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Rationale: Women, older individuals, and racial and ethnic minority groups are often underrepresented in research studies. Objectives: We evaluated the demographics and diversity of participants enrolled in randomized controlled trials (RCTs) and observational studies published by investigators in association with the Canadian Critical Care Trials Group. Methods: We performed quantitative content analysis of peer-reviewed RCTs and observational studies from December 1994 to December 2022. For each publication, we extracted participant demographic variables, including sex, gender, age, race or ethnicity, sexual orientation, pregnancy status, language proficiency, income/financial status, housing, education, disability, and geography. Results: A total of 120 publications (28 RCTs, 92 observational studies) included 211,144 enrolled participants. Most (107 of 120; 89.2%) were multicenter studies, and 70% (84 of 120) were conducted exclusively in Canadian centers; 77.5% (93 of 120) studies enrolled adult participants, and 19.2% (23 of 120) enrolled pediatric participants. All studies reported participant mean or median age, 118 (98.3%) reported binary sex or gender, and 9 (7.5%) reported race or ethnicity. No justification was provided in 35 studies that listed pregnancy as an exclusion. There was infrequent reporting of housing ( n  = 4), employment ( n  = 2), income ( n  = 2), and education ( n  = 1). No studies reported the language proficiency, sexual orientation, disability, or geography of participants. Of the studies reporting gender, women and/or girls comprised 42.3% participants (range, 8.9-67.7%). Within nine studies reporting race or ethnicity of 2,950 participants, 59.7% were White, 8% South Asian, 7% Indigenous, 3% Asian, 1% Black, 14% unknown, and 6% "other." Conclusions: Research publications from the Canadian Critical Care Trials Group infrequently report important participant demographics, and diversity of research participants is disproportionate compared with Canadian societal demographics.

Background: Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer., Methods: A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model., Results: Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18-94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65-80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%)., Conclusions: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials., (© 2021. The Author(s).)

Objective: To investigate sociodemographic characteristics and physical and mental health indicators between participants and nonparticipants of a large-scale 2-year exercise RCT including noninvited women living in nearby rural area in Finland., Study Design and Setting: From a previous OSTPRE study cohort, 914 women (aged 72-84) participated in Kuopio Fall Prevention Study in 2016-2019. The participants were compared to non-participants (n = 4,536) and noninvited OSTPRE women (n = 7,119) living outside the urban recruitment area., Results: Participants were younger (P< 0.001) with higher education (P< 0.001) and had more often regular hobbies (P< 0.001) and physical exercising (P< 0.001) than nonparticipants or noninvited. They reported better functional capability (P< 0.001), mental (P< 0.001) and subjective health (P< 0.001), lower number of medications (P< 0.001), less fear of falls (P< 0.001), but more frequent falls (P= 0.002) and more often musculoskeletal diseases (P= 0.006).  Participants also showed better functional capacity in the clinical measurements. In register analysis, urban-rural differences in the prevalence of diseases were detected., Conclusion: In population-based exercise interventions, participants are more likely to be better off in respect to physical and mental wellbeing, functional capability and sociodemographic status. Recruiting participants only from cities increases unavoidable selection bias due to urban-rural differences which should be noticed when interpreting and generalizing RCT results., Trial Registration Number: ClinicalTrials.gov identifier NCT02665169., (Copyright © 2021. Published by Elsevier Inc.)

Objective: to characterize randomized controlled trials (RCTs) that did not report the overall number of participants assessed for eligibility and to identify factors associated with higher enrollment rates., Study Design and Setting: Systematic review and meta-analysis of RCTs in several pre-defined fields in internal medicine. We randomly extracted 360 articles that were published in 2017. Trials that reported numbers of assessed for eligibility patients were compared with those who did not. Recruitment rates were calculated in order to investigate whether they were associated with trial characteristics., Results: A total of 360 RCTs were included. Only 2-thirds of the trials (242/360) reported the number of patients assessed for eligibility. Trials reporting eligibility data had better methodology, reported on the tested hypothesis, included a placebo arm, evaluated soft outcomes, published their findings in higher impact journals and recruited a higher number of randomized patients than those who did not. Recruitment rates in 225 (62.5%) trials enabling their calculation, were significantly higher in trials sponsored by industry, conducted in multiple centers and countries, including inpatients, tested non-inferiority hypothesis, included a placebo arm, and evaluated surrogate outcomes., Conclusions: Reporting of participant eligibility continues to be scarce. Inadequate reporting was associated with poor methodological characteristics in trials., (Copyright © 2021. Published by Elsevier Inc.)

What Is Known and Objective: The discussion about health equity in the United States frequently involves concerns over racial and ethnic minority under-representation in clinical trials and particularly in trials conducted in support of product approvals. The FDA has long worked to encourage diverse participation in clinical trials and through its Drug Trials Snapshots (DTS) program, the U.S. Food and Drug Administration (FDA) has moved to make trial demographic data more accessible and transparent. We conducted a demographic study of U.S. participants in clinical trials for FDA-approved new drugs (new molecular entities [NMEs], and original Biologics License Applications [BLAs]) from 2015 to 2019, as reported in DTS database with a purpose of understanding the extent to which U.S.-based trials used to support product approvals represent the racial and ethnic diversity of the U.S. population by therapeutic area., Methods: Participant-level trial data were collected by accessing the FDA electronic common technical document (eCTD), for the applications used to publish each Snapshot. The therapeutic area (TA) for each drug was determined by review division assignment. The demographic data were analysed and compared to U.S. census data., Results and Discussion: We examined 102,596 U.S. participants in trials of new drugs that were approved and presented in Drug Trials Snapshots between 2015 and 2019. White participation ranged from 51% in psychiatric trials to 90% in cardiovascular (CV) trials; Black or African American participation ranged from 5% in medical imaging to 45% in psychiatric trials; Asian participation ranged from 0.75% in CV to 4% in dermatologic trials; and Hispanic or Latino participation ranged from 1% in medical imaging to 22% in infectious diseases and gastroenterology trials., What Is New and Conclusion: Our data showed variable representation of racial and ethnic minorities across therapeutic areas at the U.S. sites. Blacks or African Americans were represented at or above U.S. census estimates across most therapeutic areas, while Asians and American Indian or Alaska Natives were consistently underrepresented. Hispanic or Latino participation across most therapeutic areas was below U.S. census estimates, however, more variable, and a sizable proportion of data was missing. The next step is a comparison of trial participation based on disease prevalence and epidemiology, which is a more accurate assessment of trial diversity., (© 2021 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Interventions designed to limit the spread of coronavirus disease 2019 (COVID-19) are having profound effects on the delivery of health care, but data showing the impact on oncology clinical trial enrollment, treatment, and monitoring are limited. We prospectively tracked relevant data from oncology clinical trials at Dana-Farber Cancer Institute from January 1, 2018, to June 30, 2020, including the number of open trials, new patient enrollments, in-person and virtual patient visits, dispensed investigational infusions, dispensed or shipped oral investigational agents, research biopsies, and blood samples. We ascertained why patients came off trials and determined on-site clinical research staffing levels. We used 2-sided Wilcoxon rank sum tests to assess the statistical significance of the reported changes. Nearly all patients on interventional treatment trials were maintained, and new enrollments continued at just under one-half the prepandemic rate. The median number of investigational prescriptions shipped to patients increased from 0 to 74 (range = 22-107) per week from March to June 2020. The median number of telemedicine appointments increased from 0 to 107 (range = 33-267) per week from March to June 2020. Research biopsies and blood collections decreased dramatically after Dana-Farber Cancer Institute implemented COVID-19-related policies in March 2020. The number of research nurses and clinical research coordinators on site also decreased after March 2020. Substantial changes were required to safely continue clinical research during the pandemic, yet we observed no increases in serious adverse events or major violations related to drug dosing. Lessons learned from adapting research practices during COVID-19 can inform industry sponsors and governmental agencies to consider altering practices to increase operational efficiency and convenience for patients., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The inclusion of participants who are Black, Indigenous people of color, and participants of various ethnicities is a priority of federally sponsored research., Objective: This study aimed to describe the reporting of race and ethnicity in federally funded research published by the Eunice Kennedy Shriver National Institute of Child Health and Human Development-funded Pelvic Floor Disorders Network., Study Design: Pelvic Floor Disorders Network publications were reviewed to determine whether race or ethnicity was reported. The number of participants included in each manuscript who were identified as White, Black, Asian, American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and "other," and the number of participants who identified as having Hispanic ethnicity were recorded. Data were analyzed by publication and by the pelvic floor disorder investigated, including urinary incontinence, pelvic organ prolapse, fecal incontinence, pregnancy-related pelvic floor disorders, and multiple pelvic floor disorders. Many publications reported on overlapping patient populations, which included primary trials and secondary analyses and studies. Data were analyzed both by counting participants every time they were reported in all papers and by counting the unique number of participants in only the original trials (primary paper published)., Results: A total of 132 Pelvic Floor Disorders Network publications were published between 2003 and 2020. Of these, 21 were excluded because they were methods papers or described research without participants. Of the 111 remaining articles, 90 (81%) included descriptions of race and 55 (50%) included descriptions of ethnicity. All 13 primary trials described race and 10 of 13 (76.9%) described ethnicity. Of those publications that described race, 50 of 90 (56%) included only the categories of "White," "Black," and "Other," and 14 of 90 (16%) only described the percentage of White patients. Of the 49,218 subjects, there were 43,058 (87%) with reported race and 27,468 (56%) with reported ethnicity. Among subjects with race and ethnicity reported, 79% were reported as White, 9.9% as Black, 0.4% as Asian, 0.1% as American Indian or Alaska Native, and 4% as "other," whereas 13% were reported to be of Hispanic ethnicity. The racial and ethnic diversity varied based on the pelvic floor disorder studied (P<.01), which was driven by pregnancy-related and fecal incontinence studies because these had lower proportions of White patients than studies of other pelvic floor disorders., Conclusion: Federally funded Pelvic Floor Disorders Network research does not consistently report the race and ethnicity of participants. Even in the publications that report these characteristics, Black, Indigenous people of color, and people of Hispanic ethnicity are underrepresented. Consistent reporting and recruitment of a diverse population of women is necessary to address this systemic inequity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The National Health Service demonstrated that regions of the United Kingdom with the highest number of patients enrolled in research studies had the lowest risk-adjusted mortality when patients were admitted to the hospital. Our goal was to investigate if this correlation was evident for patients with chronic limb threatening ischemia (CLI) treated in the United States (US). Accordingly, we examined correlations among sites participating in the Best Endovascular versus best Surgical Therapy in patients with Critical (BEST-CLI) trial, a multicenter, National Institute of Health-sponsored, international randomized controlled trial (RCT) comparing revascularization strategies in patients with CLI, and regional rates of major amputation from CLI., Methods: We measured regional participation in the BEST-CLI trial by evaluating trial participation and enrollment rosters. To determine regional rates of lower limb amputation, we queried the Medicare database (2007-2016) for patients with concurrent peripheral arterial disease (PAD) and diabetes, then assessed how many had lower extremity amputations. Correlation of regional amputation rates with distribution of BEST-CLI sites in four US geographical regions was calculated using Pearson's correlation coefficients. Simple regression equations were used to calculate the significance of these correlation coefficients., Results: Of 9,231,909 CLI patients, 342,406 underwent amputation in the Medicare dataset. Amputation rates per 1000 CLI patients differed by region (South 40.42, Midwest 40.12, West 34.81, Northeast 31.14). There were 116 US vascular centers, selected by volume and expertise that participated in BEST-CLI with the following distribution: South (n = 30, 26%), Midwest (n = 26, 22%), West (n = 29, 25%), and Northeast (n = 31, 27%). There was a negative correlation between the number of amputations per 1000 for Medicare CLI patients with diabetes and PAD and the number of BEST-CLI sites in the region which trended toward significance (Pearson R= -0.61, P = 0.39)., Conclusions: Amputation rate among Medicare CLI patients is inversely correlated with US BEST-CLI site distribution. Higher participation in clinical research, especially within large RCTs, may be a marker of optimal PAD management., Competing Interests: Conflicts of Interest: A.F.: Consultant for Sanifit. Matthew Menard: Scientific Advisory Board for Janssen; K.R.: multiple conflicts to be delivered under separate cover; No conflicts: J.S., M.E., P.G., M.S., M.V., M.V., T.H. report no conflicts., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To use the Theoretical Domains Framework (TDF) to identify barriers and enablers to participant retention in trials requiring questionnaire return and/or attendance at follow-up clinics., Study Design and Setting: We invited participants (n = 607) from five pragmatic effectiveness trials, who missed at least one follow-up time point (by not returning a questionnaire and/or not attending a clinic visit), to take part in semistructured telephone interviews. The TDF informed both data collection and analysis. To establish what barriers and enablers most likely influence the target behavior the domain relevance threshold was set at >75% of participants mentioning the domain., Results: Sixteen participants (out of 25 showing interest) were interviewed. Overall, seven theoretical domains were identified as both barriers and enablers to the target behaviors of attending clinic appointments and returning postal questionnaires. Barriers frequently reported in relation to both target behaviours stemmed from participants' knowledge, beliefs about their capabilities and the consequences of performing (or not performing) the behavior. Two domains were identified as salient for questionnaire return only: goals; and memory, attention and decision-making. Emotion was identified as relevant for clinic attendance only., Conclusion: This is the first study informed by behavioural science to explore trial participants' accounts of trial retention. Findings will serve as a guiding framework when designing trials to limit barriers and enhance enablers of retention within clinical trials., (Copyright © 2021. Published by Elsevier Inc.)

Background: Large, randomized controlled trials (RCTs) are essential in answering pivotal questions in child health., Methods: We created a bird's eye view of all large, noncluster, nonvaccine pediatric RCTs with ≥1000 participants registered in ClinicalTrials.gov (last search January 9, 2020). We analyzed the funding sources, countries, outcomes, publication status, and correlation with the pediatric global burden of disease (GBD) for eligible trials., Results: We identified 247 large, nonvaccine, noncluster pediatric RCTs. Only 17 mega-trials with ≥5000 participants existed. Industry funding was involved in only 52 (21%) and exclusively funded 47 (19%) trials. Participants were from high-income countries (HICs) in 100 (40%) trials, from lower-middle-income countries (LMICs) in 122 (49%) trials, and from both HICs and LMICs in 19 (8%) trials; 6 trials did not report participants' country location. Of trials conducted in LMIC, 43% of investigators were from HICs. Of non-LMIC participants trials (HIC or HIC and LMIC), 39% were multicountry trials versus 11% of exclusively LMIC participants trials. Few trials (18%; 44 of 247) targeted mortality as an outcome. 35% (58 of 164) of the trials completed ≥12 months were unpublished at the time of our assessment. The number of trials per disease category correlated well with pediatric GBD overall (ρ = 0.76) and in LMICs (ρ = 0.69), but not in HICs (ρ = 0.29)., Conclusions: Incentivization of investigator collaborations across diverse country settings, timely publication of results of large pediatric RCTs, and alignment with the pediatric GBD are of pivotal importance to ultimately improve child health globally., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Importance: Representative enrollment in clinical trials is critical to ensure equitable and effective translation of research to practice, yet disparities in clinical trial enrollment persist., Objective: To examine person-level factors associated with invitation to and participation in clinical trials., Design, Setting, and Participants: This cross-sectional study analyzed responses from 3689 US adults who participated in the nationally representative Health Information National Trends Survey, collected February through June 2020 via mailed questionnaires., Exposures: Demographic, clinical, and health behavior-related characteristics., Main Outcomes and Measures: History of invitation to and participation in a clinical trial, primary information sources, trust in information sources, and motives for participation in clinical trials were described. Respondent characteristics are presented as absolute numbers and weighted percentages. Associations between respondent demographic, clinical, and health behavior-related characteristics and clinical trial invitation and participation were estimated using survey-weighted logistic regression models., Results: The median (IQR) age of the 3689 respondents was 48 (33-61) years, and most were non-Hispanic White individuals (2063 [59%]; non-Hispanic Black, 452 [10%]; Hispanic, 521 [14%]), had more than a high school degree (2656 [68%]), were employed (1809 [58%]), and had at least 1 medical condition (2535 [61%]). Overall, 439 respondents (9%) had been invited to participate in any clinical trial. Respondents with increased odds of invitation were non-Hispanic Black compared with non-Hispanic White (adjusted odds ratio [aOR], 1.85; 95% CI, 1.13-3.02), had greater than a high school education compared with less than high school education (eg, ≥college degree: aOR, 4.84; 95% CI, 1.89-12.39), were single compared with married or living as married (aOR, 1.68; 95% CI, 1.04-2.73), and had at least 1 medical condition compared to none (eg, 1 medical condition: aOR, 2.25; 95% CI, 1.32-3.82). Respondents residing in rural vs urban areas had 77% decreased odds of invitation to a clinical trial (aOR 0.33; 95% CI 0.17-0.65). Of invited respondents, 199 (47%) participated. Compared with non-Hispanic White respondents, non-Hispanic Black respondents had 72% decreased odds of clinical trial participation (aOR, 0.28; 95% CI, 0.09-0.87). Respondents most frequently reported "health care providers" as the first and most trusted source of clinical trial information (first source: 2297 [59%]; most trusted source: 2597 [70%]). The most frequently reported motives for clinical trials participation were "wanting to get better" (2294 [66%]) and the standard of care not being covered by insurance (1448 [41%])., Conclusions and Relevance: The findings of this study suggest that invitation to and participation in clinical trials may differ by person-level demographic and clinical characteristics. Strategies toward increasing trial invitation and participation rates across diverse patient populations warrant further research to ensure equitable translation of clinical benefits from research to practice.

A growing number of studies within the field of gerontology have included samples recruited from Amazon's Mechanical Turk (MTurk), an online crowdsourcing portal. While some research has examined how younger adult participants recruited through other means may differ from those recruited using MTurk, little work has addressed this question with older adults specifically. In the present study, we examined how older adults recruited via MTurk might differ from those recruited via a national probability sample, the Health and Retirement Study (HRS), on a battery of outcomes related to health and cognition. Using a Latin-square design, we examined the relationship between recruitment time, remuneration amount, and measures of cognitive functioning. We found substantial differences between our MTurk sample and the participants within the HRS, most notably within measures of verbal fluency and analogical reasoning. Additionally, remuneration amount was related to differences in time to complete recruitment, particularly at the lowest remuneration level, where recruitment completion required between 138 and 485 additional hours. While the general consensus has been that MTurk samples are a reasonable proxy for the larger population, this work suggests that researchers should be wary of overgeneralizing research conducted with older adults recruited through this portal.

This article aims to evaluate "racial", ethnic, and population diversity-or lack thereof-in psychosis research, with a particular focus on socio-environmental studies. Samples of psychosis research remain heavily biased toward Western, Educated, Industrialized, Rich, and Democratic (WEIRD) societies. Furthermore, we often fail to acknowledge the lack of diversity, thereby implying that our findings can be generalized to all populations regardless of their social, ethnic, and cultural background. This has major consequences. Clinical trials generate findings that are not generalizable across ethnicity. The genomic-based prediction models are far from being applicable to the "Majority World." Socio-environmental theories of psychosis are solely based on findings of the empirical studies conducted in WEIRD populations. If and how these socio-environmental factors affect individuals in entirely different geographic locations, gene pools, social structures and norms, cultures, and potentially protective counter-factors remain unclear. How socio-environmental factors are assessed and studied is another major shortcoming. By embracing the complexity of environment, the exposome paradigm may facilitate the evaluation of interdependent exposures, which could explain how variations in socio-environmental factors across different social and geographical settings could contribute to divergent paths to psychosis. Testing these divergent paths to psychosis will however require increasing the diversity of study populations that could be achieved by establishing true partnerships between WEIRD societies and the Majority World with the support of funding agencies aspired to foster replicable research across diverse populations. The time has come to make diversity in psychosis research more than a buzzword., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Importance: Participants in clinical trials may experience benefits associated with new therapeutic strategies as well as tight adherence to best supportive care practices., Objectives: To investigate whether participation in a clinical trial is associated with improved survival among children with neuroblastoma and investigate potential recruitment bias of patients in clinical trials., Design, Setting, and Participants: This cohort study included pediatric patients with intermediate- or high-risk neuroblastoma in North American studies who were included in the International Neuroblastoma Risk Group Data Commons and who received a diagnosis between January 1, 1991, and March 1, 2020., Exposure: Enrollment in a clinical trial., Main Outcomes and Measures: Event-free survival and overall survival (OS) of patients with intermediate- or high-risk neuroblastoma enrolled in an up-front Children's Oncology Group (COG) clinical trial vs a biology study alone were analyzed using log-rank tests and Cox proportional hazards regression models. The racial/ethnic composition and the demographic characteristics of the patients in both groups were compared., Results: The cohort included 3058 children with intermediate-risk neuroblastoma (1533 boys [50.1%]; mean [SD] age, 10.7 [14.7] months) and 6029 children with high-risk neuroblastoma (3493 boys [57.9%]; mean [SD] age, 45.8 [37.4] months) who were enrolled in a Children's Oncology Group or legacy group neuroblastoma biology study between 1991 and 2020. A total of 1513 patients with intermediate-risk neuroblastoma (49.5%) and 2473 patients with high-risk neuroblastoma (41.0%) were also enrolled in a clinical trial, for a cohort total of 3986 of 9087 children (43.9%) enrolled in a clinical trial. The prevalence of prognostic markers for the clinical trial and non-clinical trial cohorts differed, although representation of patients from racial/ethnic minority groups was similar in both cohorts. Among patients with intermediate-risk neuroblastoma, OS was higher among those who participated in a clinical trial compared with those enrolled only in a biology study (OS, 95% [95% CI, 94%-96%] vs 91% [95% CI, 89%-94%]; P = .01). Among patients with high-risk neuroblastoma, participation in a clinical trial was not associated with OS (OS, 38% [95% CI, 35%-41%] in the clinical trial group vs 41% [95% CI, 38%-44%] in the biology study group; P = .23)., Conclusions and Relevance: Approximately 44% of patients in this large cohort of patients with neuroblastoma were enrolled in up-front clinical trials. Compared with children not enrolled in clinical trials, a higher prevalence of favorable prognostic markers was identified among patients with intermediate-risk neuroblastoma enrolled in clinical trials, and unfavorable features were more prevalent among patients with high-risk neuroblastoma enrolled in clinical trials. No evidence of recruitment bias according to race/ethnicity was observed. Participation in a clinical trial was not associated with OS in this cohort, likely reflecting the common practice of treating nontrial participants with therapeutic and supportive care regimens used in a previous therapeutic trial.

Importance: During the initial outbreak of the COVID-19 pandemic, cancer clinical trial participation decreased precipitously. Given the continued pandemic-especially the severe wave of new cases and deaths in winter 2020 to 2021-a vital question is whether trial enrollments have remained low or even worsened., Objective: To examine the experience of cancer clinical trial enrollment 1 year after the COVID-19 outbreak., Design, Setting, and Participants: This cohort study examines initial enrollments to treatment trials and cancer control and prevention (CCP) trials conducted by the SWOG Cancer Research Network between January 1, 2016, and February 28, 2021. Participants include patients enrolled in the trials., Exposures: Landmark time points reflecting the onset and the apex, respectively, of the initial COVID-19 wave (March 1 to April 25, 2020) and the winter 2020 to 2021 wave (October 4, 2020, to January 23, 2021)., Main Outcomes and Measures: This study used interrupted time-series analysis to examine enrollments over time related to the COVID-19-derived exposure variables using negative-binomial regression. Relative risk (RR) estimates representing weekly enrollment changes compared with expected rates (had the pandemic not occurred) were derived. The numbers of enrollments lost during the pandemic were estimated., Results: Overall, 29 398 patients (mean [SD] age, 60.3 [13.2] years) were enrolled (24 034 before the pandemic and 5364 during the pandemic), with 9198 patients (31.3%) aged 65 years or older, 17 199 female patients (58.6%), 3039 Black patients (10.8%), and 2260 Hispanic patients (7.9%). Most enrollments (19 451 [66.2%]) were to treatment trials. During the initial COVID-19 wave, there was a 9.0% model-estimated weekly reduction in enrollments (RR, 0.91; 95% CI, 0.89-0.93; P < .001), with effects compounding each week. Enrollment recovered thereafter, but decreased again during the winter 2020 to 2021 wave, although by only 2.0% each week (RR, 0.98; 95% CI, 0.97-0.99; P < .001). Overall, during the pandemic, actual enrollments were 77.3% of expected enrollments (5364 of 6913 enrollments; 95% CI, 70.5%-85.0%; P < .001). Actual enrollments were 54.0% of expected enrollments for CCP trials (1421 of 2641 enrollments; 95% CI, 43.0%-67.0%; P < .001) and 91.0% of expected enrollments for treatment trials (3922 of 4304 enrollments; 95% CI, 81.0%-102.0%; P = .12)., Conclusions and Relevance: In this cohort study, clinical trial enrollments decreased during the full year of the COVID-19 pandemic. Enrollment reductions were primarily to CCP trials, whereas, remarkably, there was not strong evidence of enrollment reductions to treatment trials. This finding suggests that clinical research rapidly adapted to the circumstances of enrolling and treating patients on protocols during the COVID-19 pandemic.

Importance: Although female representation has increased in clinical trials, little is known about how clinical trial representation compares with burden of disease or is associated with clinical trial features, including disease category., Objective: To describe the rate of sex reporting (ie, the presence of clinical trial data according to sex), compare the female burden of disease with the female proportion of clinical trial enrollees, and investigate the associations of disease category and clinical trial features with the female proportion of clinical trial enrollees., Design, Setting, and Participants: This cross-sectional study included descriptive analyses and logistic and generalized linear regression analyses with a logit link. Data were downloaded from the Aggregate Analysis of ClinicalTrials.gov database for all studies registered between March 1, 2000, and March 9, 2020. Enrollment was compared with data from the 2016 Global Burden of Disease database. Of 328 452 clinical trials, 70 095 were excluded because they had noninterventional designs, 167 936 because they had recruitment sites outside the US, 69 084 because they had no reported results, 1003 because they received primary funding from the US military, and 314 because they had unclear sex categories. A total of 20 020 interventional studies enrolling approximately 5.11 million participants met inclusion criteria and were divided into those with and without data on participant sex., Exposures: The primary exposure variable was clinical trial disease category. Secondary exposure variables included funding, study design, and study phase., Main Outcomes and Measures: Sex reporting and female proportion of participants in clinical trials., Results: Among 20 020 clinical trials from 2000 to 2020, 19 866 studies (99.2%) reported sex, and 154 studies (0.8%) did not. Clinical trials in the fields of oncology (46% of disability-adjusted life-years [DALYs]; 43% of participants), neurology (56% of DALYs; 53% of participants), immunology (49% of DALYs; 46% of participants), and nephrology (45% of DALYs; 42% of participants) had the lowest female representation relative to corresponding DALYs. Male participants were underrepresented in 8 disease categories, with the greatest disparity in clinical trials of musculoskeletal disease and trauma (11.3% difference between representation and proportion of DALYs). Clinical trials of preventive interventions were associated with greater female enrollment (adjusted relative difference, 8.48%; 95% CI, 3.77%-13.00%). Clinical trials in cardiology (adjusted relative difference, -18.68%; 95% CI, -22.87% to -14.47%) and pediatrics (adjusted relative difference, -20.47%; 95% CI, -25.77% to -15.16%) had the greatest negative association with female enrollment., Conclusions and Relevance: In this study, sex differences in clinical trials varied by clinical trial disease category, with male and female participants underrepresented in different medical fields. Although sex equity has progressed, these findings suggest that sex bias in clinical trials persists within medical fields, with negative consequences for the health of all individuals.

Introduction: Older adults, including racial and ethnic minorities, are underrepresented in research. As the US population ages, the number of older racial and ethnic minority individuals will increase. Including these individuals in research is an important step towards reducing health disparities., Methods: We used data from HealthStreet, a University of Florida community engagement program which uses community health workers to assess the health of the community, to assess willingness to participate in different types of health research by race/ethnicity. Descriptive statistics and logistic regression models were used to assess willingness to participate among adults aged 50 and older, by race/ethnicity (n = 4694)., Results: Our sample was 42.0% non-Hispanic White, 52.8% non-Hispanic Black, and 5.2% Hispanic. Non-Hispanic White participants reported more past research participation than non-Hispanic Black and Hispanic participants (28.7% vs. 19.0% and 19.2%, respectively). Compared with non-Hispanic White participants, non-Hispanic Black participants were less willing to participate in most types of studies, while Hispanic participants were less willing to participate in studies that might be seen as invasive (required blood sample, genetic sample, or participants to take medicine, or use of medical equipment)., Conclusions: Our study provides investigators with a general profile of research preferences by race/ethnicity; compared with non-Hispanic White individuals, non-Hispanic Black individuals are less willing to participate in most studies, while Hispanic individuals are less willing to participate in studies that may be seen as invasive or demanding. It is imperative to include diverse older adults in health research. By tailoring research based on preferences we can improve recruitment in underrepresented populations.

Background: Nurses are a difficult population to recruit for research. Barriers to recruitment of nurses include survey fatigue, hospital structures and institutional review boards as gatekeepers to accessing participants, and limited generalizability of findings. Social media present innovative opportunities to recruit participants for survey research. However, there is limited information about best practices for recruiting nurses through social media., Objectives: The aim of this report was to examine the advantages and disadvantages of and determine the best practices for recruiting nurses for survey studies via social media., Methods: We examined recruitment strategies of three survey studies involving nurse participants. Each study used social exchange theory and leverage-saliency theory to guide recruitment. The studies included were (a) the Travel Nurse Onboarding Study, which recruited participants from a single closed group on Facebook; (b) the Presenteeism and Nursing Study where participants were recruited using association listservs, healthcare organizations, and paid ads and postings on social media; and (c) the Pain and Nursing Study in which participants were recruited through social media, association listservs, and in person at conferences., Results: Social media offer accessible, low-cost, high-yield approaches to recruitment of nurses for survey studies., Discussion: Useful strategies for crafting effective recruitment via social media are presented, including how, where, when, and how often to post. The generalizability of social media research is also discussed. Suggestions are provided for researchers using social media as well as guidelines for institutional review boards to address gray areas of social media research. Data integrity protection techniques are proposed to ensure social media survey data are not corrupted by malicious bots. This report outlines best practices for the recruitment of nurses for survey studies using social media., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Adequate representation of demographic subgroups in premarketing and postmarketing clinical studies is necessary for understanding the safety and efficacy associated with novel cancer therapeutics., Objective: To characterize and compare the reporting of demographic data and the representation of individuals by sex, age, and race in premarketing and postmarketing studies used by the Food and Drug Administration (FDA) to evaluate novel cancer therapeutics., Design, Setting, and Participants: In this cross-sectional study, premarketing and postmarketing studies for novel cancer therapeutics approved by the FDA from 2012 through 2016 were identified. Study demographic information was abstracted from publicly available sources, and US cancer population demographic data was abstracted from US Cancer Statistics. Analyses were conducted from February 25 through September 21, 2020., Main Outcomes and Measures: The percentages of trials reporting sex, age, and race/ethnicity were calculated, and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of study participants in each demographic group by the percentage of the US cancer population in each group. PPRs were constructed for premarketing and postmarketing studies and by cancer type. Underrepresentation was defined as PPR less than 0.8., Results: From 2012 through 2016, the FDA approved 45 cancer therapeutics. The study sample included 77 premarketing studies and 56 postmarketing studies. Postmarketing studies, compared with premarketing studies, were less likely to report patient sex (42 studies reporting [75.0%] vs 77 studies reporting [100%]; P < .001) and race (27 studies reporting [48.2%] vs 62 studies reporting [80.5%]; P < .001). Women were adequately represented in premarketing studies (mean [SD] PPR, 0.91; 95% CI, 0.90-0.91) and postmarketing studies (mean PPR, 1.00; 95% CI, 1.00-1.01). Although older adults and Black patients were underrepresented in premarketing studies (older adults: mean PPR, 0.73; 95% CI, 0.72-0.74; Black patients: mean PPR, 0.32; 95% CI, 0.31-0.32), these groups continued to be underrepresented in postmarketing studies (older adults: mean PPR, 0.75; 95% CI, 0.75-0.76; Black patients: mean PPR, 0.21; 95% CI, 0.21-0.21)., Conclusions and Relevance: This study found that older adults and Black patients were underrepresented in postmarketing studies of novel cancer therapeutics to a similar degree that they were underrepresented in premarketing studies. These findings suggest that postmarketing studies are not associated with improvements to gaps in demographic representation present at the time of FDA approval.

Study Objectives: Hypothalamic amenorrhea is common in adolescents and young adults (AYAs) with anorexia nervosa (AN), and ovarian reserve is not routinely assessed. AN increases rates of fertility problems, but how or when AN negatively influences future fertility is unclear. We sought to determine whether biomarkers of ovarian reserve were impacted in AYA with AN., Design: Cross-sectional study., Setting: Tertiary care center., Participants: Females with AN and amenorrhea (n = 97) at the pre-intervention visit of a clinical trial, n = 19 females without an eating disorder or menstrual dysfunction., Main Outcome Measures: Serum anti-Müllerian hormone (AMH) concentrations., Results: AMH levels were higher in AYA with AN than unaffected adolescents (4.7 vs. 3.2 ng/mL; P = .03). Neither FSH nor inhibin B differed between groups. In 19.6% of participants with AN, AMH levels were elevated above the normal range (>6.78 ng/mL). These subjects had a longer disease duration than those with normal AMH levels (9 vs. 3 mos; P = .03); age or degree of malnutrition did not differ between AN subjects with normal or elevated AMH., Conclusions: AMH levels appear to be normal or elevated in AYA with AN. Low AMH in a patient with AN should raise clinical concern regarding ovarian reserve, and should not be attributed to degree of malnutrition alone. Currently, AMH is not regularly assessed during routine AN clinical care. However, our findings suggest some clinical utility in identifying those patients with reduced ovarian reserve. Potential links between the hypothalamic amenorrhea suffered by patients with AN and PCOS should be explored., (Copyright © 2021 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Study Objective: In this study we evaluated published studies about foster care to: (1) determine the types of data used; (2) describe the degree to which a sexual/reproductive health topic was addressed; and (3) describe the consent process., Design: Analysis of published literature., Setting: PubMed was searched using "foster care" for English articles published between January 1, 2017 and September 4, 2019., Participants: None., Interventions: None., Main Outcome Measures: Articles were coded into 4 data source categories: primary, secondary, peripheral, or perspective data. Articles with a primary data source were coded for participant ages: only 9 years old and younger, 10- to 17-year-olds (minor adolescents), and only 18 years old and older. Articles using a secondary data source were coded for the source of the data registry. All articles were coded for presence of a sexual/reproductive health outcome. The primary data articles that included minor adolescents were coded for the study topic and consent process., Results: Of the 176 articles about foster care, 72/176 (41%) used primary data, 53/176 (30%) used secondary data, and 51/176 (29%) used peripheral/perspective data. Forty-eight of the primary data articles included minor adolescents. Secondary data sources included few national research surveys. Sexual/reproductive health outcomes were measured in 17 articles, 4 of which used primary data. The consent process for minor adolescents varied and had no consistent pattern across studies., Conclusion: Research on best practices for consent processes and use of registries could be developed to increase research on sexual/reproductive health outcomes among adolescents in foster care., (Copyright © 2021 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

While artificial agents (AA) such as Artificial Intelligence are being extensively developed, a popular belief that AA will someday surpass human intelligence is growing. The present research examined whether this common belief translates into negative psychological and behavioral consequences when individuals assess that an AA performs better than them on cognitive and intellectual tasks. In two studies, participants were led to believe that an AA performed better or less well than them on a cognitive inhibition task (Study 1) and on an intelligence task (Study 2). Results indicated that being outperformed by an AA increased subsequent participants' performance as long as they did not experience psychological discomfort towards the AA and self-threat. Psychological implications in terms of motivation and potential threat as well as the prerequisite for the future interactions of humans with AAs are further discussed.

Research is important because it underpins evidence-based care. However, people who lack capacity to consent are often excluded from research, due partly to ethical concerns and practical challenges, and partly to a lack of awareness among professionals of the legal framework that supports their inclusion. The COVID-19 pandemic, which has extensively affected care home residents, has reinforced the importance of including older people with cognitive impairment in research. Nurses who care for older people with impaired cognition have an important role in ensuring these people have the opportunity to contribute to and benefit from research. This article discusses some of the challenges associated with the inclusion in research of older people who lack capacity to consent, including the involvement of relatives and friends in decision-making. The article describes the findings of recent research and shares resources with the aim of supporting nurses to ensure that older people in their care who lack capacity can participate in research., Competing Interests: None declared, (© 2020 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Climate change and population growth will increase vulnerability to natural and human-made disasters or pandemics. Longitudinal research studies may be adversely impacted by a lack of access to study resources, inability to travel around the urban environment, reluctance of sample members to attend appointments, sample members moving residence and potentially also the destruction of research facilities. One of the key advantages of longitudinal research is the ability to assess associations between exposures and outcomes by limiting the influence of sample selection bias. However, ensuring the validity and reliability of findings in longitudinal research requires the recruitment and retention of respondents who are willing and able to be repeatedly assessed over an extended period of time. This study examined recruitment and retention strategies of 11 longitudinal cohort studies operating during the Christchurch, New Zealand earthquake sequence which began in September 2010, including staff perceptions of the major impediments to study operations during/after the earthquakes and respondents' barriers to participation. Successful strategies to assist recruitment and retention after a natural disaster are discussed. With the current COVID-19 pandemic, longitudinal studies are potentially encountering some of the issues highlighted in this paper including: closure of facilities, restricted movement of research staff and sample members, and reluctance of sample members to attend appointments. It is possible that suggestions in this paper may be implemented so that longitudinal studies can protect the operation of their research programmes.

Major advances in cancer care often emerge from the development of novel targets. We randomly sampled 10% of cancer trials on clinicaltrials.gov with start dates 2013-2016 to determine the proportion of trials and research subjects directed at evaluating novel targets. We found that 87 of 378 trials (23.0%) enrolling 9225 of 44,525 patients (20.7%) tested interventions that are directed towards novel targets. 146 of 378 trials (38.6%) enrolling 19,132 of 44,525 patients (43.0%) investigated treatments that were not FDA approved but utilized a previously studied target for treating cancer. Combined, 233 of 378 trials (61.6%) enrolling 28,357 of 44,525 patients (63.9%) investigated treatments that were not FDA approved. Furthermore, 36 of 378 trials (9.5%) enrolling 6592 of 44,525 patients (14.8%) investigated FDA approved anticancer drugs in their approved indication and combination while 109 of 378 trials (28.8%) enrolling 9576 of 44,525 patients (21.5%) investigated FDA approved anticancer drugs outside of their approved indication or combination. Logistic regression found that phase 1 trials were significantly more likely to test novel target interventions than phase 2 and 3 trials (p value = 0.00197 and 0.00130 respectively). Industry sponsored trials were also significantly more likely to involve novel target interventions than non-industry trials (p value <0.001). In conclusion, most cancer trials involve unapproved treatments, but a majority of these treatments are well-characterized or involve a previously studied target to treat cancer.

Background: Informed consent forms (ICFs) are used to obtain consent from participants. However the complexity and comprehensiveness of these forms may not be appropriate. Readability can be quantified by formulas in Microsoft (MS) Word, such as the Flesch Reading Ease test. The South African (SA) ethics guidelines suggest that the MS Word Flesch-Kincaid Reading Grade score should be used to assess the complexity of ICFs and should be the equivalent of grade 8 level, or lower., Objectives: To use readability formulas to determine whether current SA ICFs are appropriate for the general population., Methods: This was a descriptive study of a sample of English ICFs (solicited from our studies, as well as from local researchers) which received approval from local ethical review boards during the past 5 years, for prospective (≥6 months) drug studies that explored treatment and prevention of HIV, tuberculosis, diabetes or cardiovascular disease. ICFs were evaluated in MS Word for Flesch Reading Ease and Flesch-Kincaid Reading Grade, with the Simple Measure of Gobbledygook (SMOG) index calculated using www.readabilityformulas.com. Recommended targets for easy readability are above 60 for the Flesch Reading Ease score, and less than or equal to a grade 8 reading level for the Flesch-Kincaid Reading Grade and SMOG., Results:   A total of 75 consent forms from 35 individual research studies conducted in SA over the last 5 years were included. The consent forms had been approved by six ethics committees across seven of the SA provinces. The median (interquartile range (IQR)) Flesch Reading Ease score was 55.8 (48.7 - 59.7) and 18 (25.0%) of the ICFs had easy or standard readability, while the median (IQR) Flesch-Kincaid Grade was 10.2 (8.8 - 11.4), with 23 (30.6%) at least a grade 8 level or lower. The median (IQR) SMOG index was 9.8 (9.0 - 11.1) and 4 (5.3%) scored below grade 8 level., Conclusions: Two-thirds of the ICFs from this study fail to meet the SA readability standard, a result matched by using alternative readability formulas. Readability can be improved with simple techniques and by actively monitoring readability metrics.

Randomized controlled trials (RCTs) enroll hundreds of millions of subjects and involve many human lives. To improve subjects' welfare, I propose a design of RCTs that I call Experiment-as-Market (EXAM). EXAM produces a welfare-maximizing allocation of treatment-assignment probabilities, is almost incentive-compatible for preference elicitation, and unbiasedly estimates any causal effect estimable with standard RCTs. I quantify these properties by applying EXAM to a water-cleaning experiment in Kenya. In this empirical setting, compared to standard RCTs, EXAM improves subjects' predicted well-being while reaching similar treatment-effect estimates with similar precision., Competing Interests: The author declares no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: The management of complex cartilage pathology in young, otherwise healthy patients can be difficult., Purpose: To determine the nature of the design, endpoints chosen, and rate at which the endpoints were met in published studies and ongoing clinical trials that investigate cartilage repair and restoration procedures., Study Design: Systematic review., Methods: A systematic review of the publicly available level I/II literature and of the publicly listed clinical trials regarding cartilage repair and restoration procedures for the knee was conducted adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Seventeen published studies and 52 clinical trials were included. Within the 17 published studies, the most common procedure studied was microfracture (MFX) + augmentation ( N = 5; 29.4%) and the most common comparison/control group was MFX ( N = 10; 58.8%). In total, 13 different cartilage procedure groups were evaluated. For published studies, the most common patient-reported outcome (PRO) measures assessed is the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analog Scale-Pain (VAS) ( N = 10 studies, 58.8% each, respectively). Overall, there are 10 different PROs used among the included studies. Ten studies demonstrate superiority, 5 demonstrate noninferiority, and 2 demonstrate inferiority to the comparison or control groups. For the clinical trials included, the most common procedure studied is MFX + augmentation ( N = 16; 30.8%). The most common PRO assessed is KOOS ( N = 36 trials; 69.2%), and overall there are 24 different PROs used among the included studies., Conclusions: Recently published studies and clinical trials evaluate a variety of cartilage repair and restoration strategies for the knee, most commonly MFX + augmentation, at various time points of outcome evaluation, with KOOS and VAS scores being used most commonly. MFX remains the most common comparison group for these therapeutic investigations. Most studies demonstrate superiority versus comparison or control groups. Understanding the nature of published and ongoing clinical trials will be helpful in the investigation of emerging technologies required to navigate the regulatory process while studying a relatively narrow population of patients.

Race plays an important role in how people think, develop, and behave. In the current article, we queried more than 26,000 empirical articles published between 1974 and 2018 in top-tier cognitive, developmental, and social psychology journals to document how often psychological research acknowledges this reality and to examine whether people who edit, write, and participate in the research are systematically connected. We note several findings. First, across the past five decades, psychological publications that highlight race have been rare, and although they have increased in developmental and social psychology, they have remained virtually nonexistent in cognitive psychology. Second, most publications have been edited by White editors, under which there have been significantly fewer publications that highlight race. Third, many of the publications that highlight race have been written by White authors who employed significantly fewer participants of color. In many cases, we document variation as a function of area and decade. We argue that systemic inequality exists within psychological research and that systemic changes are needed to ensure that psychological research benefits from diversity in editing, writing, and participation. To this end, and in the spirit of the field's recent emphasis on metascience, we offer recommendations for journals and authors.

Objectives: Research into the link between religion and physical function has shown inconsistent results. Most studies have used self-reported measures of physical function, and many have excluded those who are not religious and only compared levels of religious engagement within those groups that are religious. We aimed to assess the longitudinal associations of religious affiliation and religious attendance on two objective measures of physical function., Design: Longitudinal study using five waves of data from the Irish Longitudinal Study on Ageing (TILDA)., Setting: Community-dwelling adults in Ireland., Participants: Adults aged 50 and over who participated in two or more waves of TILDA (n = 6,122),and a supplementary analysis of a sub-sample aged 65 and over (n = 2,359)., Measurements: Timed Up and Go (TUG) and grip strength were measured on at least two occasions. Data were collected approximately every 2 years over 10 years. Longitudinal linear mixed effects models were estimated to calculate the effect of religious affiliation and attendance on TUG and grip strength over time., Results: TUG scores increased by an average of .1 seconds with each year of age, which increased to .3 seconds by age 72 years. Grip strength scores decreased by .2 kg with each year of age and increased to -.3 kg per year by age 72. No overall differences were observed between religious affiliations in scores of TUG or grip strength., Conclusion: Religious affiliation does not predict performance on objective physical function measures. Results are discussed with reference to the changing religious characteristics of the Irish population., (© 2020 The American Geriatrics Society.)

Background: Public and patient involvement in healthcare research is increasing, but the effect of involvement on individuals, service delivery, and health outcomes-particularly in specialist population groups like critical care-remains unclear, as does the best way to involve people who have experienced critical illness., Objectives: The aim of the study was to explore former patients' and family members' views and experiences of involvement in critical care research and/or quality improvement., Methods: Using a qualitative methodology, semistructured telephone interviews were conducted with seven former intensive care unit patients and three close family members across England. Data were analyzed using a standard process of inductive thematic analysis., Results: Four key themes were identified: making it happen, overcoming hurdles, it helps, and respect and value. Findings center on the need for flexibility, inclusivity, and transparency. They further highlight the particular challenges faced by critical illness survivors and their family members in relation to research involvement, the importance of individualized support and training, and the vital role that project leads have in making people feel valued and equal partners in the process., Discussion: This is the first study to explore patients' experiences of involvement in critical care research. Despite the small, homogenous sample, the study provides valuable and important data to guide future practice. It highlights the need to enable and support people to make informed choices at a time when they are ready to do so. It further highlights the importance of gatekeepers to avoid vulnerable people contributing before they are ready-a practice that could negatively affect their health status.

Background: Patients who drop out of clinical trials examining posttraumatic stress disorder (PTSD) may have different characteristics than patients who continue. These characteristics have never been examined in prior PTSD and attrition trials. Our goal was to examine how demographic and clinical characteristics of patients with PTSD impact attrition in a randomized controlled trial., Methods: A total of 18 participants were recruited. Data were collected through questionnaires to assess PTSD, depression, and mood disorders. Fisher’s exact test was used to examine the association of various categorical demographic and clinical variables with dropout. A Wilcoxon rank sum test was used to examine differences in medians., Results: The median total PTSD Checklist for DSM-5 score was 38 for patients who dropped out and 53 for those who did not. The depression scale total was also lower for the dropout group (7 vs 15). The insomnia index was lower for those who did not remain in the study (15 vs 21)., Conclusions: Posttraumatic stress disorder symptoms, depression, and insomnia were less severe in patients who dropped out compared with those who did not. Larger studies are needed to further examine these findings. This study could help guide future recruitment efforts for clinical trials examining PTSD.

Because persons who identify across the transgender spectrum (PATS) are a key population in human immunodeficiency virus (HIV) yet are underreported in HIV and cardiovascular research, we aimed to characterize this population within the REPRIEVE global clinical trial (n = 7770). Acceptance of gathering gender identity was high (96%). Participation by PATS was 1.7% overall, 2.4% among natal males, 0.3% among natal females, and varied across geographic regions (from 0% in sub-Saharan Africa to 2.3% in High Income Region). Thirty percent of natal male PATS identified other than transgender. Some characteristics differed by gender. Most notably, 38% of natal male PATS receiving gender-affirming treatment had waist circumference >102 cm (compared with ≤25% in other groups). Given that PATS is a key population, HIV research should routinely report trial participation and outcomes by gender in addition to natal sex, to provide the results needed to optimize medical care to PATS., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Individual reactions to a diagnosis of mild cognitive impairment (MCI) can vary in a wide range of both adaptive and maladaptive responses. Understanding such reactions to diagnosis is important to maximize adaptive responses that can promote continued independence., Methods: In this pilot study, the Aging and Memory Quality of Life survey was developed to facilitate an understanding of adaptive and maladaptive behaviors results from a diagnosis of MCI. The Aging and Memory Quality of Life was administered to 45 individuals diagnosed with MCI and 45 cognitively normal participants serving as control subjects matched for age, sex, and education. Study partners were surveyed to collect corroborating and or discrepant observer responses., Results: Inconsistent with study partners' reporting, MCI subjects may be underreporting physical limitations, and overreporting medication compliance. MCI subjects identified challenges to managing financial affairs., Discussion: Developing strategies to circumvent the development of maladaptive behaviors could significantly reduce morbidity and mortality in MCI patients.

Background: There is an increased interest in the analysis of large, national palliative care data sets including patient reported outcomes (PROs). No study has investigated if it was best to include or exclude data from services with low response rates in order to obtain the patient reported outcomes most representative of the national palliative care population. Thus, the aim of this study was to investigate whether services with low response rates should be excluded from analyses to prevent effects of possible selection bias., Methods: Data from the Danish Palliative Care Database from 24,589 specialized palliative care admittances of cancer patients was included. Patients reported ten aspects of quality of life using the EORTC QLQ-C15-PAL-questionnaire. Multiple linear regression was performed to test if response rate was associated with the ten aspects of quality of life., Results: The score of six quality of life aspects were significantly associated with response rate. However, in only two cases patients from specialized palliative care services with lower response rates (< 20.0%, 20.0-29.9%, 30.0-39.9%, 40.0-49.9% or 50.0-59.9) were feeling better than patients from services with high response rates (≥60%) and in both cases it was less than 2 points on a 0-100 scale., Conclusions: The study hypothesis, that patients from specialized palliative care services with lower response rates were reporting better quality of life than those from specialized palliative care services with high response rates, was not supported. This suggests that there is no reason to exclude data from specialized palliative care services with low response rates.

Background: Clinical trials are important to improve public health care. However, recruiting participants for trials can be difficult., Aims: This study assessed public knowledge of and willingness to participate in clinical trials in Jordan and examine the sociodemographic characteristics associated with knowledge and willingness and the reasons behind unwillingness to participate., Methods: The questions were part of a representative, population-based survey in 2011 that included 3196 Jordanian individuals. In a home-based interview, participants were asked about: sociodemographic characteristics, and knowledge of and participation in clinical trials., Results: Only 21.8% of respondents knew what a clinical trial was and (1.2%) had participated in a trial. About 25% of respondents indicated their willingness to enrol in a trial. Significantly more men (24.1%) than women (19.3%) knew what clinical trials were (P < 0.001), whereas more women (4.3%) than men (2.9%) said they would be very likely to agree to participate in trials. People aged 40-49 years had better knowledge of and greater willingness to participate in trials than other age groups. Income was positively associated with knowledge of trials but negatively associated with willingness to participate. Higher education was positively correlated with knowledge of and willingness to take part in trials. The main reasons for not participating in trials were concern about the risk to own health (61.1%) and not being convinced about the outcome and benefits of clinical trials (29.7%)., Conclusion: The low level of knowledge of and willingness to participate in clinical trials indicates that strategies are needed to educate the public about the nature and importance of clinical trials., (Copyright © World Health Organization (WHO) 2020. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: Equitable access to research studies needs to be increased for all patients. There is debate about which is the best approach to use to discuss participation in research in real-world clinical settings., Objective: We aimed to determine the feasibility of asking all clinical staff within one hospital Trust (an organisation that provides secondary health services within the English and Welsh National Health Service) to use a newly created form on the Trust's electronic patient records system, as a means of asking patients to consent to discuss participation in research (the opt-in approach). We also aimed to collect feedback from patients and clinicians about their views of the opt-in approach., Methods: Four pilot sites were selected in the Trust: two memory clinics, an adult mental health team and an acute adult ward. Data were collected in three phases: (1) for 6 months, pilot site staff were asked to complete a consent to discuss participation in research form with patients; (2) staff feedback on the form was collected through an online survey; and (3) patient feedback was collected through focus groups., Findings: Of 1779 patients attending services during the pilot period, 197 (11%) had a form completed by staff and 143 (8%) opted-in to finding out about research. Staff cited limited time, low priority and poor user experience of the electronic patient records system as reasons for low uptake of the form. Patients generally approved of the approach but offered suggestions for improvement., Conclusions: There were mixed results for adopting an opt-in approach; uptake was very low, limiting its value as an effective strategy for improving access to research., Clinical Implications: Alternative strategies to the opt-in approach, such as transparent opt out approaches, warrant consideration to maximise access to research within routine clinical care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Health researchers often face difficulties related to participants' recruitment for their research. However, a new strategy emerges: offering patients-but also citizens who are not ill-the possibility to volunteer as participants to hasten research processes. The French platform "Seintinelles" aims to fulfill this goal and bring together citizens who volunteered to participate to cancer related research. The "Seintinelles Barometer" aims to describe these volunteers' profile., Methods: The Seintinelles Barometer data were collected through a web-based auto-questionnaire proposed to the "Seintinelles" members from June 2017 to November 2018., Results: The sample presents a high level of overrepresentation of women. Participants are characterized by a high level of education. About a third of the participants had suffered from cancer. Two profile of volunteers emerged: the « patients » and the « supportive citizens »., Discussion: The Seintinelles Barometer participants manifest a strong wish to be involved in cancer related research. Therefore, this platform seems to be a promising tool for the development of community-based research in the field of cancer., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Importance: Use of the sodium-glucose cotransporter 2 inhibitor empagliflozin has increased substantially since 2015. Little is known about characteristics of real-world patients who use empagliflozin or about empagliflozin's effectiveness in reducing glycated hemoglobin (HbA1c) levels in routine clinical care., Objectives: To characterize real-world initiators of empagliflozin, to examine the proportion of initiators who would have been eligible for participation in phase 3 randomized clinical trials (RCTs) of empagliflozin, and to assess changes in HbA1c levels after empagliflozin initiation., Design, Setting, and Participants: This cross-sectional study used linked population-based medical databases containing complete information on redeemed prescriptions, laboratory tests, and diagnoses for all residents in Northern Denmark. A total of 7034 residents of Denmark who filled a first-time empagliflozin prescription from January 2014 to December 2018 were included. Data analysis was performed in August 2019., Exposure: Empagliflozin initiation., Main Outcomes and Measures: Proportion of real-world users ineligible for RCT inclusion and absolute reduction in HbA1c level 6 months after empagliflozin initiation., Results: Of 7034 first-time empagliflozin initiators (median [interquartile range] age, 61.50 [53.30-69.38] years; 4475 [63.6%] men), 3878 (55.1%) would have been ineligible for phase 3 RCT participation; frequent reasons were concurrent use of specific glucose-lowering drugs (1955 initiators [27.8%]), baseline HbA1c level outside the eligibility range (1772 [25.2%]), or presence of comorbidities (1067 initiators [15.3%]). Initiation of empagliflozin was associated with a mean HbA1c reduction of -0.91% (95% CI, -0.94% to -0.87%) after 6 months, similar to phase 3 RCT results. Real-world empagliflozin initiators who would have been eligible for RCT participation experienced slightly lower mean HbA1c reductions (-0.78%; 95% CI, -0.82% to -0.74%) compared with patients who would have been ineligible (-1.01%; 95% CI, -1.07% to -0.95%). Ineligible initiators had higher median (interquartile range) baseline HbA1c values than eligible initiators (8.5% [7.4% to 10.1%] vs 8.2% [7.6% to 9.8%])., Conclusions and Relevance: In this cross-sectional study, more than half of empagliflozin initiators exhibited clinical characteristics that would have led to ineligibility for the RCTs leading to the drug's approval. While the findings suggest that the efficacy of empagliflozin in reducing HbA1c levels translates into real-world effectiveness, further studies should examine clinical outcome effectiveness and drug safety in routine clinical care.

Objectives: Nonresponse can bias prevalence estimates in population surveys. Effects of selective participation in behavior change intervention trials have been little studied. We tested hypotheses that trial participants who are hard to recruit are (1) more likely to be lost-to-follow-up and (2) less responsive to intervention., Study Design and Setting: We undertook a two-stage individual participant data meta-analysis of four alcohol intervention trials involving 9,251 university students in Australia, New Zealand, and Sweden, comparing participants who enrolled "late" (after the final invitation to participate) vs. "early" (before that). Outcomes were whether participants completed assessments at each trial's primary endpoint (late/early) and number of drinks consumed per week (intervention/control) among late enrolees vs. early enrolees., Results: Late enrolees were more likely to be lost-to-follow-up than early enrolees (OR 2.3, 95% CI: 1.7, 2.9). Intervention effect estimates were smaller for late vs. early enrolees, but not significantly so (RR = 0.93; 95% CI: 0.79, 1.08)., Conclusion: Greater effort to recruit trial participants was associated with higher attrition, but there was no clear evidence of bias in effect estimation. The possibility that intervention effect estimates do not generalize beyond a relatively compliant minority of trial participants may warrant further study., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Returning genetic results to research participants is gaining momentum in the USA. It is believed to be an important step in exploring the impact of efforts to translate findings from research to bedside and public health benefits. Some also hope that this practice will incentivize research participation, especially among people from historically marginalized communities who are commonly underrepresented in research. However, research participants' interest in receiving nongenomic medical and nonmedical results that may emerge from precision medicine research (PMR) is understudied and no study to date has explored the views of people with disabilities about return of genomic and nongenomic results from PMR., Methods: In a national online survey of people with disabilities, participants were queried about their interest in receiving biological, environmental, and lifestyle results from PMR (n = 1,294). Analyses describe findings for all of the participants and comparisons for key demographic characteristics and disability subgroups., Results: The participants expressed high interest in biological and health-related results and less interest in other findings. However, the interest among the study participants was lower than that found in comparable studies of the general population. Moreover, this interest varied significantly across gender, race/ethnicity, and disability subgroups. Possible reasons for these differences are discussed., Conclusion: Insofar as return of results from PMR may impact translational efforts, it is important to better understand the role of sociomedical marginalization in decisions about return of results from PMR and to develop strategies to address existing barriers., (© 2020 S. Karger AG, Basel.)

Background: Most genetics studies lack the diversity necessary to ensure that all groups benefit from genetic research., Objectives: To explore facilitators and barriers to genetic research participation., Methods: We conducted a survey on genetics in research and healthcare from November 15, 2017 to February 28, 2018 among adult Kaiser Permanente (KP) members who had been invited to participate in the KP biobank (KP Research Bank). We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the willingness to participate in genetic research under different return of results scenarios and genetic discrimination concerns between groups, according to their demographic characteristics., Results: A total of 57,331 KP members were invited to participate, and 10,369 completed the survey (18% response rate). Respondents were 65% female, 44% non-Hispanic White (NH White), 22% Asian/Native Hawaiian or other Pacific Islander (Asian/PI), 19% non-Hispanic Black (NH Black), and 16% Hispanic. Respondents willing to participate in genetic research ranged from 22% with no results returned to 87% if health-related genetic results were returned. We also found variation by race/ethnicity; when no results were to be returned, Asian/PIs, Hispanics, and NH Blacks were less likely to want to participate than NH Whites (p < 0.05). However, when results were returned, disparities in the willingness to participate disappeared for NH Blacks and Hispanics. Genetic discrimination concerns were more prevalent in Asian/PIs, Hispanics, and NH Blacks than in NH Whites (p < 0.05)., Conclusions: Policies that prohibit the return of results and do not address genetic discrimination concerns may contribute to a greater underrepresentation of diverse groups in genetic research., (© 2020 S. Karger AG, Basel.)