Hospital-based health technology assessment on the use ... - IOS Press

Technology and Health Care 21 (2013) 535–546 DOI 10.3233/THC-130756 IOS Press

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Hospital-based health technology assessment on the use of mitral clips in the treatment of mitral regurgitation Roberto Miniatia,∗, Giulio Cecconia , Fabrizio Doria , Matteo Marchettia , Guido Biffi Gentilia, Barbara Porchiab , Giorgio Presiccec , Sara Franchic and Roberto Gusinud a Department

of Information Engineering, Biomedical Laboratory, University of Florence, Florence, Italy b School of Hygiene and Public Health at the Florence Teaching Hospital AOU Careggi, Florence, Italy c General Direction Office, Florence Teaching Hospital AOU Careggi, Florence, Italy d Head of Health Technology Assessment Unit at the Florence Teaching Hospital AOU Careggi, Florence, Italy Received 2 April 2013 Accepted 7 October 2013 Abstract. BACKGROUND: This study, carried out at the Florence Teaching Hospital Careggi (AOUC), reports the technological evaluation, through the use of Health Technology Assessment (HTA), on the application of mitral clips in the treatment of mitral insufficiency. OBJECTIVE: The assessment, carried out by analyzing the clinical, technological, social, procedural, safety and economic elements, sought to answer the following research questions: Evaluation of the general technological status of the mitral clips in the treatment process of mitral regurgitation, with particular reference to traditional methods; and contextualisation of the analyses within the hospital structure, by identifying criticality issues and improvements. METHODS: The methodology was based on the following steps: technological description; areas of evaluation and the selection of Key Performance Indicators; research of scientific facts and the collection of expert opinions; evaluation and reporting of findings. RESULTS: The results are based on an analysis which included a total of 50 indicators, effectively evaluating 86.5% of them, from the least from the clinical sector (80%) to the most in the areas of procedure, safety and social (100%). Traditional surgery (repair or valve replacement) still represents the gold standard for the treatment of mitral regurgitation due to its maturity both on a technological and clinical level. The minimally invasive procedures which use the mitral clips present interesting opportunities both on a social level (minimum stay in hospital and no post-operative rehabilitation) and clinical level, especially as an alternative to medication, even if they are still at an emergent level (the long-term results are unknown) and complex to use. From the clinical point of view they show some interesting findings related to immediate and post-operative mortality (none during the operation and a minor and equal amount 30 days and 12 months later in comparison to traditional methods) whilst economically, despite the fact that the cost of the device is greater than those used in traditional interventions, the cost-refund relationship does not show significant differences compared to the traditional types of treatment.

∗ Corresponding author: Roberto Miniati, Department of Information Engineering, Biomedical Laboratory, University of Florence, Via S. Marta 3, 50139 Florence, Italy. E-mail: [email protected].

c 2013 – IOS Press and the authors. All rights reserved 0928-7329/13/$27.50

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R. Miniati et al. / Hospital-based health technology assessment on the use of mitral clips

CONCLUSION: The HTA evaluation of minimally invasive technologies that use clips for the treatment of mitral regurgitation shows, in the hospital setting, very interesting results, particularly for inoperable patients, where the clinical and social improvements are significant compared to pharmacological treatments, whilst for ‘operable’ patients, the traditional techniques are still the most appropriate. Keyword: Health technology assessment, hospital based, mitral regurgitation, mitral clips

1. Introduction The minimally invasive technology of the application of mitral clips to the valve via percutaneous surgery (catheter with femoral access) is used to reduce mitral regurgitation. Originating in the United States (the first trial ended in 2006 and involved patients considered inoperable by traditional methods of repair and valve replacement) [1–8], this method subsequently reached Europe where more and more centres have started to use this new technology [9–13]. For this reason, it has become necessary for the AOUC to analyse the impact of the device within the hospital, by comparing it to both traditional surgical and pharmacological treatments. The objectives of the study were as follows: – Evaluate the course of treatment of patients affected by mitral regurgitation according to the current care practices and in the usage of mitral clips, for the following thematic areas: technological, safety-procedural, economic, clinical and social. – Compare, hospital-wide, the differences between the current practices and the use of mitral clips in the clinical pathway of care of patients affected by mitral regurgitation. The system for the application of the clips is composed of two main elements: the “Clip Delivery System” (Fig. 1) and the positioning system where the clip is installed (Fig. 2) [14]. Surgery is usually performed with the patient under general anaesthetic. The operation begins with an initial incision in the groin area in order to allow the guiding catheter to enter through the femoral vein and to go back up until the right atrium where it is necessary to perforate the interatrial septum and insert it in the left atrium together with the mitral clip. The external handles control both the steerable arm and the clip in order to close, open or block it [14]. The correct positioning of the clip is controlled through the use of a transesophageal echocardiagram and a fluoroscope. After the clip is applied, the residual value of regurgitation is measured. If the reduction is not considered satisfactory, the clip is reopened and repositioned, whilst if the reduction is deemed satisfactory, the clip is locked in its position. In cases where one clip is not enough, up to three clips can be applied (for example in degenerative diseases or in cases of the breaking of tendon cords with a wide prolapse). Once the definitive position has been determined, the catheter is removed and the incision in the groin is closed. After the insertion of the clip, even if the valve remains partially closed during the diastole phase, mitral stenosis is not identified [15,16]. This occurs when the mitral valve area is less than 1.5 cm2 . Finally, after the surgery the patient is monitored in intensive care for approximately two days and moved to the ward for an average of four days [17].

2. Methodology The methodology followed in the study belongs to the Health Technology Assessment area [18–20] and it is based on the following steps: a. definition of the areas of assessment and the selection of Key Performance Indicators (KPI);

R. Miniati et al. / Hospital-based health technology assessment on the use of mitral clips (a)

(b)

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(c)

Fig. 1. Clip Delivery System (CDS) composed of: (a) adjustable sleeve with clip delivery catheter, (b) steerable guide catheter and (c) dilator.

b. construction of a database through the research of scientific facts and the collection of expert opinions; c. analysis and reporting. 2.1. Areas of assessment and Key Performance Indicators (KPI) The areas selected for the study were as follows: – Clinical: clinical condition of the patient in the short, medium and long term, including the organisation of clinical activity and the subsequent procedures; – Technological: the relationship between technology and user (complexity and learning curve); – Social: aspects tied to the quality of life of the patient though the evaluation of changes in lifestyle both pre- and post-treatment, with reference also to the treatment phase; – Procedure and safety: risks to the operator and to the patient; – Economic: cost evaluation and comparison with possible BEP health refunds. For the Key Performance Indicators, those belonging to the EUnetHTA Core Model [21] were taken as a basis, contextualising them within the specific hospital use, with an analysis of the care path of the patients divided into the following phases: pre-, during and post-treatment. The indicators were divided into 5 chosen areas: clinical, technological, social, procedural and safety and economy.

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Fig. 2. a) Detail of clip delivery system with the clip open; b) Final positioning of the clip.

2.2. Construction of the data base In order to calculate the indicators defined previously it was necessary to plan the data collection, which involved both the research of scientific evidence as well as interviews with experts, along with further data extraction from hospital software already in use. Specifically, the search engines used for the research of scientific evidence were PubMed and Google Scholar. The keywords used in Google Scholar were: “MitraClip, Mitral Valve Repair, Mitral Valve Regurgitation” whilst the search strings used on Pubmed were as follows: 1) (“mitral valve” [MeSH Terms] OR (“mitral” [All Fields] AND “valve” [All Fields]) OR “mitral valve” [All Fields]) AND (“wound healing” [MeSH Terms] OR (“wound” [All Fields] AND “healing” [All Fields]) OR “wound healing” [All Fields] OR “repair” [All Fields]) AND mitraclip [All Fields]. 2) percutaneous [All Fields] AND mitral [All Fields] AND (“wound healing” [MeSH Terms] OR (“wound” [All Fields] AND “healing” [All Fields]) OR “wound healing” [All Fields] OR “repair” [All Fields]) AND mitraclip[All Fields]. 3) (“mitral valve insufficiency” [MeSH Terms] OR (“mitral” [All Fields] AND “valve” [All Fields] AND “insufficiency” [All Fields]) OR “mitral valve insufficiency” [All Fields] OR (“mitral” [All Fields] AND “regurgitation” [All Fields]) OR “mitral regurgitation” [All Fields]) AND mitraclip [All Fields]. 4) mitraclip [All Fields] AND (“mortality” [Subheading] OR “mortality” [All Fields] OR “mortality” [MeSH Terms]) AND results [All Fields]. The boundaries applied to the search were the time period [2006–2011] and language filtering through the selection of English and Italian. After cross-checking the results of the search strings and removing the duplicates 61 articles were obtained. A first selection, made by evaluating titles and abstracts, brought the number of relevant articles to 53. After a second selection on the basis of the full text, which saw the exclusion of studies with a sample of less than 30 subjects, the number of relevant works came to the final figure of 35. The criteria of inclusion/exclusion for operability with mitral clips are reported in Tables 1 and 2 [1–6,22–26]. It is important to underline that in reality not all of the criteria are necessary for a correct application of the mitral clip, but there are parameters that are essential (necessary), others which are assessed by the surgical team (important), and those of little relevance (NO). 2.3. Evaluation and reporting The evaluation, based on the assessment of the selected indicators, depends on the combination of one or more simple indices related both to the specific area and the specific technology. In order to maximize


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Table 1 List of inclusion criteria with level of priority For symptomatic patients For asymptomatic patients one of the following is sufficient

For all patients

In the case of beating leaflets if YES In the case of connecting leaflets if YES

Inclusion criteria Ventricular ejection fraction SX > 25% Ventricular diameter SX of systole end < 55 mm Ventricular ejection fraction SX > 25% and < 60% Ventricular diameter SX of systole end > 40 mm Pulmonary hypertension at rest > 50 mmHg Pulmonary hypertension during excercise > 60 mmHg New onset of atrial fibrillation Age > 18 Mitral regurgitation 3+ or 4+ Candidate for mitral repair or replacement Projection of mitral regurgitation of A2 with P2 Clinically insignificant secondary projections if present

Relevance Necessary Necessary NO NO NO NO NO NO Important NO Necessary NO

Distance between the inferior flaps > 10 mm Width of interior flaps > 15 mm Depth of coaptation > 11 mm Length of coaptation > 2 mm

Necessary Necessary Important Important

Table 2 List of exclusion criteria with level of priority

In the case of beating leaflets (if YES) In the case of connecting leaflets (if YES)

Exclusion criteria Myocardial infarction from 12 weeks prior to treatment TIA in the previous 6 months Need for other cardiac surgical interventions Surgical procedures within previous 30 days Endovascular treatments within previous 30 days Ventricular ejection fractoin SX < 25% Diamater of ventricular systole end SX > 55 mm Area of mitral valve opening < 4 cm2 Severe calcification of the mitral ring Calcification in the anchoring areas of A2 and P2 Presence of significant fissures of A2 and P2 More than one criteria near to the exlusion limit Double beating mitral leaflets Sever prolapse of both mitral leaflets Lack of both primary and secondary chord support Previous operations on the mitral valve Presence of hypertrophic cardiomyopathy Presence of emodynamic instability Valvuloplastry on the mitral valve Ventrical support devices Eco showing intracardiac masses, thrombus or vegetation Clinical history of or active endocarditis Clincial history of or active rheumatic illnesses Clinical history of inter-atrial defects Clinical history of Patent Foram Ovale associated with clinical syptoms Counterindication against use of trans-oesophagal ecocardiagrams Distance between the inferior flaps > 10 mm Width of interior flaps > 15 mm Depth of coaptation > 11 mm Length of coaptation > 2 mm

Relevance Necessary Necessary NO Necessary NO Necessary Necessary Important Necessary Necessary NO NO NO Necessary NO Necessary Necessary Necessary Necessary Necessary Necessary Necessary Necessary NO NO Necessary Necessary Necessary Important Important

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the usability of the evaluation, concise indicators were defined, obtained from the results reported in the evaluation. The methodological and operational steps were: – Standardisation phase. Each indicator is standardised to the maximum value of each technology – Prioritisation phase. The indicators are classified according to level of importance, as suggested in these cases by the experts interviewed. The defined levels are: – Essential: assigned measure 1; – Important: assigned measure 0.75; – Useful: assigned measure 0.5; – Unnecessary: assigned measure 0.25; – Useless: assigned measure 0. Finally, with the goal of creating a usable and efficient report as a real support to the hospital decision maker, the main issue of any HTA, a single index summarizing the whole assessment (shown as sum of each area contribution) was defined: Index of Advantage by Area. This is assessed by the weighted average of the previously defined standardised indicators (value_standardised) belonging to the same area, according to the priority index (prior). See Eq. (1). prior ∗ Valuestandardized (1) Index of advantage (area) = prior The five indicators of advantage were evaluated for “all”, “operable” and “inoperable” types of patients, and are represented in the final report by radar mode, in order to collect all the information in a single graph. 3. Results The assessment was based on the calculation of 86.5% of the total indicators, focusing mainly on the short to medium term and strongly characterized by type of patient: operable and inoperable. In regard to operable patients, the traditional surgical techniques, mitral repair and replacement, are still the gold standard for the treatment of mitral regurgitation, exhibiting greater values of clinical effectiveness in the short and medium term than the mitral clips (73% vs. 55% at 12 months) and a lower likelihood of ‘further action/intervention at 12 months’ compared to the mitral clips (2% vs. 20%), see Fig. 3. With regard to inoperable patients, the mitral clips instead show values of mortality at 12 months halved compared to pharmacological cures. Figure 4 shows the intra-operative mortality at 30 days and 12 months for specific technology and patient category: operable (a) and inoperable (b). The clips have the lowest values for both categories, although in operable patients the values are almost identical. From the point of view of quality of life, patients treated with the clips show better psychophysical conditions than with traditional treatments, because the days of hospital recovery are limited, there is no need for rehabilitation and drug treatment turns out to be less severe than with the traditional techniques [27–36]. The elements considered in this context were: – NYHA classification; – age of patient; – pre-operative quality and invasivity of clinical exams; – post-operative quality; – mortality;


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% of patients with further intervention at 12 months

(a) % of patients with further intervention at 12 months

(b)

Fig. 3. Percentage of patients undergoing further interventions at 12 months.

– length of recovery; – failure of operation at 12 months; – frequency of periodic medical examinations. The following parameters concerning the “pre-operative quality” and “post-operative quality” are reported in Fig. 5. The first mainly analyzes the level of invasiveness of physical exams, patients undergoing traditional techniques have a slightly better quality than patients with mitral clip or drug treatments, where it is necessary to carry out a trans-oesophageal echocardiography exam [25,37]. On the contrary, in the post-operative quality, the mitral clips present a better level than traditional techniques as drug treatment is less severe and rehabilitation is not necessary. For drug treatments, the low quality of post-operative is due to the high frequency of re-hospitalization from heart failure. Technologically, on a general level the traditional techniques are now well developed in contrast to the mitral clip. In the hospital context, the mitral clips are more complex compared to the traditional interventions, and 25 operations are indicated as the minimum number required to become an expert [38, 39], corresponding to a period of 18 months. From a procedural point of view, the traditional techniques exhibit a lower level of complexity than the mitral clips, as well from a safety point of view because of a greater radiological exposure. From the economic point of view, having personnel experienced in the use of mitral clips indicates a reduced effect on total costs, and despite the cost of the device being greater than those used in traditional interventions, the cost-reimbursement relationship does not show significant differences between the various types of treatment. The cost of the care pathway in the treatment of mitral regurgitation, in relation to different treatment methods, took into consideration: – Total cost of treatment; – Total pre-operative cost;

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R. Miniati et al. / Hospital-based health technology assessment on the use of mitral clips Table 3 Reimbursement levels estimation Reimbursement Length of hospital stay Mitral clip 20.507 Euro 7 days Mitral replacement 20.450 Euro 19 days Mitral repair 19.450 Euro 16 days Heart failure 3.000 Euro 8 days

(a)

(b) Fig. 4. Mortality rate during the operation, at 30 days and at 12 months for (a) operable patients and (b) inoperable patients.

– Total intra-operative cost; – Total post-operative cost; – Cost-refund DRG balance; – Economic bearing of experienced personnel. Whilst the estimate of the total cost of treatment also takes into account expenses incurred from personnel, the room used, fixed devices, consumables and the duration of the tests and/or surgical and therapeutic interventions, see Fig. 6. According to company estimates it was possible to calculate the average value of the DRG reimbursement according to type of care [40,41], see Table 3. For the revenue budget costs, estimated as the difference between the total cost of treatment and the revenues from the DRG reimbursement, in the case of mitral clips the financial liability is about 18.000, while in the case of traditional techniques, it is around 9.500. For inoperable patients treated with medication, the expenditure which is not reimbursed is around 5.500.


(a)

(b)

Fig. 5. Pre- and post-operative quality.

Fig. 6. Intra-operative cost.

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Fig. 7. HTA reporting system.

Figure 7 shows the graphical representation for the specific and the total indices of advantages, used in the report to support the hospital decision maker, taking into consideration all patients (a), operable (b) and inoperable (c). 4. Conclusions and future developments The study was carried out to assess the impact in different fields (clinical, technological, social, process and safety and economic) that the use of mitral clips can have in the hospital care path of patients with mitral regurgitation. Interesting results were obtained for inoperable patients, where the clinical and social improvements are significant compared to drug treatments. For “operable” patients, traditional techniques are still the gold standard. For the future, it is hoped that the assessment of the remaining selected indicators (13.5%) will be completed, particularly thanks to the availability of scientific evidence in the long term. References [1] [2]

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