Multistakeholder Advice at the European Medicines Agency: Is It Still Needed?

Abstract

To address clinical trials conducted for regulators and other decision-making purposes the European Medicines Agency offers different multistakeholder platforms (parallel advice with Health Technology Assessment (HTA) bodies or with the US Food and Drug Administration (FDA)) in which different decision makers can provide simultaneous feedback on proposals for evidence generation. In this article, we present the case for seeking such advice, how they work in practice, and which products are best targeted for which procedures. PARALLEL ADVICE BETWEEN EUROPEAN REGULATORS AND EUROPEAN HTA BODIESHealth technology assessment now features in a majority of European Member States with 48 organizations having a defined role in directly advising a decision maker with regard to HTA of new medical technologies. Different methodologies among HTA bodies are also recognized 1 but all require that the evidence for HTA addresses relative effectiveness domains, including clinical effectiveness but potentially also issues of transferability to local contexts and wider components (economic and patient aspects) when relevant. Building on the success of standard scientific advice from regulators, in which scientific advice is a tool to drive adequate data for the benefit-risk assessment at the time of marketing authorization (MA), parallel advice with HTA bodies was introduced to facilitate adequate evidence generation to meet the needs of different stakeholders and to avoid unnecessary trial duplication.In a parallel advice on a particular product, European regulators and HTA bodies give their views on the evidence generation plans at the same time. As an upstream decision maker, the regulator's position can be informative. For many HTAs, the licensed indication is a critical starting point for the appraisal process.Levels of alignment between regulators and HTA bodies on the trial designs for a product are a marker for the efficiency of the evidence generation. For a cohort of parallel advice procedures, a high level of agreement/partial agreement between the regulators and HTA bodies on the nature of the evidence to be collected was found at the end of the process supporting the potential for efficient evidence generation. 2 The current procedure provides for discussion meetings with the developers, HTA, and regulatory representatives on the most controversial aspects of the proposals. We have tracked programs that have been the subject of parallel advice with HTA bodies to see if the clinical trials were compliant with the advice given. Developers frequently changed comparators (81% of studies) and primary endpoints (74%) compared to those initially proposed in advices. In 60% of cases, the comparators implemented would meet the needs of regulators and at least one HTA body involved in the advice and in 100% of cases for the primary endpoints. This supports the need to gather external input to support decision making for clinical trial design. 3 Alignment between regulators and HTAs cannot be reached on the trial design in all case...

Towards a better use of scientific advice for developers of advanced therapies

“…Moreover, developers can seek multistakeholder advice and the products for which parallel consultation with Health Technology Assessment bodies is most relevant are those that are innovative, offer a cure rather than chronic treatment, with potential pricing issues, or target a very restricted rare population 16 . Obviously, due to such characteristics, ATMPs would be appropriate for this type of advice during their development.…”

Strengthening the Interface of Evidence-Based Decision Making Across European Regulators and Health Technology Assessment Bodies

“…6,22,24,32 Feedback on parallel early advice has been positive in both literature and unanimously in the interviews. 6,8,10,21,23,25,26,28,30,[33][34][35][36][37][38]42,50 Some interviewees remarked that an increase of such procedures would be beneficial but is constrained by HTABs/EUnetHTA resourcing. The literature and interviews further highlighted that HTABs' advice is not always reflective of all HTABs needs, because of the various contexts in which individual HTABs act.…”

“…Parallel consultation HTABs and regulators very positive toward it [6][7][8][9][10]12,15,[21][22][23][24][25][26]28,[31][32][33][34][35][36][37][38][39][40] N/A HTABs and regulators very positive toward it Avoidance of duplication Often mentioned that increased collaboration can lead to avoidance of duplication 6,10,12,16,33,34,41,42 N/A Stakeholders in agreement that collaboration can help avoid duplication of efforts Information sharing at market entry Both positive and negative. Mostly about EPARs.…”

“…Sharing of CHMP reports is positive. 2,6,12,16,[23][24][25]27,36,40,43,44 N/A All agreed webinar is helpful and EPAR needs to be improved. Requests for earlier provision of CHMP report and timeline changes were expressed by HTABs.…”

Regulation and Innovation: Role of Regulatory Science in Facilitating Pharmaceutical Innovation

“…In putting this issue together, we have attempted to cover the very large waterfront of regulatory science, ranging from biomarker validation to novel approaches and acceptability of generation of clinical evidence and regulatory licensure frameworks that now include patient‐focused drug development . We also include regulatory science topics that can improve the effectiveness and efficiency of postmarketing pharmacovigilance, generic drug approval, and strategies to facilitate demonstration of value to support reimbursement . We include topics of global import to demonstrate the impact of geopolitical forces on drug regulation, including Brexit and harmonization of regulatory requirements …”