To JSC or Not to JSC – That Is the Question

What is Joint Scientific Consultation?

Joint Scientific Consultation (JSC) is central to the EU Health Technology Assessment Regulation’s new approach to health technology assessment (HTA). The purpose of JSC is to gain parallel regulatory and EU-wide HTA advice. However, it is still possible to request European Medicines Agency only or HTA only advice; neither is excluded.¹  Manufacturers can request a JSC during the development phase of a product, with the aim being to seek advice on the data likely to be required for marketing authorisation application (MAA) and potential future joint clinical assessment (JCA).

What is the alternative?

Centralized regulatory (EMA) advice and individual country level advice (HTA advice) would include one application to the EMA for regulatory advice and individual applications to country HTA bodies for early advice (e.g. Germany, Gemeinsame Bundesausschuss (G-BA); Sweden, Tandvårds- och läkemedelsförmånsverket  (TLV); and France, Haute Autorité de santé (HAS).

1. Joint consultation should mean that advice is streamlined to meet evidence requirements for both regulators and health technology assessment (HTA). However, there are concerns over how actionable and practical these recommendations will be

The idea behind seeking Joint Scientific Advice is simple: to help manufacturers receive streamlined advice on both the regulatory and HTA evidence requirements for their products. The Joint Scientific Consultations’ (JSC) guidance documents emphasize this key aim: “streamlined logistics … [allow for] … maximum gain … by optimizing opportunities for mutual understanding between Regulators and HTAs … this promotes optimal and robust evidence generation fit-for-purpose for both Regulators and HTA bodies, ultimately bringing benefits for public health by enabling access to medicines which are effective to European patients as the ultimate goal”.²

However, there are concerns that the joint advice will not meet its intended aims, as detailed in responses to the JSC consultation.³ Concerns are two-fold: first, that for JSC to succeed, the recommendations/advice should be ‘actionable’ – meaning it should be realistic to implement into the development plan, with a clear scope and objective. Second, that the manufacturer should be able to rely on the recommendations given in the JSC to deliver meaningful clinical studies – if not, it renders the whole construct ‘futile’.

Our thoughts: It remains to be seen how actionable the recommendations coming from JSC are for joint clinical assessment (JCA), as well has how much manufacturers will be able to rely on this advice for designing clinical trials. Gaining insight from stakeholders / advisers involved in previously conducted JSC will be important to gain insight into the actionability and practicality of parallel joint advice.

2. If the decision has been made to go forward with JSC, logistical constraints on advice, may be an issue to gaining timely advice with input from all relevant stakeholders

These logistical constraints include: lack of capacity for consultations, selection criteria limiting ability to apply for JSC, challenges with recruiting European Union (EU) experts and a lack of clarity around fees.

In the immediate period (i.e. in the run up to the start of the first JCAs for Advanced Therapy Medicinal Products [ATMPs] and oncology products) a bridging process for JSC will be handled by the Gemeinsame Bundesausschuss  (G-BA) from September 2023 to January 2025.⁴ From January 2025 onwards, JSC will fall under the new EU HTA Regulation remit. For both of these periods there are concerns regarding lack of capacity for consultation and the corresponding selection criteria that have been put in place to limit consultations. In the responses to JSC consultation manufacturers stated that, although grateful for a bridging process to be put into place, it was important that leading HTA bodies “give comprehensive advice, that there are enough slots to ensure that each health technology developer can request and have the possibility to undergo a JSC and that the advice provides meaningful information about the future EU-PICOs to prepare for future JCAs”. Similarly concerns remain around the capacity for JSC from January 2025 onwards, with both Health Technology Developer’s and the European Federation of Pharmaceutical Industries and Associations (EFPIA) stating that there should be enough appointments for every manufacturer to receive advice, sufficient capacity and expertise in the system to allow for this and the removal of application selection criteria as a means to limiting the volume of consultations.

Challenges with recruiting EU experts were experienced during JSC pilots and it will therefore be key to remove hurdles for EU-level expert involvement (both patients and clinical experts) in order to gain the most from joint advice. In the responses to consultation, one company suggested the need to build a database of EU patients and healthcare practitioners (HCPs) and to train patients and HCPs on EU HTA procedures and implications in order to ‘ensure capacity and capability to systematically get relevant experts involved for JSCs’. Further, they suggested allowing for national experts to be part of the JSC process in cases where no relevant EU HTA expert is available, in order to mitigate against any expert input constraints. This approach was taken for four of the seven pilot JSCs and the EUnetHTA 21 group endorsed the proposed EU database in its final report recommendations stating “a common database development with EMA would be beneficial”.

Finally, the September EUnetHTA 21 stakeholder meeting highlighted the lack of clarity around fees for JSC.¹ The European Medicines Agency (EMA) has stated that its own scope and fees for the regulatory assessment in JSC will be the same as for their standard scientific advice. However, it is not yet known what fees HTA bodies may charge for their involvement in JSC.⁵

Our thoughts: It will be important to closely track all guidance documents being developed for the bridging period and beyond.  This will enable us to ascertain several things including whether limiting criteria remain, the number of consultations are being capped, an EU expert database is being set up, and what the fees are for JSC. Having this information will enable us to maximize the opportunities for attaining timely advice and input from all stakeholders.

3. Strategic considerations on the timing of advice and whether you would want to follow advice given at JSC (or be ready to defend against critique if not)

If there is a JSC spot available, choosing to proceed with a consultation – or not – and when, will be a strategic decision. This is because there may be certain scenarios where you may not wish to follow the anticipated advice.

The guidance documents for JSC have shown that, although the advice is not legally binding, the applicant will need to fully justify any deviations from the advice given in any subsequent marketing authorisation application (MAA) and JCA submissions and be prepared to respond to questions about why advice has not been followed² If JCA assessors will be made aware of which manufacturers have not followed advice, it is unclear what the impact, if any, will be of not following advice.

Our thoughts: A few aspects will be critical to strategically gain the most from advice. First, careful framing of questions will be needed to ensure you are not receiving contradictory advice to decisions that have already been made. Second, timing of advice will be critical; too early and evolution in landscape may render outcomes from scientific advice meaningless; too late and there is not enough time to implement advice – note, the JSC process is anticipated to take 3–4 months from receipt of the draft briefing document. Finally, and in aid with both of the previous points, engaging in early insights planning with clinical advisors/HTA experts at an external advisory board may help think through potential responses and help weigh up the benefits versus risks of seeking formal advice.

4. Economic advice is an option for JSC but economic considerations are outside the scope of EU HTA

An important point to note is that the JSC advice can include advice on health economic assessment if the manufacturer wishes; however, this advice will be outside of the remit of EU HTA. This is because the JCA will only be for clinical domains (including clinical effectiveness and product safety).

Manufacturers and EFPIA have noted their concerns with this approach, stating that all economic advice questions should be removed from the briefing template as JSC should be to inform the generation of evidence to support JCA and because health economic assessment questions should naturally be addressed by national bodies. In response, EUnetHTA 21 has said economic advice is on a voluntary basis and, during the EUnetHTA 21 JSCs, the opportunity to include economic questions has been appreciated by health technology developers.

Our thoughts: When going forward with parallel joint advice, it will also be important to consider whether to take up the option of the voluntary economic advice offered by JSC. It would offer a streamlined approach in comparison to the logistical difficulties which are often faced with scheduling separate national level scientific advice meetings. However, there are also legitimate concerns that the relevance of the advice may be based on those countries selected for the hands-on-group (HOG) for advice. Importantly, and related to the last point below, there may be concerns with this approach until confidentiality concerns are addressed given the highly sensitive nature of economic discussions.

5. Concerns about confidentiality

One proposal in the guidance documents for JSC was to make previous national level advice available to the JSC. However, some consultees to the process noted that supporting information which might be shared during national advice may contain highly confidential, country-specific information which is not in scope of the JSC. Therefore, it should be optional for the health technology developers to share the full advice documents and, a suitable confidentiality framework must be in place under the EU HTA regulation.

Our thoughts: Concerns about the level of national information disclosure and confidentiality will be a key consideration when contemplating JSC, given the highly sensitive nature of information that is shared during national scientific advice meetings. It will be important to closely monitor updates to procedure and guidance documents to see how this requirement changes and also to consider how important it will be to your company to keep national level discussions confidential.

References

1. EUnetHTAd. EUnetHTA 21 – Stakeholder Meeting, 8th September 2023. Available at: https://www.eunethta.eu/wp-content/uploads/2023/09/EUnetHTA-21-Stakeholder-Meeting-08.09.2023-v0.2.pdf. Accessed: 15 November 2023.
2. EUnetHTAa. Guidance on Parallel EMA/HTA body (HTAb) Scientific Advice for the Interim Period. 2023. Available at: https://www.eunethta.eu/wp-content/uploads/2023/07/Guidance-on-Parallel-EMA-HTA-body-HTAb-Scientific-Advice-for-the-Interim-Period.pdf. Accessed: 15 November 2023.
3. EUnetHTA21. EUnetHTA 21 Public Consultation Comments and Responses – D6.2.1 Briefing Document Template & D6.4.1 External Guidance with EMA 2023b. Available at: https://www.eunethta.eu/wp-content/uploads/2023/09/EUnetHTA-21_Public-Consultation_Comments-and-Responses_D6.2.1-D6.4.1_28082023-1.pdf. Accessed: 15 November 2023.
4. EUnetHTAc. Parallel EMA/HTA body (HTAb) Scientific Advice during Interim Period post EUnetHTA 21. Available at: https://www.eunethta.eu/jsc/. Accessed: 15 November 2023.
5. Agency EM. Information on Parallel joint scientific consultation with regulators and health technology assessment bodies. 2023. Available at: https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-advice-protocol-assistance/parallel-joint-scientific-consultation-regulators-health-technology-assessment-bodies. Accessed: 15 November 2023.