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Using value-of-information methods when the disease is rare and the treatment is expensive--the example of hemophilia A.

ABSTRACT: BACKGROUND: Hemophilia A is a rare, sex-linked genetic disorder treated with intravenous administration of factor VIII (FVIII) to prevent bleeding; however, approaches vary across and within countries. Value-of-information (VOI) methods identify situations in which the cost-benefit evidence is sufficient to adopt one treatment strategy over another; when the evidence is insufficient, VOI methods provide the optimal sample size for additional research. OBJECTIVE: The objective of the study was to use VOI methods in a cost-benefit decision context to evaluate the current evidence in support of using (1) alternate day prophylaxis (AP), (2) tailored prophylaxis (TP) or (3) on-demand treatment (OD) with FVIII to prevent arthropathy in children with severe hemophilia A. METHODS: To apply VOI methods, several parameters such as incidence, time horizon for the decision, costs, and threshold values to avoid MRI-detected joint damage or arthropathy were defined. Two baseline threshold values of willingness to pay for avoiding arthropathy--$200,000 and $400,000--were selected for comparing the treatment strategies. RESULTS: For threshold values??$400,000 prophylaxis strategies had higher expected net benefit; however, a new trial with 38 patients per arm was needed to compare AP and TP, yielding an expected net gain of over $17 million. In sensitivity analyses, the results were robust to assumptions regarding discount rate, trial fixed and variable costs, enrollment fraction, and the time horizon. CONCLUSIONS: In rare diseases, evidence is often scarce and insufficient for decision making. In considering the funding of new research and patient reimbursement in rare diseases, VOI methodology may provide more relevant determinations of the value and costs of additional research, compared to standard frequentist methods.

SUBMITTER: Abrahamyan L

PROVIDER: S-EPMC4124117 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Using value-of-information methods when the disease is rare and the treatment is expensive--the example of hemophilia A.

Abrahamyan Lusine L Willan Andrew R AR Beyene Joseph J Mclimont Marjorie M Blanchette Victor V Feldman Brian M BM

Journal of general internal medicine 20140801

<h4>Background</h4>Hemophilia A is a rare, sex-linked genetic disorder treated with intravenous administration of factor VIII (FVIII) to prevent bleeding; however, approaches vary across and within countries. Value-of-information (VOI) methods identify situations in which the cost-benefit evidence is sufficient to adopt one treatment strategy over another; when the evidence is insufficient, VOI methods provide the optimal sample size for additional research.<h4>Objective</h4>The objective of the ...[more]

PMID: 25029970

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Project description:BackgroundHaemophilia is a rare hereditary haemorrhagic disease that requires regular intravenous injections of clotting factor (CF) concentrates. This study sought to estimate the health and economic burden of haemophilia in Belgium. This is the first study of its type to be conducted, and reflects the Belgian authorities' growing interest for haemophilia as part of their priority planning for rare and chronic diseases.MethodsA probabilistic model was developed in order to estimate the lifetime haemophilia burden for the 2011 birth-year Belgian cohort. The health burden was initially expressed in terms of disability-adjusted life years (DALYs), the number of healthy life years lost due to living with disability and dying prematurely. An incidence perspective was used in line with World Health Organization recommendations. The economic burden calculated from direct and indirect haemophilia-related costs was expressed in euros. Data were drawn from the literature if none were available from federal institutions or health insurance. Disability weights for DALY calculation were derived using generic quality-of-life tools such as SF-6D from the SF-36 (36-item Short-Form Health Survey; for adults) and KINDL (generic quality-of-life instrument; for children) compared to population norms. Analyses were stratified according to haemophilia type and severity.ResultsIn Belgium, haemophilia resulted in 145 undiscounted and unweighted DALYs in total (95% credible interval [CrI]?=?90-222), which represents an average of 11 DALYs per incident case with haemophilia (95% CrI?=?8-15) during his life, varying according to haemophilia severity (17 DALYs for severe haemophilia, 12 DALYs for moderate, and 4 DALYs for mild). Mean total lifetime costs reached €7.8 million per people with haemophilia, 94.3% being direct costs and 5.7% indirect costs. Clotting factors accounted for 82.5% of direct costs.ConclusionsHaemophilia represents both an economic and health burden, especially regarding individual health on an individual patient level. Initiatives to counteract this burden should be clearly identified and given full support, as this burden is likely to increase in the future, especially from an economic perspective. Our study may also contribute towards a better global evaluation of haemophilia in the future.

Project description:Systematically evaluating scientific literature is a time consuming endeavor that requires hours of coding and rating. Here, we describe a method to distribute these tasks across a large group through online crowdsourcing. Using Amazon's Mechanical Turk, crowdsourced workers (microworkers) completed four groups of tasks to evaluate the question, "Do nutrition-obesity studies with conclusions concordant with popular opinion receive more attention in the scientific community than do those that are discordant?" 1) Microworkers who passed a qualification test (19% passed) evaluated abstracts to determine if they were about human studies investigating nutrition and obesity. Agreement between the first two raters' conclusions was moderate (κ = 0.586), with consensus being reached in 96% of abstracts. 2) Microworkers iteratively synthesized free-text answers describing the studied foods into one coherent term. Approximately 84% of foods were agreed upon, with only 4 and 8% of ratings failing manual review in different steps. 3) Microworkers were asked to rate the perceived obesogenicity of the synthesized food terms. Over 99% of responses were complete and usable, and opinions of the microworkers qualitatively matched the authors' expert expectations (e.g., sugar-sweetened beverages were thought to cause obesity and fruits and vegetables were thought to prevent obesity). 4) Microworkers extracted citation counts for each paper through Google Scholar. Microworkers reached consensus or unanimous agreement for all successful searches. To answer the example question, data were aggregated and analyzed, and showed no significant association between popular opinion and attention the paper received as measured by Scimago Journal Rank and citation counts. Direct microworker costs totaled $221.75, (estimated cost at minimum wage: $312.61). We discuss important points to consider to ensure good quality control and appropriate pay for microworkers. With good reliability and low cost, crowdsourcing has potential to evaluate published literature in a cost-effective, quick, and reliable manner using existing, easily accessible resources.

Project description:BACKGROUND:The ASTERIX project developed a number of novel methods suited to study small populations. The objective of this exercise was to evaluate the applicability and added value of novel methods to improve drug development in small populations, using real world drug development programmes as reported in European Public Assessment Reports. METHODS:The applicability and added value of thirteen novel methods developed within ASTERIX were evaluated using data from 26 European Public Assessment Reports (EPARs) for orphan medicinal products, representative of rare medical conditions as predefined through six clusters. The novel methods included were 'innovative trial designs' (six methods), 'level of evidence' (one method), 'study endpoints and statistical analysis' (four methods), and 'meta-analysis' (two methods) and they were selected from the methods developed within ASTERIX based on their novelty; methods that discussed already available and applied strategies were not included for the purpose of this validation exercise. Pre-requisites for application in a study were systematized for each method, and for each main study in the selected EPARs it was assessed if all pre-requisites were met. This direct applicability using the actual study design was firstly assessed. Secondary, applicability and added value were explored allowing changes to study objectives and design, but without deviating from the context of the drug development plan. We evaluated whether differences in applicability and added value could be observed between the six predefined condition clusters. RESULTS AND DISCUSSION:Direct applicability of novel methods appeared to be limited to specific selected cases. The applicability and added value of novel methods increased substantially when changes to the study setting within the context of drug development were allowed. In this setting, novel methods for extrapolation, sample size re-assessment, multi-armed trials, optimal sequential design for small sample sizes, Bayesian sample size re-estimation, dynamic borrowing through power priors and fall-back tests for co-primary endpoints showed most promise - applicable in more than 40% of evaluated EPARs in all clusters. Most of the novel methods were applicable to conditions in the cluster of chronic and progressive conditions, involving multiple systems/organs. Relatively fewer methods were applicable to acute conditions with single episodes. For the chronic clusters, Goal Attainment Scaling was found to be particularly applicable as opposed to other (non-chronic) clusters. CONCLUSION:Novel methods as developed in ASTERIX can improve drug development programs. Achieving optimal added value of these novel methods often requires consideration of the entire drug development program, rather than reconsideration of methods for a specific trial. The novel methods tested were mostly applicable in chronic conditions, and acute conditions with recurrent episodes.

Dataset Information

Using value-of-information methods when the disease is rare and the treatment is expensive--the example of hemophilia A.

Publications

Using value-of-information methods when the disease is rare and the treatment is expensive--the example of hemophilia A.

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