Abstract
Long Term Follow up of Family Cohort Study in Rural Thailand; Building Trust for Research Engagement
Dararat Kanjana1, Darunee Buddhari1, Aaron Farmer2, Stefan Fernandez3, Kathryn Anderson4, Sopon Iamsirithaworn5, and Surachai Kaewhiran6
1Armed Forces Research Institute of Medical Sciences, Kamphaeng Phet, Thailand
2Armed Forces Research Institute of Medical Sciences, Krung Thep, Thailand
3Department of Virology, Armed Forces Research Institute of Medical Sciences, Krung Thep, Thailand
4SUNY Upstate New York, NY, USA
5Bureau of Communicable Diseases, Ministry of Public Health of Thailand, Nonthaburi, Thailand
6Kamphaeng Phet Hospital, Kamphaeng Phet, Thailand
Research engagement in rural areas is challenging due to the diverse groups of people and limited understanding of how research directly effects their lives. This study represents an example of a long-term follow up study that regularly engaged the community and thereby improved retention and participant awareness.
This novel long term prospective family cohort in Kamphaeng Phet, Thailand, a rural area in northern Thailand, was implemented in 2015 to determine dengue virus (DENV) infection incidence and risk and expanded in 2020 to include SARS-CoV-2 infection given the ongoing pandemic. We approached the public health office (at distinct levels of province, district and sub-districts) to clearly describe and specify the scientific purpose as well as the research benefit to community. In addition, with public health approval, we collaborated with the village health workers as the primary contact for potential participant's enrollment and annual follow up. The demographic data, clinical interview and phlebotomy were performed on enrollment and annually and weekly contact occurred via phone call to allow active surveillance for dengue infection. If an illness was identified, other cohort participants from the same family unit as the infected subject were evaluated in a household contact investigation to determine dengue transmission patterns in each household.
Investigators have enrolled 551 families comprised of 3,500 participants since 2015 and maintained follow up for 7 years to date. The lost to follow up rate each year was up to 7% (range from 0.6 to 6.2%). The overall rate of elective withdrawal was 9.8%. To date, there have been no complaints or negative feedback from the community related to the study activities. The weekly phone call “missed follow up” rate was less than 5% each week throughout the study period. During the most recent annual follow up, the study staff received feedback from the local community of their desire to continue the study for an even longer period and how they could assist the team in doing so. On quality review performed after each visit, less than 1% minor error were noted, largely consisting of findings such as documentation errors.
The major limitation for collecting data was uncontrolled factors leading to participants withdrawn such as inability to collect cord blood due to immediate newborn delivery at labor room, the participant temporarily moving out of the study area for a job due to economic reasons. In addition, the study paused during COVID-19 pandemic which led to some missed visits. However, the participants have been able to keep contact with the study team through weekly phone calls.
Building trust through consistency and concrete action is the most important factor for research achievement, and also is vital for making the research participant experience as beneficial to the community as possible. Although, the economic benefit is helpful, participants greatly appreciated non-monetary gifts such as ‘Hero Certificates’ for their participation time and the benefit from weekly health checks and dengue education, resulting in long-term research support and success. Some statements such as ‘So glad and Proud to participate’ in the research reflects this trust and long term engagement in this rural community.
HIV Cure-related Study Vignettes Capture Perspectives on Ethical Payment Amounts
Andrea N. Polonijo1, Brandon Brown2, Zhiwei Zhang3, Karine Dubé4, Karah Y. Greene5, and Jerome T. Galea5
1Department of Sociology and the Health Sciences Research Institute, University of California Merced, Merced, CA, USA
2Department of Social Medicine, Population, and Public Health, University of California Riverside School of Medicine, Riverside, CA, USA
3Mathematical Statistician, National Cancer Institute, USA
4University of California San Diego, School of Medicine, USA
5University of South Florida School of Social Work, FL, USA
Cash payments are common in research among people with HIV (PWH), including research towards finding a cure. Researchers propose payment amounts in grant applications and prior to IRB review, oftentimes without consulting prospective participants. Consequently, payment amounts are not data-driven and may lead to amounts that are inappropriately low or high.
In collaboration with a national community advisory board, and based on results from focus groups, interviews, and a conjoint analysis exercise, we created hypothetical HIV cure research vignettes including 6 factors with 2–3 possible levels per factor: A = comorbidity (arthritis/mild depression/heart disease), B = first in humans (yes/no), C = invasiveness (low/moderate/high), D = long-term risks (yes/no), E = time burden (no/some/significant impact on daily activities), and F = ancillary care (yes/no). In 2022, we collected data from 15 participants representing 3 different stakeholder groups (5 PWH, 5 IRB members, 5 researchers) who received a $50 incentive. Each participant read up to 24 vignettes, half of which were identical across participants. For each vignette, respondents suggested a recommended range of appropriate payment amounts in U.S. dollars. Descriptive statistics (min, max, quartiles, median, mean) were calculated for the vignettes and specific to each participant type. Boxplots were created to illustrate maximum and minimum payment amounts with dollar amounts on a log scale because data were often skewed upward.
Participants’ mean age was 48 years. The majority were women (53%) and White (67%). Two-thirds (67%) considered payment a benefit of research. Payment data for 192 vignettes showed greater variability between participants than between vignettes. The average maximum proposed payment amount among all participants for all vignettes was $2,042 ($843 PWH, $3,980 IRB, $1,336 researchers), while the average minimum proposed payment amount was $1,020 ($681 PWH, $1,614 IRB, $776 researchers). In a multivariable generalized estimating equations (GEE) analysis of the geometric mean (calculated for each pair of reported maximum and minimum payment amounts), factors B (first in humans), C (invasiveness), D (long-term risks), and E (time burden) were all significantly associated (p < .05) with proposed payment amounts, while A (comorbidity) and F (ancillary care) were not.
The study was limited to 15 non-randomly selected participants who may not represent their stakeholder groups on a national scale. We focused on HIV cure research in our vignettes, which may not be applicable to all other clinical HIV research. Two of the factors selected for the vignettes were not associated with payment amounts, despite the factors being generated by a community advisory board comprised of representatives from all three stakeholder groups.
Stakeholders in the research process in our study have different perceptions of appropriate payment to HIV cure research study participants and different study factors had varying impacts on payment decision-making. Findings can help drive discussions of what is fair payment in research with a focus on avoiding exploitation versus concern over undue influence, particularly in IRB review given higher proposed payment amounts among IRB members compared to researchers and PWH in our study. Payment decision-making is complex, and future research should allow for input from additional stakeholders and integrate additional study factors to address this complication.
Motivations to Participate in HIV Biomedical Research: Findings from Focus Groups with People Living with HIV in the United States
Karah Y. Greene1, Andrea N. Polonijo2, Karine Dubé3, Jerome T. Galea1, and Brandon Brown4
1University of South Florida School of Social Work, FL, USA
2Department of Sociology and the Health Sciences Research Institute, University of California Merced, Merced, CA, USA
3University of California San Diego, School of Medicine, USA
4Department of Social Medicine, Population, and Public Health, University of California Riverside School of Medicine, Riverside, CA, USA
Providing payment for participation in HIV biomedical research is common practice. Nonetheless, we lack understanding of how payment and other factors influence the decision to participate. We assessed perceptions of research payment and tangible and intangible motivators to participate in clinical research studies among people living with HIV (PLWH).
In 2022, PLWH participated in focus groups about the impact of incentives on clinical trial participation. Our 12-member Community Advisory Board (comprised of PLWH, ethics committee members, and HIV researchers) helped develop the informed consent and focus group questions to ensure participant understanding. Following informed consent, study participants completed a demographic survey and 90-min virtual focus group. Focus groups assessed participants’ perceptions of incentives, as well as tangible and intangible motivations for research participation. Participants received $25 USD. Recorded focus groups were transcribed, preliminarily coded using thematic analysis, and then systematically analyzed using a codebook.
Participants (N = 55) were 23–71-years-old (mean = 57.4, SD = 10.7); 25.5% were female and 49.1% non-White. Participants reported receiving $0–$6,000 USD payment in previous research studies. Perceptions of research incentives were that some participants viewed access to efficacious interventions post-study and/or comprehensive healthcare received while participating in research studies as incentives. All believed participants should not incur out-of-pocket expenses. Most stated cash as their preferred form of payment for research participation, but several wished studies offered different payment options to participants (e.g., Visa gift card, ClinCard). Intangible motivations included memorializing a loved one who had died from AIDS and to contribute to advancements that make HIV a more manageable, and perhaps one day curable, condition. Barriers to participation included HIV-related stigma, lack of trust in the scientific community due to historical unethical research conduct involving underrepresented and minoritized community members, and transportation challenges.
One limitation of our study was that virtual study participation may have excluded individuals with low technology literacy and those without internet access.
Increased consideration of research incentives and their effects on participant decision making is needed. Study recruitment and retention efforts may benefit by giving participants options for how they are paid. Our findings can guide future ethical incentive decision-making practices in clinical research.
Cultivating a Culture of Compliance with Clinical Trials Disclosure on ClinicalTrials.gov
Niem-Tzu “Rebecca” Chen1 and Cheryl Forst1
1The State University of New Jersey, New Brunswick, NJ, USA
Under a finite workforce and tight resources, the challenge of maintaining compliance with numerous clinical trials disclosures at ClinicalTrials.gov can appear daunting and unfeasible. The Human Research Protection Program (HRPP) at Rutgers University implemented an innovative approach that shifted the state into a win-win situation for investigators and the institution.
The Human Research Protection Program (HRPP) at Rutgers University is responsible for quality assurance reviews of human research studies. In 2013, the Program was tasked with the oversight of the required registration and results reporting at ClinicalTrials.gov. In 2017, the Program expanded their existing routine review procedures by adding a ClinicalTrials.gov-focused Routine Review. This innovative hybrid approach aims to (1) monitor the compliance with FDAAA801, and (2) provide indispensable support for investigators to act timely and to fully meet the requirements of the federal regulations. As an additional category of routine review, applicable interventional studies (i.e., “Applicable Clinical Trials (ACTs)” and “probably Applicable Clinical Trials (pACTs)”) required to meet compliance of FDAAA801 within ClinicalTrials.gov were provided a routine review conducted by the HRPP. The standard procedures were followed with an overview session that outlined the requirements of responsible party per the institutional policy and the federal regulations. All applicable studies were monitored through their research cycle accordingly. In May 2023, a subsequent review of study records was conducted and the results reporting status were recorded.
Between May 2017 and June 2019, a total of 18 Principal Investigators whose 24 studies were selected and reviewed through the HRPP ClinicalTrials.gov-focused routine review procedures. For the stage at the time of the initial review, among the 10 ACTs, one was at Before, and 9 During; among the 14 pACTs, two were at During, and 12 After. Five of the 10 ACTs and 11 of the 14 pACTs are oncology studies. Two late registrations (both ACTs) were identified at the time of the initial review and rectified to completion. The Table summarizes the numbers of clinical trials requiring results to be submitted in time that were submitted either on time, late, or not submitted at all, at the time points of initial review conducted during May 2017 through August 2019, and the subsequent review in May 2023. At the initial review, 11 pACTs did not submit results at all, 3 pACT and all 10 ACTs had forthcoming results reporting due dates. At the subsequent review, 1 pACT and 3 ACTs submitted the results on time, 12 pACTs and 0 ACT submitted late, 1 pACT and 2 ACTs not submitted at all. A total of 18 Principal Investigators (PIs) were interviewed during the initial review period. Of which, a total of 15 PIs had a single study and 3 PIs had multiple studies, respectively, for review. The subsequent review found that 6 PIs were no longer affiliated with the institution, and one PI was severely impacted by COVID and as a result impeded the corresponding results reporting responsibility
Since the status of compliance is required to be maintained throughout a period dictated by the study's research cycle, the findings of this study are limited by the time points of the data collection. These time points were (1) the time of the initial review and (2) the subsequent review conducted by the HRPP analyst/ ClinicalTrials.gov PRS Administrator.
The main takeaway is the earlier the ClinicalTrials.gov-focused routine review is conducted, the higher chance the investigator/ protocol may achieve compliance in its research cycle. Findings of these routine reviews have been regularly provided to the senior management for infrastructure support update which is essential for investigators. Besides an increase in registration, data reporting, and a reduction in problematic items, investigators now view HRPP as a valuable partner and resource, not merely a compliance overseer. The dissemination of routine review findings continues to enhance institutional compliance with federal regulations FDAAA801 and NIH Policy to uphold protection of human subjects in clinical research.
Hila Berger, MPH, CIP, CHC, Assistant Vice President for Research Regulatory Affairs, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States.
Perceived Barriers to the Recruitment and Retention of Underrepresented Racial and Ethnic Groups (URGs) in Clinical Research
Victoria McNamara1, Elise Smith2, and Emma Tumilty2
1University of Texas Medical Branch, Galveston, TX, USA
2Institute for Translational Sciences, Institute for Bioethics & Health Humanities, The University of Texas Medical Branch, Galveston, TX, USA
The inclusion of underrepresented racial and ethnic groups (URGs) in clinical research is critical for ethical and scientific reasons. This initiative aimed to assess the perspectives, barriers, needs, and recommendations encountered by research teams when enrolling and retaining URGs in clinical research.
An anonymous, web-based survey comprised of quantitative and qualitative questions was administered to individuals involved in clinical research at an academic medical center. The survey assessed three main domains: 1. Research teams’ perceptions and experiences with enrolling URGs in clinical research, 2. Factors that discourage URGs from participating in clinical research, and 3. Research teams’ overall willingness to support URG enrollment. Demographics were also collected. The survey was reviewed by experts in clinical research, research ethics, and diversity, equity, inclusion, and accessibility (DEIA). The assessment was piloted among research professionals and edits were made accordingly prior to official dissemination. Data were analyzed using descriptive statistics.
There was a total of 63 responses. A majority (62.1%) of respondents indicated that they have more success enrolling patients whose primary language is the same as their own and that time arranging for an interpreter has negatively impacted enrollment efforts (53.4%). Approximately half of the respondents (51.7%) believe that the race and/or ethnicity of the potential study participant influences enrollment success. Factors discouraging URGs from participating in clinical research include unavailability for follow-up visits due to transportation issues (72.4%), distrust in doctors and/or researchers (56.9%), fear of unknown side effects (56.9%), and unavailability of medical interpreters (50%). However, despite these potential challenges, respondents overwhelmingly report that they are not discouraged from enrolling URGs (77.6%). Overall, respondents would likely utilize various resources related to encouraging the inclusion of URGs. However, a small percentage of respondents (4.8%) expressed that DEIA and initiatives such as this assessment are racist, divisive, and/or regressive
This assessment was carried out at a single institution with a relatively small sample size. Therefore, these results may not be generalized across other academic medical institutions and may not accurately reflect the perspectives, barriers, and needs of research teams at other institutions. Additionally, the institution surveyed includes researchers involved in NIH-funded research, which places an emphasis on, and encourages, the recruitment of women and minorities.
Language appears to be a more influential factor than ethnicity or race when it comes to enrolling and retaining URGs. Therefore, the dedication of resources to address language barriers may increase the enrollment of URGs in clinical research. Overall, it appears that enrolling URGs is a bigger challenge than retaining URGs. Major themes that emerge with respect to retaining enrolled participants include the inability to attend follow-up visits and the lack of incentives/compensation. Therefore, streamlining processes at the institutional level, particularly related to compensation and transportation, may be an effective strategy for retaining URGs once enrolled in clinical research.
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding provided by the Clinical and Translational Science Award (UL1TR001439) from the National Center for Advancing Translational Sciences, National Institutes of Health.
Decisional Capacity for Research Consent Among Youth Living with HIV: Findings from the UBACC
Serena Wasilewski1, Eric Sumpter1, Kaitlyn Ligman1, Kemesha Gabbidon1, Carina A. Rodriguez1, and Tiffany Chenneville1
1University of South Florida, USA
Youth are especially vulnerable to HIV, as 22% of new HIV infections occur in youth between the ages of 13–24. While many people living with HIV are introduced to high-quality medical care though participation in clinical trials, conducting research with youth living with HIV (YLWH) presents ethical dilemmas involving consent/assent and how to best balance autonomy and protection. Decisional capacity (DC) to consent/assent (i.e., the understanding, appreciation, reasoning, and ability to express a choice) to clinical research gains significance in the context of balancing autonomy rights with the need to protect young research participants including YLWH. Given the vulnerability of YLWH, strategies to improve DC to assent/consent are warranted.
As part of a randomized controlled pilot study that explored the feasibility and acceptability of a multimedia intervention designed to improve the decisional capacity of YLWH to consent/assent to HIV research (results reported elsewhere), we administered the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC; Jeste et al., 2007) to 30 youth aged 13–24 living with HIV (15 in intervention condition, 15 in control condition). UBACC interviews were recorded and transcribed, and items were scored 0–2 points using criteria established by authors. A predetermined cutoff score was used to determine decisional capacity. Descriptive statistics were used to analyze participant demographics. Differences in UBACC scores between the intervention and control group were analyzed using the Mann-Whitney U test for independent samples. Thematic analysis was used to analyze qualitative data from the UBACC interviews.
Participants were predominantly Black (63.3%), non-Hispanic (60.0%), males (73.3%) aged 13–24 (M = 19.5, SD = 3.3). There was a significant difference in total UBACC scores between the intervention and control groups (U = 161.0, p = .045, r = .37), with youth in the intervention group scoring significantly higher than youth in the control group. An analysis of individual items revealed a difference between groups, U = 169.5, p = .02, r = .48 on one item (Please describe some of the risks or discomforts that people may experience if they participate in this study) with youth in the intervention group scoring significantly higher than youth in the control group. Despite significant differences between groups, neither group met the pre-established cutoff score for DC. Qualitative analyses provided data on the types of errors contributing to scores of 0 (no credit) and 1 (partial credit) across conditions. Common errors were related to understanding the study's purpose, requirements, risks, and benefits.
The use of a small sample size from a restricted geographic area limits the generalizability of results. Further, the transition from in-person to remote data collection due to COVID-19 may have affected findings.
This study contributes to the existing literature on the importance of decisional capacity to consent to research, particularly among vulnerable groups such as youth living with HIV. An examination of common decisional capacity errors is important for creating consent procedures that ensure participants truly understand and appreciate study components. Further research is needed on ways to improve decisional capacity for research consent, particularly among vulnerable populations including minors and people living with chronic illnesses such as HIV.
Understanding Our QA/QI Programs: Research Compliance Network Metrics Survey Results
Leslie M. Howes1 and Sana Shakour2
1Harvard T.H. Chan School of Public Health, Boston, MA, USA
2University of Michigan, Ann Arbor, MI, USA
Unlike the IRBs, QA/QI criteria are not outlined in the regulations and QA/QI functions vary between organizations. To better define the characteristics, scope, and time trends of these functions, a national consortium representing more than 100 institutions conducted surveys in 2019 and 2022. This poster will highlight some findings.
An online survey was distributed to all members of the consortium via the Qualtrics platform. The survey included 74 closed-ended questions organized in five sections including: organizational characteristics, QA/QI program scope, policy and procedures, single IRB issues, and resources. Ten business days were provided to complete the survey with two reminders. The survey was anonymous, and members were instructed to submit one response per organization. Minor modifications were made to the survey in 2022 to evaluate the impact of the pandemic on QA/QI work arrangements and workload. However, the core questions were similar in order to identify time trends. Descriptive statistics were conducted on data collected from both surveys. Qualitative data will be presented graphically and in tables.
Forty-five organizations responded to 2022 survey. Over half were academic medical centers or universities and 78% were AAHRPP-accredited (a 17% increase since 2019). Organizations conducted both biomedical and SBER and ranged in size. Half indicated having <4,000 active protocols. Most respondents (84%) had a QA/QI Program/function which was well-established, i.e., 5+ years implementation. Programs were independent of the IRB (62%) with most housed within the HRPP or compliance unit. Most QA/QI Programs operated in hybrid fashion (68%). QA/QI Programs offered varying activities though auditing remained a hallmark. Roughly half did not conduct audits of external IRB studies, i.e., studies in which the organization serves as a participating site (57%); however, even less reported auditing participating sites when serving as a single IRB (38% as compared to 30% reported in 2019). Related, there was a 37% increase of remote audits of external sites since the 2019 survey
QA/QI Programs are not well defined. As a result, the survey relied upon AAHRPP elements I.5.A and I.5.B to inform this threshold. Doing so may inadvertently conflate AAHRPP accreditation status and unnecessarily narrow the scope of organizations having a QA/QI Program or function. Additionally, the survey was conducted anonymously; therefore, the 2022 survey may not draw from the exact sample of organizational respondents solicited in 2019.
QA/QI Programs continue to evolve. The results of these surveys help us understand their current landscape, including organizational characteristics such as demographics and program structure; scope of work, including the range of activities and initiatives; policies and procedures; how Programs adapt to changes in regulations and policy, namely the NIH single IRB policy, and resources such as staffing and training. Still further, there is a need to collect more data in order to identify trends over time and propose best practices.
Clinical Research Study Coordinators’ Training – A Deep Dive into Informed Consent: An Assessment of CRC Knowledge
Claudia N. Gunawan1,2,3, Priscilla Adler1,2,3, Jane Otado1,4, John Kwagyan1,4, and Mary Anne Hinkson5
1Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS), Washington, DC, USA
2Veterans Affairs Medical Center
3Institute for Clinical Research, Inc., Washington, DC, USA
4Howard University College of Medicine, USA
5MedStar Health Research Institute
Clinical research coordinators (CRC) need continuous trainings in Human Protection Research, Ethics, and Regulatory Updates. This training workshop was designed for clinical study coordinators but was open to clinical research personnel at all levels. The workshop was held to provide a deep dive and continuing education about informed consent processes.
We promoted the in-person workshop through the communication systems within member institutions. This in-person session was critical due to regulatory changes that had occurred as a result of the COVID pandemic. A detailed flyer was emailed using a list serve to all levels of clinical researchers. A registration form created on the REDCap platform provided a link for registration and the means to capture data. A follow-up email reminder was sent every two weeks. The training was organized in modules, each of which included didactic materials, hands-on training, case studies, and teach-back sessions. A Jeopardy game was conducted at the end of the workshop to reiterate the information that was covered during the training. A survey pertinent to regulatory and informed consent processes was developed. The survey, which contained a 15-item questionnaire, was provided to the attendees pre- and post-workshop to assess knowledge gained.
A total of 42 people registered, and 30 people attended the event. Of the 30 attendees, 21 (70%) were study coordinators. Of the study coordinators, 8 (38%) had been a study coordinator for less than 1 year, 2 (10%) had been a study coordinator for 1–2 years, 4 (19%) had been a study coordinator for 3–4 years, and 7 (33%) had been a study coordinator for more than 4 years. Other attendees included investigators, administrators, nurses, and regulatory personnel. Many of the questions that focused on consent elements were answered correctly by the participants prior to the workshop. Conversely, only 14% initially knew the correct Human Health Service regulations for the Common Rule. This number increased to 33% post-workshop. Additionally, knowledge of the required reading grade level language on informed consent forms (ICFs) improved from 71% pre- to 100% post- workshop.
All responses to the survey questionnaire items were anonymous and were not connected in any way. Thus, a person-by-person comparison (pre-vs. post- workshop) was not able to be performed.
Overall, there was a significant improvement in the number of correct responses to the questionnaire items post-workshop. The improvement shows that study coordinators benefit from continuous review of informed consent form elements. This includes a discussion on the information required in ICFs, government agencies that oversee clinical trials, and the reading grade levels for ICFs. Of importance, study coordinators need further guidance on where to find specific federal regulations for informed consent processes. Responses to a 6-Month Follow-Up also reflect these findings. As such, it may be beneficial to hold clinical research coordinator training workshops every 6–12 months to ensure knowledge is retained and correct practices are implemented.