Generating health technology assessment evidence for rare diseases

Objectives: Rare diseases are often heterogeneous in their progression and response to treatment, with only a small population for study. This provides challenges for evidence generation to support HTA, so novel research methods are required. Methods: Discussion with an expert panel was augmented with references and case studies to explore robust approaches for HTA evidence generation for rare disease treatments. Results: Traditional RCTs can be modified using sequential, three-stage or adaptive designs to gain more power from a small patient population or to focus trial design. However, such designs need to maintain important design aspects such as randomization and blinding and be analyzed to take account of the multiple analyses performed. N-of-1 trials use within-patient randomization to test repeat periods of treatment and control until a response is clear. Such trials could be particularly valuable for rare diseases and when prospectively planned across several patients and analyzed using Bayesian techniques, a population effect can be estimated that might be of value to HTA. When the optimal outcome is unclear in a rare disease, disease specific patient reported outcomes can elucidate impacts on patients’ functioning and wellbeing. Likewise, qualitative research can be used to elicit patients’ perspectives, with just a small number of patients. Conclusions: International consensus is needed on ways to improve evidence collection and assessment of technologies for rare diseases, which recognize the value of novel study designs and analyses in a setting where the outcomes and effects of importance are yet to be agreed.</p

Model consent clauses for rare disease research

Background: Rare Disease research has seen tremendous advancements over the last decades, with the development of new technologies, various global collaborative efforts and improved data sharing. To maximize the impact of and to further build on these developments, there is a need for model consent clauses for rare diseases research, in order to improve data interoperability, to meet the informational needs of participants, and to ensure proper ethical and legal use of data sources and participants' overall protection. Methods: A global Task Force was set up to develop model consent clauses specific to rare diseases research, that are comprehensive, harmonized, readily accessible, and internationally applicable, facilitating the recruitment and consent of rare disease research participants around the world. Existing consent forms and notices of consent were analyzed and classified under different consent themes, which were used as background to develop the model consent clauses. Results: The IRDiRC-GA4GH MCC Task Force met in September 2018, to discuss and design model consent clauses. Based on analyzed consent forms, they listed generic core elements and designed the following rare disease research specific core elements; Rare Disease Research Introductory Clause, Familial Participation, Audio/Visual Imaging, Collecting, storing, sharing of rare disease data, Recontact for matching, Data Linkage, Return of Results to Family Members, Incapacity/Death, and Benefits. Conclusion: The model consent clauses presented in this article have been drafted to highlight consent elements that bear in mind the trends in rare disease research, while providing a tool to help foster harmonization and collaborative efforts

Validation of the Body Concealment Scale for Scleroderma (BCSS): Replication in the Scleroderma Patient-centered Intervention Network (SPIN) Cohort

© 2016 Elsevier Ltd Body concealment is an important component of appearance distress for individuals with disfiguring conditions, including scleroderma. The objective was to replicate the validation study of the Body Concealment Scale for Scleroderma (BCSS) among 897 scleroderma patients. The factor structure of the BCSS was evaluated using confirmatory factor analysis and the Multiple-Indicator Multiple-Cause model examined differential item functioning of SWAP items for sex and age. Internal consistency reliability was assessed via Cronbach's alpha. Construct validity was assessed by comparing the BCSS with a measure of body image distress and measures of mental health and pain intensity. Results replicated the original validation study, where a bifactor model provided the best fit. The BCSS demonstrated strong internal consistency reliability and construct validity. Findings further support the BCSS as a valid measure of body concealment in scleroderma and provide new evidence that scores can be compared and combined across sexes and ages

Variation in the prices of oncology medicines across Europe and the implications for the future

Introduction/ Objectives: There are increasing concerns among health authorities regarding the sustainability of healthcare systems with growing expenditure on medicines including new high-priced oncology medicines. Medicine prices among European countries may be adversely affected by their population size and economic power to negotiate. There are also concerns that prices of patented medicines do not change once the prices of medicines used for negotiations substantially change. This needs to be investigated as part of the implications of low-cost generic oncology medicines. Methodology: Analysing principally reimbursed prices of patented oral oncology medicines (imatinib, erlotinib and fludarabine) between 2013 and 2017 across Europe and exploring correlations between GDP, population size, and prices. Comparing the findings with previous research regarding prices of oral generic oncology medicines. Results: The prices of imatinib, erlotinib and fludarabine did vary among European countries but showed limited price erosion over time in the absence of generics. There appeared to be no correlation between population size and prices. However, higher prices were seen among countries with higher GDP per capita which is a concern for lower income countries referencing these. Discussion and Conclusion: It is likely that the limited price erosion for patented oncology medicines will change across Europe with increased scrutiny over their prices and value as more medicines used for pricing decisions lose their patents combined with growing pressures on the oncology drug budget. In addition, discussions will continue regarding fair pricing for new oncology medicines and other approaches given ever rising prices with research showing substantial price reductions for oral oncology medicines (up to -97.8% for imatinib) once generics become available. We are also seeing appreciable price reductions for biosimilars further increasing the likelihood of these developments