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 reimbursement requests. 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. Joint or parallel advice may be offered to help increase alignment across agencies, where possible, and create efficiencies in the medicines development process. This collaborative approach can improve efficient data collection, improve the clarity of the process and provide 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
- Regulatory European advice: from the European Medicines Agency (EMA)
- HTA national advice: from individual national HTA organisations
- Joint HTA and regulatory national advice within one country: for example, in the UK, joint NICE-MHRA advice
- European parallel regulatory and HTA advice: from EMA and HTA bodies (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 can produce evidence that is relevant 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 trials options, support learning about different approaches for other products, and potentially help with considering more strategic decisions for a company.
When to seek scientific advice?
Usually this is sought during the planning stages of the pivotal trial programme, before the evidence development plans are finalised (typically any time after the completion of the first trial in people for HTA organisations or earlier for 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).
How long does it take?
The time between requesting and receiving advice varies depending on the process and the organisations involved. The parallel regulatory-HTA advice process can take up to 20 weeks after documentation is received from the company.
How much does it cost?
Many agencies charge for scientific advice services, but the price varies from country to country, and sometimes takes into consideration the complexity of the assessment. The cost of advice from HTAs is currently between £15,000 and £50,000 for NICE single-procedures and NICE–MHRA scientific advice in the UK, is free for Haute Autorité de Santé (HAS) in France and is 10,000€ at the Federal Joint Committee in Germany (or Gemeinsamer Budesausschuss [GBA]). EMA scientific advice costs vary depending on the product status.
What issues are raised?
Issues typically raised related to the clinical trial programme may include:
- study population and subgroups
- position of intervention in treatment pathway
- relevant comparators
- relevant outcomes
- 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 usually include:
- exploration of the cost-effectiveness modelling
- sources of data
- incorporation of real-world evidence and observational studies
- analyses used to support the assumptions in the model 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