthpiece between teeth and lips Inhale forcefully and deeply Hold breath for 5 seconds Exhale away from mouthpiece Close inhaler

*Checklists based on previous published literature (van der Palen et al. 1998), (Basheti et al. 2005). Bold steps are 'Essential Steps' (i.e. steps if not performed correctly by the patients, little or no medication would reach their lung) (van der Palen et al. 1998).

61


2.3.4. PFM technique assessment A PFM checklist, describing the 11 steps required for the correct use of a PFM was used to assess PFM technique (Appendix E). The PFM checklist was developed from the manufacturers' checklist and from the National Asthma Education and Prevention Program (National Asthma Education and Prevention Program - Expert Panel Report II 2002). Pharmacists were required to demonstrate how they would usually demonstrate the use of the PFM to their patients, based on the following statement: "Show me how you would normally demonstrate to your patients the use of a PFM, from the start to the finish". Pharmacists received one point for each step performed correctly. Based on this, pharmacists received a score out of "11", according to the number of steps they were able to perform correctly. 2.4. Data analysis Data were analysed using the Statistical Package for Social Science (SPSS) version 12. Data were compared at two time points, pre-education and post-education. Data collected pre-education were used to compare the following between the pharmacistAc and the pharmacistC groups: 1) demographic data (gender, age, years of practice, and location of pharmacy; 2) source of previous education on PFM, TH and ACC technique; 3) time since previous education on PFM, TH and ACC technique; 4) mean inhaler technique score, proportion of pharmacists with Correct Technique, proportion of pharmacists with Correct Essential Technique, proportion of pharmacists correctly completing each individual step of the TH and ACC checklists. Data collected post-education for the pharmacistAc and pharmacistC groups were used to compare the mean PFM technique score and proportion of pharmacists with correct PFM technique between the two groups. Data collected post-education for the pharmacistAc group were used to compare the following with data collected pre-education: 1) mean inhaler technique score, proportion of pharmacists with Correct Technique, proportion of pharmacists with. Correct Essential Technique, and proportion of pharmacists correctly performing each individual step in the

62


TH and ACC checklists. Pharmacists in the pharmacistC group were not assessed on their TH and ACC technique post-education. The mean values and the 95% confidence interval (CI) were used to describe the normally distributed continuous data (normality of distribution was determined using the Kolmogorov-Smirnov

test).

Comparisons

between

groups

were

performed

by

Independent Samples Student's t-test (for normally distributed data) or Mann Whitney Utest (for non-normally distributed data). Pre-post comparisons were conducted using the Paired Samples Student's t-test (for normally distributed data) and Wilcoxon Signed Rank test (for non-normally distributed data). Proportional data were analysed using Pearson's Chi-Square test (or Fisher's exact test). For all statistical analysis, p-values of 0.05 or less were considered statistically significant. 2.5. Results 2.5.1. Pharmacists recruitment Of the one hundred and twenty pharmacists contacted by phone to participate in the study, thirty one (26%) pharmacists attended the workshop (Figure 2.4). Prior to the workshop, sixteen pharmacists were randomly assigned to the pharmacistAc group and fifteen to the pharmacistC group.

63


Figure 2.4. CONSORT diagram for pharmacists, showing disposition and retention throughout the workshop, 6 months followup study and 2 years post workshop assessment (Chapter 3).

Approached by telephone (n=120)

Agreed to receive information (n=98) 2 pharmacists declined, 48 failed to respond Agreed to attend Workshop (n=48) 17 pharmacists failed to attend Attended workshop (n=31)

Randomisation pharmacist Ac training (n=16)

1 withdrew (local language problems)

3 moved out of area/overseas

PharmacistC training (n=15)

Visit 1 (n=16)

Screening

Visit 2 * (n=15)

Baseline, first education

Visit 2 * (n=13)

Visit 3 (n=15)

1 month

Visit 3 (n=13)

Visit 4 (n=15)

2 months

Visit 4 (n=13)

Visit 5 (n=15)

3 months

Visit 5 (n=13)

1 withdrew (moved out of area)

Visit 6 (n=15)

6 months

Visit 6 (n=12)

3 moved out of area/overseas

Follow-up (n=12)

2 years

Visit 1 (n=15)

2 withdrew (1 moved out of area, 1 too busy)

This part of the study is discussed in Chapter 3

Follow-up (n=9)

* Two pharmacists in the pharmacist Ac and three in the pharmacistC groups recruited ACC users only.

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2.5.2. Pharmacists' characteristics There were no statistically significant differences between the pharmacistAc and the pharmacistC groups in terms of gender, age, years in practice (Table 2.4) and location of pharmacy (p= 0.640, Table 2.5). The pharmacists who attended the workshop were mostly very experienced community pharmacists (Table 2.4), with their pharmacies being mostly located in a shopping area (Table 2.5).

Table 2.4. Comparison of baseline demographics for the pharmacist Ac (n=16) and pharmacistC (n=15) groups. Variables

pharmacist Ac

pharmacistC

P value

Gender, males n (%)

7 (43.8%)

10 (66.7%)

0.285

Age, mean (SD)

40.4 (10.7)

33.4 (9.3)

0.063

16.1 (11.4)

10.1 (9.4)

0.104

Years in practice, mean (SD)

Table 2.5. Location of pharmacy for the pharmacistAc (n=16) and pharmacistC (n=15) groups. Location of pharmacy

pharmacist Ac

pharmacistC

In a shopping area, n (%)

13 (81.3%)

10 (66.7%)

Next to a surgery, n (%)

2 (12.5%)

3 (20.0%)

1 (6.3%)

2 (13.3%)

In a shopping area and next to a surgery, n (%)

65


2.5.3. Inhaler training history Eighty seven percent of pharmacists reported that they had received past education on PFM, TH and ACC use, however the education was not recent for any of these asthma inhalers (Table 2.6). With regards to TH and ACC education, the main source of this education was the Pharmaceutical Manufacturer Representatives (Figures 2.5 and 2.6 respectively). For the PFM, the most common source of education was the pharmacy school or it was self-taught (Figure 2.7).

Table 2.6. Years since most recent training in device use for the pharmacistAc (n=16) and pharmacistC (n=15) groups. Pharmacist Ac PharmacistC Years

since

most

recent

PFM

P value

4.2 (3.2)

4.3 (4.5)

0.749

3.5 (3.1)

3.6 (3.7)

0.920

2.3 (1.7)

2.8 (3.0)

0.968

training, mean (SD) Years since most recent TH training, mean (SD) Years

since

most

recent

ACC

training, mean (SD)

66


Figure 2.5. Sources of previous TH technique education (PharmacistAc n=16; PharmacistC n=15). 100

% pharmacistAc & C

80

60

Active Control 40

20

0

Self-taught

Pharmacy school

Pharmaceutical Manufacturer Representative

Continuing education

Figure 2.6. Sources of previous ACC technique education (PharmacistAc n=16; PharmacistC n=15). 100

% pharmacistAc & C

80

60

Active Control

40

20

0

Self-taught

Pharmacy school

Pharmaceutical Continuing Manufacturer education Representative

67


Figure 2.7. Sources of previous PFM technique education (Pharmacist Ac n=16; PharmacistC n=15). 100

% pharmacistAc & C

80

60

Active Control 40

20

0

Self-taught

Pharmacy Pharmaceutical Continuing Hospital Manufacturer education school Representative

2.5.4. PFM technique Post PFM technique education, there was no statistically significant difference between the pharmacistAc and pharmacistC with regards to mean PFM technique score (out of 11) (pharmacistAc: 9.9±0.8; pharmacistC: 9.5±1.1, p=0.362, Independent Sample Student's ttest). The second PFM technique assessment of pharmacists was completed at their pharmacies (prior to commencement of the follow-up study - Chapter 3) and showed no statistically significant difference between the pharmacistAc and pharmacistC mean PFM technique score (pharmacistAc: 10.8±0.5; pharmacistC: 10.9±0.3, p= 0.441). 2.5.5. Inhaler technique outcomes Pre-education, the proportion of pharmacists demonstrating Correct TH Essential Technique (correctly demonstrating the 4 Essential Steps in the TH checklist, Table 2.3) was 37.5% for the pharmacistAc and 13.3% for the pharmacistC groups (p=0.124,

68


Fisher's exact test). Post-education, all pharmacists in the pharmacistAc group were able to demonstrate Correct Essential Technique for the TH. The proportion of pharmacists demonstrating Correct TH Technique pre-education (correctly demonstrating all 9 steps in the checklist, Table 2.3) was 12.5% for the pharmacistAc and 13.3% for the pharmacistC groups (p=0.945; Fisher's Exact test). Posteducation, all pharmacists in the pharmacistAc group demonstrated Correct TH Technique. As for the ACC, the proportion of pharmacists demonstrating Correct Essential Technique pre-education (correctly demonstrating the 3 Essential Steps in the ACC checklist, Table 2.3) was 87.5% for the pharmacistAc and 80.0% for the pharmacistC groups (p=0.570, Fisher's Exact test). Post-education, all pharmacists in the pharmacistAc group were able to demonstrate Correct Essential Technique for the ACC. The proportion of pharmacists demonstrating Correct ACC Technique pre-education was 6.3% for the pharmacistAc and 6.7% for the pharmacistC groups (p=0.962). Posteducation, 75% of pharmacistAc were able to demonstrate Correct Technique. Pharmacists in the pharmacistC group were not assessed on their TH and ACC technique post-education. Inhaler technique score (mean scores out of 9) for the TH pre-education was 5.6±1.8 for the pharmacistAc and 5.5±1.9 for the pharmacistC groups (p=1.000, Mann Whitney Utest). Post-education, inhaler technique score improved significantly to 9.0±0.00 (p=0.001, Wilcoxon Signed Rank test) (Figure 2.8). Inhaler technique score for the ACC pre-education was 5.6±1.7 for the pharmacistAc and 5.7±1.1 for the pharmacistC groups (p=0.820, Mann Whitney U-test). A statistically significant improvement in inhaler technique score for the pharmacistAc post-education was observed, with the inhaler technique score improving significantly to 8.6±0.9 (p=0.001, Wilcoxon Signed Rank test) (Figure 2.8).

69


Figure 2.8. Mean score of inhaler technique for pharmacistAc for the TH and ACC, pre-education and post-education (n= 16).

Inhaler technique score, mean (95% CI)

9 8 7

p=0.001

p=0.001

6 5 4 3

Pre-education

Post-education TH

Pre-education

Post-education ACC

2.5.6. Individual performance steps in the TH checklist Of the 9 steps in the TH checklist (Table 2.3), the most frequent errors performed by pharmacists in the pharmacistAc and pharmacistC groups pre-education were failing to keep the inhaler upright, exhale to residual volume, exhale away from the mouthpiece and hold the breath for 5 seconds. There was no statistically significant difference between the pharmacistAc and pharmacistC groups with regards to which steps were performed incorrectly (p>0.05, Fisher‟s Exact test) (Figure 2.9). Post-education, all steps in the TH checklist were preformed correctly by the pharmacistAc group (Figure 2.10).

70


Figure 2.9. Proportion of pharmacists in the pharmacist Ac and pharmacistC groups performing correctly each of the 9 steps in the TH checklist pre-education (pharmacistAc n=16; pharmacistC n=15).

% pharmacistAc & C

100 80 60 Active 40 Control 20 0 1

2

3

4

5

6

7

8

9

*Steps in the TH checklist *The 9 steps in the TH checklist are shown in Table 3.

Figure 2.10. Proportion of pharmacists in the pharmacistAc group performing correctly each of the 9 steps in the TH checklist, pre-education and post-education. (pharmacistAc n=16). 100

% pharmacistAc

80 60 40

Pre education

20

Post education

0 1

2

3

4 5 6 7 *Steps in the TH checklist

8

9

*The 9 steps in the TH checklist are shown in Table 3.

2.5.7. Individual steps in the ACC checklist Of the 9 steps in the ACC checklist (Table 2.3), the most frequent error performed by pharmacists in the pharmacistAc and pharmacistC groups pre-education, were failing to exhale to residual volume, exhale away from the mouthpiece before and after inhalation and hold the breath for five seconds. No statistically significant difference between the

71


pharmacistAc and pharmacistC groups was found with regards to which steps were performed incorrectly (p>0.05, Fisher‟s Exact test) (Figure 2.11). Figure 2.12 shows that post-education, 19% (n=3) of pharmacists in the pharmacistAc group did not demonstrate step 3 (exhale to residual volume) correctly, and 13% (n=2) of pharmacists did not demonstrate steps 4 and 7 correctly (exhale away from mouthpiece and hold breath for five seconds respectively). These pharmacists were re-educated until Correct Technique was achieved prior to study commencement (Chapter 3). Figure 2.11. Proportion of pharmacists in the pharmacist Ac and pharmacistC groups, performing correctly each of the 9 steps in the ACC checklist pre-education. (pharmacistAc n=16; pharmacistC n=15).

% pharmacistAc & C

100 80 60 Active 40 Control 20 0 1

2

3

4 5 6 7 *Steps in the ACC checklist

8

9

*The 9 steps in the ACC checklist are shown in Table 3.

Figure 2.12. Proportion of pharmacists in the pharmacist Ac group performing correctly each of the 9 steps in the ACC checklist, pre-education and post-education. (pharmacistAc n=16).

% pharmacistAc

100 80 60 40

Pre education

20

Post education

0 1

2

3

4

5

6

7

8

9

*Steps in the ACC checklist *The 9 steps in the ACC checklist are shown in Table 3. 72


2.6. Discussion Prior to the educational workshop, community pharmacists demonstrated a lack of correct TH and ACC technique, and following a single workshop session, community pharmacists' PFM, TH and ACC technique significantly improved. Despite the potential for pharmacists to have a positive impact on asthma management (Self et al. 1983), (Cordina et al. 2001) the results of this study supports previous findings (Kesten et al. 1993), (Chopra et al. 2002) i.e. that pharmacists lack the foundations needed to allow them to play a role in educating patients about correct inhaler technique. Previous studies have shown that pharmacists rarely review or educate asthma patients on correct inhaler technique (Basheti et al. 2005), (Mehuys et al. 2006). Pharmacists' lack of knowledge and skills can be identified as the main reason hindering them from delivering their role in this area (Mickle et al. 1990), (Henry et al. 1993), (Kesten et al. 1993). Baseline data from this study are consistent with previous studies, which have shown that poor inhaler technique is common amongst community pharmacists (Mickle et al. 1990), (Kesten et al. 1993), (Cain et al. 2001) and that there is evidently a need for improving inhaler technique with some type of education (Amirav et al. 1995), (Chopra et al. 2002). However, this study also shows that a single feasible workshop can optimise pharmacist's inhaler technique. In this study, even though more than 80% of the pharmacists reported receiving previous education on inhaler technique, only about 10% of the pharmacists had correct technique with the TH and ACC pre-education. This could be due to the fact that this education was delivered to the pharmacists long before the workshop (two to four years). Pharmacists' incorrect use of inhalers can result in their inability to offer the advice needed on correct inhaler technique to their patients (Mickle et al. 1990), or in the provision of incorrect instructions on inhaler technique (Guidry et al. 1992), (Interiano and Guntupalli 1993), (Kesten et al. 1993). With regards to the source of information for community pharmacists on inhaler technique, pharmacists in this study indicated that the pharmaceutical manufacturer representatives were the main source of education on inhaler technique. Previous studies 73


have also shown that information from the pharmaceutical companies (either in the form of a package insert or other information supplied) and observation of pharmaceutical manufacturer representatives are the most common sources of information on inhalers and inhaler technique (Guidry et al. 1992), (Kesten et al. 1993), (Hanania et al. 1994). This points to the importance of appropriately preparing the pharmaceutical manufacturer representatives to have the skills needed to continuously educate and update community pharmacists on correct inhaler technique. This workshop was delivered to the pharmacists to optimise their inhaler technique skills and knowledge, and to enable them to successfully deliver this education to their patients in the follow-up study (Chapter 3). Educating pharmacists before they deliver the education to their patients has been identified as an essential aspect to educational studies (Cairns and Eveleigh 1999), (Osman et al. 1999), (Singhal et al. 1999), (Newman et al. 2004), as it prevents any inadequate implementation of the educational service and lack of uniformity in the education provision between the participating pharmacists (Singhal et al. 1999). The educational workshop delivered in this study significantly improved not only pharmacists' inhaler technique, but also their PFM technique. This confirms the findings of Chafin et al (Chafin et al. 2000), where health care professionals were shown to improve dramatically in their PFM technique after a short educational intervention. Our approach in educating pharmacists on correct inhaler technique, and further teaching them to deliver this education to their patients (Chapter 3), was designed to enhance confidence and improve inhaler technique counselling rates in community pharmacies. In order to achieve this, we used a "train the trainer" approach (Saini et al. 2004), (Mangiapane et al. 2005), (Armour et al. 2007), with an interactive workshop based on adult learning principles, including physical demonstration, training with inhalers, peer assessment and instant feedback (Caffarella 2002). Our results support previous findings that physical demonstration of inhaler technique followed by hands-on education result in optimising pharmacists' inhaler technique (Lee-Wong and Mayo 2003). Peer assessment was used to allow pharmacists to judge the work of their colleagues, increasing their

74


ability to assess inhaler technique and make independent judgment leading to a greater sense of involvement and improved inhaler technique assessment ability (McNeil et al. 2006). What makes this workshop stand out is the fact that it was based not just on adult learning principles, but also designed to enhance the pharmacists' motivation to learn (Herzberg 2003), (Amabile et al. 2007). Strategies incorporated in the design of the workshop to help in enhancing pharmacists' motivation to learn included ensuring the pharmacists' desire to attend the workshop, keeping the atmosphere of the rooms relaxed and friendly at all times, allowing the opportunity for exchange of ideas between the pharmacists, not giving extra work after the workshop to be completed at home, providing the workshop free of charge, and presenting quality learning by ensuring the relevance of the information given, providing easy to read forms, with the education needed for the study being covered in a mix of learning activities (Herzberg 2003), (Amabile et al. 2007). Setting the environment in which the educational activities took place was also considered closely due to its effects on the learning outcomes (Caffarella 2002). Standards needed to satisfy the requirements for a good learning environment were set in the design of the rooms used for the workshop (Caffarella 2002). Many studies have used a checklist to assess pharmacists' inhaler technique (Kesten et al. 1993), (Chopra et al. 2002). This study indicates that the use of such a tool is feasible, quick, and reliable. TH and ACC technique was assessed using published inhaler-specific checklists developed by the Dutch Asthma Foundation (van der Palen et al. 1998), (Basheti et al. 2005). The individual steps in these checklists largely corresponded to the steps described in the Patient Information Statements issued by the respective inhaler manufacturers. However, for the TH, it should be noted that the manufacturer‟s instructions did not require a breath-hold following inhalation (Step 8 of the checklist). This step is, however, included in the TH instructions on the Global Initiative for Asthma (GINA) website (Inhaler charts for use with GINA documents 2007) possibly in order to avoid patient confusion between instructions for different inhalers (van der Palen et al. 1998). Also for the ACC, the manufacturer‟s instructions had a different wording to the

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step “Inhale forcefully and deeply”. It was actually worded as “Suck in steadily and deeply”. It is not considered that this slight difference in wording is likely to have had an impact on the results of this study. Evaluation of the pharmacists' capability to demonstrate the individual steps correctly in the TH and ACC checklists showed that the most frequent errors performed for the TH were failing to hold the TH vertically during loading, exhale to residual volume before inhalation, exhale away from the mouthpiece, and hold the breath for five seconds after inhalation. This was found to be consistent with the findings of Kesten et al (Kesten et al. 1993), Cain et al (Cain et al. 2001) and Chopra et al (Chopra et al. 2002). As for the ACC, the most frequent errors performed by pharmacists were similar to the TH (Exhaling to residual volume, exhaling away from the mouthpiece and holding the breath for five seconds). Only Chopra et al (Chopra et al. 2002) have reported previously on pharmacists' performance of individual steps. However, Chopra et al (Chopra et al. 2002) reported a higher percentage of pharmacists performing the steps: exhale to residual volume and exhale away from the mouthpiece correctly (70% of pharmacists) than that reported in this study (16% and 10% respectively). As for holding the breath for five seconds, results from this study and Chopra's study were alike (55%). It is interesting to note however, that loading the ACC was completed correctly by almost all the pharmacists in our study (97%), whereas in Chopra's study only 20% of the pharmacists demonstrated this step correctly. This can be explained by the fact that Chopra requested the pharmacists slide the lever away as far as it will go until it clicks while keeping the ACC horizontally. We did not request the ACC to be kept horizontally because there is no literature to support the need of performing this manoeuvre. The fact that the checklists used in the Kesten et al (Kesten et al. 1993), Cain et al (Cain et al. 2001) and Chopra et al (Chopra et al. 2002) studies are somewhat different from each other and from our checklist, may not allow for the direct comparison and could be responsible for the variation seen in results amongst the different studies. The issue of inhaler technique checklist heterogeneity is important and has been addressed previously (Brocklebank et al. 2001). Results of this study support the fact that further work needs to be done in this area (Brocklebank et al. 2001).

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Previous studies have shown that when it comes to the pMDIs, the errors that health care professionals perform are similar to those performed by patients (Taylor and Tunstell 1991). This was also found to be true for the TH and the ACC (van der Palen et al. 1995), (van der Palen et al. 1998), (Epstein et al. 2001), (Molimard et al. 2003), (Melani et al. 2004), (Basheti et al. 2005), (Ronmark et al. 2005). In this study, we have attempted to resolve the universal phenomena of incorrect inhaler use by health care professionals (Interiano and Guntupalli 1993), (Hanania et al. 1994), (Jones et al. 1995), (Tsang et al. 1997), (Plaza and Sanchis 1998), (Fink and Rubin 2005), by establishing feasible educational strategies. Pharmacists' incorrect use of inhalers can lead to patients' incorrect use of the inhaler devices as well (Tal et al. 1987), (Mickle et al. 1990), (Guidry et al. 1992), (Interiano and Guntupalli 1993), (Kesten et al. 1993) leading to a reduction in the amount of medication reaching their lung and hence decreasing the effect of the treatment (Lahdensuo et al. 1986), (Newman et al. 1991), (Giraud and Roche 2002). This eventually would result in poor control of airway disease (Lindgren et al. 1987), (McFadden 1995), and increase in emergency visits (Giraud and Roche 2002). Incorrect inhaler technique may also lead to an increase in daily inhaled corticosteroids, leading to higher intensity and prevalence of side-effects of the treatment (such as thrush and hoarseness of the voice) (Foster et al. 2006). In addition, incorrect inhaler technique can mislead patients into thinking that the treatment is inadequate and eventually lead to their dissatisfaction with their therapy, affecting their adherence to their inhalers (Boe et al. 1992), (Ekedahl 1996), (Osman 1997), (Farber et al. 2003), (Rau 2005), (Barnes 2005). Ultimately, incorrect inhaler technique would lead to a higher cost of the treatment (Chopra et al. 2002), (Fink and Rubin 2005). Selection bias is the main limitation of this part of the study, as only thirty one pharmacists out of one hundred and twenty contacted attended the workshop. Thus pharmacists who attended the workshop may have been more motivated and have a greater predisposition to learn correct inhaler technique. This in turn can limit the generalisability of the results achieved by this educational workshop.

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In summary, data collected within this workshop have revealed a lack of inhaler technique skills among community pharmacists for both the TH and the ACC, and showed that a single educational session on device technique can significantly improve community pharmacists‟ ability to demonstrate correct inhaler and PFM technique. The workshop designed was short in duration and thus feasible to reproduce on numerous occasions. The implications of this phase of the study are that it is feasible to train pharmacists to educate and assess asthma patients on correct inhaler technique. The next chapter investigates the impact of pharmacists' training on asthma patients in terms of assessing and correcting inhaler technique and on asthma outcomes.

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Chapter 3- The Educational Intervention

CHAPTER 3 The Impact Of Inhaler Technique: A Blinded Cluster Randomised Parallel Group Study Showing Improved Asthma Outcomes With A Simple Intervention By Community Pharmacists

3.1. Introduction The studies reviewed in chapter one (part II) showed that correct inhaler technique is essential for effective drug delivery in asthma. High rates of incorrect technique (28-68%) with pMDIs have been reported (Fink and Rubin 2005), and poor technique with corticosteroid pMDIs has been shown to be associated with poor asthma control and increased Emergency Department visits (Giraud and Roche 2002). Dry powder inhalers such as TH and ACC were developed to reduce the problem associated with drug administration, i.e. poor technique. Nevertheless incorrect technique was found to be common, affecting 23-54% of TH users (van der Palen et al. 1998), (Melani et al. 2004), and 24-50% of ACC users (van der Palen et al. 1998), (Melani et al. 2004). The pharmacists' role in terms of delivering advice about the correct administration of respiratory medications was extensively reviewed in chapter one (part III). From these studies, it can be concluded that pharmacists are in an excellent position to educate patients about inhaler technique, as they are the last health care professional to be seen by the patient, and can be considered the link between purchase and correct medication use.

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Community pharmacists have become more active in patient care in recent years, with the implementation of complex pharmacist delivered asthma care services, resulting in statistically significant improvements in clinical and humanistic health outcomes (Cordina et al. 2001), (Saini et al. 2004), (Mangiapane et al. 2005). Many of these studies have incorporated inhaler technique education as one aspect of the different extensive educational packages delivered (Narhi et al. 2000), (Cordina et al. 2001), (Herborg et al. 2001), (Schulz et al. 2001), (Weinberger et al. 2002), (Barbanel et al. 2003), (McLean et al. 2003), (Saini et al. 2004), (Stuurman-Bieze et al. 2005), (Armour et al. 2007). However, no previous studies have evaluated the specific impact of inhaler technique education alone on patients' asthma outcomes, in community pharmacies. Several studies have examined ways of improving patients' inhaler technique, but these have not been conducted within community pharmacy. These studies have shown that regular assessment and education are needed in order to maintain optimal inhaler technique (Skaer et al. 1996), (Crompton et al. 2006). Previous research undertaken by our group further highlights that physical demonstration of correct inhaler technique is the most effective method by which this can be done in the community pharmacy (Basheti et al. 2005). The objective of this blinded cluster randomised study was to investigate the effect on clinical and humanistic outcomes of a simple educational intervention targeting inhaler technique, delivered by community pharmacists to patients with asthma. 3.2. Methods 3.2.1. Research objectives and Hypotheses This study aims to fulfill the following specific objectives and test the following specific hypotheses:-

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Primary objective 1. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique compared to the standard care, on patients' average change in Min%Max (the lowest morning PEF over 2 weeks, expressed as a percentage of the highest PEF over the same 2 week period) from baseline to 3 and 6 months post baseline, in the community pharmacy setting. Hypothesis 1: There is a statistically significant difference between patients' change in Min%Max, at 3 and 6 months from baseline, between the Active and the Control groups.

Secondary objectives (objectives 2-14)

2. At baseline, to compare the history of patients' inhaler technique education and their perception of their ability to use the TH/ACC correctly between the Active and the Control groups. Hypothesis 2: At baseline, there are statistically significant differences between the Active and the Control groups with regards to: - Primary source of information on inhaler technique - Format of inhaler technique education previously received - Timing of inhaler technique education previously received - Frequency of previous advice received on inhaler technique - Frequency of previous inhaler technique assessment - Patients' perception of their inhaler technique.

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3. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique with standard care, on patients' TH technique score, at 6 months from baseline. Hypothesis 3: There is a statistically significant difference in patients' TH technique score between patients receiving a community pharmacist delivered intervention targeting inhaler technique and patients receiving standard care, at 6 months from baseline. 4. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique with the standard care, on patients' ACC technique score, at 6 months from baseline. Hypothesis 4: There is a statistically significant difference in patients' ACC technique score between patients receiving a community pharmacist delivered intervention targeting inhaler technique and patients receiving standard care, at 6 months from baseline. 5. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique with standard care, on patients' asthma severity (as assessed based on the Asthma Severity Table in the Australian Asthma Management Handbook (National Asthma Council Australia 2002)), at 3 and 6 months from baseline. Hypothesis 5: There is a statistically significant difference in the proportion of patients in the mild, moderate and severe asthma categories between patients receiving a community pharmacist intervention targeting inhaler technique and patients receiving standard care, at 3 and 6 months from baseline. 6. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique with the standard care, on patients' reliever use (mean puffs/day), at 3 and 6 months from baseline. Hypothesis 6: There is a statistically significant difference in patients' reliever use (mean puffs/day), between patients receiving a community pharmacist delivered intervention 82


targeting inhaler technique and patients receiving standard care, at 3 and 6 months from baseline. 7. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique with standard care on patients' Asthma-related quality of life (AQOL) score, at 3 and 6 months from baseline. Hypothesis 7: There is a statistically significant difference in patients' AQOL score, between patients receiving a community pharmacist delivered intervention targeting inhaler technique and patients receiving standard care, at 3 and 6 months from baseline. 8. To compare the effect of a community pharmacist delivered intervention targeting inhaler technique with the standard care on patients' Perceived Control over asthma (PC) score, at 3 and 6 months from baseline. Hypothesis 8: There is a statistically significant difference in patients' PC score, between patients receiving a community pharmacist delivered intervention targeting inhaler technique and patients receiving standard care, at 3 and 6 months from baseline. 9. To determine whether the change in TH technique score and change in Min%Max between baseline and 6 months from baseline correlate. Hypothesis 9: There is a statistically significant correlation between the change in TH technique score and change in Min%Max between baseline and 6 months from baseline. 10. To determine whether the change in TH technique score and change in AQOL score between baseline and 6 months from baseline correlate. Hypothesis 10: There is a statistically significant correlation between the change in TH technique score and change in AQOL score between baseline and 6 months from baseline. 11. To determine whether the change in ACC technique score and change in Min%Max between baseline and 6 months from baseline correlate.

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Hypothesis 11: There is a statistically significant correlation between the change in ACC technique score and change in Min%Max between baseline and 6 months from baseline. 12. To determine whether the change in ACC technique score and change in AQOL score between baseline and 6 months from baseline correlate. Hypothesis 12: There is a statistically significant correlation between the change in ACC technique score and change in AQOL score between baseline and 6 months from baseline. 13. To compare the time required to deliver the intervention targeting TH technique by the community pharmacist with the time required to deliver the intervention targeting ACC technique. Hypothesis 13: There is no statistically significant difference between the time required to deliver an intervention targeting TH technique compared with the time required to deliver an intervention targeting ACC technique 14. To compare the minimum number of times an intervention targeting inhaler technique needs to be repeated to achieve correct technique for TH compared with ACC. Hypothesis 14: There is no statistically significant difference between the TH and the ACC with regards to the minimum number of times the intervention targeting inhaler technique needs to be repeated in order to achieve correct technique. 3.2.2. Participants In order to avoid confusion when referring to participants who are pharmacists and participants who are patients, the terms "pharmacists" and "patients" will be used throughout this thesis. Following the pharmacist training workshop (Chapter 2), pharmacists were asked to approach every second patient with asthma, who presented a prescription for TH or ACC to the community pharmacist, between April and September 2003.

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3.2.3. Inclusion and Exclusion criteria Patients were included in this study if they were aged ≥14 years, had self-reported doctordiagnosed asthma, were currently using inhaled corticosteroids via TH or ACC, and had been on the same asthma medication and dose for a minimum of one month prior to study enrolment. Patients were excluded if they did not self-administer their medication, did not speak or understand English, were not able to return for all visits, or were involved in another clinical study. 3.2.4. Sample size Sample size determination was based on the primary outcome variable of change in Min%Max, for four treatment groups (Turbuhaler Active (THAc), Turbuhaler Control (THC), Accuhaler Active (ACCAc), and Accuhaler Control (ACCC)). In order to detect a clinically important difference of change in Min%Max of 5.5 percentage points, with a significance level of 5%, and power of 80%, with the standard deviation of the change being 8.4 percentage points (Reddel et al. 2000), a sample size of 19 patients in each group was required. The sample size was increased to 28 for each group (total 112), to allow for a 40% drop out rate. Due to the small cluster size (1-4 patients per inhaler type per pharmacist), no adjustment was needed for the cluster design (Campbell et al. 2004). This is consistent with previous pharmacy intervention cluster size effects, determined from other community pharmacy studies conducted by researchers in the Faculty of Pharmacy, at the University of Sydney. 3.2.5. Informed Consent In accordance with the relevant regulations, an informed consent agreement that explained the procedures of the study was administered and explained to potential participating patients, and then signed by each patient during recruitment. Patients were assured of the freedom to withdraw from the study at any stage. Patients were told about the duration of the study, number of visits, the commitment required on their part, the voluntary basis of their participation and the confidentiality of all information gathered during the course of the study. Contact details of the study supervisors and the Human

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Ethics Committee were also provided (Appendix H and Appendix I). The process of obtaining informed consent was carried out by the pharmacist. The true objective of the study was not disclosed to the pharmacists (as discussed in Chapter 2) or to the patients. Pharmacists were advised that the study was about asthma management, involving meeting with asthma patients on 5 visits over a 6 months period, to collect data and educate patients on correct PFM use (Appendix A). Patients were informed that the study was about receiving extra counselling on asthma from their pharmacists, in order to optimise the benefits of their medications, involving the completion of short questionnaires in relation to asthma, measuring PEF two times a day for 2 weeks after the first visit, as well as 3 and 6 months afterwards, and returning to the pharmacy on 5 visits over a 6 months period for a short discussion (appendix H). 3.2.6. Ethical review The protocol for the study was reviewed and approved by the University of Sydney Human Ethics Committee on December 2002 (Appendix C). The approved protocol was valid for 5 years. This study took place between April 2003 and April 2004, with followup assessment of pharmacists in May 2005. 3.2.7. Confidentiality Pharmacists were asked to keep the patients record forms confidential, in a safe locked area, and to deliver the intervention in a private counselling area in their pharmacies. All pharmacies involved in the study had private counselling areas for delivering the intervention to their patients. 3.2.8. Location of study The study was conducted in the Sydney Metropolitan area, with the pharmacies involved spread over a radius of 7 km East, 28 km North, 50 km West, and 31 km South. Patients were asked to return to the same pharmacy throughout the study. All data were collected in the community pharmacies, apart from assessments conducted by the researcher, for which a convenient location was used. 86


3.2.9. Study design Each patient was enrolled in the study for a period of 6 months, plus a two week run-in period. Patients were required to visit the pharmacy on 6 occasions (Visit1 (t-1/2m), Visit2 (t0m), Visit3 (t1m), Visit4 (t2m), Visit5 (t3m), and Visit6 (t6m). The time between Visit1 and Visit2 was a 2 week run-in period. The time intervals between Visit2, Visit3, Visit4 and Visit5 were each one month. The time interval between Visit5 and Visit6 was 3 months (Figure 3.1).

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Figure 3.1. Overall study design and assessments performed for patients enrolled in the Active and Control groups. Recruitment and informed consent

Time (months)

Visits

t0

t1m

t2m

2

3

4

t-1/2m

1

t3m

5

t6m

No education or assessment

6

*Inhaler technique assessment Inhaler technique education #Asthma severity assessment PEF, AQOL, PCAQ

Active

Control

* Inhaler technique assessment for Control patients was carried out by the researcher. # Categorisation of asthma severity was based on the Asthma Severity Table in the Australian Asthma Management Handbook (National Asthma Council Australia 2002), excluding spirometry for the purposes of this study. PEF = Peak Expiratory Flow AQOL = Asthma-related quality of life (Marks et al. 1992) PCAQ = Perceived Control of Asthma Questionnaire (Katz et al. 2002). Active = Patients receiving intervention targeting inhaler technique Control = Patients receiving standard care t-1/2m = time 1/2 month prior to study commencement t0m = time of study commencement t1m = 1 month after t0m (study commencement) t2m = 2 month after t0m (study commencement) t3m = 3 month after t0m (study commencement) t6m= 6 month after t0m (study commencement)

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Visit1 (t -1/2 m = -2 weeks; recruitment visit)

Active During Visit1 – recruitment visit, pharmacists collected data relating to the patients' asthma history (Previous Inhaler Technique Education Questionnaire, Appendix J), past PFM use, asthma severity (see section 3.3.6) and asthma medications (Patients' Record Forms, Appendix K), (Appendix K contains Patients' Record Forms for TH Ac patients only. Patients' Record Forms for ACCAc group replicates that for THAc group, and hence are not included in the Appendix). Patients were assessed on their PFM technique (if used before), then educated on the correct PFM use and assessed again. Patients were also educated on how to record their PEF readings and reliever use on the PFM diaries provided (Appendix M). Each patient was issued with a PFM (MiniWright or AirZone), and received a questionnaire booklet i.e. "Patients' Questionnaire Booklet" (which included the AQOL and PC questionnaires) (Appendix N). Patients were asked to record their reliever use and PEF during the 2 week run-in period up until Visit2 (baseline), and to complete the questionnaire booklets the night before Visit2. Pharmacists assessed patients' TH or ACC technique using a checklist (see section 3.2.10). No feedback was given to the patients at this visit about inhaler technique. Pharmacists recorded the time (minutes) it took them to complete the visit. During the 2 week run-in period, the researcher, independent of the community pharmacist, assessed TH and ACC technique in half the patients (randomly selected) in the Active group. Control During Visit1 – recruitment visit, pharmacists collected data relating to the patients' asthma history (Previous Inhaler Technique Education Questionnaire, Appendix J), past PFM use, asthma severity (see section 3.3.6) and asthma medications (Patients' Record Forms, Appendix L), (Appendix L contains Patients' Record Forms for TH C patients only. Patients' Record Forms for ACCC group replicates that for THC group, and hence are not included in the Appendix). As for the Active group, patients were assessed on their PFM technique (if used before), then educated on the correct PFM use and assessed again. 89


Patients were also educated on how to record their PEF readings and reliever use on the PFM diaries provided (Appendix M). Each patient was issued with a PFM (MiniWright or AirZone), and received a questionnaire booklet i.e. "Patients' Questionnaire Booklet" (which included the AQOL and PC questionnaires) (Appendix N). Patients were asked to record their reliever use and PEF during the 2 week run-in period up until Visit2 (baseline), and to complete the questionnaire booklets the night before Visit 2. Pharmacists recorded the time (minutes) it took them to complete the visit. During the 2 week run-in period, the researcher, independent of the community pharmacist, assessed TH or ACC technique in all patients, using a checklist (see section 3.2.10). No feedback was given to the patients about inhaler technique. Visit2 (t0m = Baseline visit) Visit2 was conducted 2 weeks after Visit1 for both the Active and Control groups. Active Diaries and questionnaire booklets completed during the run-in period were returned to the pharmacist at Visit2. asthma severity was assessed; asthma medications and PFM use were documented. Any interventions by any health care personnel conducted during the last 2 weeks regarding patients' asthma were recorded. Patients had their inhaler technique assessed and the "Inhaler Technique Education" was delivered (see section 3.2.10). Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit and to deliver the "Inhaler Technique Education".

Control Diaries and questionnaire booklets completed during the run-in period were returned to the pharmacist at Visit2. asthma severity was assessed; asthma medications and PFM use were documented. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit.

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Visit3 (t1m = 1 month) & Visit4 (t2 m = 2 months) Visit3 and Visit4 took the same format. Visit3 was conducted 1 month after Visit2 and Visit4 was conducted 1 month after Visit3, for both the Active and Control groups. Active Asthma severity was assessed; asthma medications and PFM use were documented. Any interventions by any health care personnel conducted during the last one month regarding patients' asthma were recorded. Patients had their inhaler technique assessed and the "Inhaler Technique Education" was delivered. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit and to deliver the "Inhaler Technique Education".

Control Asthma severity was assessed; asthma medications and PFM use were documented. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit.

Visit5 (t3 m = 3 months) Visit5 was conducted 1 month after Visit 4 (i.e. 3 months following Visit2), for both Active and Control groups. Active Patients were mailed new questionnaires (Patients' Questionnaire Booklet, which included the AQOL and PC questionnaires) (Appendix N) and a new PFM diary (Appendix M) 3 weeks prior to Visit5 . Patients were given reminder phone calls by their pharmacist or researcher to start completing their diary cards (diary of PEF measurements and reliever use) daily for 2 weeks prior to Visit5, and to complete their questionnaires the night before Visit5 . During Visit5, asthma severity was assessed; asthma medications and PFM use were

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documented. Any interventions by any health care personnel conducted during the last one month regarding patients' asthma were recorded. Patients had their inhaler technique assessed and the "Inhaler Technique Education" was delivered. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit and to deliver the "Inhaler Technique Education". Control Patients were mailed new questionnaires (Patients' Questionnaire Booklet, which included the AQOL and PC questionnaires) (Appendix N) and a new PFM diary (Appendix M) 3 weeks prior to Visit5 . Patients were given reminder phone calls by their pharmacist or researcher to start completing their diary cards (diary of PEF measurements and reliever use) daily for 2 weeks prior to Visit5, and to complete their questionnaires the night before Visit5 . During Visit5, asthma severity was assessed; asthma medications and PFM use were documented. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit. Visit6 (t6m = 6 months) Visit6 was conducted 3 months after Visit5 (i.e. 6 months following Baseline), for both Active and Control groups. Active Patients were mailed new questionnaires (Patients' Questionnaire Booklet, which included a questionnaire on AQOL and PQ) (Appendix N) and a new PFM diary (Appendix M) 3 weeks prior to Visit6 . Patients were given reminder phone calls by their pharmacist or researcher to start completing their diary cards (diary of PEF measurements and reliever use) daily for 2 weeks prior to Visit6, and to complete their questionnaires the night before Visit6 . During Visit6, asthma severity was assessed; asthma medications and PFM use were

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documented. Any interventions by any health care personnel conducted during the last one month regarding patients' asthma were recorded. Patients were assessed on their PFM technique. Patients had their inhaler technique assessed and the "Inhaler Technique Education" was delivered. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit and to deliver the "Inhaler Technique Education". The researcher independent of the community pharmacists, assessed inhaler technique in half of the patients in this group. Control Patients were mailed new questionnaires (Patients' Questionnaire Booklet, which included a questionnaire on AQOL and PC) (Appendix N) and a new PFM diary (Appendix M) 3 weeks prior to Visit6 . Patients were given reminder phone calls by their pharmacist or researcher to start completing their diary cards (diary of PEF measurements and reliever use) daily for 2 weeks prior to Visit6, and to complete their questionnaires the night before Visit6 . During Visit6, asthma severity was assessed; asthma medications and PFM use were documented. Patients were assessed on their PFM technique. Pharmacists documented any questions asked by the patients in relation to the study. Pharmacists recorded the time (minutes) it took them to complete the visit. The researcher assessed inhaler technique independently of the community pharmacists in all patients in this group. After final assessment, patients received the "Inhaler Technique Education" for the first time. 3.2.10. Inhaler Technique Education Pharmacists in the Active group only delivered the "Inhaler Technique Education", at Visit2, Visit3, Visit4 , Visit5 , and Visit 6. The "Inhaler Technique Education' consisted of a series of steps (as shown in Figure 3.2):

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i-

Inhaler technique assessment (each patient received a score out of 9 for both TH and ACC) based on the TH and ACC technique checklists (Table 3.1).

ii-

Inhaler technique education (verbal information plus physical demonstration of technique with placebo inhalers, using the provided checklists (Table 3.1))

iii-

If the patient did not perform all 9 steps correctly, then steps (i) and (ii) were repeated until the patient demonstrated Correct Technique, or up to a maximum of three repeats (Figure 3.2). If the patient did perform the 9 steps correctly, then steps iv and v were performed.

iv-

The "Inhaler Technique Labels" were highlighted with steps performed incorrectly by the patient before education (Figure 3.3).

v-

Labels were placed on the patients' replacement inhaler (or on the old one if still in use) (Figure 3.3).

Figure 3.2. Process of "Inhaler Technique Education" for each Active group patient (TH Ac and ACC Ac).

(i) Assess technique

(iv) Highlight label with initial problems

(iii) (ii) Educate (verbal information + physical demonstration)

(v) Attach label to inhaler

(iii) – Repeat the 'Demonstration with return Demonstration' (i & ii) until patient demonstrate Correct Technique, or up to a maximum of three repeats

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Table 3.1. Checklists for assessment of TH and ACC techniques. *Checklist for Turbuhaler technique

10. Remove the cap from the inhaler 11. Keep inhaler upright 12. Rotate grip anti-clockwise then back until a click is heard 13. Exhale to residual volume 14. Exhale away from the mouthpiece 15. Place mouthpiece between teeth and lips 16. Inhale forcefully and deeply 17. Hold breath for 5 seconds 18. Exhale away from mouthpiece

*Checklist for Accuhaler technique

10. 11. 12. 13. 14. 15. 16. 17. 18.

Open inhaler Push lever back completely Exhale to residual volume Exhale away from mouthpiece Mouthpiece between teeth and lips Inhale forcefully and deeply Hold breath for 5 seconds Exhale away from mouthpiece Close inhaler

*Checklists based on previous published literature (van der Palen et al. 1998), (Basheti et al. 2005). Bold steps are 'Essential Steps' (i.e. steps if not performed correctly by the patients, little or no medication would reach their lung).

Figure 3.3. Example of an Inhaler Technique Label for a TH and an ACC with incorrect steps highlighted (based on steps in Table 3.1).

3.2.11. Validity of inhaler technique assessment by Active group pharmacists (Interrater reliability) Inter-rater reliability with regards to technique assessment (the agreement between the technique scores, given by different pharmacists for the same patient), was accounted for in this study by firstly educating pharmacists on correct inhaler technique until they were able to demonstrate the technique correctly for the PFM, TH and ACC. Secondly, the researcher independently assessed inhaler technique for 30 Active patients (15 TH Ac

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and 15 ACCAc) during the run-in period (between Visit1 and Visit2) and at the end of the study. Inhaler technique assessments completed by the researcher and the pharmacists (for the 30 Active patients) were compared. 3.2.12. Final assessment of pharmacists' inhaler technique The inhaler technique of all pharmacists enrolled in this study (Chapter 2) was assessed by the researcher one year after the completion of the study (two years after the workshop). This assessment was completed at the pharmacists' pharmacies, in the private counselling area of the pharmacy. After the final assessment, pharmacists in the Control group received the "Inhaler Technique Education" for the first time. All pharmacists received Certificates upon completion of study (Appendix O). 3.2.13. Qualitative assessment of the study and "Inhaler Technique Labels" At the end of the study, pharmacist and patient opinions of the "Inhaler Technique Label" were documented. Comments were reported by the pharmacists and patients, and recorded by both the pharmacists and researcher. Pharmacists' opinion of the study was also summarised following comments given by the pharmacists during and at the end of the study. 3.3. Data management 3.3.1. Data collection Table 3.2 summarises the data recorded/collected during the study, the method/tools used to collect the data and by whom (patient, pharmacist, or researcher).

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Table 3.2. Summary of data recorded/collected throughout the study, the method/tools used to collect the data and by whom (patient, pharmacist, or researcher). Data recorded/collected

By Whom

Patient Demography

Pharmacist

Previous inhaler Patient technique education

Current medications

Pharmacist

Inhaler technique score Pharmacist (for THAc, ACCAc patients) Inhaler technique score Researcher (for THC, ACCC Patients)

Method/tool

Visit at which data were recorded/ collected Interview (as per t-1/2 m Patients' Record Forms). "Previous Inhaler t-1/2 m Technique Education Questionnaire" Interview (as per Every visit Patients' Record Forms). Inhaler technique Every visit checklists Inhaler checklists

technique t-1/2m and t6m

PFM technique score

Pharmacist

PFM technique checklist

t-1/2m and t6m

PEF measurements Reliever use

Patient Patient

Patients' PFM diaries Patients' PFM diaries

t-1/2m, t3m and t6m t-1/2m, t3m and t6m

Asthma severity

Pharmacist

*Asthma Severity Table

Every visit

AQOL score

Patient

t-1/2m, t3m and t6m

PC score

Patient

Frequency of PFM use

Pharmacist

Patients' Questionnaire Booklet (AQOL) Patients' Questionnaire Booklet (PCAQ) Interview (as per Patients' Record Forms). Interview (as per Patients' Record Forms).

Time of delivering the Pharmacist "Inhaler Technique Education" Time to complete the Pharmacist visit

t-1/2m, t3m and t6m All visits, except t0 All visits, except t-1/2m

Interview (as per Every visit Patients' Record Forms).

* Modification of Asthma Severity Table in the Australian Asthma Management Handbook (National Asthma Council Australia 2002), excluding spirometry for the purposes of this study (see section 3.3.6). AQOL - Asthma-related quality of life (Marks et al. 1992), PCAQ - Perceived Control of Asthma questionnaire (Katz et al. 2002) (Appendix N). Patients' Record Forms (THAc: Appendix K and THC: Appendix L). "Previous Inhaler Technique Education Questionnaire" (Appendix J). PFM technique checklist (Appendix E). Inhaler technique checklists (see section 3.2.10 - Table 3.1). THAc= TH Active group; ACCAc = ACC Active group; THC= TH Control group; ACCC= ACC Control group; t-1/2 m = time 1/2 month prior to study commencement; t 0m = time of study commencement; t1m = 1 month after t0m; t2m = 2 month after t0m; t3m = 3 month after t0m; t6m= 6 month after t0m; PEF = Peak Expiratory Flow.

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3.3.2. Previous Inhaler Technique Education Patients were required to self complete a questionnaire on their previous source of information. This questionnaire was designed to collect data about patients' previous source of inhaler technique education, mode of education and when any previous inhaler technique assessment was received, inhaler technique assessment and education within the last 12 months, and patients' perception of their inhaler technique. This questionnaire was developed and tested for clarity in our previous pilot study (Basheti et al. 2005), and updated according to the researchers remarks (Appendix J). 3.3.3. Inhaler Technique scores Inhaler technique was assessed in the same way for both the TH and the ACC, using 9step checklists specific for each of the two inhalers (Table 3.1). Each item in the checklists represented one step associated with drug administration. Certain steps in the checklists for the TH and ACC were identified as 'Essential Steps', based on previous literature (van der Palen et al. 1998), (Basheti et al. 2005). These steps have been described as 'essential', as if incorrectly performed little or no medication would reach the lung. Patients were required to demonstrate how they would usually use their inhalers based on the following statement: "Show me how you normally use your TH/ACC, from the start to the finish. This TH/ACC does not contain any active medication". Patients received one point for each item (step) performed correctly. Based on this, patients received a score out of "9", which related to the number of steps they were able to perform correctly. Correct Technique indicated a "score of 9/9". Correct Essential Technique indicated a score of 4/4 for the TH and 3/3 for the ACC (based on performing correctly the Essential Steps identified in the checklists (Table 3.1). 3.3.4. PFM use and PFM technique assessment A PFM technique checklist, describing the 11 steps required for the correct use of a PFM was used to assess PFM technique (Appendix E). Patients were required to

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demonstrate how they would usually use their PFMs, based on the following statement: "Show me how you would normally use a PFM from the start to the finish. This PFM may look a little different from the one you are used to". Patients received one point for each step performed correctly. Based on this, patients received a score out of "11", according to the number of steps they were able to perform correctly. Pharmacists documented information relating to patients' PFM use outside that specifically associated with this study (i.e. in addition to two weeks of PEF readings before baseline (t0m), t3m and t6m. 3.3.5. Medication use Pharmacists were required to collect data from the patients on their asthma medication regimen at every visit. Patients gave the name and strength of their asthma medications, the number of days a week and number of times a day the medications were taken, and the number of puffs/pills taken of each of the medications each time. On subsequent visits, pharmacists collected data on any changes in medication from the previous visit. Patients provided information on their medication use based on the following question: “have you had any change to your medication since our last meeting?”. If the patients answered with „yes‟, then pharmacists asked the date of change and what this included. During the two week period when PEF was measured and recorded, patients were also asked to record the name and strength of their asthma medications, and the number of puffs/pills of each medication administered. 3.3.6. Clinical outcomes Patients were required to record their PEF measurements on the PFM diaries, using the PFMs provided by their pharmacists. Patients were asked to record the best of three values immediately after waking and in the evening. Patients were told to use the symbol "x" if a reliever was used up to 3 hours before recording and the symbol "●" if no reliever was used 3 hours prior.

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Min%Max was calculated by the pharmacists and the researcher for each diary at t 0m, t3m and t6m. Min%Max was calculated for diaries which had at least 6 continuous days of PEF measurements completed by the patients before their visit to the pharmacy. Min%Max was calculated as the lowest morning PEF (l-min-1 ) for each patient over 2 weeks, expressed as a percentage of the highest PEF (l-min-1) over the same 2 week period. Mean PEF was recorded by the researcher by calculating the mean of all the PEF (l-min-1) readings for each patient over the 2 week period. Patients were also required to record their daily reliever use (puffs per day) on their PEF diaries over each two-week diary period. Reliever use was then calculated for each patient by the researcher at t0m, t3m and t6m and expressed as the average number of puffs per day. Pharmacists were asked to complete the asthma severity assessment for each patient by asking each patient 6 questions (Table 3.3), then circling the most appropriate response that described the patients' asthma status in the last one month. The questions were based on the “Asthma Severity Table” included in the National Asthma Council‟s Asthma Management Handbook (National Asthma Council Australia 2002). The table considers the duration, intensity and frequency of symptoms, as was suggested by O‟Connor and Weiss (O'Connor and Weiss 1994), and classifies asthma severity into mild, moderate or severe. Patients were assigned to the most severe grade in which any feature occurred (Table 3.3). This table was modified by excluding spirometry (FEV

1

(% predicted), and morning peak flow on waking), to make it feasible for the pharmacists to determine each patient's current asthma control, depending on the frequency and intensity of their symptoms. In order to evaluate asthma control rather than asthma severity, assessment based on Table 3.3 was also completed by excluding the overriding effect of the 2 components of the table "Hospital admission or emergency room admission, Life threatening attack in the last 5 years". The term "asthma control" was given to this second assessment.

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Table 3.3. Severity of asthma table, modified from the National Asthma Campaign - Asthma Management Handbook 2002) (National Asthma Council Australia 2002). Asthma Feature Wheeze, chest tightness, cough, breathlessness Night time symptoms Asthma symptoms on waking

Frequency Occasional

Most days

Every day

No

Less than once a week

Once a week or more

No

Less than once a week

Once a week or more

Hospital admission or emergency room in past year

No

Yes

Life threatening Attack ( ICU or ventilator) in the last 5 years

No

Yes

Reliever use

Less than twice a week

Most days

More than 3-4 times per day

* Modification of Asthma Severity Table in the Australian Asthma Management Handbook (National Asthma Council Australia 2002), excluding spirometry for the purposes of this study (see section 3.3.6).

3.3.7. Humanistic outcomes Asthma-related quality of life (AQOL) (Marks et al. 1992) and Perceived Control (PC) (Katz et al. 2002) assessments were a part of the „Patients' Questionnaire Booklet‟ (Appendix N), given to the patients by their pharmacists, and self completed at their own time. AQOL was assessed by the use of the validated 20-item AQOL questionnaire (range: 0-4 for best→worst quality of life) (Marks et al. 1992). The Percieved Control was assessed by the use of a Perceived Control of Asthma Questionnaire (PCAQ- range 0-55 for worst→best) (Katz et al. 2002), which provides a measures of the patients' perceived ability to deal with asthma and its exacerbations effectively. This questionnaire is a valid instrument, consists of 11 items, self – administered, follows a Likert scale, and provides a measure of self-efficacy, locus of control and learned helplessness.

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3.3.8. Practicality of the intervention Pharmacists were required to record the starting time and finishing time for each visit. Pharmacists in the Active group were also asked to record the time it took them to deliver the “Inhaler Technique Education” for each patient. Pharmacists were also required to record the number of times they repeated the "Demonstration with return demonstration” part of the “Inhaler Technique Education” process (Figure 3.2). 3.3.9. Exposure to inhaler technique education in addition to study Active pharmacists were required to ask the patients about any information they might have received from another health care professional regarding inhaler technique education. Patients provided information on this, based on the following question, “Have you been given any information about TH/ACC technique since our last meeting?”. For patients who answered with “yes”, they were also asked about the time, source and mode (verbal, written, and/or physical) of that education. All pharmacists were required to record any relevant questions asked by the patients, and the answers they gave. In addition, pharmacists had to complete a checklist at the end of each visit regarding the activities they performed during that visit. 3.3.10. Pharmacists' inhaler technique assessment Pharmacists were asked to demonstrate how they would usually demonstrate inhaler technique to their patients. This was completed one year after the end of the study (two years after the end of the workshop), based on the following question: "Show me how you normally demonstrate to patients the technique of the TH/ACC, from start to finish, using the placebo inhalers”. Pharmacists' inhaler technique assessment was completed at their pharmacies in a private area. Pharmacists' inhaler technique demonstration was assessed using the same checklists as those used for patients (Table 3.1), and scored as discussed previously (see section 3.3.3).

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3.4. Documentation for data collection In order to document all data collected and assessments performed, data collection forms were developed. These forms included the "Previous Inhaler Technique Education Questionnaire" (Appendix J), "Patients' Record Forms" (Appendix K and Appendix L), PFM Diary Card (Appendix M), and "Patients' Questionnaire Booklet" (Appendix N). The Patients' Record Forms were used by the pharmacists. The Previous Inhaler Technique Education Questionnaire, Patients' Questionnaire Booklet and the PFM Diary Card were completed by the patients. 3.4.1. Pharmacists' documentation Pharmacists were provided with the "Patients' Record Forms" (Appendix K and Appendix L) to document all data collected and assessments performed. The forms were designed to obtain both demographic and disease information about the patients. The basic aim was to develop a Patient Record Form that was easy to read and use by the pharmacists. Whilst writing, several drafts were prepared and the research team ensured that these manuscripts followed some basic principles. These principles included readable style, where size 14 "Times New Romans" fonts was used (a serif font known to be easier to read) (Fleming 1993). Bold print was used to attract the eye of the pharmacists to important points in the form, and enhance its legibility (Fleming 1993). Colour coding was used to distinguish between record forms to be completed at the pharmacy for TH (green) and ACC (purple), and forms to be completed at home by the patients (yellow and white) (Fleming 1993). The Inhaler Technique Labels followed the same colour coding (TH: green; ACC: purple). A folder with four sections (one section for each patient) was provided to each pharmacist. Everything the pharmacists needed for the study was included in this folder, including a reminder card of the time span between the visits, a summary sheet with the most important information about the study (inclusion and exclusion criteria and who to contact for further questions or in emergencies), an appointment diary card for each patient (detailing their name and number, the date and time of visits, and what they need to bring with them at each visit), inhaler technique labels for the Active pharmacists (both TH and ACC labels) with a highlighter.

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3.4.2. Patients' Questionnaire Booklet Similar principles were followed in the development of the Patients' Questionnaire Booklet (which included the AQOL and PC questionnaires) as in the Patients' Record Form (see section 3.4.1). At the top of each questionnaire, there was an explanation as to why we were asking the patient to complete the questionnaire (Appendix N). 3.4.3. PFM Diary Card The PFM diary card was developed with the intention of being easy to read and use by the patients. The diary was small and shaped like a card (Appendix M). Morning and night readings were clearly positioned on the diary for each day. Even though the patients were asked to complete their readings for fourteen days before they came back to their pharmacies, a space for eighteen days‟ measurements was provided on the card, considering that patients may not be able to see their pharmacists after exactly fourteen days of starting the diary. Under each day, there was a place for patients to record their preventer use (puffs/tablets) and reliever use (number of puffs) on that day. Patient number, visit number, dates of chart (start and end) were also clearly marked on each card. 3.5. Quality measures A series of process measures were implemented in order to ensure both pharmacists' and patients' satisfaction, adequacy of resources and attendance rate. These measures include the following: 1- Inhaler Technique Assessment - all pharmacists were trained to demonstrate and accurately assess correct TH, ACC and PFM technique prior to patient recruitment. 2- Pharmacist Checklist - A checklist was completed by the researcher for each pharmacist while delivering the intervention to one patient (completed at a random visit, at least two times for each pharmacist) during the course of the study to ensure correct conduct of the intervention.

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3- Visit Checklist - Each pharmacist completed a checklist at the end of each visit for each patient, indicating the procedures they completed during that visit. The same checklist was also completed by the researcher at the first visit for each pharmacist, and the checklists were compared at the end of that visit with any differences brought to the attention of the pharmacist. 4- Reminder Phone Calls – Reminder phone calls were conducted by the researcher for both patients and pharmacists before each visit. In addition, the researcher conducted regular reminder phone calls for the patients to guarantee their completion of their diaries and questionnaires on time. 5- Review of Data Collection Process - The researcher collected and audited Patients' Record Forms, Patients' Questionnaire Booklets and PFM Diaries on a regular basis to ensure correct collection of data. Feedback was provided to the pharmacists if a consistent problem was found. 3.6. Data analysis Data were analysed using the Statistical Package for Social Science (SPSS) version 12. All record forms (Previous Inhaler Technique Education Questionnaire, Patients' Record Forms, Patients' Questionnaire Booklets and PFM Diaries) were collected from the pharmacists, and variables were coded for all questions and assessments in the record forms. All data were entered twice by the researcher, in two separate files, which were later compared to minimise data entry errors. 3.6.1. Normality of data Normality of distribution was determined using the Kolmogorov-Smirnov test. Visual confirmation of normality was obtained by construction of a histogram, normal Q-Q plot, detrended normal Q-Q plot, and box and whiskers plot. The normal Q-Q plot graphs observed values against an "expected" value from a normal distribution. The expected value was based on the rank of the observed value and the number of cases in the sample.

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For normally distributed data, the points in the normal Q-Q plot should lie in a straight line. The following independent variables were tested for normality of distribution: age, duration of preventer use, inhaler technique score at t -1/2m, inhaler technique score at t0m, inhaler technique score at t1m, inhaler technique score at t 2m, inhaler technique score at t3m, inhaler technique score at t6m, PFM technique score at t-1/2m, PFM technique score at t0m, PFM technique score at t6m, Min%Max at t0m, Min%Max at t3m, Min%Max at t6m, change in Min%Max from baseline to t3m, change in Min%Max from baseline to t6m, mean PEF at t 0m, mean PEF at t3m, mean PEF at t6m, change in mean PEF from t0m to t3m, change in mean PEF from t0m to t6m, AQOL at t0m, AQOL at t3m, AQOL at t6m, PC at t0m, PC at t3m, PC at t6m. 3.6.2. Analysis plan Figure 3.4 outlines the data analysis plan used in the analysis of the results of this section of the thesis. Figure 3.4. Data analysis plan used in the analysis of the results of this section of the thesis. Categorical variables

Continuous variables

Descriptive statistics (using frequencies)

Normality test (Kolmogorov-Smirnov)

Betwee groups comparison

Within group comparison

Between groups comparison Normal data Independent Samples Student's t-test

Pearson's Chi-Square test

One-way ANCOVA

Non-normal data

Mann Whitney Utest

Within group comparison Normal data

Non-normal data

Paired Samples Student's t-test

Wilcoxon Signed Rank test

Pearson‟s productmoment correlation

Spearman rank order correlation

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3.6.3. Comparisons over time Group comparisons were based on measurements at t0m, t3m and t6m. The mean values and the 95% confidence interval (CI) were used to describe the distribution of normally distributed continuous data. For non-normally distributed variables, the median and interquartile range (IQR) were used. Comparisons between groups were performed by Independent Samples Student's t-test (for normally distributed data) or Mann Whitney Utest (for non-normally distributed data). Within group comparisons were conducted using the Paired Samples Student's t-test (for normally distributed data) and Wilcoxon Signed Rank test (for non-normally distributed data). Comparisons of binary outcome variables were performed by Pearson's Chi-Square test (or Fishers' exact test). For continuous variables, the difference between the Active and Control groups after 3 and 6 months was evaluated by one-way ANCOVA, controlling for baseline (Figure 3.4). For all statistical analyses, p-values of 0.05 were considered statistically significant. All analysis performed in this thesis were pre-specified. 3.6.4. Baseline data analysis The data collected at t0m was used to compare the following between Active and Control groups: 1) demographic data (gender, age, patient working status (working/not working), age of onset of asthma), 2) asthma management profiles (type of preventer, duration of preventer use (years), mean daily dose of preventer medication (mcg), mean daily dose of beclomethasone equivalent (mcg), PFM use) 3) Inhaler Technique (mean of inhaler technique score, proportion of patients with Correct Essential Technique, proportion of patients with Correct Technique, mean of PFM technique score) 4) Clinical parameters (Min%Max, mean PEF, reliever use (average number of puffs a day), asthma severity, asthma control (see section 3.3.6)) 5) Humanistic parameters (AQOL and Percieved C). Comparisons were completed for all patients (TH Ac, ACC Ac, THC, ACCC), then for patients in the Active and Control groups for TH (TH Ac, THC), and ACC (ACCAc, ACCC) users separately.

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3.6.5. Discontinued Patients Comparison was completed initially between discontinued patients, who were enrolled in the study at t-1/2m, but did not come back after the run-in period (at t0m), and patients who came back at t0m to complete the study. 3.6.6. Comparing clinical and humanistic outcomes at t 3m and t 6m For all data analysis, comparisons were completed for all patients (TH Ac, ACCAc, THC, ACCC) first, then for patients in the Active and Control groups for TH (TH Ac, THC), and ACC (ACC Ac, ACCC) users separately. All clinical (Min%Max, mean PEF, reliever use), and humanistic outcomes (AQOL and PC), were evaluated by One-way ANCOVA. One-way ANCOVA controls for baseline data, which is important for this analysis, because of the statistically significant variations found between the groups at baseline. All One-way ANCOVA assumptions (measurement of covariate, reliability of covariate, correlations among covariates, linearity, and homogeneity of regression slopes) were tested before the analysis was run. One-way ANCOVA was completed between the Active and the Control groups (THAc + ACCAc & THC +ACCC) and between the Active and Control groups using both inhalers separately: TH (TH Ac & THC) and ACC (ACCAc & ACCC). Analysis of asthma severity was completed by Pearson's Chi-Square test, to compare the proportion of patients in each group with mild, moderate and severe asthma. 3.6.7. Inhaler technique analysis For inhaler technique analysis, Mann Whitney U-test was used to compare the inhaler technique scores between the groups at t0m and at t6m. Pearson's Chi-Square test was used to compare the proportion of patients with Correct Technique (all steps in the checklists correct, i.e. score is 9 out of 9), the proportion of patients with Correct Essential Technique (essential steps in the checklists correct, i.e. 4 out of 4 for the TH and 3 out of 3 for the ACC) and the proportion of patients correctly performing each individual step in the TH and ACC checklists at t0m and at t6m. 108


3.6.8. Analysing the practicality of the intervention The length of visits and the time taken for the "Inhaler Technique Education" was evaluated, and a between groups' comparison was completed. 3.6.9. Validity of inhaler technique assessment by Active pharmacists (Inter-rater reliability) In order to analyse the validity of the assessment of inhaler technique by the community pharmacists (testing the Inter-rater reliability), Bland and Altman analysis of difference was used (Bland and Altman 1986). This is a graphical method, that plots the difference between the researcher score and pharmacist score (score of patients' inhaler technique), with the researcher's score being the gold standard. The size of the mean difference between the two assessments revealed by this method would determine the validity of the assessment, and hence the inter-rater reliability of the study. 3.6.10. Correlations (Post Hoc analysis) The relationship between the change in inhaler technique score and the change in Min%Max from t0m to t6m was evaluated. The relationship between the change in inhaler technique score and the change in AQOL from t0m to t6m was also evaluated. The analysis included all patients, not just those in the Active group, because any patient would have the potential to change with time in respect to Min%Max, AQOL score and inhaler technique score. Correlations provide an indication as to whether a relationship between two variables exists; it does not however, indicate that one variable causes the other. The strength of the correlation was interpreted by considering Pearson's r values, the amount of shared variance between the two variables, and two tailed test of significance. Correlation analysis was completed for all patients (THAc +THC + ACCAc + ACCC), then for patients in the Active and the Control groups using the TH (TH Ac +THC) and ACC (ACCAc +ACCC) separately.

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3.6.11. Determining predictors of Clinical outcomes (Min%Max), and Humanistic outcomes (AQOL) Multivariant regression analysis was used to detrmine potential predictors of the change in Min %Max (dependent variable) from t0m to t3m, and from baseline to t 6m. The same analysis was also completed for the AQOL score at t 6m. The models were generated for all patients (THAc +THC + ACC Ac

+

ACCC) first, then for TH users and ACC users

separately. 3.6.12. Variables in the regression equation Selecting the independent variables to be included into the model to give the best regression equation was started by including all the variables collected at t0m. Regression models were obtained using stepwise selection. The backward stepwise regression method was chosen. It removes variables stepwise, down to the minimum number which still provides a P value greater than 0.05. Correlation coefficients were obtained for all independent variables against the other independent variables. Some degree of correlation between the variables in the regression equation is to be expected, since multiple regression is supposed to show that certain independent variables may be used to predict dependent variables. However, large intercorrelations (bivariate correlation of 0.7 or more (Tabachnick and Fidell 2001), between the independent variables can substantially affect the results of the multiple regression analysis. If two independent variables in a model were highly correlated (bivariate correlation of 0.7 or more), then the independent variable, which demonstrated the stronger significance in the regression model was left in the model at the expense of the other. The independent (predictor) variables evaluated for inclusion into the model for each of the three dependent variables (change in Min%Max from t0m to t3m, change in Min%Max from t0m to t6m, AQOL at t 6m) were: Min%Max at t0m, intervention type (Active or Control), type of preventer, age, gender, patient working status, asthma severity, age of onset of asthma, duration of preventer use, daily dose of Beclomethasone equivalent

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(mcg), score of inhaler technique at t0m, Correct Essential Technique at t0m, Correct Technique at t0m, long-acting 2 -agonist use, reliever use (Average no of puffs a day), AQOL at t0m, and change in inhaler technique score from t0m to t6m. Because we did not assess Control patients' inhaler technique at t3m, it was decided to use the change in inhaler technique score from t0m to t6m in this model, to give an indication of the improvement that occurred in the inhaler technique for both groups. 3.6.13. Assumptions for the Multivariant regression The following assumptions for the regression models were all validated: Multicolliniarity (which refers to the situation in which there is a high multiple correlation when one of the independent variables is regressed on the other); Colliniarity (which was assessed by observing the tolerance and variance inflation factor (VIF)); Tolerance (which is an indicator of how much of the variability of the specified independent is not explained by the other independent variables in the model. If this value was found to be very small (less than 0.1), it indicates that the multiple correlation with other variables is high, suggesting the possibility of multicolliniarity); VIF value (which is just the inverse of the Tolerance value, indicating multicolliniarity if its value was found to be above 10). 3.6.14. Examination of residuals For each model obtained, the residual scatter-plots were checked to see whether the assumptions of the regression model were held (i.e. to check wether the errors were normally distributed about a mean of zero and with constant variance). 3.6.15. "Goodness of fit" of regression model R2 is the "coefficient of determination" indicating how much of the variance in the dependent variables is explained by the model. An R2 value, however, tends to give an optimistic overestimate of the true value in the population. Hence an adjusted R2 value given by SPSS can "correct" this value to provide a better estimation of the true

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population value. Therefore, the adjusted coefficient of variation was used to measure the goodness of fit of the regression model. To assess the statistical significance of the result, it is important to take into account the result of the null hypothesis. The null hypothesis was that there was no linear relationship between the independent and dependent variables. Hence the model would reach statistical significance if p0.05, Pearson's Chi-Square test). Table 3.5. Proportion of TH (TH Ac n=23, THc n=20) and ACC (ACC Ac n=32, ACCC n= 29) users, using the different reliever (short-acting 2-agonist) medications. Ventolin

Bricanyl

Asmol

THAc n (%)

16 (69.6%)

4 (17.4%)

0 (0.0%)

THC n (%)

17 (85.0%)

1 (5.0%)

0 (0.0%)

ACCAc n (%)

26 (81.3%)

1 (3.1%)

2 (6.3%)

ACCC n (%)

22 (75.9%)

2 (6.9%)

0 (0.0%)

THAc= TH Active group; ACCAc = ACC Active group; THC= TH Control group; ACCC= ACC Control group. Ventolin (salbutamol); Bricanyl (terbutaline); Asmol (salbutamol).

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There was a statistical significant difference between ACC users and TH users with regards to long-acting 2-agonist use, as more ACC users were using long-acting 2agonist than TH users (p0.05). With regards to Correct Essential Technique, a statistically significant higher proportion of ACC users were able to demonstrate Correct Essential Technique at baseline when compared to TH users (TH: 30% and 26%; ACC 60% and 52% for Active and Control respectively, p=0.006). No significant difference in the proportion of patients demonstrating Correct Essential Technique between the TH and ACC was found at 3 and 6 months (p>0.05). 3.7.5.2. Validity of inhaler technique assessment by Active group pharmacists Patients' inhaler technique assessment by pharmacists in the Active group was validated, as results revealed a mean difference between the pharmacists' assessment scores and the researchers' assessment scores at t0m of 0.24 (95% CI -0.09 to 0.58) (Figure 3.10), and a mean difference of 0.54 at t6m (95% CI 0.33 to 0.74) (Bland and Altman analysis of difference) (Figure 3.11).

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Results were similar for the TH assessment scores (mean difference at t0m: -0.13 (95% CI -0.64 to 0.37); mean difference at t6m: 0.20 (95% CI -0.11 to 0.51)), and the ACC assessment scores (mean difference at t0m: -0.33 (95% CI -0.61 to -0.063); mean difference at t6m: 0.07 (95% CI -0.20 to 0.35)).

Mean difference between researcher's and pharmacist's inhaler technique assessment scores.

Figure 3.10. Mean difference between researcher's and pharmacists' inhaler technique assessment scores for patients in the Active group (n=30) at t0m (Bland and Altman plots).

2 1 0

Zero bias

-1 -2 -3 2

4

6

8

Researcher's inhaler technique assessment scores

Mean difference between researcher's and pharmacist's inhaler technique assessment scores.

Figure 3.11. Mean difference between researcher's and pharmacists' inhaler technique assessment scores for patients in the Active group (n=30) at t 6m (Bland and Altman plots). 2.5 2 1.5 1 0.5 0

Zero bias

-0.5 -1 -1.5 3

5

7

9

Researcher's inhaler technique assessment scores

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3.7.5.3. Inhaler technique score The mean inhaler technique score improved significantly from t0m to t6m, for both Active and Control groups, but the magnitude of improvement was statistically significantly greater for the Active group than the Control group (TH and ACC combined, mean±SD difference in score 2.8±1.6 cf. 0.9±1.4, p