Cost Effectiveness of Preventive Interventions in Type 2 Diabetes ...

Pharmacoeconomics 2006; 24 (5): 425-441 1170-7690/06/0005-0425/$39.95/0

REVIEW ARTICLE

 2006 Adis Data Information BV. All rights reserved.

Cost Effectiveness of Preventive Interventions in Type 2 Diabetes Mellitus A Systematic Literature Review Sylvia M.C. Vijgen, Mirjam Hoogendoorn, Caroline A. Baan, G. Ardine de Wit, Wien Limburg and Talitha L. Feenstra Department for Prevention and Health Services Research, National Institute of Public Health and Environment (RIVM), Bilthoven, The Netherlands

Contents Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425 1. Method of Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427 2. General Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428 3. Primary Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 4. Secondary Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 5. Tertiary Prevention of Macrovascular Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 5.1 Education Only . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 5.2 Diet and Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 5.3 Medication to Reduce Weight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434 5.4 Medication to Reduce Hyperglycaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 5.5 Medication to Reduce Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 5.6 Medication to Reduce Dyslipidaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 5.7 Medication to Reduce Weight and Hyperglycaemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 6. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438

Abstract

A systematic review of the literature was conducted to give an overview of economic evaluations of preventive interventions in type 2 diabetes mellitus. The interventions were sorted by type of preventive intervention (primary, secondary or tertiary) and by category (e.g. education, medication for hypertension). Several databases were searched for studies published between January 1990 and May 2004 on the three types of preventive intervention. For each study selected, inclusion of specific components from a standardised list of items, including quality, was recorded in a database. Summary tables were generated based on the database. A number of conclusions were drawn from this review. The most important was that strict blood pressure control was a more cost-effective intervention than less strict control, as shown by six studies reporting cost savings to very low costs per life-year gained. Primary and secondary prevention of type 2 diabetes were also highly cost effective, but these results were based on very few studies. Medications to reduce weight and hyperglycaemia together were cost effective compared with conventional interventions. Finally, the separate results regarding

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medications to reduce weight, hyperglycaemia and hypercholesterolaemia varied enormously, thus no conclusion could be drawn and further economic analysis is required.

Diabetes mellitus comprises a clinically and genetically heterogeneous group of disorders that have one common feature: abnormally high levels of glucose in the blood. The most common form is type 2 diabetes, which affects approximately 80–90% of all patients with diabetes. Other forms include type 1 diabetes and gestational diabetes. Diabetes is a complex disease with various complications, both microvascular (e.g. neuropathy, retinopathy and nephropathy) and macrovascular (cardiovascular diseases such as angina pectoris, myocardial infarction, stroke, chronic heart failure and coronary heart disease). The incidence and prevalence of diabetes have increased in recent decades and it is expected that both will continue to rise.[1] The increase particularly concerns type 2 diabetes, which is the focus of this review. Many patients with type 2 diabetes are unaware of its presence and thus remain undiagnosed,[2] despite being at high risk of developing complications. The discussion as to whether or not to screen for undiagnosed diabetes is continuing in many countries.[3,4] Because of the growing burden of type 2 diabetes and its sequelae, interest in prevention strategies for diabetes and its complications is increasing. In The Netherlands, care for diabetes-related macrovascular complications accounts for approximately 43% of the total costs of diabetes (including productivity costs), while care for microvascular complications accounts for approximately 9%.[5] There are three types of prevention strategies for diabetes: primary, secondary and tertiary. The aim of primary prevention is to prevent the development of diabetes in high-risk individuals or in the general population. Several risk factors of diabetes have been identified; the major ones are obesity and lack of physical activity. The aim of secondary prevention (screening) is the early detection and subsequent treatment of patients with undiagnosed diabetes. Tertiary prevention aims to obtain health gains  2006 Adis Data Information BV. All rights reserved.

by delaying or even preventing complications by intensive follow-up and treatment of diagnosed diabetes patients. The prevention of diabetes itself, screening for undiagnosed diabetes and the reduction, or delay of, complications are all interesting from an economic perspective. Much benefit can be gained by effective interventions in terms of health outcomes and costs of care for complications. Interventions range from educational and lifestyle programmes to intensive insulin therapy in selected groups. For policy makers with limited budgets, the question is to which areas of diabetes prevention healthcare funds can be most effectively allocated. The growing interest in this topic is reflected in three recent reviews of economic evaluations in diabetes.[6-8] However, all three had a relatively limited perspective. The review by Raikou and McGuire[6] used very stringent inclusion criteria, i.e. only studies based on primary data and with a patient population of exclusively type 2 diabetes were included. As a result, only nine studies were selected, four of which were based on data from the UKPDS (UK Prospective Diabetes Study).[9-11] The second review, published in 2000,[7] is an almost complete review of costeffectiveness studies (published between January 1984 and December 1997) for all interventions available in diabetes management, and includes both type 1 and type 2 diabetes. Besides being somewhat outdated, the review did not include interventions for intensive treatment of high cholesterol or high blood pressure. The third review[8] was an update of the data presented by Klonoff and Schwartz.[7] Zhang et al.[8] searched MEDLINE for articles published between 1997 and 2003 using only the terms ‘diabetes mellitus’ and ‘cost-effectiveness’. We present a systematic review of economic evaluations of preventive interventions in type 2 diabetes reported between January 1990 and May 2004. The review aimed to address the following questions: Pharmacoeconomics 2006; 24 (5)

Cost Effectiveness of Prevention in Diabetes Mellitus

1. What prevention strategies have been economically evaluated and what were the results of these evaluations? 2. What prevention strategies need further research? The result is an overview of the cost effectiveness of various diabetes prevention strategies. Because of the Klonoff and Schwartz review,[7] we decided to adhere strictly to the period 1990–2004 and not include any studies published before 1990. To be as complete as possible, we used a wider set of selection criteria than used by Raikou and McGuire.[6] Papers presenting results in type 2 populations, but also including type 1 data and based on primary or secondary data were included in this review. All primary prevention interventions, screening combined with treatment, and interventions to prevent macrovascular complications in diagnosed diabetes patients were included. This review focuses only on studies concerning macrovascular complications, or a combination of macro- and microvascular complications, because the costs of macrovascular complications are much higher than those of microvascular.[5] Hence, studies solely evaluating the prevention of microvascular complications were excluded. Evaluations of managed care interventions or other organisational measures were also excluded, since the results of such studies tend to be specific to a setting and location. This review can be used as a basis for further research in prevention of diabetes and its complications, and as an aid to policy makers in their decision-making process regarding the allocation of healthcare budgets. 1. Method of Review MEDLINE, EMBASE, SciSearch, IPA, Heclinet, International Health Technology Assessment, Social SciSearch, Cochrane and Econlit databases were searched for studies on the three types of prevention: 1. primary prevention of diabetes; 2. screening for diabetes followed by treatment; 3. prevention of diabetes-related macrovascular complications alone, and combinations of macrovascular and microvascular complications. The period covered was January 1990 to May 2004. Keywords used were:  2006 Adis Data Information BV. All rights reserved.

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1. those that indicate a focus on type 2 diabetes: ‘Diabet*’ AND ‘type 2/II’ OR ‘non insulin dependent/niddm’; 2. those for the various interventions, e.g. ‘screening’ OR ‘detect*’; 3. keywords for economic evaluations: ‘cost-benefit-analysis’ OR ‘costs and cost-analysis’ OR ‘economics’ OR (‘cost benefit*’ or ‘cost effect*’ or ‘cost utility’ or ‘cost efficient*’ or ‘econom*’ or ‘pharmacoeconomic*’) in title OR ([‘cost*’ in title] AND [‘effect*’ or ‘benefit*’ or ‘quality’ in title]). Searches were based on (1), (2) AND (3), with varying keywords in (2) to cover a wide range of interventions. Exclusion criteria were no diabetes, only type 1 diabetes (or IDDM), no original economic evaluation, cost of illness or related type of study, effectiveness study with incomplete cost results, quality of effectiveness study insufficient, comment, letter, one-page article, news, congress report, note, erratum, abstract only, managed care interventions, care directed at symptoms of diabetes complications or prevention of microvascular complications, studies that looked only at prevention of microvascular complications, language other than English and country with predominantly non-Caucasian population. The titles, bibliographic data and abstracts of the results of these searches were scanned for relevance based on the exclusion criteria. Relevant articles were obtained and evaluated. Furthermore, the reference lists from the articles were searched for additional studies, and a number were identified. After applying the exclusion criteria mentioned above to the full text articles, the remaining economic evaluations were checked for completeness and quality. To be included, studies had to give a full evaluation of effects of the interventions and had to be based on good quality effectiveness studies. Studies that only presented monetary costs and benefits and did not measure health effects, other than those reflected in a lower resource use for complications, were excluded. Studies were then assessed for quality using the British Medical Journal (BMJ) checklist,[12] resulting in a quality weight for each study included. The BMJ list focusses on completeness of presentation, which is a prerequisite for a good assessment of Pharmacoeconomics 2006; 24 (5)

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quality and contains items on methodological quality. One of these is the sensitivity, or ‘uncertainty’, analyses used to assess the robustness of study results. Apart from the methodological quality, the score reflects that publications also had to present their methods in sufficient detail. For instance, they had to present information on the patient population, outcome measures, time horizon, modelling approach and type of costs included. Studies were excluded if they combined two or more of the following shortcomings: • no control group in the effectiveness study; • sample size of 45kg excess weight

Standard care

5

$A12 300/LY gained (12 300, 19 100), 1997

Metformin

Standard care

5

Dominant, 2002

Dominant

Intensive lifestyle changes

Standard care

5

Dominant, 2002

Dominant

Targeted screening, people with hypertension No screening No screening

3

$US360 966/QALY, 1997

>100 000/QALY

3 3

$US62 934/QALY, 1997 $US34 375/QALY, 1997

3

SwF2 583/LY gained, 1996

3

Dominant, 1996

3

$US16 000/QALY, 1994

10 000–20 000/QALY

3

€23 522/LY gained, 2000

20 000–50 000/LY gained

Palmer et al.,[26] Australia (79)

Secondary prevention (screening for DM) Hoerger et al.,[22] US (70) Universal screening Universal screening Targeted screening, people with hypertension

Medication to reduce weight Lamotte et al.,[29] Belgium (74)

Orlistat + hypocaloric diet

Hypocaloric diet