Background Class III cardiovascular device premarket approval (PMA) studies often fail to fully represent the intended-use population (IUP) owing to low enrollment of racial and ethnic minority subjects and women. The impact of research site selection on this is unknown. Objectives In this study, we sought to determine if site characteristics predict enrollment of demographic minority and female participants in coronary stent PMA trials and evaluate if site selection could improve representation of the IUP. Methods We pooled data from 8,859 U.S. participants enrolled in 9 pivotal coronary stent PMA studies (2003-2018) across 196 sites. Site characteristics included U.S. region, surrounding county demographics, teaching status, Veterans Administration affiliation, trial volume, female principal investigator (PI) involvement, and number of acute hospital beds. Multivariable regression identified predictors of minority and female enrollment. Participant-to-prevalence ratios (PPRs) were modeled under varying site selection scenarios. Results Minority participants (12%; PPR = 0.48) and women (30%; PPR = 0.77) were underrepresented. Minority enrollment varied markedly across sites and was predicted by West and South regions, county minority population, population density, and per-capita income (R2 = 0.50; P < 0.001). Modeling estimated that reallocating enrollment from low to high minority-enrolling sites could normalize Black and Hispanic representation (PPRs ≥0.80) without compromising that of non-Hispanic Whites (PPR = 1.00). Female enrollment showed less variation and was poorly predicted by research site characteristics and site PI gender (non-VA status only; R2 = 0.095; P < 0.001); however there were few female PIs (<6%), limiting correlation. Conclusions Coronary stent PMA studies do not fully reflect the IUP, owing to marked underrepresentation of minority participants and modest underrepresentation of women. Because minority enrollment is influenced by site characteristics, targeted site selection could improve representation; however, improving female enrollment requires alternative strategies. These insights have implications on the planning and design of future cardiovascular device trials.

Objective A lack of transparent reporting of race and ethnicity in clinical research limits the ability to identify health inequities and evaluate to what extent clinical research includes diverse populations. Our objectives are: (1) to identify study characteristics associated with reporting race and ethnicity of clinical study participants and (2) to document temporal trends in race and ethnicity reporting on ClinicalTrials.gov.Design Cross-sectional analysis of interventional trials and observational studies from 2009 to 2024; multivariable logistic regression assessed study-level factors associated with reporting race and ethnicity.Setting Global registry of clinical studies (ClinicalTrials.gov).Participants 58 163 studies with posted results and without early termination.Exposures Study characteristics: sponsor trial phase, study type and country.Main outcomes and measures Reporting of race, reporting of ethnicity, reporting of both.Results Among 58163 studies (mean enrolment=1215 participants), 44.8% did not report race or ethnicity to the repository (mean enrolment=1481 participants). The proportion of studies reporting both race and ethnicity rose from 7.4% in 2013 to 54.6% in 2024. In multivariable models, observational studies had lower odds of reporting race and ethnicity (OR 0.55, 95% CI 0.49 to 0.61) compared with interventional trials. Phase 4 trials were least likely phase to report race and ethnicity (OR=0.32; 95% CI 0.29 to 0.35), and studies with only National Institute of Health funding were more likely to report race and ethnicity compared with studies with any industry funding or sponsorship (OR=1.70, 95% CI 1.61 to 1.79). For studies that reported race, White participants comprised ≥50% each year based on study-level percentages; proportions of Asian participants declined, and Black participants fluctuated. ‘Not Hispanic or Latino’ remained ≥80% of reported ethnicity annually.Conclusions Race and ethnicity reporting on ClinicalTrials.gov has improved markedly yet remains incomplete, with shortfalls in late-phase and observational studies.

This Viewpoint discusses developing better evidence about appropriate use of stimulants, understanding and reducing nonmedical use of these medications, and responding to shortages.

Collaboration between the FDA and other stakeholders could improve the way in which evidence is generated and interventions are developed and implemented to help address common chronic diseases.

This Viewpoint discusses declining vaccination rates in the US, specifically against COVID-19, and the ways in which clinicians and the Food and Drug Administration can counter the current large volume of vaccine misinformation.

Despite enormous advances in biomedical science, corresponding improvements in health outcomes lag significantly. This is particularly true in the United States, where life expectancy trails far behind that of other high-income countries. In addition, substantial disparities in life expectancy and other health outcomes exist as a function of race, ethnicity, wealth, education, and geographic location. A major reformation of our national system for generating medical evidence-the clinical research enterprise-is needed to facilitate the translation of biomedical research into useful products and interventions. Currently, premarket systems for generating and evaluating evidence work reasonably well, but the postmarket phase is disaggregated and often fails to answer essential questions that must be addressed to provide optimal clinical care and public health interventions for all Americans. Solving these problems will require a focus on three key domains: (1) improving the integration of and access to high-quality data from traditional clinical trials, electronic health records, and personal devices and wearable sensors; (2) restructuring clinical research operations to support and incentivize the involvement of patients and frontline clinicians; and (3) articulating ethical constructs that enable responsible data sharing to support improved implementation. Finally, we must also address the systemic tendency to optimize individual components of the clinical research enterprise without considering the effects on the system as a whole. Overcoming suboptimization by creating incentives for integration and sharing will be essential to achieve more timely and equitable improvement in health outcomes.

In Reply The Letter from Drs Berenbrok and Mormer describes a care delivery model, versions of which are currently being promoted at the University of Pittsburgh, 1,2 the University of Maryland, 3 and elsewhere nationally, that involves educating and empowering pharmacists to serve as a front-line interface with consumers seeking hearing aids, and as a conduit for appropriate referrals to audiologists and otologists when needed.We agree with Berenbrok and Mormer that this represents a promising approach.As we noted in our Viewpoint, 4 many people could potentially benefit from hearing aid technology.While continued efforts aimed at developing and advancing therapeutic technologies are essential, it is also urgent to improve delivery of these therapeutics to ensure that all persons, including those who are part of marginalized communities or who experience geographic challenges in accessing care, are able to benefit from them and receive the best care possible.Furthermore, these improvements will require the combined efforts of the clinical, research, and technology development communities, and additional investigations will be needed to determine the best service delivery models for maximizing benefit for consumers. 4 With regard to collaboration between pharmacists, audiologists, and otologists, we particularly welcome health services and implementation science research to better understand the optimal health care team configuration to deliver the best care across various populations, and to ensure that expert guidance is readily accessible by patients and consumers when needed.

In Reply The Letter from Drs Berenbrok and Mormer describes a care delivery model, versions of which are currently being promoted at the University of Pittsburgh, 1,2 the University of Maryland, 3 and elsewhere nationally, that involves educating and empowering pharmacists to serve as a front-line interface with consumers seeking hearing aids, and as a conduit for appropriate referrals to audiologists and otologists when needed.We agree with Berenbrok and Mormer that this represents a promising approach.As we noted in our Viewpoint, 4 many people could potentially benefit from hearing aid technology.While continued efforts aimed at developing and advancing therapeutic technologies are essential, it is also urgent to improve delivery of these therapeutics to ensure that all persons, including those who are part of marginalized communities or who experience geographic challenges in accessing care, are able to benefit from them and receive the best care possible.Furthermore, these improvements will require the combined efforts of the clinical, research, and technology development communities, and additional investigations will be needed to determine the best service delivery models for maximizing benefit for consumers. 4 With regard to collaboration between pharmacists, audiologists, and otologists, we particularly welcome health services and implementation science research to better understand the optimal health care team configuration to deliver the best care across various populations, and to ensure that expert guidance is readily accessible by patients and consumers when needed.

In this Viewpoint, authors from the FDA discuss how COVID-19 vaccination is an integral part of establishing a new normal, now that SARS-CoV-2, the virus that causes COVID-19, will likely circulate worldwide for the foreseeable future.

Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real‐world evidence (RWE) in the evaluation of new treatments or products. The RWE label has been used to refer to a variety of departures from the methods of traditional randomized controlled trials. Recognizing this complexity and potential confusion, the National Academies of Science, Engineering, and Medicine convened a series of workshops to clarify and address questions regarding the use of RWE to evaluate new medical treatments. Those workshops identified three specific dimensions in which RWE studies might differ from traditional clinical trials: use of real‐world data (data extracted from health system records or data captured by mobile devices), delivery of real‐world treatment (open‐label treatments delivered in community settings by community practitioners), and real‐world treatment assignment (including nonrandomized comparisons and variations on random assignment such as before‐after or stepped‐wedge designs). For any RWE study, decisions regarding each of these dimensions depends on the specific research question, characteristics of the potential study settings, and characteristics of the settings where study results would be applied.

Changes that accompany older age can alter the pharmacokinetics (PK), pharmacodynamics (PD), and likelihood of adverse effects (AEs) of a drug. However, older adults, especially the oldest or those with multiple chronic health conditions, polypharmacy, or frailty, are often under-represented in clinical trials of new drugs. Deficits in the current conduct of clinical evaluation of drugs for older adults and potential steps to fill those knowledge gaps are presented in this communication. The most important step is to increase clinical trial enrollment of older adults who are representative of the target treatment population. Unnecessary eligibility criteria should be eliminated. Physical and financial barriers to participation should be removed. Incentives could be created for inclusion of older adults. Enrollment goals should be established based on intended treatment indications, prevalence of the condition, and feasibility. Relevant clinical pharmacology data need to be obtained early enough to guide dosing and reduce risk for participation of older adults. Relevant PK and PD data as well as patient-centered outcomes should be measured during trials. Trial data should be analyzed for differences in PK, PD, effectiveness, and safety arising from differences in age or from the presence of conditions common in older adults. Postmarket evaluations with real-world evidence and drug labeling updates throughout the product lifecycle reflecting new knowledge are also needed. A comprehensive plan is needed to ensure adequate evaluation of the safety and effectiveness of drugs in older adults.

BackgroundThe General Anxiety Disorder-7 (GAD-7) questionnaire is a standard tool used for screening and follow-up of patients with Generalized Anxiety Disorder (GAD). Although it is generally accepted that anxiety correlates with clinical and psychosocial stressors, precise quantitative data is limited on the relations among GAD-7, traditional biomarkers, and other measures of health. Further research is needed about how GAD-7 relates to race, ethnicity, and socioeconomic status (SES) as an assembly. We determined how multiple demographic and socioeconomic data correlate with the participants' GAD-7 results when compared with laboratory, physical function, clinical, and other biological markers.MethodsThe Project Baseline Health Study (BHS) is a prospective cohort of adults representing several populations in the USA. We analyzed a deeply phenotyped group of 2502 participants from that study. Measures of interest included: clinical markers or history of medical diagnoses; physical function markers including gait, grip strength, balance time, daily steps, and echocardiographic parameters; psychometric measurements; activities of daily living; socioeconomic characteristics; and laboratory results.ResultsHigher GAD-7 scores were associated with female sex, younger age, and Hispanic ethnicity. Measures of low SES were also associated with higher scores, including unemployment, income ≤$25,000, and ≤12 years of education. After adjustment for 158 demographic, clinical, laboratory, and symptom characteristics, unemployment and overall higher SES risk scores were highly correlated with anxiety scores. Protective factors included Black race and older age.LimitationsCorrelations identified in this cross-sectional study cannot be used to infer causal relationships; further, we were not able to account for possible use of anxiety treatments by study participants.ConclusionsThese findings highlight the importance of understanding anxiety as a biopsychosocial entity. Clinicians and provider organizations need to consider both the physical manifestations of the disorder and their patients' social determinants of health when considering treatment pathways and designing interventions.

Objectives We assessed the relationship between the Patient Health Questionnaire-9 (PHQ-9) at intake and other measurements intended to assess biological factors, markers of disease and health status. Design, setting and participants We performed a cross-sectional analysis of 2365 participants from the Baseline Health Study, a prospective cohort of adults selected to represent major demographic groups in the USA. Participants underwent deep phenotyping on demographic, clinical, laboratory, functional and imaging findings. Importance Despite extensive research on the clinical implications of the PHQ-9, data are limited on the relationship between PHQ-9 scores and other measures of health and disease; we sought to better understand this relationship. Interventions None. Main outcomes and measures Cross-sectional measures of medical illnesses, gait, balance strength, activities of daily living, imaging and laboratory tests. Results Compared with lower PHQ-9 scores, higher scores were associated with female sex (46.9%–66.7%), younger participants (53.6–42.4 years) and compromised physical status (higher resting heart rates (65 vs 75 bpm), larger body mass index (26.5–30 kg/m 2 ), greater waist circumference (91–96.5 cm)) and chronic conditions, including gastro-oesophageal reflux disease (13.2%–24.7%) and asthma (9.5%–20.4%) (p<0.0001). Increasing PHQ-9 score was associated with a higher frequency of comorbidities (migraines (6%–20.4%)) and active symptoms (leg cramps (6.4%–24.7%), mood change (1.2%–47.3%), lack of energy (1.2%–57%)) (p<0.0001). After adjustment for relevant demographic, socioeconomic, behavioural and medical characteristics, we found that memory change, tension, shortness of breath and indicators of musculoskeletal symptoms (backache and neck pain) are related to higher PHQ-9 scores (p<0.0001). Conclusions Our study highlights how: (1) even subthreshold depressive symptoms (measured by PHQ-9) may be indicative of several individual- and population-level concerns that demand more attention; and (2) depression should be considered a comorbidity in common disease. Trial registration number NCT03154346 .

Abstract Because of significant adaptations forced by the COVID-19 pandemic, resultant changes within health care delivery and clinical research introduced the potential for evaluation of novel evidence generation approaches in oncology. On July 26 and 27, 2021, the National Academies of Science, Engineering, and Medicine, National Cancer Policy Forum hosted a virtual workshop entitled “Cancer Care and Cancer Research in the Context of the COVID-19 Pandemic: A Workshop on Lessons Learned.” This workshop examined changes in cancer care and cancer research that occurred in response to the COVID-19 pandemic and considered lessons learned from that experience. The goal was to identify what changes could improve the delivery of high-quality cancer care and the conduct of cancer clinical trials in the postpandemic era, with an emphasis on health equity. How can we sustain the valuable lessons learned that might accelerate progress and enhance clinical evidence generation for patients and clinicians? In this overview, we discuss ways in which the COVID-19 experience has catalyzed research efficiencies as well as fostered a broader array of trial design and research methods that may facilitate improved cancer drug development during the pandemic and beyond.

Earlier this year, when I was confirmed as the new commissioner of the US Food and Drug Administration (FDA), the world faced ongoing public health issues related to the pandemic and war in Ukraine, among other challenges. Most notably, the US is experiencing a flattening or decline in life expectancy compared with other high-income countries. As part of a wider effort to reverse this decline, relationships between FDA and the biomedical ecosystem should be reimagined to facilitate more effective translation of science into successful health interventions.