Nothing about us without us: Advocacy and engagement in genetic medicine.

The development of new genetic medicines to treat sickle cell disease highlights the need for greater collaboration between researchers and people with lived experiences. Drawing on the adage "Nothing about us, without us," we call for increased investments in community advocacy and engagement.

Exploring alternative financing models and early access schemes for orphan drugs: a Belgian case study.

BACKGROUND: Although some jurisdictions have implemented particular adjustments to accommodate often-expensive orphan drugs in their healthcare systems, availability of these drugs remains complex. This study investigates alternative financing models and early access schemes for orphan drugs in the context of the Belgian healthcare system. METHODS: Three focus group discussions were held with a panel of eleven experts from the Belgian Drug Reimbursement Committee, the Colleges for Orphan Drugs, the pharmaceutical industry, physicians, ethicists and pharmacists. Retrieved data were pseudonymised, analysed and coded according to the Qualitative Analysis Guide of Leuven. RESULTS: Experts disfavoured the insulated fund as well as private insurance for financing orphan drugs, as, respectively, isolation of a separate budget and a mostly profit-driven mechanism would contradict the Belgian fundamental principle of solidarity. Moreover, an insulated fund could, albeit on a smaller scale, reproduce the same budgetary constraints as the general reimbursement system. As the Special Solidarity Fund is intended for urgent care and exclusively accommodates financial needs subject to eligibility criteria, its design would not allow general financing of orphan drugs. Overall, implementation of an alternative financing model was not endorsed, instead, improving the current reimbursement system was preferred. Suggestions mentioned were; increased collaboration and transparency, robust and quality real-world evidence but also digitalization of data. Alleviating administrative burden and simplifying the admission process of compassionate use program, medical need program and early treatment reimbursement should be prioritized to facilitate early access. Furthermore, a legal framework for off-label use could stimulate proper implementation. Efforts on collaboration of expertise centres and coordination of orphan drug databases across Europe could foster a robust data network to support orphan drug availability in individual countries. CONCLUSIONS: This research reveals that reassessing current financing models and early access schemes by eliminating inadequacies, may be more conducive than establishing alternative systems to increase availability of orphan drugs in Belgium. Other jurisdictions may rely on this information to review their own models of early access and financing to cultivate a more sustainable delivery of orphan drugs.

How to balance valuable innovation with affordable access to medicines in Belgium?

Background: Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This Perspective aims to discuss challenges and avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries). Methods: This Perspective focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars. The authors conducted a narrative review of the peer-reviewed literature, of the grey literature (such as policy documents and reports of consultancy agencies), and of their own research. Results: Health care stakeholders need to consider various initiatives for balancing innovation with access to medicines, which relate to clinical and non-clinical outcomes (e.g. supporting the conduct of pragmatic clinical trials, treatment optimisation and patient preference studies, optimising the use of real-world evidence in market access decision making), value assessment (e.g. increasing the transparency of the reimbursement system and criteria, tailoring the design of managed entry agreements to specific types of uncertainty), affordability (e.g. harnessing the role of generics and biosimilars in encouraging price competition, maximising opportunities for personalising and repurposing medicines) and access mechanisms (e.g. promoting collaboration and early dialogue between stakeholders including patients). Conclusion: Although there is no silver bullet that can balance valuable innovation with affordable access to medicines, (Belgian) policy and decision makers should continue to explore initiatives that exploit the potential of both the on-patent and off-patent pharmaceutical markets.

A Comparative Analysis of Pricing and Reimbursement of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Europe.

Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor), have substantially improved patients' lives yet significantly burden healthcare budgets. This analysis aims to compare pricing and reimbursement of aforementioned cystic fibrosis medicines, across European countries. Methods: Clinical trial registries, national databases, health technology assessment reports and grey literature of Austria, Belgium, Denmark, France, Germany, Ireland, Poland, Spain, Sweden, Switzerland, Netherlands, the United Kingdom were consulted. Publicly available prices, reimbursement statuses, economic evaluations, budget impact analyses and managed entry agreements of CFTR modulators were examined. Results: In Belgium, lowest list prices were observed for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €417 per defined daily dose (DDD) and €372 per average daily dose (ADD), respectively. Whereas, Switzerland had the lowest price for Orkambi® (lumacaftor/ivacaftor) listed at €309 per DDD. Spain had the highest prices for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €850 per DDD and €761 per ADD, whereas Orkambi® (lumacaftor/ivacaftor) was most expensive in Poland at €983 per DDD. However, list prices were subject to confidential discounts and likely varied from actual costs. In all countries, these treatments were deemed not to be cost-effective. The annual budget impact of the CFTR modulators varied between countries and depended on factors such as local product prices, size of target population, scope of costs and discounting. However, all modulators were fully reimbursed in ten of the evaluated countries except for Sweden and Poland that, respectively, granted reimbursement to one and none of the therapies. Managed entry agreements were confidential but commonly adopted to address financial uncertainties. Conclusion: Discrepancies concerning prices, reimbursement and access were detected for Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor) across European countries.

Methodological Quality Assessment of Budget Impact Analyses for Orphan Drugs: A Systematic Review.

Objectives: This research aims to evaluate the methodological quality of budget impact analyses for orphan drugs and to provide suggestions for future analyses. Methods: Conference abstracts and peer-reviewed literature on budget impact analyses were collected through searches of Pubmed and Embase. ISPOR good practice guidelines were used as a methodological standard for budget impact analyses. Examined parameters encompassed: perspective, target population, data sources, intervention and comparator(s), time horizon, scope of costs, discounting, validation, assumptions and sensitivity analysis. Results: Seventy studies on individual orphan drugs and 21 studies on a combination of orphan drugs analyzing budget impact were identified. Overall, analyses considered a third-party payer perspective, reported periodic budget impacts over a one-to-five-year time horizon, and did not apply discounting. A dynamically fluctuating population and costs beyond drug costs were accounted for in 18.7% and 51.7% of studies, respectively. Input data were retrieved from published literature, clinical trials, registries, claims databases, expert opinions, historical data and market research. Assumptions were mostly made about population size and intervention/comparator(s) market uptake, but these assumptions were rarely justified and their impact was insufficiently explored through sensitivity analyses. Budget impact results were rarely validated. Conclusion: Existing budget impact analyses for orphan drugs are concise, vary greatly and are of substandard methodological quality. To eliminate possible bias in future budget impact analyses, future studies should adhere to national or ISPOR good practice guidelines on budget impact analysis.