Recruitment and Retention Strategies for Randomized Clinical Trials Involving Family Members of ICU Patients.

OBJECTIVES: To review recruitment and retention strategies of randomized family-centered interventional studies in adult ICUs. DATA SOURCES: The MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library database from inception to February 2023. STUDY SELECTION: Randomized controlled trials with family-centered interventions in the ICU setting that reported at least one family-centered outcome that were included in our previously published systematic review. DATA EXTRACTION: For recruitment: Number of family members approached and enrolled, type of approach, location, time of day approached, whether medical team approached first, compensation offered, and type of consent. For retention: Number of family members enrolled and completed initial follow-up visit, mode of follow-up, location of follow-up visit, data collection method, timing of follow-up visits, number of follow-up visits, and compensation offered. Recruitment (participants approached/enrolled) and retention (participants enrolled/completed initial follow-up) percentage were calculated. DATA SYNTHESIS: There were 51 studies in the analysis. The mean recruitment percentage was 49.3% ± 24.3%. There were no differences in recruitment percentage by study country, ICU type, recruitment approach, or whether the medical team approached the family member first (all p > 0.05). The mean retention percentage for the initial follow-up visit was 81.6% ± 18.0%. There were no differences in retention percentage by mode of participant contact, data collection type, or follow-up location (all p > 0.05). Minimal data were available to determine the impact of time of day approached and compensation on recruitment and retention outcomes. CONCLUSIONS: About half of family members of ICU patients approached participated in trials and more than eight in ten completed the initial follow-up visit. We did not identify specific factors that impacted family recruitment or retention. There is a strong need for further studies to characterize optimal strategies to ensure family participation in clinical trials.

Research with Refugee Populations in North America: Applying the NIH Guiding Principles for Ethical Research.

This article examines the ethics of research design and the initiation of a study (e.g., recruitment of participants) involving refugee participants. We aim to equip investigators and members of IRBs with a set of ethical considerations and pragmatic recommendations to address challenges in refugee-focused research as it is developed and prepared for IRB review. We discuss challenges including how refugees are being defined and identified; their vulnerabilities before, during, and following resettlement that impacts their research participation; recruitment; consent practices including assent and unaccompanied minors; and conflicts of interest. Ethical guidance and regulatory oversight provided by international bodies, federal governments, and IRBs are important for enforcing the protection of participants. We describe the need for additional ethical guidance and awareness, if not special protections for refugee populations as guided by the National Institutes of Health (NIH) Guiding Principles for Ethical Research.

Rationale and Study Checklist for Ethical Rejection of Participants on Crowdsourcing Research Platforms.

Online participant recruitment ("crowdsourcing") platforms are increasingly being used for research studies. While such platforms can rapidly provide access to large samples, there are concomitant concerns around data quality. Researchers have studied and demonstrated means to reduce the prevalence of low-quality data from crowdsourcing platforms, but approaches to doing so often involve rejecting work and/or denying payment to participants, which can pose ethical dilemmas. We write this essay as an associate professor and two institutional review board (IRB) directors to provide a perspective on the competing interests of participants/workers and researchers and to propose a checklist of steps that we believe may support workers' agency on the platform and lessen instances of unfair consequences to them while enabling researchers to definitively reject lower-quality work that might otherwise reduce the likelihood of their studies producing true results. We encourage further, explicit discussion of these issues among academics and among IRBs.

Equitable inclusion of diverse populations in oncology clinical trials: deterrents and drivers.

The burden of cancer exerts a disproportionate impact across different regions and population subsets. Disease-specific attributes, coupled with genetic and socioeconomic factors, significantly influence cancer treatment outcomes. Precision oncology promises the development of safe and effective options for specific ethnic phenotypes and clinicodemographic profiles. Currently, clinical trials are concentrated in resource-rich geographies with younger, healthier, white, educated, and empowered populations. Vulnerable and marginalized people are often deprived of opportunities to participate in clinical trials. Despite consistent endeavors by regulators, industry, and other stakeholders, factors including diversity in trial regulations and patient and provider-related cultural, logistic, and operational barriers limit the inclusiveness of clinical trials. Understanding and addressing these constraints by collaborative actions involving regulatory initiatives, industry, patient advocacy groups, community engagement in a culturally sensitive manner, and designing and promoting decentralized clinical trials are vital to establishing a clinical research ecosystem that promotes equity in the representation of population subgroups.

Determining capacity of people with dementia to take part in research: an electronic survey study of researcher confidence, competence and training needs.

BACKGROUND: Researchers are required to determine whether a person has capacity to consent to a research study before they are able to participate. The Mental Capacity Act and accompanying Code of Practice for England and Wales provide some guidance on this process, but researchers have identified that it can be difficult to determine capacity to consent when a person has complex cognitive or communication needs. This study aimed to understand the experiences and opinions of researchers who recruit people with dementia to research projects, to inform the future development of training resources. METHODS: A mixed method, cross-sectional, electronic survey was circulated via social media and research networks in England and Wales. The survey remained open for ten weeks and included open and closed questions exploring respondents' confidence in determining capacity in the context of recruiting people with dementia to consent, their views on training and support they have experienced and their suggestions for future training and support needs. RESULTS: 60 respondents completed the survey from across England and Wales. Although 75% of respondents had experience of determining capacity to consent with people with dementia to research, only 13% rated themselves as feeling 'very confident' in this. Qualitative content analysis of open responses led to the generation of six themes, explaining researchers' confidence, competence and future training needs in this area: (1) Researcher uncertainties, (2) Lack of time, (3) Balancing information complexity with accessibility, (4) Gatekeepers, (5) Existing enablers and (6) Envisioning future training. CONCLUSIONS: Researchers would benefit from specific training in undertaking conversations around consent with people with dementia. People with dementia may have fluctuating capacity, and despite support from caregivers, researchers have little practical guidance on methods of determining a person's ability to understand or appreciate the information they have provided during the consent process. Given the development of large complex trials within dementia research, there is an urgency to develop specific and practical guidance and training for researchers working with people with dementia and their families.

Should Children Be Included in Human Challenge Studies?

Human challenge studies, in which human research subjects are intentionally exposed to pathogens to contribute to scientific knowledge, raise many ethical complexities. One controversial question is whether it is ethically permissible to include children as participants. Commentary of the past decades endorses the exclusion of children, while new guidance suggests that pediatric human challenge studies can be ethically permissible. This paper argues that neither children's exclusion nor their inclusion are well justified. I examine and reject three arguments for exclusion, but suggest that these arguments establish pediatric human challenge studies as a complex ethical category of research that requires caution. I then argue for a strong presumption against children's inclusion, by drawing on an analogy to children's inclusion in phase I trials, emphasizing a requirement of necessity, and suggesting that accommodating children's vulnerability promotes an age de-escalation approach for pediatric human challenge studies research. In the final section, I suggest a procedure for ethics review.

Challenges and Lessons from Conducting a Community-Engaged Evaluation of a Community Advisory Board-A Case Study from Flint.

Community-engaged research often poses challenges due to exactly those qualities that make it desirable: it provides a new model of research that differs in many ways from top-down, university-led, prospectively designed approaches. While many have discussed the challenges to conducting community-engaged research, few have provided precise and generalizable lessons for how to surmount these challenges. Here we discuss the challenges experienced in a project that was community-engaged at three levels: 1) a research team consisting of an academic and a community partner as well as a community and academic research assistant, 2) the research team engaged with a Community Advisory Board called the CBOP-CERB (Community Based Organization Partners-Community Ethics Research Board) throughout the project, and 3) the research involved recruiting community participants from an area with a historical distrust of researchers and research: Flint Michigan. We also discuss administrative challenges that this multilevel community-engagement posed. Most important, we provide practical lessons in order for future community-engaged research to avoid or mitigate many of these challenges.

Financial ''risk-sharing'' or refund programs in assisted reproduction: an Ethics Committee opinion.

Financial "risk-sharing" fee structures in assisted reproduction programs charge patients a higher initial fee that includes multiple cycles but offers a partial or complete refund if treatment fails. This opinion of the American Society for Reproductive Medicine Ethics Committee analyzes the ethical issues raised by these fee structures, including patient selection criteria, conflicts of interest, success rate transparency, and patient-informed consent. This document replaces the document of the same name, last published in 2016.

A pilot recruitment strategy to enhance ethical and equitable access to Covid-19 pediatric vaccine trials.

BACKGROUND/AIMS: The SARS-CoV-2 pandemic disproportionately impacted communities with lower access to health care in the United States, particularly before vaccines were widely available. These same communities are often underrepresented in clinical trials. Efforts to ensure equitable enrollment of participants in trials related to treatment and prevention of Covid-19 can raise concerns about exploitation if communities with lower access to health care are targeted for recruitment. METHODS: To enhance equity while avoiding exploitation, our site developed and implemented a three-part recruitment strategy for pediatric Covid-19 vaccine studies. First, we publicized a registry for potentially interested participants. Next, we applied public health community and social vulnerability indices to categorize the residence of families who had signed up for the registry into three levels to reflect the relative impact of the pandemic on their community: high, medium, and low. Finally, we preferentially offered study participation to interested families living in areas categorized by these indices as having high impact of the Covid-19 pandemic on their community. RESULTS: This approach allowed us to meet goals for study recruitment based on public health metrics related to disease burden, which contributed to a racially diverse study population that mirrored the surrounding community demographics. While this three-part recruitment strategy improved representation of minoritized groups from areas heavily impacted by the Covid-19 pandemic, important limitations were identified that would benefit from further study. CONCLUSION: Future use of this approach to enhance equitable access to research while avoiding exploitation should test different methods to build trust and communicate with underserved communities more effectively.

How informative were early SARS-CoV-2 treatment and prevention trials? a longitudinal cohort analysis of trials registered on ClinicalTrials.gov.

BACKGROUND: Early in the SARS-CoV-2 pandemic, commentators warned that some COVID trials were inadequately conceived, designed and reported. Here, we retrospectively assess the prevalence of informative COVID trials launched in the first 6 months of the pandemic. METHODS: Based on prespecified eligibility criteria, we created a cohort of Phase 1/2, Phase 2, Phase 2/3 and Phase 3 SARS-CoV-2 treatment and prevention efficacy trials that were initiated from 2020-01-01 to 2020-06-30 using ClinicalTrials.gov registration records. We excluded trials evaluating behavioural interventions and natural products, which are not regulated by the U.S. Food and Drug Administration (FDA). We evaluated trials on 3 criteria of informativeness: potential redundancy (comparing trial phase, type, patient-participant characteristics, treatment regimen, comparator arms and primary outcome), trials design (according to the recommendations set-out in the May 2020 FDA guidance document on SARS-CoV-2 treatment and prevention trials) and feasibility of patient-participant recruitment (based on timeliness and success of recruitment). RESULTS: We included all 500 eligible trials in our cohort, 58% of which were Phase 2 and 84.8% were directed towards the treatment of SARS-CoV-2. Close to one third of trials met all three criteria and were deemed informative (29.9% (95% Confidence Interval 23.7-36.9)). The proportion of potentially redundant trials in our cohort was 4.1%. Over half of the trials in our cohort (56.2%) did not meet our criteria for high quality trial design. The proportion of trials with infeasible patient-participant recruitment was 22.6%. CONCLUSIONS: Less than one third of COVID-19 trials registered on ClinicalTrials.gov during the first six months met all three criteria for informativeness. Shortcomings in trial design, recruitment feasibility and redundancy reflect longstanding weaknesses in the clinical research enterprise that were likely amplified by the exceptional circumstances of a pandemic.

Research Involving Participants With Impaired Consent Capacity: An Examination of Methods to Determine Capacity to Consent.

OBJECTIVE: To examine methods of assessing consent capacity in research protocols involving participants with impaired consent capacity, and examine instruments used to evaluate research consent capacity. METHODS: A retrospective review of 330 active research protocols involving participants lacking capacity to consent over a 10-year period (January 1, 2009, through March 1, 2019) was conducted to collect protocol characteristics (medical specialty, level of risk and type of study, consent and assent procedures, and type of vulnerable or protected population). Methods to assess consent capacity are described, and instruments to assess consent capacity are summarized. RESULTS: The specialties most frequently involving participants with impaired consent capacity in research were Neurology (27.3%), Critical Care (16.7%), and Surgery (10%). Type of studies are observational (43.9%), clinical trials (33%), chart review (11.5%), biobank (6.1%), and biomarker (5.5%). Minimal risk (53.3%) outnumbered greater than minimal risk (46.7%) studies. Most obtained written informed consent (77%) and assent (40.9%). The most common method to assess consent capacity was direct assessment by investigators (32.7%). Only 86 (26%) studies used instruments to assess consent capacity. Of the 13 instruments used, the most common was the Evaluation of Decision-Making Capacity for Consent to Act as a Research Subject, and is the only instrument that assesses all four components of decisional capacity: understanding, appreciation, reasoning, and choice. CONCLUSION: Generally, there was lack of uniformity in determining capacity to consent to research participation. Very few studies used instruments to assess consent capacity. Institutional review boards can provide greater guidance for research consent capacity determination.

A literature review of consent declines and consent withdrawals in randomized controlled trials conducted during the COVID-19 pandemic.

Objectives: We evaluated the extent of consent declines and consent withdrawals during the COVID-19 pandemic as seen in published randomized controlled trials (RCTs) and compared it with non-COVID-19 RCTs published at the same time and two historical controls. Methods: PubMed/Medline only was searched using key-word "COVID-19" and "RCTs" separately, and filtered for COVID-19 RCTs and non-COVID-19 RCTs respectively, published during a nine-month period (1 Feb - 1 Nov 2020). Exclusions were study protocols, observational studies, interim analysis of RCT data and RCTs with missing data. Primary outcome measures were the proportion of consent declines and consent withdrawals as percentage of total participants screened and randomized respectively in COVID-19 RCTs. We compared consent declines and consent withdrawals of COVID-19 RCTs with non-COVID-19 RCTs and two earlier studies on the same topic that served as historical controls (non-pandemic setting). Results: The search yielded a total of 111 COVID-19 RCTs and 49 non-COVID-19 RCTs. Of these, 39 (35.13%) COVID-19 RCTs and 11 (22.45%) non-COVID-19 RCTs were finally analysed. A total of 770/17759 (4.3%) consent declines and 100/7607 (1.31%) consent withdrawals were seen in 39 COVID-19 RCTs. A significant difference was observed in consent declines between COVID-19 vs non-COVID-19 RCTs [4.3% vs 11.9%, p < 0.0001] and between COVID-19 RCTs vs two historical controls [(4.3% vs 8.6%, p < 0.0001) and (4.3% vs 21.1%, p < 0.0001), respectively]. Conclusion: RCTs conducted during the COVID-19 pandemic appear to have significantly lower consent declines relative to non-COVID-19 RCTs during pandemic and RCTs conducted in non-pandemic settings.

Interventional bronchoscopy for chronic obstructive pulmonary disease: more than a pipe dream.

Endoscopic lung volume reduction (ELVR) is recognised in both national and international expert guidelines as one of the few additive treatments to benefit patients with advanced chronic obstructive pulmonary disease (COPD) who are otherwise receiving optimal medical and supportive care. Despite these recommendations and a growing evidence base, these procedures are not widely offered across Australia and New Zealand, and general practitioner and physician awareness of this therapy can be improved. ELVR aims to mitigate the impact of hyperinflation and gas trapping on dyspnoea and exercise intolerance in COPD. Effective ELVR is of proven benefit in improving symptoms, quality of life, lung function and survival. Several endoscopic techniques to achieve ELVR have been developed, with endobronchial valve placement to collapse a single lobe being the most widely studied and commonly practised. This review describes the physiological rationale underpinning lung volume reduction, highlights the challenges of patient selection, and provides an overview of the evidence for current and investigational endoscopic interventions for COPD.