1. Introduction
The European Union (EU) Regulation 2021/2282 on health technology assessment (HTA) (HTA-R) has been applicable in all EU Member States (MSs) since 12 January 2025 (article 36.2 HTA-R) (European Union, 2021). Next to joint scientific consultations and voluntary cooperation on HTA, it establishes a joint clinical assessment (JCA) framework for medicinal products as well as class IIb/III medical devices (‘high-risk medical devices’) and class D in vitro diagnostic medical devices. Following a stepwise approach (recital 16 HTA-R), the scope of JCAs initially includes anti-cancer treatments and advanced therapy medicinal products (ATMPs; article 7.2(a) HTA-R), as well as high-risk medical devices and in vitro diagnostics (European Union, 2021). On 13 January 2028, this scope will be expanded to medicinal products with an orphan designation as per Regulation (EC) 141/2000; finally, on 13 January 2030, all medicinal products for which marketing authorisation approval by the European Medicines Agency (EMA) is applied for will be subject to JCAs (article 7.2(b)–(c) HTA-R) (European Union, 2021). For medicinal products, an application for marketing authorisation has been filed with EMA, while medical devices are subject to a scientific opinion by expert panels under EMA coordination (European Union, 2021; Tarricone et al., Reference Tarricone, Banks, Ciani, Brouwer, Drummond, Leidl, Martelli, Sampietro-Colom and Taylor2023; Van Engen et al., Reference Van Engen, Krüger, Parnaby, Rotaru, Ryan, Samaha and Tzelis2024). Recitals 7 and 19 of the Implementing Regulation (EU) 2024/1381 (JCA-IR) stipulate that the JCA-related procedure for medicinal products is scheduled in parallel with the EMA marketing authorisation process (European Commission, 2024a). This parallel occurrence is also reflected in recital 36 and articles 7.1(a)–(b) and 11.1(a) HTA-R, respectively (European Union, 2021).
The purpose of the JCA framework is ‘to ensure the highest scientific quality of [JCA] reports’ that ‘reflects the state of the art’ (recital 45 HTA-R; recital 4 JCA-IR) (European Commission, 2024a; European Union, 2021). To this end, external stakeholders ‘with relevant in-depth expertise’, namely patients, clinicians, corresponding stakeholder organisations, and ‘other relevant experts’ (recital 45, articles 8.6 and 11.4 HTA-R; recital 4, articles 6, 8 JCA-IR) are to be involved in a JCA procedure (European Commission, 2024a; European Union, 2021). A prerequisite of these external experts shared with other individuals participating in a JCA procedure (JCA subgroup representatives, assessor, and co-assessor) is that they must be free from conflicts of interest (CoI) (article 5.2 HTA-R; article 1 Implementing Regulation (EU) 2024/2745 (CoI-IR)) (European Commission, 2024b; European Union, 2021).
A fundamental part of the JCA process involves determining the assessment scope, consisting of patient population, intervention(s), comparator(s), and health outcomes (PICOs; article 8.6 HTA-R) (EunetHTA 21, 2022; European Union, 2021). As this scope provides the foundation for the JCA (article 11.1 HTA-R) (European Union, 2021), the health technology developer (HTD) must address it to the extent possible in the submitted dossier. Subsequently, a published JCA report based on the PICO-related scope must be given ‘due consideration’ in national HTA procedures (article 13.1 HTA-R) (European Union, 2021).
Since the HTA-R entered into force in January 2022, issues linked to the practical implementation of the PICO scheme have extensively been discussed in the literature. A distinct challenge in this regard concerns the multiplicity of PICOs across MSs, which is particularly due to comparator heterogeneity (European Commission, 2025a; Julian et al., Reference Julian, Pavlovic, Sola-Morales, Gianfrate, Toumi, Bucher, Dierks, Greiner, Mol, Bergmann, Salmonson, Hebborn, Grande, Cardone and Ruof2022; Kisser et al., Reference Kisser, Knieriemen, Fasan, Eberle, Hogger, Werner, Taube and Rasch2022; Schuster, Reference Schuster2024; Van Engen et al., Reference Van Engen, Krüger, Parnaby, Rotaru, Ryan, Samaha and Tzelis2024). Previous research has provided suggestions on how to approach these issues in connection with dossier submission (Eberle et al., Reference Eberle, Hagemann, Schweitzer, Justl, Maurer, Carls and Reuter2025; Morgese et al., Reference Morgese, Majors and Patel2025). Moreover, short deadlines linked to milestones in the EMA marketing authorisation process have raised scepticism about HTDs’ capacity to comply with the deadlines regarding dossier and (further) evidence submission and the successful implementation of the HTA-R overall (Falla et al., Reference Falla, Kullnigg and Van Engen2024; Rutten-van Mölken and IJzerman, Reference Rutten-van Mölken and IJzerman2024). Another recent publication highlighted the CoI-IR within the HTA-R framework (Gentilini and Parvanova, Reference Gentilini and Parvanova2024). Additionally, legal analyses have been conducted on the scope of EU law on HTA and market access policies, as well as on the interpretation of article 13.1 HTA-R (Ernst and Stöger, Reference Ernst and Stöger2024; Stühlinger, Reference Stühlinger2020).
However, little dedicated research has been conducted on the legal aspects and consequences with regard to PICO disparities and the involvement of conflicted expert stakeholders in the JCA process. Therefore, this article aims to discuss potential legal implications of these issues related to JCAs and to highlight open questions in this regard. Firstly, we investigate potential legal implications of PICO-related issues. Secondly, we consider legal aspects in connection with potential CoIs of experts involved in JCAs. Finally, we highlight the potential impact of these issues and legal implications on patient access, particularly from a healthcare provider perspective, including cross-border healthcare considerations.
2. PICO disparities
2.1. Regulatory landscape and feasibility implications
The scope of a JCA must ‘reflect [MSs’] needs in terms of parameters and of the information, data, analysis and other evidence to be submitted by the [HTD]’ (article 8.6 HTA-R) (European Union, 2021). MSs are expected to specify the comparator applicable within their respective healthcare system; stating it as ‘standard of care’ is not sufficient (EunetHTA 21, 2022). In this regard, the rapid evolution of treatments in some oncological indications in recent years must be considered. For instance, treatment trajectories for metastasised renal cell carcinoma have changed substantially between 2019 and 2021, with several treatments having become obsolete (de Vries, Reference de Vries2023). Such developments lead to fast changes regarding the applicable comparator within the PICO scope.
In practice, these changes may not apply across MSs simultaneously. Indeed, newly authorised oncological treatments are consistently available sooner in MSs in Northern and Western Europe compared to Central and Eastern Europe (EFPIA, 2024; Newton et al., Reference Newton, Stoddart, Travaglio and Troein2025; Uyl-de Groot et al., Reference Uyl-de Groot, Heine, Krol and Verweij2020). This heterogeneity in ‘time to access’ can contribute to disparities in PICOs as different comparators apply in different MSs. For JCAs, this would necessitate comparing an innovative product targeting a specific indication to treatments already obsolete in high-income countries but still considered as the standard treatment in lower-income MSs. Furthermore, some comparators may not be available at all in an MS at the time of the intervention’s marketing authorisation approval (Cosset et al., Reference Cosset, Janssen, Sirena and Masutti2024).
This issue contributes to the above-described heterogeneity in comparators. Therefore, HTDs face the difficult and time-consuming challenge to provide data involving the relevant comparators within the JCA scope. This complicates the feasibility and implementation of JCAs (Brinkhuis et al., Reference Brinkhuis, Julian, Van Den Ham, Gianfrate, Strammiello, Berntgen, Pavlovic, Mol, Wasem, Van Dyck, Cardone, Dierks, Schiel, Bernardini, Solà-Morales, Ruof and Goettsch2024; Julian et al., Reference Julian, Pavlovic, Sola-Morales, Gianfrate, Toumi, Bucher, Dierks, Greiner, Mol, Bergmann, Salmonson, Hebborn, Grande, Cardone and Ruof2022; Schweitzer et al., Reference Schweitzer, Dold, Genet, Gossens, Klein-Hessling, Löffler, Rabel, Rasch, Reuter, Schmelcher, Wolfram and Werner2024).
The discussed PICO disparities across countries potentially carries several implications for both HTDs and MSs. Firstly, the manageability of the PICO requirements has been voiced by HTDs as a crucial uncertainty (Severens et al., Reference Severens, Dillon, Meyer, Jommi, Lipska, Canonico, Solà-Morales and Altmann2025). Providing sufficiently robust evidence on all applicable PICO sets through trial data is likely neither feasible for HTDs (Schuster, Reference Schuster2024) nor – due to substantially increased research-related costs to employ outdated comparators – in their commercial interest. This may subject HTDs to non-compliance with the dossier submission request. Secondly, the JCA subgroup may fail to consider all relevant PICO parameters in the scoping process. This may render some MSs unable to duly consider the JCA report in their national HTA procedure. Thirdly, some MS might not have procedures in place which qualify as (adequate) national HTA procedures (Ernst and Stöger, Reference Ernst and Stöger2024), prompting the question on the applicability of the obligation to give due consideration to the published JCA report.
2.2. Legal implications
2.2.1. Non-compliance with requested PICOs
A JCA report reflects the assessment scope – and thus the PICOs – specified pursuant to article 8.6 HTA-R (article 9.1 HTA-R) (European Union, 2021). Upon specification of the JCA scope, the Commission requests the HTD to submit a dossier that meets the requirements stipulated in article 9.2–4 HTA-R (‘first request’; article 10.1 HTA-R). In particular, the dossier must contain ‘complete and up-to-date’ evidence ‘to assess the parameters included in the assessment scope’ and include the documentation underpinning the submitted information in accordance with the respective Annex I HTA-R and the JCA-IR (European Commission, 2024a; European Union, 2021). Annex I JCA-IR specifies the HTD’s obligation to provide results for each addressed PICO but also to identify PICO(s) not included in the dossier and to justify their exclusion (European Commission, 2024a).
The dossier submission is subject to a deadline of 100 days (60 days in case of an accelerated marketing authorisation procedure or indication expansion) from the first request (article 12.2 JCA-IR) (European Commission, 2024a). If these requirements are not fully met, making the submitted dossier incomplete, the Commission requests the missing evidence from the HTD (‘second request’; article 10.5 HTA-R) (European Union, 2021). Additional information must be submitted within 15 days, or ten days in the cases described above (article 12.4 JCA-IR) (European Commission, 2024a). Failure of the HTD to comply with the second request triggers discontinuation (or no-start) of the JCA procedure (article 10.6 HTA-R) (European Union, 2021). This also applies if the omission of PICOs is not appropriately addressed and justified in the submitted dossier, as the evidence cannot be considered complete to inform the assessment as per article 9.3(a) HTA-R.
Re-initiation of the JCA procedure is possible within six months after the initial (incomplete) dossier submission deadline upon submission of the required data; the Coordination Group (CG) has discretion on the re-initiation (article 10.7 HTA-R) (European Union, 2021). Once the six-month deadline has passed or if the data timely provided by the HTD did not fulfil the requirements, or if the CG decides against re-initiation, the discontinuation/no-start of the JCA is permanent. Permanent discontinuation of the assessment means that no JCA report is published. Recital 31 HTA-R accounts for this possibility by explicitly referring to the unavailability of such report (European Union, 2021). In this scenario, an MS’s obligation to give due consideration to the published JCA report as per article 13.1(a) HTA-R is, e contrario, rendered inapplicable. However, this does not create a vacuum for the MSs’ national HTA procedure. Recital 31 HTA-R states that a JCA report’s unavailability should not delay national HTA, reimbursement, and market access processes (European Union, 2021). Hence, MSs can still perform their HTA procedures without the JCA report to inform national decision-making.
In this context, recital 34 HTA-R clarifies that HTA bodies of individual MSs can only request evidence from HTDs at national level that were not submitted at EU level (European Union, 2021). However, article 10.6 HTA-R stipulates that evidence underpinning a discontinued JCA is exempt from article 13.1(d) HTA-R (European Union, 2021). Correspondingly, such evidence submitted prior to discontinuation is not subject to accessibility on the IT platform under article 30.3(d) HTA-R: documentation must only be made available when a JCA report is published, or a temporarily discontinued JCA is re-initiated (European Union, 2021). Regarding discontinued JCAs, only a list of requested but not submitted evidence is provided (article 30.3(o) HTA-R) (European Union, 2021). Therefore, since article 13.1(d) HTA-R is rendered inapplicable in this scenario (article 10.6 HTA-R), national HTA institutions can request (additional) evidence without restriction for their national HTA procedures with regard to the technology subject to the discontinued JCA.
Based on the deliberations above, the only legal consequence of HTDs not (timely) providing sufficient evidence to the JCA subgroup is the discontinuation/no-start of the JCA. Further legal consequences affecting HTDs at EU level are not stipulated. Given the MSs’ retained autonomy regarding national HTA procedures (recital 26 HTA-R) (European Union, 2021), HTDs remain obligated to comply with the corresponding national regulations for an assessment of the product’s effectiveness and reimbursement.
2.2.2. Non-consideration of JCA reports and JCA-related evidence by MSs
In view of the MSs’ obligation to give due consideration to the ‘published JCA reports and all other information available’ (article 13.1(a) HTA-R), recital 31 HTA-R defines the term ‘give due consideration’ such that the report should be considered ‘for any HTA at MS level’ included in the documentation ‘that supports the national HTA process’ (European Union, 2021). As consequences of non-compliance with this provision are not explicitly specified, its legal implications for national HTA procedures require clarification. In this regard, it is also important to consider possible causes of non-compliance. Here, two examples are provided. Firstly, the JCA report and evidence available at European level might not be used in a national HTA procedure. Secondly, as an organisational issue, the national HTA jurisdiction might be split based on health technology characteristics (eg., inpatient versus outpatient use), and not all HTA bodies might have access to the submitted evidence to the same extent.
Regarding an MS not considering the JCA report or the submitted evidence for their own HTA procedures, the legal nature of a JCA and the obligation to ‘give due consideration’ must be assessed first. Recital 31 HTA-R states that ‘the content of the joint clinical assessment report is scientific in nature and should not be binding on [MSs]’; additionally, recital 26 HTA-R clarifies that national HTA procedures and the subsequent decisions (eg, a health technology’s reimbursement) remain the MSs’ exclusive responsibility (Ernst and Stöger, Reference Ernst and Stöger2024; European Union, 2021), which is consistent with the distribution of healthcare-related responsibilities under article 168.7 Treaty on the Functioning of the EU (Ernst and Stöger, Reference Ernst and Stöger2024; Kellerbauer et al., Reference Kellerbauer, Klamert and Tomkin2024). In accordance with case law on non-binding legal acts, not following or deviating from a JCA report in a national HTA procedure is not per se disallowed but must be justified (Ernst and Stöger, Reference Ernst and Stöger2024; European Court of Justice, 2006; Korkea-aho, Reference Korkea-aho2018).
Applying this interpretation to the first example described above, an MS is not bindingly obliged to apply the outcomes held in a JCA report to its national HTA procedure. However, if a JCA report and/or the underpinning evidence is not considered, it must be transparently justified in their communication (article 13.2 HTA-R; article 19 JCA-IR) (European Commission, 2024a; European Union, 2021). For instance, if the PICOs in a JCA fail to reflect an MS’ clinical practice (eg., due to inappropriate comparators), leading to limited or no relevance of the corresponding JCA report for the national HTA process (Cosset et al., Reference Cosset, Janssen, Sirena and Masutti2024), this circumstance lends itself to justify non-consideration of the report and underpinning evidence. This is also consistent with recitals 15 and 30 HTA-R which allow the request and consideration of evidence in national procedures beyond the JCA’s scope (European Union, 2021).
A legal remedy against a national HTA institution’s (insufficiently justified) non-consideration of the JCA report is not provided at European level. Rather, since the responsibility for HTA procedures and the subsequent decision-making is strictly retained at national level (recital 26 HTA-R), this also involves the provision of legal remedies and appellate procedures against, for instance, negative reimbursement decisions (European Union, 2021). If a chain of causality can successfully be drawn between a JCA report not being given due consideration in a national HTA procedure without proper justification and a subsequent negative decision on reimbursement or market entry authorisation, HTDs should have a legal means to challenge such decision. This requires transparent regulatory and judicial frameworks at national level.
The second case concerns the capacity of a national HTA body to comply with article 13.1(a),(d) HTA-R in connection with its access to evidence underpinning a JCA report. Fragmentation of health systems in MSs is reflected in diversity regarding decision-making bodies but also HTA institutions (European Commission, 2025b; Stühlinger, Reference Stühlinger2020). In MSs with multiple HTA bodies, where only one of them is represented in the CG and the JCA subgroup, the remaining HTA bodies might not have full access to all the evidence informing the JCA report. This especially applies to data considered as commercially confidential information (CCI) by the HTD. Disclosure of CCI to third parties (eg., experts involved in JCAs) requires corresponding confidentiality agreements (recital 41 HTA-R; article 7 JCA-IR) (European Commission, 2024a; European Union, 2021; Wested, Reference Wested2022). The classification of relevant evidence as CCI must be justified by the HTD (recital 29, article 11.5 HTA-R; article 14.4 JCA-IR) (European Commission, 2024a; European Union, 2021). Outside the scope of such agreements, successfully justified CCI remains undisclosed and is redacted from the documentation underpinning the JCA report (article 20.1 JCA-IR e contrario).
Subsequently, when conducting national HTA procedures within their jurisdiction, national HTA bodies not represented in the CG and JCA subgroup have no access to CCI redacted from the JCA reports. CCI that concerns relevant evidence for these procedures can complicate the national HTA. An example illustrating this issue concerns the split HTA jurisdiction concerning inpatient medicinal products in the Netherlands. For newly authorised products placed in a ‘lock’ procedure (ie., temporarily barred from reimbursement) due to their high price, the Dutch Healthcare Institute (ZIN) – which is represented in the CG and the JCA subgroup for medicinal products (European Commission, 2025b) – has competence to provide HTA-informed advice to the Ministry of Health, Welfare and Sport regarding their reimbursement (Ministerie van Volksgezondheid, 2024). However, national HTA procedures for inpatient products not subject to the ‘lock’ procedure are conducted by the Committee for the Evaluation of Add-On Medicinal Products (CieBAG), which represents Dutch healthcare insurance companies. Such products are reimbursed if their effectiveness is consistent with the current state of science and practice (Vereniging Innovatieve Geneesmiddelen, 2024). The relevance of CieBAG’s current role with regard to JCAs particularly derives from its jurisdiction to evaluate inpatient anticancer products and ATMPs that barely avoid the ‘lock’ procedure (Vereniging Innovatieve Geneesmiddelen, 2024). The assessment regarding a health technology’s consistency with the current state of science and practice primarily concerns its effectiveness compared to the respective standard treatment, which involves the use of scientific, evidence-based methods (Zorginstituut Nederland, 2023a, 2023b). This qualifies as a HTA procedure in accordance with the literature and recital 2 HTA-R (European Union, 2021; Stühlinger, Reference Stühlinger2020).
If CieBAG performs such HTA procedure within its jurisdiction, it must give due consideration the published JCA report and all other information available on the IT platform (articles 13.1, 30.3 HTA-R) (Vereniging Innovatieve Geneesmiddelen, 2024). However, if the JCA involves CCI that remains inaccessible to HTA bodies outside the CG and the JCA subgroup, CieBAG cannot take such information into consideration. In this regard, the Vereniging Innovatieve Geneesmiddelen considered it unclear whether and how CieBAG would have to adapt their own HTA procedures and reporting to meet the requirements stipulated in article 13.1 HTA-R (Vereniging Innovatieve Geneesmiddelen, 2024). As CieBAG is not part of the CG nor the JCA subgroup, it has no access to the secure information exchange system and intranet as per article 30.1(b),(c) HTA-R, and successfully justified CCI is not included in the documentation underpinning the JCA report nor publicly accessible on the IT platform (article 20.1 JCA-IR e contrario) (European Commission, 2024a). However, a solution to this issue can be derived from the HTA-R recitals. Within its jurisdiction, CieBAG executes its unrestricted responsibility to perform a national HTA (recital 26 HTA-R) (European Union, 2021). Should CieBAG require evidence classified as CCI in addition to the JCA report and the evidence accessible on the IT platform, it can request such evidence from the HTD in its own HTA procedure. National HTA institutions retain their capacity to request further evidence from HTDs to perform complementary analyses (recital 15 HTA-R). In consistency with this recital, the scope of evidence that was ‘not part of the [JCA]’ that can be requested at national level (recital 30 HTA-R) (European Union, 2021) can be extended to confidential evidence that is not accessible on the IT platform. However, such request for additional evidence is not warranted if the national HTA procedure can be conducted sufficiently by giving due consideration to the JCA report and publicly accessible information alone (article 13.1(d) HTA-R) (European Union, 2021).
3. Conflicts of interest of individual experts
3.1. Regulatory landscape and feasibility implications
The HTA-R and the JCA-IR explicitly provide for the involvement of individual experts (ie., patients, clinical experts and other relevant experts) in a JCA procedure to ‘ensure that joint work is of the highest scientific quality and reflects the state of the art’ (recital 45, articles 8.6, 11.4 HTA-R; recitals 12, 24, articles 6, 14.1, 15.1 JCA-IR) (European Commission, 2024a; European Union, 2021). When participating in a JCA, individual experts must be independent and impartial, without ‘any financial or other interests in the [HTDs’] industrial sector which could affect their independence or impartiality’ (Article 5.2 HTA-R) (European Union, 2021). Their impartiality and independence is of high importance to ‘preserve the scientific integrity’ of JCAs (recital 45 HTA-R) (European Union, 2021). The CoI-IR contains detailed rules for the application of the HTA-R provisions on CoIs (European Commission, 2024b). Individual experts must provide a declaration of interest (DOI) containing all (in-)direct financial or other interests in the HTD’s industrial sector (article 2.1 CoI-IR) (European Commission, 2024b). The DOI is subsequently assessed by the Commission (article 4.1 CoI-IR).
Annex II CoI-IR provides a detailed overview of interests constituting a CoI, as well as their consequences for their involvement in joint work (including JCAs; recital 5 CoI-IR) (European Commission, 2024b). These interests consist of seven attributes: employment, consultancy, strategic advisory, financial interests (payments or expense reimbursements exceeding €1,000 over the past three years), (principal) investigator position, membership in an organisation/institution receiving funding from HTDs, and interests of immediate family members (European Commission, 2024b).
Based on article 7.1 CoI-IR, Annex II CoI-IR further specifies to which extent a conflicted individual expert is generally excluded from participating in a specific JCA (European Commission, 2024b). The exclusion can take four forms: exclusion from any JCA (in case of any ongoing CoI regarding employment, consultancy, strategic advisory role, or (co)ownership/shareholding); a JCA involving a specific HTD’s technology (under assessment or a comparator), specific health technologies in the PICO, or health technologies from the respective HTD within the applicable therapeutic area (European Commission, 2024b). The jurisdiction to decide on a conflicted expert’s exclusion lies with the Commission (article 5.4 HTA-R, articles 7.1, 8.1 CoI-IR) (European Commission, 2024b; European Union, 2021). The occurrence of CoIs among individual experts within the scope of a JCA procedure should not be understated. Two essential aspects can make CoI management challenging. Due to the specific skillset required for JCA participation, the pool of viable (co-)assessors and experts, especially at a national level, is small (Hantke, Reference Hantke2024). This issue is even more prevalent in small MSs and for rare diseases (Hantke, Reference Hantke2024). Additionally, some experts may have previously been affiliated with, or have advised HTDs as key opinion leaders (eg., in clinical trials); this especially applies to experts from European countries with small organisations and to experts on innovative technologies or rare diseases (European Hematology Association, 2024; European Multiple Sclerosis Platform, 2024; Medtronic, 2024). In such cases, CoIs as per the CoI-IR are virtually inevitable.
3.2. Legal implications for practice
While article 5 HTA-R itself does not explicitly provide any exceptions to a conflicted expert’s exclusion from joint work, articles 7.3 CoI-IR provides a mechanism for the ‘appropriate involvement’ of conflicted individual experts in a JCA ‘in exceptional cases’, where ‘no individual experts free from [CoIs] that have the relevant in-depth specialised expertise are available’ (European Commission, 2024b). Similarly, individual experts for whom a new CoI arises during an ongoing JCA procedure may retain an ‘appropriate involvement’ (article 8.5 CoI-IR) (European Commission, 2024b). In both cases, the involvement of conflicted individual experts is proposed by the Commission (articles 7.3, 8.5 CoI-IR) and decided by the JCA subgroup (article 6.5 JCA-IR) (European Commission, 2024b, 2024a).
The wording of article 7.3 CoI-IR – specifically the term ‘may’ – indicates that the Commission has discretion on proposing the involvement of a conflicted individual expert in a JCA. However, in this context, recitals 12 and 45 HTA-R and recital 15 CoI-IR provide guidance on the interpretation of this provision in the context of the HTA-R framework. These recitals highlight a JCA’s requirement for scientific excellence and in-depth expertise (European Commission, 2024b; European Union, 2021). This is complemented by recital 4 JCA-IR, which specifies the importance of including individual experts to ‘ensure the highest scientific quality of [JCA] reports’ (European Commission, 2024a). Additionally, recital 23 HTA-R incorporates the CG’s duty to ‘ensure that the scientific joint work as well as the procedures and methodology for the preparation of [JCA] reports […] guarantee the highest quality […] and reflect the state of the art of medical science at the time of their preparation’ (European Union, 2021).
These recitals indicate a prioritisation of scientific excellence and state-of-the-art status in the scoping, assessment, and reporting phases of a JCA. This prioritisation also concerns the CoI management regarding experts: as can be derived from article 7.3 CoI-IR, conflicted experts can be involved in a JCA procedure if this involvement serves the purpose of providing the scientific expertise required to perform the JCA to the highest scientific standard (European Commission, 2024b). Hence, the Commission’s proposal to involve a conflicted expert, and their subsequent appointment by the JCA subgroup (article 6.5 JCA-IR) should be guided by the question whether the JCA’s highest scientific quality can still be ensured if the conflicted expert is excluded from the procedure. By extension, the same applies to the proposal and decision on the continuous inclusion of an expert for whom a new CoI arises (article 8.5 CoI-IR; article 6.5 JCA-IR).
However, the application of articles 7.3 and 8.5 CoI-IR in conjunction with article 6.5 JCA-IR leaves some points potentially unclear. Firstly, neither the HTA-R nor the implementing regulations contain provisions outlining remedies against the ‘final’ selection of experts by the JCA subgroup. Secondly, there is no clarity on measures to be taken by the CG, the JCA subgroup, or the (co-)assessor to mitigate the risk of bias through the involvement of conflicted experts (Gentilini and Parvanova, Reference Gentilini and Parvanova2024). A possible answer to both aspects can be based on the non-binding nature of a JCA report as per article 13.1(a) HTA-R and the MSs’ sole responsibility for national HTA procedures (recital 26 HTA-R) (European Union, 2021).
As described above, an MS’ obligation to ‘give due consideration’ to a JCA report does not impede deviations from it if they are justified (Ernst and Stöger, Reference Ernst and Stöger2024). Based thereon, a national HTA institution can consider the JCA report (though not the underlying evidence) irrelevant for its HTA procedure if it considers the exclusion or inclusion of a conflicted expert in the JCA procedure as incompatible with the objective of ensure the JCA’s highest scientific quality. Subsequently, if the respective regulatory framework so provides, the national HTA institution can involve such experts (either the same person or other experts with comparable expertise) in their own HTA procedure. Legal remedies for HTDs to challenge such decisions in case of, eg., a subsequently negative reimbursement decision, are to be provided and sought at national level (see the section ‘Non-consideration of JCA reports and JCA-related evidence by MSs’).
4. Implications for patient access
4.1. PICO disparities and deviations from JCA reports
A key objective of the HTA-R and the JCA framework concerns the improvement of patient access to new health technologies (recital 36 HTA-R; see also recitals 22, 26 JCA-IR) (European Commission, 2024a; European Union, 2021). Despite the contribution to ‘timely availability’ of such technologies being an explicit goal of coordinating the marketing authorisation and JCA procedures (recital 36 HTA-R) (European Union, 2021), the process – provided due compliance with the respective deadlines – encompasses a lengthy period of >300 days (Monteil, Reference Monteil2024). However, re-initiation after discontinuation (article 10.7 HTA-R) may stretch the timeline by up to six months (European Union, 2021). This alone harbours potential for impeding patient access acceleration as intended by the HTA-R.
However, this effect could be mitigated if due to the JCA, national market access procedures manage to offset the longer centralised procedure. This is possible since most available evidence relevant to the MSs should be provided in the JCA report, and in accordance with their responsibilities concerning HTA procedures (recital 26 HTA-R), each country can weight that evidence within their national context (European Union, 2021). National HTA institutions are faced with the challenge to adapt their HTA procedures in a way to duly consider JCA reports in a transparent manner (Desmet et al., Reference Desmet, Brijs, Vanderdonck, Tops, Simoens and Huys2024). Based on reported positioning of national HTA institutions, some MSs (eg., Germany, France) are poised to use JCA reports as a supplementary tool to their own HTA processes, while others (eg., Netherlands, Poland, Spain) intend to consider them more extensively, or even as the sole basis for a health technology’s clinical value appraisal (Cosset et al., Reference Cosset, Janssen, Sirena and Masutti2024; Severens et al., Reference Severens, Dillon, Meyer, Jommi, Lipska, Canonico, Solà-Morales and Altmann2025). In theory, this provides a ‘common starting point’ for national HTA procedures (Willemsen et al., Reference Willemsen, Rutten-van Mölken, Al Dulaimi, Schelleman, Goettsch and Timmers2025). However, given the heterogeneity of HTA procedures across MSs regarding the application of clinical value assessments and pharmaco-economic evaluations (Sarri et al., Reference Sarri, Vinals, Leisle, Chau, Smalbrugge, Lucassen and Jemiai2025), the timing and extent of incorporating and considering JCA findings in national procedures may differ (Ahnert and Subbotina, Reference Ahnert and Subbotina2023; Jakubowski et al., Reference Jakubowski, Holko, Nowak, Warmuth, Dooms, Salminen, Cortial, Selke, Georgi, Magnússon, Crisafulli, Strijbosch, Mueller, Grieve, Danés and Kawalec2024).
While the incorporation of JCA findings in national HTA procedures might yield accelerated decision-making and, thus, patient access in some MSs, PICO disparities in the JCA and respective national practice might squander this potential. As discussed above, the obligation to give due consideration to a JCA report under article 13.1(a) HTA-R is legally non-binding (recital 31 HTA-R) (European Union, 2021); however, national HTA institutions must reasonably justify the extent of a JCA’s (non-)consideration (Ernst and Stöger, Reference Ernst and Stöger2024; European Court of Justice, 2006; Korkea-aho, Reference Korkea-aho2018). While PICO disparities can serve as such justification, the national HTA procedure would require additional evidence suited for the relevant PICOs. Corresponding requests with the purpose of performing complementary analyses beyond the JCA’s scope (recitals 15, 30 HTA-R) are not incompatible with article 13.1(d) HTA-R (European Union, 2021); however, these increase the workload on the national HTA institution and the relevant HTD. This is exacerbated by differing regulatory criteria concerning the choice of comparator across MSs (Eberle et al., Reference Eberle, Hagemann, Schweitzer, Justl, Maurer, Carls and Reuter2025) and a lack of harmonisation regarding HTA templates and evidence requirements at EU and national level (Schuster, Reference Schuster2024). Additionally, HTDs might be required to allocate resources to markets where, due to potentially negative assessment outcomes and reimbursement decisions, access might remain uncertain (Morgese et al., Reference Morgese, Majors and Patel2025).
If the JCA and the respective national HTA procedure are performed in succession, this situation could lead to a prolonged HTA and decision-making procedure, delaying patient access. However, given that the JCA procedure does not influence an MS’ responsibility regarding national HTA procedures (recital 26 HTA-R) (European Union, 2021), national HTA institutions are not barred from initiating domestic procedures while the JCA is still ongoing. Moreover, while the HTA-R considers the JCA ‘one of several preparatory steps in a multi-step procedure’ preparing national decision-making, the framework does not regulate when a national HTA procedure, including additional data collection, should be initiated in relation to the JCA. Hence, based on recitals 15, 26, and 30 HTA-R (European Union, 2021), a national HTA institution can request additional evidence not covered by the JCA scope once the scoping process under article 8 HTA-R has been concluded, and the need for such additional evidence is clear.
Such an approach is consistent with the Dutch practice of ‘parallel procedure’, enabling HTDs to submit evidence for HTA during an ongoing marketing authorisation procedure for the purpose of accelerating patient access (Zorginstituut Nederland, n.d.). Hence, based on the HTA-R framework, national HTA institutions have the legal possibility to adapt their HTA procedures to accommodate for PICO disparities. However, the success of such adaptations in practice would be dependent on the HTD’s capacity and willingness to provide evidence in parallel HTA procedures at both EU and national level. Given the observed reluctance of HTDs to engage in the Dutch ‘parallel procedure’, this capacity and willingness is doubtful (Willemsen et al., Reference Willemsen, Rutten-van Mölken, Al Dulaimi, Schelleman, Goettsch and Timmers2025).
4.2. Conflicts of interest of experts
As discussed above, the relevant HTA-R and CoI-IR provisions offer a pathway for involving conflicted individual experts, aiming to balance impartiality requirements and the scarcity of human resources with the necessary expertise for involvement in a JCA to ensure its scientific excellence (articles 7.3, 8.5 CoI-IR) (European Commission, 2024b). However, there is a risk of misaligned priorities if individual experts from small MSs are (or become) caught in a CoI and subsequently excluded from a JCA despite their expertise ensuring the JCA’s required scientific quality. In such cases, patient preferences and relevant clinical perspectives related to these MSs are at risk of being ignored or considered less significant. Consequently, the JCA report might not sufficiently reflect these preferences and perspectives. Considering that HTA-related responsibilities solely lie with the MSs (recital 26 HTA-R) (European Union, 2021), this might burden the respective MSs with additional data collection and elicitation of clinical and patient-related perspectives for their national HTA procedures (recitals 15, 30 HTA-R) (European Union, 2021), potentially delaying the subsequent reimbursement decision-making procedure to the detriment of patient access.
This risk could be mitigated through consistent involvement of European umbrella organisations representing patients or clinical experts in a JCA. The legal basis for their involvement is provided by article 8 (regarding the JCA procedure as a whole) and article 9.1 (concerning the scoping process) JCA-IR (see also recital 15 JCA-IR) (European Commission, 2024a); moreover, their inclusion reflects their growing role in clinical trial design and national HTA procedures (Severens et al., Reference Severens, Dillon, Meyer, Jommi, Lipska, Canonico, Solà-Morales and Altmann2025). Moreover, HTDs could (as an anticipatory measure) engage with stakeholders and prepare solid dossiers for national HTA procedures to account for individual experts being excluded, although their input would have been relevant for the required scientific excellence, and to appropriately represent perspectives of (small) MSs (Lipska et al., Reference Lipska, Meyer, Canonico, Altmann and Solà-Morales2025; Schuster, Reference Schuster2024).
5. Concluding thoughts
The aim of this study was to investigate legal implications of current important issues regarding the performance of JCAs under the HTA-R and its implementing regulations. In this regard, we focused on disparities of PICOs across MSs within the JCA scope and on CoIs of individual experts. Additionally, we explored implications of these issues on patient access to newly authorised health technologies that are subject to JCAs.
Under the JCA framework, MSs retain full responsibility over their national HTA procedures (recital 26 HTA-R) (European Union, 2021); the obligation to give due consideration to a JCA report (article 13.1(a) HTA-R) does not reflect a legally binding character (see recital 31 HTA-R), but rather an MS’ duty to explain and justify the extent of its incorporation in the respective national HTA procedure (Ernst and Stöger, Reference Ernst and Stöger2024; European Union, 2021). Hence, PICO disparities across MSs, reflected particularly by heterogeneity in comparators, may increase the burden on both HTDs to generate and provide additional relevant evidence, and on national HTA bodies to collect and assess additional data within their national procedures beyond the evidence provided at European level. Subsequently delayed or (permanently) discontinued JCA procedures and prolonged national HTA processes may impede the HTA-R’s objective of accelerated patient access. Legal action following a negative reimbursement decision due to a JCA report not being given due consideration without sufficient justification must be sought at national level. Additionally, strict handling of CoI rules regarding stakeholders and experts may put MSs with smaller expert resource pools at a disadvantage, as their perspectives may remain unheard in JCA procedures. Corresponding relevant stakeholder input would require elicitation in national HTA procedures.
A systematic and purpose-oriented interpretation and application of the provisions within the HTA-R framework, while considering the legal character of a JCA, provides clarity on the use and incorporation of JCA-related reporting and evidence in national HTA procedures. Encompassing PICO scoping and a prioritisation of the required scientific excellence in the selection of internal experts may alleviate the burden related to national HTA. Ultimately, considering the perspectives of all MS in JCA procedures could facilitate more streamlined HTA procedures at a national level and thus, contribute to faster market and patient access in MSs.
Acknowledgements
The authors wish to thank James Evans, Despoina Makridaki, and Anna Mirabile (all affiliated with the European Association of Hospital Pharmacists) for their contributions to this manuscript.
Financial support
This paper was created as part of the ASCERTAIN project. The ASCERTAIN project is funded by the European Union (HORIZON-HLTH-2022-IND-13-03). Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HaDEA). Neither the European Union nor the granting authority can be held responsible for them. Grant Agreement 101094938.
Competing interests
Nicolas S.H. Xander has no competing interests to declare. Carin A. Uyl-de Groot and Maureen P.M.H. Rutten-van Mölken have no personal conflicts of interest, but the institute for Medical Technology Assessment received funding from the following companies in 2023–2024: Astellas, AstraZeneca, Bayer, Boehringer lngelheim, Gilead, Janssen Cilag, Merck, Novartis, Roche and Sanofi. Nenad Miljković and Louis Bertin have no competing interests to report.
Author contributions
All authors contributed to the study conception and design. Literature search and legal analysis was performed by NX. The first draft of the manuscript was written by NX. All other authors critically reviewed and commented on the manuscript. All authors read and approved the final manuscript.
Ethical standards
No ethical approval was required for this study.
Data availability statement
All data collected for this study is exclusively based on publicly accessible legislation and publications.
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