HTA challenges for appraising rare disease interventions viewed through the lens of an institutional multidimensional value framework.

INTRODUCTION: Evaluating rare disease interventions poses challenges for HTA agencies, including uncertainties and ethical issues and tensions. INESSS has recently adopted a Statement of Principles and Ethical Foundations which proposes a multidimensional approach to value appraisal as well as five principles to frame the evaluation process. AREAS COVERED: Our aim was to identify and analyze HTA challenges for appraising interventions for rare diseases, using the Statement's approach to value appraisal as an analytical framework, and outline how the Statement's principles can help address these challenges. Challenges, covering a diversity of aspects, were identified by leveraging institutional experience in diverse domains of expertise and consolidated through narrative literature review. Challenges were categorized by value dimension (clinical, populational, economic, organizational, and sociocultural), which allowed to pinpoint how each challenge affects the ability to appraise the value of an intervention. Key ethical tensions across dimensions were also identified. Specific approaches to addressing these challenges - related to knowledge mobilization and integration, deliberation, and recommendation-making - were outlined on the basis of the principles promulgated in the Statement. EXPERT OPINION: A multidimensional approach can be fruitful for analyzing challenges for appraising the value of rare disease interventions and help guide approaches to tackle them.

Methodological guidance for incorporating equity when informing rapid-policy and guideline development.

OBJECTIVES: We provide guidance for considering equity in rapid reviews through examples of published COVID-19 rapid reviews. STUDY DESIGN AND SETTING: This guidance was developed based on a series of methodological meetings, review of internationally renowned guidance such as the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for equity-focused systematic reviews (PRISMA-Equity) guideline. We identified Exemplar rapid reviews by searching COVID-19 databases and requesting examples from our team. RESULTS: We proposed the following key steps: 1. involve relevant stakeholders with lived experience in the conduct and design of the review; 2. reflect on equity, inclusion and privilege in team values and composition; 3. develop research question to assess health inequities; 4. conduct searches in relevant disciplinary databases; 5. collect data and critically appraise recruitment, retention and attrition for populations experiencing inequities; 6. analyse evidence on equity; 7. evaluate the applicability of findings to populations experiencing inequities; and 8. adhere to reporting guidelines for communicating review findings. We illustrated these methods through rapid review examples. CONCLUSION: Implementing this guidance could contribute to improving equity considerations in rapid reviews produced in public health emergencies, and help policymakers better understand the distributional impact of diseases on the population.

What Makes Artificial Intelligence Exceptional in Health Technology Assessment?

The application of artificial intelligence (AI) may revolutionize the healthcare system, leading to enhance efficiency by automatizing routine tasks and decreasing health-related costs, broadening access to healthcare delivery, targeting more precisely patient needs, and assisting clinicians in their decision-making. For these benefits to materialize, governments and health authorities must regulate AI, and conduct appropriate health technology assessment (HTA). Many authors have highlighted that AI health technologies (AIHT) challenge traditional evaluation and regulatory processes. To inform and support HTA organizations and regulators in adapting their processes to AIHTs, we conducted a systematic review of the literature on the challenges posed by AIHTs in HTA and health regulation. Our research question was: What makes artificial intelligence exceptional in HTA? The current body of literature appears to portray AIHTs as being exceptional to HTA. This exceptionalism is expressed along 5 dimensions: 1) AIHT's distinctive features; 2) their systemic impacts on health care and the health sector; 3) the increased expectations towards AI in health; 4) the new ethical, social and legal challenges that arise from deploying AI in the health sector; and 5) the new evaluative constraints that AI poses to HTA. Thus, AIHTs are perceived as exceptional because of their technological characteristics and potential impacts on society at large. As AI implementation by governments and health organizations carries risks of generating new, and amplifying existing, challenges, there are strong arguments for taking into consideration the exceptional aspects of AIHTs, especially as their impacts on the healthcare system will be far greater than that of drugs and medical devices. As AIHTs begin to be increasingly introduced into the health care sector, there is a window of opportunity for HTA agencies and scholars to consider AIHTs' exceptionalism and to work towards only deploying clinically, economically, socially acceptable AIHTs in the health care system.

Deliberative Processes by Health Technology Assessment Agencies: A Reflection on Legitimacy, Values and Patient and Public Involvement Comment on "Use of Evidence-informed Deliberative Processes by Health Technology Assessment Agencies Around the Globe".

Legitimacy of deliberation processes leading to recommendations for public financing or clinical practice depends on the data considered, stakeholders involved and the process by which both of these are selected and organised. Oortwijn et al provides an interesting exploration of processes currently in place in health technology assessment (HTA) agencies. However, agencies are struggling with core issues central to their legitimacy that goes beyond the procedural exploration of Oortwijn et al, such as: how processes reflect the mission and values of the agencies? How they ensure that recommendations are fair and reasonable? Which role should be given to public and patient involvement? Do agencies have a positive impact on the healthcare system and the populations served? What are the drivers of their evolution? We concur with Culyer commentary on the need of learning from doing what works best and that a reflection is indeed needed to "enhance the fairness and legitimacy of HTA."

Co-construction of health technology assessment recommendations with patients: An example with cardiac defibrillator replacement.

CONTEXT: The National Institute of Excellence in Health and Social Services (INESSS), which functions as the Québec health technology assessment (HTA) agency, tested a new way to engage patients along with health-care professionals in the co-construction of recommendations regarding implantable cardioverter-defibrillator replacement. OBJECTIVE: The objective of this article was to describe the process of co-construction of recommendations and to propose methods of building best practices for patient involvement (PI) in HTA. DESIGN: Throughout the process, documents were collected and participant observations were made. Individual interviews were conducted with patients, health-care professionals and the INESSS scientific team, from January to March 2018. RESULTS: Three committees were established: an expert patient committee to reflect on patient experience literature; an expert health professional committee to reflect on medical literature; and a co-construction committee through which both patients and health-care professionals contributed to develop the recommendations. The expert patients validated and contextualized a literature review produced by the scientific team. This allowed the scientists to consider aspects related to the patient experience and to integrate the feedback from patients into HTA recommendations. The most important factor contributing to a positive PI experience was the structured methodology for selecting patient participants, and a key factor that inhibited the process was a lack of training in PI on the part of the scientific team. CONCLUSIONS: This experience demonstrates that it is possible to co-construct recommendations, even for technically complex HTA subjects, through a more democratic process than usual which led to more patient-focused guidance.

Can reflective multicriteria be the new paradigm for healthcare decision-making? The EVIDEM journey.

BACKGROUND: Multiple technologies, procedures and programs call for fairly-based decisions for prioritization of healthcare interventions. There is a diversity of perspectives of what constitutes a legitimate decision, which depends on both the process and the reasoning applied. Current approaches focus on technical aspects while methods to support alignment of decisions with the compassionate impetus of healthcare systems is lacking. METHODS: The framework was developed based on an analysis of the foundations of healthcare systems, the reasoning underlying decisions and fair processes. The concept of reflective multicriteria was created: it assumes that decisionmakers guided by a generic interpretative frame rooted in the compassionate impetus of healthcare systems, can sharpen their reasoning, raise awareness of their motivation and increase legitimacy of decisions. The initial framework was made available through a not for profit organization (the EVIDEM Collaboration, 2006-2017) to stimulate its development with thought leaders and stakeholders in an open source philosophy. Development was tailored to the real-life needs of decisionmakers and drew on several domains of knowledge including healthcare ethics, evidenced-based medicine, health economics, health technology assessment and multicriteria approaches. RESULTS: The 10th edition framework builds on four dimensions: (1) the universal impetus of healthcare systems, (2) reasoning, values and ethics, (3) evidence and knowledge on interventions, and (4) a transformative process. Mathematical aspects of the framework are designed to help clarify, express and share individual reasoning; this non-conventional use of numbers requires a cultural change and needs to be phased in slowly. The framework includes four tools for easy adaptation and operationalization: (a) concepts and operationalization, (b) adapt and pilot, (c) evidence matrix, (d) mathematical representation of reasoning. Application is useful throughout all types of healthcare interventions, for all levels of decision, and across the globe. CONCLUSION: By clarifying their reasoning while keeping decisionmakers aware of the impetus of healthcare systems, reflective multicriteria provides an effective approach to increase the legitimacy of decisions. Beyond a tool, reflective multicriteria pioneered by EVIDEM is geared to transform our vision of the value of healthcare interventions and how they might contribute to relevant, equitable and sustainable healthcare systems.

Development of a Framework Based on Reflective MCDA to Support Patient-Clinician Shared Decision-Making: The Case of the Management of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NET) in the United States.

INTRODUCTION: Well- or moderately differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often slow-growing, and some patients with unresectable, asymptomatic, non-functioning tumors may face the choice between watchful waiting (WW), or somatostatin analogues (SSA) to delay progression. We developed a comprehensive multi-criteria decision analysis (MCDA) framework to help patients and physicians clarify their values and preferences, consider each decision criterion, and support communication and shared decision-making. METHODS: The framework was adapted from a generic MCDA framework (EVIDEM) with patient and clinician input. During a workshop, patients and clinicians expressed their individual values and preferences (criteria weights) and, on the basis of two scenarios (treatment vs WW; SSA-1 [lanreotide] vs SSA-2 [octreotide]) with evidence from a literature review, expressed how consideration of each criterion would impact their decision in favor of either option (score), and shared their knowledge and insights verbally and in writing. RESULTS: The framework included benefit-risk criteria and modulating factors, such as disease severity, quality of evidence, costs, and constraints. Overall and progression-free survival being most important, criteria weights ranged widely, highlighting variations in individual values and the need to share them. Scoring and considering each criterion prompted a rich exchange of perspectives and uncovered individual assumptions and interpretations. At the group level, type of benefit, disease severity, effectiveness, and quality of evidence favored treatment; cost aspects favored WW (scenario 1). For scenario 2, most criteria did not favor either option. CONCLUSIONS: Patients and clinicians consider many aspects in decision-making. The MCDA framework provided a common interpretive frame to structure this complexity, support individual reflection, and share perspectives. FUNDING: Ipsen Pharma.

EXPLORING VALUES OF HEALTH TECHNOLOGY ASSESSMENT AGENCIES USING REFLECTIVE MULTICRITERIA AND RARE DISEASE CASE.

OBJECTIVES: Tackling ethical dilemmas faced by reimbursement decision makers requires deeper understanding of values on which health technology assessment (HTA) agencies are founded and how trade-offs are made. This was explored in this study including the case of rare disease. METHODS: Representatives from eight HTA explored values on which institutions are founded using a narrative approach and reflective multicriteria (developed from EVIDEM, criteria derived from ethical imperatives of health care). Trade-offs between criteria and the impact of incorporating defined priorities (including for rare diseases) were explored through a quantitative values elicitation exercise. RESULTS: Participants reported a diversity of substantive and procedural values with a common emphasis on scientific excellence, stakeholder involvement, independence, and transparency. Examining the ethical imperatives behind EVIDEM criteria was found to be useful to further explore substantive values. Most criteria were deemed to reflect institutions' values, while 70 percent of the criteria were reported by at least half of participants to be considered formally by their institutions. The quantitative values elicitation highlighted the difficulty to balance imperatives of "alleviating or preventing patient suffering," "serving the whole population equitably," "upholding healthcare system sustainability," and "making decisions informed by evidence and context" but may help share the ethical reasoning behind decisions. Incorporating "Priorities" (including for rare diseases) helped reveal trade-offs from other criteria and their underlying ethical imperatives. CONCLUSIONS: Reflective multicriteria are useful to explore substantive values of HTAs, reflect how these values and their ethical underpinnings can be operationalized into criteria, and explore the ethical reasoning at the heart of the healthcare debate.

Appraising the holistic value of Lenvatinib for radio-iodine refractory differentiated thyroid cancer: A multi-country study applying pragmatic MCDA.

BACKGROUND: The objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts. METHODS: The study was designed to enable comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current disease context (watchful waiting, sorafenib) of France, Italy and Spain. Data on the value of lenvatinib was collected from diverse stakeholders during country-specific panels and included: criteria weights (individual and social values); performance scores (judgments on evidence-collected through MCDA systematic review); qualitative impacts of contextual criteria; and verbal and written insights structured by criteria. The value contribution of each criterion was calculated and uncertainty explored. RESULTS: Comparative effectiveness, Quality of evidence (Spain and Italy) and Disease severity (France) received the greatest weights. Four criteria contributed most to the value of lenvatinib, reflecting its superior Comparative effectiveness (16-22% of value), the severity of RR-DTC (16-22%), significant unmet needs (14-21%) and robust evidence (14-20%). Contributions varied by comparator, country and individuals, highlighting the importance of context and consultation. Results were reproducible at the group level. Impacts of contextual criteria varied across countries reflecting different health systems and cultural backgrounds. The MCDA process promoted sharing stakeholders' knowledge on lenvatinib and insights on context. CONCLUSIONS: The value of lenvatinib was consistently positive across diverse therapeutic contexts. MCDA identified the aspects contributing most to value, revealed rich contextual insights, and helped participants express and explicitly tackle ethical trade-offs inherent to balanced appraisal and decisionmaking.

DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR ORPHAN DRUGS.

OBJECTIVES: The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). METHODS: The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members. The criteria weighting was done using two different techniques (nonhierarchical and hierarchical). Reliability was assessed by re-test. RESULTS: The EVIDEM framework and methodology was found useful and feasible for Orphan drugs evaluation and decision making in Catalonia. All the criteria considered for the development of the CatSalut Technical Reports and decision making were considered in the framework. Nevertheless, the framework could improve the reporting of some of these criteria (i.e., "unmet needs" or "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and scope of healthcare system", "Environmental impact") or adapted ("population priorities and access") for CatSalut purposes. Independently of the weighting technique considered, the most important evaluation criteria identified for orphan drugs were: "disease severity", "unmet needs" and "comparative effectiveness", while the "size of the population" had the lowest relevance for decision making. Test-retest analysis showed weight consistency among techniques, supporting reliability overtime. CONCLUSIONS: MCDA (EVIDEM framework) could be a useful tool to complement the current evaluation methods of CatSalut, contributing to standardization and pragmatism, providing a method to tackle ethical dilemmas and facilitating discussions related to decision making.

TESTING MULTI-CRITERIA DECISION ANALYSIS FOR MORE TRANSPARENT RESOURCE-ALLOCATION DECISION MAKING IN COLOMBIA.

OBJECTIVES: In 2012, Colombia experienced an important institutional transformation after the establishment of the Health Technology Assessment Institute (IETS), the disbandment of the Regulatory Commission for Health and the reassignment of reimbursement decision-making powers to the Ministry of Health and Social Protection (MoHSP). These dynamic changes provided the opportunity to test Multi-Criteria Decision Analysis (MCDA) for systematic and more transparent resource-allocation decision-making. METHODS: During 2012 and 2013, the MCDA framework Evidence and Value: Impact on Decision Making (EVIDEM) was tested in Colombia. This consisted of a preparatory stage in which the investigators conducted literature searches and produced HTA reports for four interventions of interest, followed by a panel session with decision makers. This method was contrasted with a current approach used in Colombia for updating the publicly financed benefits package (POS), where narrative health technology assessment (HTA) reports are presented alongside comprehensive budget impact analyses (BIAs). RESULTS: Disease severity, size of population, and efficacy ranked at the top among fifteen preselected relevant criteria. MCDA estimates of technologies of interest ranged between 71 to 90 percent of maximum value. The ranking of technologies was sensitive to the methods used. Participants considered that a two-step approach including an MCDA template, complemented by a detailed BIA would be the best approach to assist decision-making in this context. Participants agreed that systematic priority setting should take place in Colombia. CONCLUSIONS: This work may serve as the basis to the MoHSP on its interest of setting up a systematic and more transparent process for resource-allocation decision-making.

Pragmatic Multicriteria Decision Analysis (MCDA) Combined With Advanced Pharmacoepidemiology for Benefit-Risk Assessments of Medicines Adapted to the Real-Life Constraints of Regulators: Development and Case Study.

BACKGROUND: Multicriteria decision analysis (MCDA) represents a promising method for benefit-risk assessment. Our goal was to develop features of pragmatic MCDA (EVIDEM [Evidence and Value: Impact on DEcisionMaking]) addressing real-life regulatory decision-making needs, incorporate advanced pharmacoepidemiology, and test the resulting benefit-risk framework using a case study. METHODS: The Intervention Outcomes domain of EVIDEM was transformed into a generic benefit-risk framework including clinical efficacy, patient-reported outcomes, and adverse event (AE) criteria. The concept of relative benefit-risk balance (RBRB) was developed for comparability across products and therapeutic areas and over time. Evidence matrix was designed to include most relevant data from trials, observational studies, and models, including Bayesian and longitudinal modeling. The framework was tested with a panel of stakeholders using efalizumab for psoriasis as retrospective case study. Uncertainty was explored. RESULTS: The MCDA benefit-risk tree was adapted with psoriasis-specific subcriteria. Panelists assigned similar weights to benefits (0.48; SD, 0.20-0.70) and risks (0.52; SD, 0.10-0.60), with large variations reflecting diverse perspectives. Panelist scores reflected higher efficacy versus placebo, lower efficacy versus active comparators, and serious and fatal AEs identified postlicensing. Efalizumab's RBRB was positive at licensing in 2004 (0.29, scale -1 to +1) and ranged from -0.41 (vs active comparators) to 0.01 (vs placebo) in 2009, when its market authorization was withdrawn. Retesting indicated good reproducibility. Panelists acknowledged good face validity and the importance of criteria beyond benefit-risk in real-life assessments. CONCLUSIONS: The approach allows quantification and visualization of benefit-risk over time and across comparators. Combination of pragmatic MCDA designed to integrate criteria beyond benefit-risk and advanced statistics supports application of MCDA to further accountable benefit-risk assessments for real-life decision making.

Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.

BACKGROUND: The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. METHODS: Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. RESULTS: Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. CONCLUSION: The adapted framework measures value in its widest sense, while being responsive to rare disease issues and policies. It provides an operationalizable platform to integrate values, competing ethical dilemmas, and uncertainty in appraising healthcare interventions.

Balancing costs and benefits at different stages of medical innovation: a systematic review of Multi-criteria decision analysis (MCDA).

BACKGROUND: The diffusion of health technologies from translational research to reimbursement depends on several factors included the results of health economic analysis. Recent research identified several flaws in health economic concepts. Additionally, the heterogeneous viewpoints of participating stakeholders are rarely systematically addressed in current decision-making. Multi-criteria Decision Analysis (MCDA) provides an opportunity to tackle these issues. The objective of this study was to review applications of MCDA methods in decisions addressing the trade-off between costs and benefits. METHODS: Using basic steps of the PRISMA guidelines, a systematic review of the healthcare literature was performed to identify original research articles from January 1990 to April 2014. Medline, PubMed, Springer Link and specific journals were searched. Using predefined categories, bibliographic records were systematically extracted regarding the type of policy applications, MCDA methodology, criteria used and their definitions. RESULTS: 22 studies were included in the analysis. 15 studies (68 %) used direct MCDA approaches and seven studies (32 %) used preference elicitation approaches. Four studies (19 %) focused on technologies in the early innovation process. The majority (18 studies - 81 %) examined reimbursement decisions. Decision criteria used in studies were obtained from the literature research and context-specific studies, expert opinions, and group discussions. The number of criteria ranged between three up to 15. The most frequently used criteria were health outcomes (73 %), disease impact (59 %), and implementation of the intervention (40 %). Economic criteria included cost-effectiveness criteria (14 studies, 64 %), and total costs/budget impact of an intervention (eight studies, 36 %). The process of including economic aspects is very different among studies. Some studies directly compare costs with other criteria while some include economic consideration in a second step. CONCLUSIONS: In early innovation processes, MCDA can provide information about stakeholder preferences as well as evidence needs in further development. However, only a minority of these studies include economic features due to the limited evidence. The most important economic criterion cost-effectiveness should not be included from a technical perspective as it is already a composite of costs and benefit. There is a significant lack of consensus in methodology employed by the various studies which highlights the need for guidance on application of MCDA at specific phases of an innovation.

Exploring the perspectives and preferences for HTA across German healthcare stakeholders using a multi-criteria assessment of a pulmonary heart sensor as a case study.

BACKGROUND: Health technology assessment and healthcare decision-making are based on multiple criteria and evidence, and heterogeneous opinions of participating stakeholders. Multi-criteria decision analysis (MCDA) offers a potential framework to systematize this process and take different perspectives into account. The objectives of this study were to explore perspectives and preferences across German stakeholders when appraising healthcare interventions, using multi-criteria assessment of a heart pulmonary sensor as a case study. METHODS: An online survey of 100 German healthcare stakeholders was conducted using a comprehensive MCDA framework (EVIDEM V2.2). Participants were asked to provide i) relative weights for each criterion of the framework; ii) performance scores for a health pulmonary sensor, based on available data synthesized for each criterion; and iii) qualitative feedback on the consideration of contextual criteria. Normalized weights and scores were combined using a linear model to calculate a value estimate across different stakeholders. Differences across types of stakeholders were explored. RESULTS: The survey was completed by 54 participants. The most important criteria were efficacy, patient reported outcomes, disease severity, safety, and quality of evidence (relative weight >0.075 each). Compared to all participants, policymakers gave more weight to budget impact and quality of evidence. The quantitative appraisal of a pulmonary heart sensor revealed differences in scoring performance of this intervention at the criteria level between stakeholder groups. The highest value estimate of the sensor reached 0.68 (on a scale of 0 to 1, 1 representing maximum value) for industry representatives and the lowest value of 0.40 was reported for policymakers, compared to 0.48 for all participants. Participants indicated that most qualitative criteria should be considered and their impact on the quantitative appraisal was captured transparently. CONCLUSIONS: The study identified important variations in perspectives across German stakeholders when appraising a healthcare intervention and revealed that MCDA can demonstrate the value of a specified technology for all participating stakeholders. Better understanding of these differences at the criteria level, in particular between policymakers and industry representatives, is important to focus innovation aligned with patient health and healthcare system values and constraints.

Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada.

BACKGROUND: Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. OBJECTIVE: To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. METHODS: A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. RESULTS: In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. CONCLUSIONS: The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.

HISTORIQUE: L'infection à Clostridium difficile (ICD) est un problème de santé publique à l'incidence et à la gravité croissantes. OBJECTIF: Évaluer les conséquences cliniques et économiques de la vancomycine par rapport à la fidaxomicine pour traiter l'ICD dans le système de santé canadien. MÉTHODOLOGIE: Les chercheurs ont élaboré un modèle d'arbre décisionnel pour comparer la vancomycine et la fidaxomicine dans le traitement des graves ICD. Selon ce modèle, le taux de guérison initial était identique et incluait les premiers épisodes récurrents d'ICD (cas de référence). L'autre méthode d'analyse examinée était le traitement des patients atteints d'ICD. Les coûts inclus étaient ceux du médicament à l'étude, des services des médecins et de l'hospitalisation. Les chercheurs ont mesuré l'efficacité des coûts sous forme de coût incrémentiel par récurrence évitée. Ils ont effectué les analyses de sensibilité des principaux paramètres d'entrée. RÉSULTATS: Dans une cohorte de 1 000 patients ayant eu un épisode initial de grave ICD, le traitement à la fidaxomicine suscitait 137 récurrences de moins à un coût incrémentiel de 1,81 million de dollars, pour un coût incrémentiel de 13 202 $ par récurrence évitée. Chez 1 000 patients ayant eu une ICD récurrente, 113 deuxièmes récurrences ont été évitées, à un coût incrémentiel de 18 190 $ par deuxième récurrence évitée. Les coûts incrémentiels par récurrence évitée grimpaient proportionnellement à l'augmentation de la proportion des cas causés par la souche NAP1/B1/027. Les résultats étaient sensibles aux variations des taux de récurrence et de la durée de traitement, mais robustes aux variations des autres paramètres. CONCLUSIONS: L'utilisation de fidaxomicine s'associe à une augmentation des coûts dans le système de santé canadien. Les avantages cliniques de la fidaxomicine par rapport à la vancomycine dépendent de la proportion de cas causés par la souche NAP1/B1/027 chez les patients atteints d'une grave ICD.

Does technique matter; a pilot study exploring weighting techniques for a multi-criteria decision support framework.

BACKGROUND: There is an increased interest in the use of multi-criteria decision analysis (MCDA) to support regulatory and reimbursement decision making. The EVIDEM framework was developed to provide pragmatic multi-criteria decision support in health care, to estimate the value of healthcare interventions, and to aid in priority-setting. The objectives of this study were to test 1) the influence of different weighting techniques on the overall outcome of an MCDA exercise, 2) the discriminative power in weighting different criteria of such techniques, and 3) whether different techniques result in similar weights in weighting the criteria set proposed by the EVIDEM framework. METHODS: A sample of 60 Dutch and Canadian students participated in the study. Each student used an online survey to provide weights for 14 criteria with two different techniques: a five-point rating scale and one of the following techniques selected randomly: ranking, point allocation, pairwise comparison and best worst scaling. RESULTS: The results of this study indicate that there is no effect of differences in weights on value estimates at the group level. On an individual level, considerable differences in criteria weights and rank order occur as a result of the weight elicitation method used, and the ability of different techniques to discriminate in criteria importance. Of the five techniques tested, the pair-wise comparison of criteria has the highest ability to discriminate in weights when fourteen criteria are compared. CONCLUSIONS: When weights are intended to support group decisions, the choice of elicitation technique has negligible impact on criteria weights and the overall value of an innovation. However, when weights are used to support individual decisions, the choice of elicitation technique influences outcome and studies that use dissimilar techniques cannot be easily compared. Weight elicitation through pairwise comparison of criteria is preferred when taking into account its superior ability to discriminate between criteria and respondents' preferences.