What is scientific advice?
Scientific advice (or early dialogue process) is a fee-based service offered by regulators and health technology assessment (HTA) agencies to companies developing medicines. Some HTA agencies may also offer this advice for devices and diagnostics. It gives the company an opportunity to discuss and ask questions about their product development plan. The advice is then used to help ensure that the evidence they produce is adequate to support a regulatory submission or a request for reimbursement. The focus is on development strategies and study design rather than the evaluation of data. As part of this process, patient representatives, clinicians, and experts may be invited to contribute to the discussion.
The advice given is confidential, based on documentation provided by the company. It is not legally binding and does not affect the company’s responsibility for developing their product.
There are different options for obtaining scientific advice. In particular, Joint or Parallel advice may be sought from a range of agencies at the same time. This may help to increase alignment across agencies, and create efficiencies in the medicines development process. This collaborative approach can improve efficient data collection, as well as improving the clarity of the process and providing earlier conversations about the possibility of conditional reimbursement schemes or risk-sharing agreements.
Options for obtaining scientific advice include:
- Regulatory national advice: from individual national regulators
- European Regulatory advice: from the European Medicines Agency (EMA)
- HTA national advice: from individual national HTA organisations
- Joint national HTA and regulatory advice within one country: for example, in the UK, joint NICE-MHRA advice
- European parallel regulatory and HTA advice: from EMA and HTA bodies via EUnetHTA
- European joint HTA (or multi-HTA): joint advice from multiple HTA bodies across Europe.
Why seek scientific advice?
The main reason why a company may request scientific advice is to ensure that the proposed development plans have the ability to produce evidence that is considered relevant (and sufficient) for a future regulatory and/or HTA evaluation.
Other reasons may include:
- understanding the perspective of decision makers
- understanding pros and cons of trial options
- maximising relevance of trial programme outputs
- exploring alternative strategies to address data gaps
- incorporating cost-effectiveness considerations into early decision-making (relevant for HTA organisations).
Additionally, seeking scientific advice may help to convince or influence colleagues within the company about the benefits of alternative trial options, provide suggestions about approaches that can be applied to related medicines in development, and potentially may provide considerations for more strategic decisions for the company.
When to seek scientific advice?
Usually scientific advice is sought during the planning stages of the pivotal trial programme, before the evidence development and specific clinical trial plans are finalised. Typically this is any time after the completion of the first trial in people for discussions with HTA organisations, but may be earlier for discussions with regulatory agencies.
However, regulatory advice from the EMA may be offered at any time during medicines development process, including advice on post-authorisation safety studies (PASS) and post authorisation efficacy studies (PAES).
What issues are raised?
Issues typically raised related to the clinical trial programme may include:
- definition of study population and possible subgroups of importance
- position of the new intervention in the treatment pathway
- relevant comparators to be included
- relevant outcomes to be measured
- health-related quality of life data collection (generic and disease-specific).
Companies may also request advice from HTA organisations (alone or as part of a joint or parallel process) related to the economic evaluation of their technology. Topics for questions here may include:
- proposed approach for cost-effectiveness modelling
- sources of data
- incorporation of real-world evidence and observational studies
- analyses required to support modelling assumptions, such as extrapolation
- utility values, resource use and costs.
Heather Stegenga and Pillar Pinilla-Dominguez, NICE
Craig Johnson, GSK
Stefan Schwoch, Lilly
Marie-Laure Prudhomme, Sanofi