The SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants, based on qualitative findings from trial participants and site staff.

BACKGROUND: Sharing trial results with participants is a moral imperative, but too often does not happen in appropriate ways. METHODS: We carried out semi-structured interviews with patients (n = 13) and site staff (n = 11), and surveyed 180 patients and 68 site staff who were part of the Show RESPECT study, which tested approaches to sharing results with participants in the context of the ICON8 ovarian cancer trial (ISRCTN10356387). Qualitative and free-text data were analysed thematically, and findings used to develop the SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants. This paper presents the framework, with illustrations drawn from the Show RESPECT study. RESULTS: Our adaptable 'SHOW RESPECT' framework covers (1) Supporting and preparing trial participants to receive results, (2) HOw will the results reach participants?, (3) Who are the trial participants?, (4) REsults-what do they show?, (5) Special considerations, (6) Provider-who will share results with participants?, (7) Expertise and resources, (8) Communication tools and (9) Timing of sharing results. While the data upon which the framework is based come from a single trial, many of our findings are corroborated by findings from other studies in this area, supporting the transferability of our framework to trials beyond the UK ovarian cancer setting in which our work took place. CONCLUSIONS: This adaptable 'SHOW RESPECT' framework can guide researchers as they plan how to share aggregate trial results with participants. While our data are drawn from a single trial context, the findings from Show RESPECT illustrate how approaches to communication in a specific trial can influence patient and staff experiences of feedback of trial results. The framework generated from these findings can be adapted to fit different trial contexts and used by other researchers to plan the sharing of results with their own participants. TRIAL REGISTRATION: ISRCTN96189403. Registered on February 26, 2019. Show RESPECT was supported by the Medical Research Council (MC_UU_12023/24 and MC_UU_00004/08) and the NIHR CRN.

An investigation into gender distributions in scholarly publications among dental faculty members in Iran.

BACKGROUND: Research on gender inequality is crucial as it unveils the pervasive disparities that persist across various domains, shedding light on societal imbalances and providing a foundation for informed policy-making. AIM: To investigate gender differences in scientometric indices among faculty members in dental schools across Iran. This included overall data and speciality-specific data. METHODS: The publication profiles of academic staff in all dental schools were examined using the Iranian Scientometric Information Database (ISID, http://isid.research.ac.ir). Variables analyzed were working field, academic degree, the total number of papers, papers per year, total number of citations, percentage of self-citation, h-index, g-index, citations per paper, gender, university type, number of years publishing, proportion of international papers, first-author papers, and corresponding-author papers. Mann-Whitney and Kruskal-Wallis nonparametric tests were used to analyze the relationship between background characteristics and scientometric indicators. The extracted data were analyzed using R v4.0.1. RESULTS: The database included 1850 faculty members, of which about 60% (1104 of 1850) were women. Men (n = 746) had a higher number of papers (6583 vs. 6255) and citations (60410 vs. 39559) compared with women; 234 of the 376 faculty members with no papers were women. Almost half of the women (N = 517 of 1104) were in Type 2 universities, and nearly half of the men (N = 361 of the 746) were faculty members at Type 1 universities (Type 1 universities ranking higher than Type 2 and 3 universities). The medians of scientometric indices were higher in men, except for self-citation percentage (0 (IQR = 2) vs. 0 (IQR = 3), P = 0.083), international papers percentage (0 (IQR = 7.5) vs. 0 (IQR = 16.7), P<0.001). The proportion of corresponding-author papers was more than 62% higher in women (25 (IQR = 50) vs. 15.4 (IQR = 40), P<0.001). Men had a two-fold higher median h-index (2 (IQR = 4) vs. 1 (IQR = 3), P<0.001). Restorative dentistry and pediatric dentistry had the highest men-to-women ratios (1.5 for both). Dental materials and oral and maxillofacial surgery showed the lowest men-to-women ratios (0.42 and 0.5, respectively). CONCLUSIONS: Women made up the majority of dental faculty members in Iran. Nevertheless, men showed better scientometric results in several significant indices. Having identified scientometric information reflecting differences across faculty members, further research is now needed to better understand the drivers of these differences.

Proposed Increases in Government Authority Over Research Misconduct Proceedings.

This Viewpoint discusses changes proposed by the US Department of Health and Human Services' Office of Research Integrity that would shift control of research misconduct proceedings from institutional oversight to federal authority.

Acupuncture for hot flashes in hormone receptor-positive breast cancer: A pooled analysis of individual patient data from parallel randomized trials.

BACKGROUND: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. METHODS: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. RESULTS: In total, 158 women with stage 0-III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (-5.3 ± 0.9 vs. -1.4 ± 0.9; p < .003), and the FACT-Breast total score (8.0 ± 1.6 vs. -0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005). CONCLUSIONS: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.

A Federally Qualified Health Center-led Ethics & Equity Framework & Workflow Checklist: An Invited Commentary in Response to a Relational Public Health Framing of FQHCs During COVID-19.

With disparate rates of morbidity and mortality among minoritized communities, COVID-19 illuminated the need for equity-informed practices in public health. Pacia et al posit FQHCs as entities that addressed inequity when others failed. This commentary further situates how FQHCs address the public health crisis of institutional racism and related health inequities every day and presents a FQHC-led Ethics and Equity Framework and Workflow Checklist to guide ethical and equitable engagement with FQHCs.

Education and training of clinical research professionals and the evolution of the Joint Task Force for Clinical Trial Competency.

Clinical research professionals play a critical role in the design, conduct, and oversight of clinical trials, and they must have the knowledge, skills, and abilities to ensure that trials are conducted ethically, safely, and in accordance with regulatory requirements. As clinical research has evolved from being a necessary activity for the development and regulatory approval of new medicines to an accredited academic discipline and, more recently, to a globally recognized profession, the methods of education and training of professionals have also evolved. Initially, on-the-job informal coaching and specialized training organizations led to formalized and accredited academic degree programs and, more recently, to international competency standards and competency maintenance through continuous professional development. The Joint Task Force (JTF) for Clinical Trial Competency is a multidisciplinary, international group of experts who came together to aggregate and refine competency standards for clinical research professionals, first published in 2014. The 8 domains and 49 specific core competencies of the JTF Framework have become a globally recognized standard upon which education and training programs, role descriptions, and upward mobility criteria for professionals are now based. The JTF meets regularly and, through its workgroups, continues to evolve in response to the changing needs of the profession. The JTF is committed to continuous improvement to ensure that clinical research professionals have the competence necessary to conduct safe, ethical, and high-quality clinical research.

Returning Individual Research Results from Digital Phenotyping in Psychiatry.

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.

Deprioritization of Ongoing Clinical Trials.

To be ethical, clinical trials must exhibit a favorable risk-benefit balance at the time of their initiation. However, in some cases, the expected value of a study decreases while the study is ongoing, due to developments outside of the study itself, such as findings from other studies or an otherwise shifting evidence base. While such situations are acknowledged in the research community, they have not received sufficient attention, given the high costs of uninformative studies, both in material and human capital. In addition, the Covid-19 pandemic has exposed serious shortcomings with current approaches to monitoring studies for continued relevance and value. In this article, with reference to a case study from the Covid-19 pandemic, we identify and describe the importance and challenge of ensuring that clinical trials continue to exhibit scientific relevance and value once initiated. We explore the ethical dynamics of these situations and identify unresolved issues. While more empirical work is needed to ensure that proposed solutions to the issues are evidence based, we offer some provisional considerations that amount to a framework for approaching these challenging situations.

Defining "recklessness" in research misconduct proceedings.

To find research misconduct in research that has been supported by federal funds, an institution must determine that the misconduct was committed intentionally, knowingly, or recklessly. "Intentional" and "knowing" are straightforward standards. Yet "reckless" often mystifies institutions, which struggle to assess whether a respondent's conduct should be deemed "reckless," or merely negligent. This difficulty is most pronounced when allegations are lodged against the author under whose supervision the primary research was conducted - most often, the senior and/or corresponding author of a published paper who may not have been directly involved in performing the experiments or preparing the data under scrutiny. In these situations, investigation committees and the institutional "deciding official" must assess whether the supervising scientist is guilty of research misconduct - based on the theory that their supervision of the research and development of the publication containing falsified, fabricated, or plagiarized information was reckless - even if that person did not perform the experiment or assemble the research records in question. This paper seeks to provide a framework for evaluating the circumstances in which past supervisory conduct should be deemed "reckless" and thus a basis on which a finding of research misconduct may be made.

Characterization of key information sections in informed consent forms posted on ClinicalTrials.gov.

Introduction: Recent revisions to the US Federal Common Rule governing human studies funded or conducted by the federal government require the provision of a "concise and focused" key information (KI) section in informed consent forms (ICFs). We performed a systematic study to characterize KI sections of ICFs for federally funded trials available on ClinicalTrials.gov. Methods: We downloaded ICFs posted on ClinicalTrials.gov for treatment trials initiated on or after the revised Common Rule effective date. Trial records (n = 102) were assessed by intervention type, study phase, recruitment status, and enrollment size. The ICFs and their KI sections, if present, were characterized by page length, word count, readability, topic, and formatting elements. Results: Of the 102 trial records, 76 had identifiable KI sections that were, on average, 10% of the total length of full ICF documents. KI readability grade level was not notably different from other sections of ICFs. Most KI sections were distinguished by section headers and included lists but contained few other formatting elements. Most KI sections included a subset of topics consistent with the basic elements of informed consent specified in the Common Rule. Conclusion: Many of the KI sections in the study sample aligned with practices suggested in the preamble to the revised Common Rule. Further, our results suggest that some KI sections were tailored in study-specific ways. Nevertheless, guidelines on how to write concise and comprehensible KI sections would improve the utility and readability of KI sections.

Review of diversity, equity, and inclusion by ethics committees: A Delphi consensus statement.

The appropriate representation of diverse populations in interventional trials remains problematic. A Delphi process was used to affirm the central role that ethics committees and institutions play in this process and to establish consensus upon 25 consolidated recommendations across four themes to promote diversity and inclusion in interventional clinical research.

Enhancing diversity of clinical trial populations in multiple sclerosis.

BACKGROUND: Demographic characteristics, social determinants of health (SDoH), health inequities, and health disparities substantially influence the general and disease-specific health outcomes of people with multiple sclerosis (MS). Participants in clinical trials do not represent all people with MS treated in practice. OBJECTIVE: To provide recommendations for enhancing diversity and inclusion in clinical trials in MS. METHODS: We held an international workshop under the Auspices of the International Advisory Committee on Clinical Trials in MS (the "Committee") to develop recommendations regarding diversity and inclusivity of participants of clinical trials in MS. Workshop attendees included members of the Committee as well as external participants. External participants were selected based on expertise in trials, SDoH, health equity and regulatory science, and diversity with respect to gender, race, ethnicity, and geography. RESULTS: Recommendations include use of diversity plans, community engagement and education, cultural competency training, biologically justified rather than templated eligibility criteria, adaptive designs that allow broadening of eligibility criteria over the course of a trial, and logistical and practical adjustments to reduce study participant burden. Investigators should report demographic and SDoH characteristics of participants. CONCLUSION: These recommendations provide sponsors and investigators with methods of improving diversity and inclusivity of clinical trial populations in MS.

Terms and conditions apply: an ethical analysis of mobile health user agreements in research.

Mobile health (mHealth) technologies raise unique risks to user privacy and confidentiality that are often embedded in lengthy and complex Privacy Policies, Terms of Use, and End User License Agreements. We seek to improve the ethical review of these documents ('user agreements') and their risks in research using mHealth technologies by providing a framework for identifying when these risks are research risks, categorizing the key information in these agreements under relevant ethical and regulatory categories, and proposing strategies to mitigate them. MHealth user agreements typically describe the nature of the data collected by mHealth technologies, why or for what purposes user data are collected and shared, who will have access to the different types of data collected, and may include exculpatory language. The risks raised by data collection and sharing typically increase with the sensitivity and identifiability of the data and vary by whether data are shared with researchers, the technology developer, and/or third-party entities. The most important risk mitigation strategy is disclosure of the key information found in user agreements to participants during the research consent process. In addition, researchers should prioritize mHealth technologies with favorable risk-benefit balances.

Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial.

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants.

Losartan in hospitalized patients with COVID-19 in North America: An individual participant data meta-analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients. METHODS: We searched ClinicalTrials.gov in January 2021 for U.S./Canada-based trials where an angiotensin-converting enzyme inhibitors/ARB was a treatment arm, targeted outcomes could be extrapolated, and data sharing was allowed. Our primary outcome was a 7-point COVID-19 ordinal score measured 13 to 16 days post-enrollment. We analyzed data by fitting multilevel Bayesian ordinal regression models and standardizing the resulting predictions. RESULTS: 325 participants (156 losartan vs 169 control) from 4 studies contributed IPD. Three were randomized trials; one used non-randomized concurrent and historical controls. Baseline covariates were reasonably balanced for the randomized trials. All studies evaluated losartan. We found equivocal evidence of a difference in ordinal scores 13-16 days post-enrollment (model-standardized odds ratio [OR] 1.10, 95% credible interval [CrI] 0.76-1.71; adjusted OR 1.15, 95% CrI 0.15-3.59) and no compelling evidence of treatment effect heterogeneity among prespecified subgroups. Losartan had worse effects for those taking corticosteroids at baseline after adjusting for covariates (ratio of adjusted ORs 0.29, 95% CrI 0.08-0.99). Hypotension serious adverse event rates were numerically higher with losartan. CONCLUSIONS: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.

Data visualization explorer: A tool for participant representation in pivotal trials of FDA-approved medicinal products.

This paper presents a 2015-2021 US Food and Drug Administration (FDA) Drug Trials Snapshots (DTS) Data Visualization Explorer-an interactive data visualization web-based tool (https://arielcarmeli.shinyapps.io/fda-drug-trial-snapshots-data-explorer) built in R and based on publicly available FDA clinical trial participation data and disease incidence data from the National Cancer Institute and Centers for Disease Control and Prevention. FDA data can be explored by race, ethnicity, sex, age group, therapeutic area, pharmaceutical sponsor, and approval year for clinical trials that supported each of the 339 FDA drug and biologic approvals between 2015 and 2021. This work provides several advantages relative to past literature and DTS reports: a dynamic data visualization tool; race, ethnicity, sex, and age group data presented in one place; data on sponsor; and emphasis on data distributions instead of averages. We present recommendations for improved data access, reporting, and communication to assist leaders in making evidence-based decisions to improve trial representation to enhance health equity.

Implementation of single IRB review for multisite human subjects research: Persistent challenges and possible solutions.

Revisions to the Common Rule and NIH policy require the use of a single Institutional Review Board (sIRB) for the review of most federally funded, multisite research, with the intent of streamlining the review process. However, since initial implementation in 2018, many IRBs and institutions continue to struggle with the logistics of implementing this requirement. In this paper, we report the findings of a workshop held in 2022 to examine why sIRB review remains problematic and propose possible solutions. Workshop participants identified several issues as major barriers, including new responsibilities for study teams, persistent duplicative review processes, the lack of harmonization of policies and practices across institutions, the absence of additional guidance from federal agencies, and the need for greater flexibility in policy requirements. Addressing these problems will require providing additional resources and training to research teams, the commitment of institutional leaders to harmonize practice, and policymakers to critically evaluate the requirement and provide flexibility in applicability.