The Joint Scientific Consultation is part of European cooperation under the EU HTA Regulation. It takes place before the subsequent clinical assessment and is intended to support the generation of evidence that addresses the likely requirements of a JCA. The consultation includes a meeting with the Health Technology Developer (HTD) and concludes with a JSC Outcome Document. The scientific recommendations it contains are not legally binding and do not prejudge the outcome of a subsequent JCA.
Joint Scientific Consultation as early scientific advice under EU HTA
A Joint Scientific Consultation is a scientific consultation on planned evidence generation for a health technology that is likely to be subject to a Joint Clinical Assessment at a later stage.
The JSC takes place during clinical development. The clinical studies or clinical investigations for which advice is sought must still be in the planning stage. The consultation therefore takes place at a point when key elements of the development programme can still be influenced.
For medicinal products, the consultation covers relevant aspects of clinical study design in particular. These include patient population, intervention, comparator and health outcomes. In addition to these PICO components, statistical methods, subgroups, patient-reported outcomes or questions relating to Post-Launch Evidence Generation may also be addressed.
The Joint Scientific Consultation therefore differs fundamentally from the subsequent JCA: the JSC provides advice on planned evidence generation. The JCA subsequently assesses the comparative clinical evidence that is actually available.
Eligibility for a Joint Scientific Consultation
A health technology is eligible for a Joint Scientific Consultation if it is likely to be subject to a subsequent JCA and the relevant clinical studies are still in the planning stage.
For medicinal products, HTDs can request a JSC for new products or for existing medicinal products with a new indication. In addition to information on the medicinal product and the proposed indication, the JSC Request includes information on regulatory status, previous scientific advice and the planned clinical studies.
The official Request Template also asks which areas are intended to be covered by the consultation. These include:
- Population
- Intervention
- Comparator
- Outcomes
- Study design, including statistical analysis methods
- Post-Launch Evidence Generation (PLEG)
- optional Health Economic Assessment
- other justified questions
For a parallel HTACG/EMA JSC, regulatory questions relating to Quality and Non-Clinical Development may also be addressed.
The timing of the JSC is therefore an important part of preparation. The consultation should take place before the relevant decisions within the clinical development programme have already been implemented and can no longer be meaningfully changed.
Request and selection for a Joint Scientific Consultation
A request for a Joint Scientific Consultation is submitted via the HTA IT Platform during defined Request Periods. The HTA Coordination Group publishes the Request Periods and the planned number of JSCs for each period.
If the number of eligible requests exceeds the available JSC capacity, a selection is made. Article 17(3) of the EU HTA Regulation defines six criteria:
- unmet medical needs
- first in class
- potential impact on patients, public health or healthcare systems
- significant cross-border dimension
- major Union-wide added value
- Union clinical research priorities
The JSC Request Template requires the HTD to identify and substantiate the applicable criteria. Information on the planned study and at least basic information on population, intervention, comparator and outcomes can also be included.
Within 15 working days after the end of the relevant Request Period, the HTA Coordination Group informs the HTD whether the requested JSC will be conducted. If the request is refused, the reasons must be explained with reference to the selection criteria.
Joint Scientific Consultation process
A Joint Scientific Consultation proceeds from the JSC Request through the Briefing Package and the consultation meeting to the final JSC Outcome Document. The assessor and co-assessor lead the scientific work on behalf of the JSC Subgroup and are appointed from different Member States.
The process can be divided into four main phases.
Phase 1: JSC Request and selection
The HTD submits the request via the HTA IT Platform during a Request Period. Following review and, where necessary, selection, the HTA Secretariat informs the HTD of the decision.
The JSC Subgroup then appoints an assessor and co-assessor. Suitable individual experts are also identified and checked for potential conflicts of interest. Patients, clinical experts and other relevant experts may contribute to the scientific consultation.
Phase 2: Briefing Package and scientific preparation
Once the JSC has been accepted, the HTD submits the Briefing Package via the HTA IT Platform. Compliance with the required templates is checked. If further specifications or clarifications are required, an amended version may be requested.
The Briefing Package provides the scientific basis for the consultation. The planned studies, relevant evidence questions and the HTD's position therefore need to be presented in a transparent and comprehensible manner.
Phase 3: List of Issues and JSC meeting
Based on the Briefing Package, the assessor and co-assessor prepare a List of Issues (LoI). Following comments from the JSC Subgroup, the LoI is shared with the HTD via the HTA Secretariat.
The HTD may respond to the List of Issues no later than 10 days before the meeting. A virtual meeting is then held to discuss the outstanding issues and the proposed development programme with the HTD.
Phase 4: JSC Outcome Document
After the meeting, the assessor and co-assessor prepare the draft JSC Outcome Document. Members of the JSC Subgroup may provide comments.
Once finalised, the document is submitted to the HTA Coordination Group for approval. The final JSC Outcome Document is subsequently sent to the HTD via the HTA Secretariat.
PICO and study design as core elements of the Joint Scientific Consultation
Population, intervention, comparator and outcomes are among the central areas of advice in a Joint Scientific Consultation. The EU HTA Regulation explicitly identifies these aspects as relevant elements of clinical study design that may be addressed within a JSC.
Comparative evidence is critical for a subsequent JCA. The official JSC Briefing Document therefore goes beyond a simple description of the planned study. The planned evidence generation may address aspects including:
- definition of the population and relevant subgroups
- choice of comparator
- primary and secondary endpoints
- patient-reported outcomes and health-related quality of life
- randomisation and blinding
- study duration and timing of data collection
- statistical analysis methods
- evidence synthesis, including indirect comparisons or network meta-analyses
- transferability of study data
- evidence for subgroups
- relative effectiveness and safety
The Briefing Document also requires explicit consideration of potential evidence gaps. The focus is on information, data and analyses that are likely to be required for the subsequent JCA.
The JSC therefore provides an opportunity to address potential evidence gaps before the clinical development programme relevant to the subsequent JCA has been completed.
Briefing Package for the Joint Scientific Consultation
The JSC Briefing Package consists of the Briefing Document together with the corresponding annexes and literature references. The Briefing Document should contain all information necessary for the consultation and function as a stand-alone scientific argument.
The official template structures the Briefing Document into several key areas.
Disease background and treatment landscape in the JSC Briefing Package
The disease background describes the disease, its epidemiology, natural history and disease burden.
The current treatment landscape is particularly important. The template requires a description of the current standard of care and relevant treatment alternatives. Differences between Member States should also be addressed.
With a view to a subsequent JCA, relevant medicinal products, medical devices and procedures that may constitute treatment alternatives for the respective disease, disease stage and line of treatment should be described.
Product and intended indication in the JSC Briefing Package
The Briefing Document describes the mechanism of action and key characteristics of the medicinal product as well as the proposed indication.
The intended indication should describe as precisely as possible where the medicinal product is intended to be positioned in the treatment pathway. This includes, for example, the line of treatment, monotherapy or combination therapy, posology and the precise target population.
Clinical development programme in the JSC Briefing Package
The clinical development programme should provide a transparent overview of completed, ongoing and planned clinical studies.
The template recommends a tabular overview covering study design, patient population, number of patients, dose, comparator, treatment duration, study status and available results. Data from earlier development phases may also be relevant where they support the rationale for the planned further development.
Planned clinical studies in the JSC Briefing Package
The template requires a more detailed description of the studies that are the subject of the JSC.
This includes, among other aspects:
- study objective
- study design
- inclusion and exclusion criteria
- subgroups and stratification
- sample size planning
- line of treatment
- comparator
- primary and secondary endpoints
- PROs
- follow-up
- statistical analysis
- handling of multiplicity
The Briefing Document also includes a structured Short Study Synopsis that summarises the key elements of the planned study.
Evidence gaps and Post-Launch Evidence Generation in the JSC Briefing Package
The Briefing Document should identify evidence gaps with a view to a subsequent JCA.
Advice on Post-Launch Evidence Generation is possible when it is requested in conjunction with discussion of the pivotal study design and is contextualised with the clinical data expected from the pivotal Phase II or Phase III studies.
Topics may include remaining research questions, population, comparator, outcomes, study design, timeframe and the quality of proposed data sources.
Questions and HTD positions in the JSC Briefing Document
The specific questions and corresponding HTD positions form the core of the scientific argument in the JSC Briefing Document.
The template recommends limiting the number of questions to a maximum of 10. Questions should be focused and contain no more than one or two sub-questions. The wording should be clear and unambiguous and may, for example, begin with "Does the HTACG agree that/with ...?".
Each question must be followed by a separate HTD's position. It provides the scientific justification for the approach proposed by the HTD and should be understandable as a stand-alone scientific argument.
An HTD position may include:
- context of the question
- proposed approach
- possible alternatives
- advantages and disadvantages of the different approaches
- potential consequences of the selected approach
- measures to address identified limitations
The template generally recommends a length of one to three pages for each HTD position. Complex statistical methods and their properties should be justified with appropriate scientific literature.
Questions concerning a future appraisal, reimbursement or coverage decision are outside the intended scope of HTACG advice.
List of Issues and meeting in the Joint Scientific Consultation
The List of Issues brings together the points to be explored in greater depth between the HTD and the participating experts before and during the JSC meeting.
The assessor and co-assessor first prepare a draft List of Issues. Members of the JSC Subgroup may provide comments. The HTA Secretariat then shares the LoI with the HTD.
Before the meeting, the HTD has an opportunity to review and respond to the identified discussion points. A response may be submitted no later than 10 days before the meeting.
The subsequent meeting discusses the List of Issues and the proposed development programme. Participants include the HTD, representatives of the JSC Subgroup, the assessor and co-assessor, and participating individual experts. For a parallel HTACG/EMA JSC, the EMA also participates.
Parallel HTACG/EMA JSC combines HTA and regulatory advice
A Parallel HTACG/EMA JSC combines European HTA advice with EMA Scientific Advice in a coordinated process with synchronised timing. The respective remits of the HTACG and EMA remain separate.
Under this format, the HTD requests both the JSC and EMA Scientific Advice. The timelines are synchronised and an identical Briefing Package is submitted to both procedures at the same time. The HTACG and EMA exchange information throughout the process.
The joint Briefing Document distinguishes between different areas of questions. Regulatory questions may, for example, be addressed to the CHMP. HTA questions relating to population, intervention, comparator, outcomes or study design may be addressed to the HTACG or, where relevant, jointly to the HTACG and CHMP.
|
HTACG JSC |
Parallel HTACG/EMA JSC |
|---|---|
|
Focus on HTA-relevant evidence questions |
HTA and regulatory questions |
|
Advice by the HTACG |
Coordinated advice by the HTACG and EMA |
|
JSC meeting |
Joint virtual meeting |
|
JSC Outcome Document |
JSC Outcome Document and EMA Scientific Advice |
A Parallel JSC therefore does not merge regulatory assessment and HTA. Instead, it enables the requirements of both perspectives to be addressed in a coordinated manner during evidence planning.
JSC Outcome Document as the result of the Joint Scientific Consultation
The JSC Outcome Document contains the scientific recommendations from the Joint Scientific Consultation but is not legally binding on the HTD, the HTA Coordination Group or the Member States.
The recommendations reflect the state of scientific knowledge at the time of the consultation. The Outcome Document does not prejudge a subsequent JCA of the same health technology.
The HTA Coordination Group approves the finalised JSC Outcome Document. The European Commission sends it to the requesting HTD no later than 10 working days after it has been finalised. Only anonymised, aggregated and non-confidential information on completed JSCs is made publicly available.
Link between Joint Scientific Consultation and Joint Clinical Assessment
The Joint Scientific Consultation addresses planned evidence generation, while the Joint Clinical Assessment subsequently assesses the available comparative clinical evidence. JSC and JCA therefore represent different stages of European HTA cooperation.
The link between the two procedures is already embedded in the JSC Briefing Document. Evidence gaps should be identified specifically with regard to information, data and analyses likely to be required for a subsequent JCA.
The EU HTA Regulation also establishes a direct connection. If a health technology has previously been subject to a JSC, the subsequent JCA dossier must include an explanation from the HTD for any deviation from the recommended evidence.
A JSC therefore guarantees neither a particular assessment scope nor a particular outcome of the subsequent JCA. It does, however, provide an opportunity to address key evidence questions at a point when the clinical development programme can still be adapted.
For evidence planning, this results in the following sequence:
Joint Scientific Consultation → clinical evidence generation → JCA scoping → JCA dossier → Joint Clinical Assessment
Joint Scientific Consultation and national HTA advice
A Joint Scientific Consultation does not preclude additional scientific advice at national level. The EU HTA Regulation allows Member States to conduct a national scientific consultation on a health technology that has already been subject to a JSC.
National advice may complement the European JSC or address specific questions relating to the respective national HTA system. In this case, the Member State concerned informs the HTA Coordination Group via the HTA IT Platform.
For manufacturers, national requirements in subsequent HTA procedures therefore remain relevant alongside European evidence planning.