How to fast track approval and reimbursement of innovative medicines

What everyone wants is getting new, innovative medicines to market quickly, but at the same time insuring we have enough data to confirm that these medicines are safe and effective. How do we balance these two aims?

A paper by Ollendorf et al. (2024) provides some guidance. Some of their suggestions are summarized below.

Make criteria for expedited regulatory approval clear. FDA and EMA list unmet need and disease severity as key factors influencing the need for expedited regulatory approval. However, these evaluations are made qualitatively. Could we do better if we used quantitative measures such as the disability-adjusted life year (DALY) or quality adjusted life year (QALY) shortfall? Also, getting drugs to market quickly may require the use of surrogate endpoints in order to rapidly signal whether or not a medicine is likely to be efficacious. As shown in Ciani et al. (2017), surrogates are more likely to be valid when they have a strong association with the critical outcomes and the medicine reaches a “threshold for benefit in the surrogate that would generate meaningful clinical improvement.”Improve stakeholder coordination. Regulators may use one set of guidelines for drug approvals and payers may use another for reimbursement decisions. For instance, one trial design may be most useful for determining safety and efficacy, but be less useful for determination of economic value. More collaboration between CMS and FDA–as recommended by the Bipartisan Policy Center–could help. Specific recommendations include (i) quarterly communication, (ii) creation of common clinical trial and real-world data warehouses, and (iii) allowing HTA representatives in discussions between manufactures and regulators. Additionally, patient and caregiver input is paramount to incorporate into clinical trial and other research protocol designs. Create accelerated pathway in HTA for payers. The authors write: ” Creating a distinct accelerated pathway for appraisal would send appropriate signals to manufacturers, patient organizations, and other stakeholders that a unique process is in play that recognizes both urgency of need and inherent uncertainty in evidence. A more rapid timeline for review could be contemplated given the limited evidence available. Additional requirements for manufacturers could be included, such as proposals for outcomes-based contracts, real-world evidence studies to bridge the gap between initial regulatory approval and confirmatory trials, or other risk-mitigation strategies.” For instance, manufacturers and HTA bodies could agree ahead of time on how surrogate endpoints should be linked to long-term health outcomes. Develop joint guidance on study design. While regulators (e.g., FDA, EMA) provide guidance on outcomes, trial design, and other factors, including HTA agency input into these discussions could help streamline clinical development so that pivotal clinical trials could be most insightful both from a safety/efficacy perspective (regulatory approval) and value perspective (HTA, payer reimbursement)Link pricing policy to data uncertainty. The authors argue that while “managed entry” and outcomes based agreement where premium prices are paid initially, but rebates/clawbacks are owed if long-term outcomes are not reached. One could also set prices lower and increase the prices as evidence accumulates (i.e., three-part pricing model), however in the US with IRA, drug prices are constrained to grow with inflation so implementing the three-part pricing in practice may be challenging. Improving stakeholder understanding of accelerated approval process. The authors argue for the development of lay-friendly summaries of clinical studies that can be informative to patient advocates as well as HTA bodies. The authors also argue that regulators and HTA bodies should publish their rationale–and allow for public comments–for any drug approval or reimbursement decision.

The article is not just interesting, but provides some practical steps for getting medicines to patients faster in a way that is most likely to improve patient outcomes.