Integrating Regulatory and HTA Requirements During Medicines Development

Thomas Kühler
Regulatory Science & Policy, EU/AMESA
Sanofi R&D

E

arly Dialogue, Parallel Scientific Advice, or Joint Consultation are all variations on the same theme: aiming to provide a vehicle for sponsors to integrate Health Technology Assessment (HTA) requirements upfront into drug development that targets European Medicines Agency (EMA) regulatory approval. Combining evidence generation requirements from the EMA and the HTA bodies into one single process has the potential to avoid duplication of effort and allows documentation satisfying both actors to be generated in the first development cycle. This brings added benefit to regulators, health technology assessors, and healthcare product developers, but most importantly to the EU healthcare system and its patients.

EMA and HTA bodies started to explore Early Dialogue through different pilot programs as far back as 2010. These have matured over the years; an important step was taken in 2017 when a one-stop-shop was launched for all Early Dialogues in the EU. This process is governed by EUnetHTA, a collaboration of European HTA organizations, and comprises two principal routes for the sponsor to choose. The first is Parallel Consultation which allows a) scientific advice with EMA and at least three HTA bodies; or b) scientific advice with EMA, three HTA bodies, and the full EUnetHTA Early Dialogue Working Party. The second option is EUnetHTA multi-HTA Early Dialogue which does not include EMA in the scientific advice dialogue.

Patient Engagement 

Patient engagement is a recurring theme in the EU and patient input is built into the Early Dialogue as an integral part of the process. Patient inputs offer a different perspective by providing real life experiences and raising issues not previously considered. Patient voices can also help focus the clinical research program and influence the choice of endpoints to better reflect their expectations for the drug under development. Selection of inclusion and exclusion criteria, comparator arm considerations, or views on the use of wearables are other important areas where structured patient input can be of value. Patient engagement renders better outcomes, contributes towards a transparent and holistic decision-making process, increases acceptability, and builds trust.

Early Dialogue has grown popular with sponsors. As of September 2019, 80 Early Dialogues have been conducted since program launch, with the vast majority classified as Parallel Consultations and thus involving both EMA and HTA bodies. Topics discusses at Early Dialogues cover the entire drug development spectrum spanning biomarkers, dosing, comparators, study design, and outcomes, to name a few.

Notwithstanding the above, the current Early Dialogue process is vulnerable as it is only mandated until 2020. In order to preserve the experience gathered, the expertise that has been established, and the added value that has been garnered over time, the European Commission (the lawmaking body in the EU) has developed a proposal for a financially sustainable and permanent cooperation framework, the Proposal for a Regulation of the European Parliament and of the Council on Health Technology and amending Directive 2011/24/EU. This framework aims at reducing duplication of effort (that is, each Member State should not necessarily conduct their own HTA assessment but rather rely on each other’s assessments); promote alignment of HTA tools and methodologies (that is, different HTA bodies should to the widest extent possible ask for similar if not identical evidence packages and evaluate them in a concerted way); and strengthening the quality of health technology assessments across the EU (that is, sharing learnings and stimulating the uptake of best practices across the entire network). The overarching objective is to conduct one common assessment for the entire HTA body network and to ensure its joint uptake in all Member States.

Any law proposed by the European Commission must be passed by the European Parliament and then ratified by the European Council in a co-legislative process. The European Parliament has finalized its first reading (i.e., discussed the proposal and proposed amendments), and discussions are currently ongoing in the European Council. Issues that still must find their solution are related to some Member States’ belief that the proposed Regulation is too far-reaching and will interfere with Member State sovereignty; they feel that they would give away some of their independence and freedom to operate when it comes to reimbursement discussions if they must rely on a joint assessment that is expected to apply across the entire EU.

Setting aside the political dimension and considering the draft Regulation from a strict medicines access point of view, the European Commission’s proposal appears to be spot-on.

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