Bruno Falissard

Rationale: Health technology assessment (HTA) is the principal instrument wealthy health systems use to decide what to fund, and it measures the health a technology adds for treated patients rigorously. Yet population‐health considerations—disease burden, prevention, externalities such as herd protection, fairness between groups, and democratically chosen priorities—are weakly built into how HTA judges value. Aims and Objectives: To specify the nature of this gap and to offer a conceptual framework that clarifies it: to distinguish three paradigms of value assessment (clinical, cost‐effectiveness and public‐health HTA), and to separate two frequently conflated ideas—respecting public‐health priorities versus yielding to political pressure. Methods: A conceptual analysis informed by a narrative reading of HTA methodological guidance and the health‐economics, public‐health and priority‐setting literatures. Results: First, contemporary HTA clusters around two paradigms—clinical assessment and cost‐effectiveness assessment—while a population‐health paradigm is named but instantiated in no major agency's reference case. Second, public‐health objectives (burden, prevention, transmission externalities, distribution, priorities) are only partially operationalised—acknowledged but rarely weighed in the formal value calculation. Third, the three‐paradigm model shows the gap is systematic, not incidental: today's methods ask “how much does it help the patient?” and “how much health per euro?”, seldom “how do we improve population health, fairly?”. Fourth, the gap is tractable—the necessary instruments exist and are compatible with opportunity cost, and two common objections (that QALYs already capture population value, and that priorities equal interference) do not withstand scrutiny. Conclusion: A public‐health‐informed HTA—explicit disease‐burden assessment, transmission modelling, transparent treatment of priorities and formal equity analysis—could better align appraisal with population health, fairly distributed. We call on EUPHA and HTAi to convene a joint working group.

Objectives. Regulation (EU) 2021/2282 introduces the Joint Clinical Assessment (JCA), a common descriptive clinical evaluation that Member States must take into account in national appraisal. Because national health technology assessment (HTA) systems have developed distinct methodologies, their alignment with the JCA is uncertain. We characterised it across six European jurisdictions and interpreted how the pattern arose. Methods. Qualitative comparative study combining structured expert-consensus rating with documentary process tracing. Two EU-HTA methodologists derived 35 methodological dimensions in five domains from the Regulation, its Implementing Regulation and HTA Coordination Group guidance, fixing and source-tracing the JCA reference position for each before any national rating. Expert pairs in six jurisdictions (France, Germany, Italy, Spain, the Netherlands and England) rated their system against every reference position by consensus, on an anchored three-point qualitative alignment scale. Reporting follows the SRQR. Results. Germany was aligned on 33 of 35 dimensions, with no substantial divergence. England was most distant (23 substantially divergent), followed by France (18); Italy and the Netherlands were intermediate (14 each). Spain recorded no aligned dimension but the fewest substantial divergences of any non-German system (7), diverging in degree rather than in kind. Divergence concentrated in the domains the JCA excludes and in appraisal posture, yet German proximity persisted once these were removed (27 of 29; 19 of 20). Documentary evidence on the legislative compromise, EUnetHTA21 methodological production and subgroup leadership suggests the JCA has emerged as a German-compatible default rather than a neutral synthesis of national traditions. Conclusions. National methodologies align with the JCA to markedly different degrees, the closest fit being the most codified national model. The alignment finding is empirical, the influence account interpretive; neither ranks any national model as superior. Because divergence concentrates where national appraisal remains sovereign, the framework may displace methodological heterogeneity downstream rather than resolve it.

Background: Health care professionals must consider multiple dimensions of prevention when consulting with adolescents. Identifying risky behaviors early in adolescence is crucial for reducing both morbidity and mortality. General practitioners are increasingly eager to incorporate digital tools for prevention into their consultations with adolescents; however, the relevance and clinical validity of these digital tools are not always established or well-known. Consequently, primary care professionals require guidance and support in selecting relevant mobile health (mHealth) tools. Objective: The aim of this study is to identify relevant and useful digital apps to help primary care professionals detect at-risk adolescents across all recommended areas of prevention: orthopedics, mental health, substance abuse, risk behaviors, sexual health, vaccinations, social relationships, and nutrition. Methods: A systematic review of smartphone apps, with an analysis of content quality, was carried out by 4 researchers using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The App Store and Google Play Store platforms were surveyed. The inclusion criteria were as follows: free of charge, date of last update, availability in French or English, relevance of the preventive approach to adolescents, and scientific validation. Four health care professionals assessed the apps: 2 selected the apps relevant to health care professionals, then 3 analyzed these apps using the French version of the Mobile App Rating Scale (MARS-F). Intraclass correlation coefficient, model (2,1) (2-way random effects, absolute agreement, single measures); standard error of measurement; and mean absolute error were also calculated. Results: A total of 976 apps were identified, 49 of which had disappeared from the platforms prior to analysis. Nine apps were retained. Seven (0.72%) were included after evaluation using the MARS-F: 2 on mental health and 5 on sexual health (including 3 on contraception only). The mean MARS-F interrater score ranged from 2.5/5 to 3.8/5. The global MARS-F score demonstrated a pooled SD of 0.60 and an intraclass correlation coefficient (2,1) of 0.0003, resulting in a calculated standard error of measurement of 0.60. The average discrepancy between raters was a mean absolute error of 0.53. Conclusions: No similar studies have been identified in the literature that specifically focus on mobile apps designed to support health care professionals in delivering preventive care to adolescents. Of the 8 areas of prevention identified as relevant for adolescents, only 3 are addressed by the apps validated through our methodology (5 focus on sexual health). Consequently, current apps are insufficient to support health care professionals in their overall preventive work with adolescents. Such a review should be conducted systematically prior to the development of any new tool to prevent duplication and channel creative efforts toward truly innovative digital solutions. Furthermore, a thorough analysis of relevant, recommended websites is essential, as these resources complement the use of mobile apps designed for health care professionals.

Background: Major depressive disorder (MDD) is highly prevalent and associated with significant disability and mortality. Treatment-resistant depression (TRD), defined as inadequate response to ⩾2 antidepressant lines, remains a major therapeutic challenge. Esketamine nasal spray, approved in 2019 for TRD, demonstrated efficacy and safety in randomized trials, but real-world evidence remains limited. Objectives: The ELLIPSE study aimed to describe patient characteristics, treatment patterns, and 12-month outcomes of esketamine in routine clinical practice in France. Design: ELLIPSE was a prospective, multicenter, observational cohort study including adults with unipolar MDD initiating esketamine between Dec 2021 and Jul 2023, followed for 12 months. Methods: Data were collected via standardized clinical assessments. Effectiveness was evaluated using the Montgomery–Åsberg Depression Rating Scale (MADRS). Response was defined as ⩾50% MADRS reduction; remission as MADRS ⩽ 10. Results: A total of 200 patients (mean age 46.6 years; 56.5% female) were enrolled; 97.5% met TRD criteria. Median esketamine exposure was 4.5 months. Mean MADRS decreased from 31.9 at baseline to 12.4 at month 12 (mean change −17.9; 95% CI: −21.6 to −14.2). Response and remission rates reached a plateau at month 2, where the response rate was 55.2% and the remission rate was 33.6%, maintained up to month 12. Adverse events (AEs) occurred in 65.7% of patients, most commonly dissociative states (28.0%) and transient blood pressure increases (11.6%). Conclusion: This real-world study in patients with treatment-resistant depression, including those with comorbidities/prior suicide attempts, showed clinically relevant improvement from month 2, sustained through 12 months. Dissociative symptoms were the most frequent treatment-related AE.

Health technology assessment is a discipline that has developed, over five decades, an elaborate scientific and institutional identity centered on the evaluation of clinical evidence, comparative effectiveness, and economic value

Rationale. Health technology assessment (HTA) is the principal instrument wealthy health systems use to decide what to fund, and it measures the health a technology adds for treated patients rigorously. Yet population-health considerations—disease burden, prevention, externalities such as herd protection, fairness between groups, and democratically chosen priorities—are weakly built into how HTA judges value. Aims and objectives. To specify the nature of this gap and to offer a conceptual framework that clarifies it: to distinguish three paradigms of value assessment (clinical, cost-effectiveness and public-health HTA), and to separate two frequently conflated ideas—respecting public-health priorities versus yielding to political pressure. Method. A conceptual analysis informed by a narrative reading of HTA methodological guidance and the health-economics, public-health and priority-setting literatures. Results. First, contemporary HTA clusters around two paradigms—clinical assessment and cost-effectiveness assessment—while a population-health paradigm is named but instantiated in no major agency’s reference case. Second, public-health objectives (burden, prevention, transmission externalities, distribution, priorities) are only partially operationalised—acknowledged but rarely weighed in the formal value calculation. Third, the three-paradigm model shows the gap is systematic, not incidental: today’s methods ask “does it help the patient?” and “how much health per euro?”, seldom “how do we improve population health, fairly?”. Fourth, the gap is tractable—the necessary instruments exist and are compatible with opportunity cost, and two common objections (that QALYs already capture population value, and that priorities equal interference) do not withstand scrutiny. Conclusion. A public-health-informed HTA—explicit disease-burden assessment, transmission modelling, transparent treatment of priorities and formal equity analysis—could better align appraisal with population health, fairly distributed. We call on EUPHA and HTAi to convene a joint working group.

Rationale. Evidence-based medicine (EBM) and health technology assessment (HTA) rest on a positivist epistemology in which value is treated as objective, measurable and generalisable across populations. This framing struggles to represent how individual patients construct the meaning and value of health states. Aims and Objectives. To analyse the epistemological tension between positivist and constructivist approaches to evidence, value and decision-making in EBM and HTA, and to examine its consequences for clinical practice and reimbursement. Method. Conceptual analysis. A philosophical account of positivism and constructivism was combined with six illustrative clinical vignettes drawn from clinical practice and selected to make the tension visible, and each vignette was mapped onto the methodological rules that govern HTA. Results. Across the vignettes, valid positivist endpoints (survival, relapse rates, quality-adjusted life years) systematically diverged from what individual patients valued (dignity, identity, meaning, cultural belonging). Utility weights, surrogate endpoints and cost-effectiveness rules could not represent this constructed value; and HTA, in turn, shapes clinical practice through reimbursement, service availability and opposable guidance. Modern HTA increasingly incorporates patient involvement, patient-reported outcomes, discrete choice experiments, deliberative processes and multi-criteria decision analysis, but these remain structurally secondary to population-level quantitative evidence. Conclusion. Positivism and constructivism are complementary rather than opposed. A more pluralist HTA — one that makes preference heterogeneity, experienced utility and the underlying facts, norms and values explicit — would be more, not less, evidence-based, and would widen the room clinicians have to practise person-centred care. The vignettes are pedagogical illustrations, not empirical evidence.

The European Health Technology Assessment (EU HTA) guidance on Multiplicity of Hypothesis Testing (MHT)

Background: The EU Health Technology Assessment Regulation (EU-HTA R), effective January 2025, mandates Joint Clinical Assessments (JCAs) to harmonize HTA across Member States. However, its implementation raises fundamental questions about methodological coherence, institutional capacity, and epistemological alignment. Objectives: This manuscript (1) systematically assesses whether the stated strategic and operational objectives of the EU-HTA R are achievable under current implementation conditions; (2) examines the implications for EU institutional legitimacy if these objectives are not met; and (3) proposes an epistemological framework as a prerequisite for developing a coherent joint HTA methodology. Methods: We conducted a critical policy analysis of the EU-HTA R, its implementing guidance documents, and published templates, supplemented by a comparative review of Member State HTA methodologies and their underlying philosophical foundations. Results: The analysis reveals that the EU-HTA R is unlikely to achieve its strategic goals under current conditions. Key findings include: guidance documents of substandard methodological quality; a restricted assessment scope that excludes scientific judgement and contextualization; insufficient resources and additional workload for national HTA bodies without reducing existing obligations; unresolved epistemological divergences among Member States spanning Bayesian vs. frequentist approaches, Fisher vs. Neyman–Pearson frameworks, and utilitarian vs. deontological ethical foundations; and procedural shortcomings in stakeholder consultation and expert involvement. These shortcomings risk undermining the epistemic authority and legitimacy of EU institutions. Conclusions: Prior epistemological and normative alignment across Member States is a prerequisite for any robust shared HTA methodology. Revisions to the EU-HTA R and comprehensive updates of guidance documents are necessary, with concrete safeguards—including independent peer review, identified authorship, and adequate resourcing—to ensure substantive rather than merely nominal implementation. A phased roadmap is proposed: establishing clear objectives, aligning epistemological foundations, developing institutional structures, and creating operationally consistent guidance.