Peter J. Neumann

Objectives: Cost-effectiveness thresholds inform whether health interventions represent good value for money, yet their use varies across countries. This study compares thresholds cited in published cost-effectiveness analyses (CEAs) in the United States with those in countries designated as the Most Favored Nations (MFNs) under the 2025 President's Executive Order on prescription drug pricing. Methods: We analyzed 6876 cost-per-QALY studies published between 1979 and 2023 from the Tufts CEA Registry. We standardized thresholds as multiples of each country's GDP per capita, and used logistic regression to estimate the probability of citing a threshold >1 × GDP per capita, adjusting for region, intervention type, disease area, and study period. Results: Over time, MFN studies shifted toward citing lower thresholds, whereas US thresholds consistently cited thresholds >1 × GDP per capita. After adjusting for other factors, MFN studies were less likely to cite higher thresholds than US studies. Cancer-related CEAs and CEAs of pharmaceutical interventions were more likely to cite higher thresholds. Conclusions: CEAs in the United States and peer high-income nations cite remarkably different thresholds, with MFNs citing lower value benchmarks over time. Policymakers should be cautious about adopting pricing policies that would implicitly subject US pharmaceutical spending to benchmarks developed in different institutional and fiscal contexts.

Introduction: Prescription drug list prices, often cited in policy discussions, do not account for rebates negotiated between manufacturers and payers. Methods: This study examines factors influencing rebates in the US, focusing on specialty drugs – i.e., high priced therapies (often biologics) for which payers issue specific coverage policies. Rebate data came from SSR Health and drug attributes from the Tufts Medical Center Specialty Drug Evidence and Coverage Database. We stratified rebate data by drug type and characteristics. Results: We identified 161 drugs found in SSR Health and SPEC as of December 2023. We found that rebates vary substantially across drugs (median of 27%, IQR 16-53%). Biosimilar and originator drugs have the highest, most variable rebates (median of 71%, IQR 53-79%), while rebates for cancer treatments and orphan drugs are lower (medians of 19% and 23%, respectively) and vary less (IQR of 12-28% and 14-29%, respectively). Drugs that face more competition from alternative options within the same therapeutic class, are self- administered, or received Food and Drug Administration (FDA) approval further in the past have higher rebates. Conclusion: Our findings indicate that rebates are sizeable and vary along several dimensions, many relating to market competition, complicating policy discussions around drug pricing.

Caregivers can play an important role in supporting and caring for people with progressive, life-threatening, or debilitating conditions. However, this supportive role can expose caregivers to various detrimental financial, physical, and psychosocial issues. When evaluating medical technologies for reimbursement decisions, health technology assessment (HTA) agencies typically focus on the treatment’s impact on patients and ignore or downplay the impact on caregivers. Including caregiver impacts within a wider societal perspective may better enable health systems to maximize health benefits from available resources. However, the lack of clear guidance or methodological recommendations from decision makers on the inclusion of caregiver impacts limits the number of HTA submissions that consider these effects. We outline a conceptual framework based on intensity and duration of caregiving to guide researchers, industry, and decision makers when developing policies for the inclusion of caregiver outcomes and justify their inclusion based on expected caregiver burden in identified circumstances.

Introduction Studies have reported health-related quality-of-life impacts of Duchenne muscular dystrophy (DMD); however, further research is needed to understand how those with DMD experience their condition and how psychosocial impacts evolve over time in response to disease progression. This qualitative study explores the social and emotional implications of key transitions, challenges and adaptations throughout the disease course from the perspective of patients and family caregivers. Methods Semi-structured interviews were conducted with men and boys with DMD, and/or their caregivers, in the USA. Thematic analysis was used to examine patterns in data collected across the interviews. Results Nineteen participants were included. Three major themes were identified: (1) barriers to participation are multifaceted; (2) an emotional journey shaped by ‘inevitable progression;' (3) family provides critical tangible and emotional support. This study illustrates that psychosocial impacts of DMD are shaped by knowledge of the condition’s natural history alongside other factors including the extent of social barriers, personal growth and adaptation, and family support. Conclusions Findings provide insight into the strength and resilience with which individuals and their families respond to daily challenges and major clinical milestones and highlight the relative importance of loss of upper limb function as a transition in DMD affecting health-related quality-of-life.

Context: The Food and Drug Administration (FDA)'s accelerated-approval pathway expedites patient access to promising treatments. However, increasing use of this pathway has challenged the Medicare program, which often pays for expensive therapies despite substantial uncertainty about benefits and risks to Medicare beneficiaries. We examined approaches to improve coordination between the FDA and Centers for Medicare and Medicaid Services (CMS) for drugs granted accelerated approval.Methods: We argue that policymakers have focused on expedited pathways at the FDA without sufficient attention to complementary policies at the CMS. Although differences between the FDA and CMS decisions are to be expected given the agencies' different missions and statutory obligations, procedural improvements can ensure that Medicare beneficiaries have timely access to novel therapies that are likely to improve health outcomes. To inform policy options and recommendations, we conducted semistructured interviews with stakeholders to capture diverse perspectives on the topic.Findings: We recommend ten areas for consideration: clarifying the FDA's evidentiary standards; strengthening FDA authorities; promoting earlier discussions among the FDA, the CMS, and drug companies; improving Medicare's coverage with evidence development program; tying Medicare payment for accelerated-approval drugs to evidence generation milestones; issuing CMS guidance on real-world evidence; clarifying Medicare's "reasonable and necessary" criteria; adopting lessons from international regulatory-reimbursement harmonization efforts; ensuring that the CMS has adequate staffing and expertise; and emphasizing equity.Conclusions: Better coordination between the FDA and CMS could improve the transparency and predictability of drug approval and coverage around accelerated-approval drugs, with important implications for patient outcomes, health spending, and evidence generation processes. Improved coordination will require reforms at both the FDA and CMS, with special attention to honoring the agencies' distinct authorities. It will require administrative and legislative actions, new resources, and strong leadership at both agencies.