Receiving scientific advice from Health Technology Assessment (HTA) bodies is becoming an increasingly important part of the clinical development process. Scientific advice allows for evidence generation more targeted towards the needs of payers, smoothing the reimbursement process and ensuring that new therapies get to market, and ultimately to patients, more efficiently.
The Evolution of Parallel Scientific Advice
In the last decade, HTA bodies have teamed up with each other and regulatory bodies to offer parallel scientific advice (PSA) for pharmaceutical companies. An early example of PSA on a national level is the collaboration between the National Institute of Clinical Excellence (NICE) and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK (2). Following this, the European Network of Health Technology Assessment (EUnetHTA) was formed in 2005, creating a Europe-wide HTA network (3). In 2010, EUnetHTA and the European Medicines Agency (EMA) began collaborating to help harmonize the advice for evidence generation in Europe (4). The most recent example of this is the collaborative work of NICE and the Canadian Agency for Drugs and Health Technology (CADTH). The agencies announced in February 2019 the implementation of a new joint advice service for companies seeking to understand the requirements of both English and Canadian markets (1).
Does it work in practice?
There are considerable advantages to HTA and regulatory bodies offering PSA. The opportunity for collaborative face-to-face discussions between important stakeholders should benefit both patients and companies. Optimizing development plans by gaining early consensus on key concepts should lead to plans that better address unmet needs for patients. Ultimately, the aim is to get effective health technologies to patients, and problem-solving with multiple bodies at the same time should hopefully make this process more efficient.
While on paper these collaborations seem like a good idea, do they work in practice? HTA bodies and regulators have very different evidence requirements. Regulatory requirements have been standardized via international guidelines, whereas HTA bodies evaluate medicines in local clinical contexts and therefore evidence requirements can vary by setting (5). Tafuri et al. analyzed meeting minutes of scientific advice meetings between the EMA and different HTA bodies in the EU. The authors found good consensus on decisions overall: consensus reached a peak for questions on patient population (77%), while disagreements were highest for choice of comparator questions (30%) (6). Primary endpoint questions gained good consensus (60%), however, there were examples of disagreement regarding surrogate endpoints. Regulators generally agreed with proposed surrogate endpoints, while HTA bodies often required evidence of a link between surrogate endpoints and clinical outcomes or quality of life (6).
Collaboration between HTA bodies and regulators over the past two decades shows that there is already substantial alignment on requirements, and patients may be expected to benefit further as these collaborations gather pace.
nice.org.uk [Internet]. NICE[cited 2019 April 5]. Available from. https://www.nice.org.uk/about/what-we-do/life-sciences/scientific-advice/nice-mhra-scientific-advice
cadth.ca [Internet]. CADTH [updated 2019 February 6; cited 2019 April 5]. Available from. https://cadth.ca/news/new-opportunity-parallel-scientific-advice-cadth-and-nice
eunethta.eu [Internet]. EUnetHTA [updated 2012; cited 2019 April 5]. Available from. https://www.eunethta.eu/about-eunethta/history-of-eunethta/
eunethta.eu [Internet]. EUnetHTA[updated 2017; cited 2019 April 5]. Available from. https://www.eunethta.eu/ema-eunethta-3-year-work-plan/
Wang T, McAuslane N, Liberti L, Leufkens H, Hövels A. Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures—Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions. Value in Health. 2018 Jun 1;21(6):707-14.
Tafuri G, Pagnini M, Moseley J, Massari M, Petavy F, Behring A, Catalan A, Gajraj E, Hedberg N, Obach M, Osipenko L. How aligned are the perspectives of EU regulators and HTA bodies? A comparative analysis of regulatory‐HTA parallel scientific advice. British journal of clinical pharmacology. 2016 Oct 1;82(4):965-73.