Approximately 10–20% of individuals suffering from COVID-19 develop prolonged symptoms known as long COVID or post-COVID condition (LC). This review aimed to assess healthcare resource use (HCRU) and healthcare costs associated with LC. Because LC is not clearly defined and often remains undiagnosed, studies reporting on long-term follow-up of individuals with a COVID-19 diagnosis were also included. Among the 41 publications included, 36 reported on HCRU and 16 on costs. Individuals with LC had significantly elevated HCRU and healthcare costs vs. controls without a COVID-19 diagnosis over ≥15 months, with a 7.6–13.1% increase in total healthcare costs per person per month as assessed by difference-in-difference analysis. Among studies that did not specifically refer to LC, having a COVID-19 diagnosis was associated with a significant 4–10% increase in long-term total HCRU over 6–8 months and a 1.3- to 2.9-fold relative increase in total healthcare costs over 6 months. Due to the heterogeneity of the included studies, high-quality evidence is needed to better understand the economic burden of LC. In the absence of effective treatments, prioritizing the prevention of acute COVID-19, e.g., through vaccination, may be crucial for preventing LC and the associated long-term HCRU and medical spending.

The Joint Clinical Assessment (JCA) evaluates the relative effectiveness (RE) of interventions over comparators. While randomised control trials (RCTs) are considered the gold standard, single-arm trials (SATs) require an external control for accurate RE estimation. This study reviewed Health Technology Assessment (HTA) outcomes for medicinal products supported by SATs in France, Germany, Poland, and Spain, and simulated the JCA for these products based on evidence submitted in France. Among HTA evaluations published in France in 2019–2024, 16% were SAT-driven, and 5.6% of them included external controls. SAT-supported drugs had a high reimbursement approval rate (74%) and showed better HTA outcomes when controls were used. In Germany, 64% of SAT-based HTA outcomes indicated no added benefit and 30% a non-quantifiable benefit. In Poland and Spain, 63% and 72% HTA evaluations recommend reimbursement, respectively. Despite wide acceptance by Member States, experts determined that 94% of SAT-supported products would not qualify for JCA review due to insufficient evidence. Only 6% would qualify for JCA for a likely limited number of PICOs (Population–Intervention–Comparator–Outcome), but the certainty rating would be low. These findings suggest that SATs, as primary evidence, may not be suitable for JCA, potentially undermining HTA in EU Member States.

The Joint Clinical Assessment (JCA) evaluates the relative effectiveness (RE) of 4 interventions over comparators. While randomized control trials (RCTs) are considered 5 the gold standard, single-arm trials (SATs) require an external control for accurate RE 6 estimation. This study reviewed Health Technology Assessment (HTA) opinions for 7 medicinal products supported by SATs in France, Germany, Poland, and Spain, and 8 simulated the JCA assessment for these products based on evidence submitted in France. 9 Among HTA opinions published in France in 2019-2024, 16% were SAT-driven, and 5.6% 10 of them included external controls. SAT-supported drugs had a high reimbursement 11 approval rate (74%) and showed better HTA outcomes when controls were used. In 12 Germany, 64% of SAT-based opinions indicated no added benefit and 30% - non- 13 quatifiable benefit. In Poland and Spain, 63% and 72% opinions recommending 14 reimbursement, respectively. Despite wide acceptance by Member States, experts 15 determined that 94% of SAT-supported products would not qualify for JCA review due 16 to insufficient evidence. Only 6% would qualify for JCA for a likely limited number of 17 PICOs (Population-Intervention-Comparator-Outcome), but the certainty rating would be 18 low. These findings suggest that SATs, as primary evidence, may not be suitable for JCA, 19 potentially undermining HTA assessments in EU Member States.

The Joint Clinical Assessment (JCA), introduced by Regulation (EU) 2021/2282, is often presented as a procedurally neutral input that leaves national health technology (HTA) appraisal and decision-making untouched. This paper argues that this neutrality is only apparent. Because national appraisal systems differ profoundly in how they process evidence on relative effect and certainty, an identical JCA conclusion will not carry identical consequences across Member States. Germany’s IQWiG/G-BA system, tightly structured around confidence intervals, endpoint categories and certainty grading, shares the JCA’s own vocabulary and therefore has comparatively little room to reinterpret a JCA conclusion once issued. Systems built around broader clinical deliberative frameworks — as in France, Italy, and countries with formal cost-effectiveness components — retain greater latitude to contextualise, weigh or offset the same conclusion. This asymmetry is practical and epistemic rather than legal: the JCA remains formally non-binding, yet its methodological architecture may be more readily absorbed by some national traditions than others. The paper argues that this risk — uniform in form, divergent in the interpretive latitude it leaves Member States — deserves explicit attention while JCA practice and methodological guidance are still being established, and proposes measures to make the JCA’s methodological choices more transparent to rule-based and deliberative systems alike.