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Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial.

ABSTRACT:

Background

New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic "Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)" randomized trial that required a reappraisal of the IRB submission, review, and approval processes are discussed.

Main text

ADAPTABLE is a pragmatic, multicenter, open-label RCT evaluating the comparative effectiveness of two doses of aspirin widely used for secondary prevention (81?mg and 325?mg) in 15,000 patients with an established history of atherosclerotic cardiovascular disease. The electronic informed consent form is completed online by the participants at the time of enrollment, and endpoint ascertainment is conducted through queries of electronic health records. IRB challenges encountered regarding centralized IRB evaluation, electronic informed consent, patient engagement, and risk determination in ADAPTABLE are described in this manuscript. The experience of ADAPTABLE encapsulates how pragmatic protocol components intended to facilitate the study conduct have been tempered by unexpected, yet justified concerns raised by local IRBs. How the lessons learned can be applied to future similar pragmatic trials is delineated.

Conclusion

Development of engaging communication channels between IRB and study personnel in pragmatic randomized trials as early as at the time of protocol design allows to reduce issues with IRB approval. Integrations of the lessons learned in ADAPTABLE regarding the IRB process for centralized IRBs, informed consent, patient engagement, and risk determination can be emulated and will be instrumental in future pragmatic studies.

SUBMITTER: Marquis-Gravel G

PROVIDER: S-EPMC7831187 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial.

Marquis-Gravel Guillaume G Robertson Holly H Jones W Schuyler WS Riley Danielle D Ford Daniel E DE Crenshaw David D Joosten Yvonne A YA Rudov Lindsey L Hernandez Adrian F AF Hess Rachel R

Trials 20210125 1

<h4>Background</h4>New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic "Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)" randomized trial that required a reappraisal of the IRB submission, review, ...[more]

PMID: 33494785

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Project description:BackgroundMany large-scale cardiovascular clinical trials are plagued with escalating costs and low enrollment. Implementing a computable phenotype, which is a set of executable algorithms, to identify a group of clinical characteristics derivable from electronic health records or administrative claims records, is essential to successful recruitment in large-scale pragmatic clinical trials. This methods paper provides an overview of the development and implementation of a computable phenotype in ADAPTABLE (Aspirin Dosing: a Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness)-a pragmatic, randomized, open-label clinical trial testing the optimal dose of aspirin for secondary prevention of atherosclerotic cardiovascular disease events.Methods and resultsA multidisciplinary team developed and tested the computable phenotype to identify adults ≥18 years of age with a history of atherosclerotic cardiovascular disease without safety concerns around using aspirin and meeting trial eligibility criteria. Using the computable phenotype, investigators identified over 650 000 potentially eligible patients from the 40 participating sites from Patient-Centered Outcomes Research Network-a network of Clinical Data Research Networks, Patient-Powered Research Networks, and Health Plan Research Networks. Leveraging diverse recruitment methods, sites enrolled 15 076 participants from April 2016 to June 2019. During the process of developing and implementing the ADAPTABLE computable phenotype, several key lessons were learned. The accuracy and utility of a computable phenotype are dependent on the quality of the source data, which can be variable even with a common data model. Local validation and modification were required based on site factors, such as recruitment strategies, data quality, and local coding patterns. Sustained collaboration among a diverse team of researchers is needed during computable phenotype development and implementation.ConclusionsThe ADAPTABLE computable phenotype served as an efficient method to recruit patients in a multisite pragmatic clinical trial. This process of development and implementation will be informative for future large-scale, pragmatic clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02697916.

Project description:BackgroundInstitutional Review Boards (IRBs) have been criticized for inconsistency, delay, and bias, suggesting an opportunity for quality improvement. To aid such quality improvement, this study aimed at determining IRB members' and investigators' priorities regarding IRB review at 10 Veterans Affairs (VA) IRBs.Methods680 anonymous internet surveys were sent to 252 IRB members and staff, and 428 principal investigators and project coordinators at 9 VA Medical Centers and the VA Central IRB. Surveys included 27 statements adapted from Koocher and Kieth-Spiegel's IRB-RAT describing IRB activities or functions (e.g., "An IRB that is open to reversing its earlier decisions"). Respondents indicated how each statement described both their "ideal" and "actual" IRBs. The difference between the ratings of the actual and ideal IRBs was calculated for each item along with estimated 95% confidence intervals. Ratings outside those intervals indicated activities or functions with relatively good or poor performance compared to the ideal IRB.Results390 (57.4%) responses from 165 IRB members and staff (65.5%) and 225 investigators and project coordinators (52.6%) demonstrated that these IRBs were closest to the ideal when protecting human subjects, treating investigators with respect, and taking appropriate action for alleged scientific misconduct. The IRBs were furthest from the ideal regarding duplicative forms, timeliness of review, and provision of complete rationales for decisions. Although IRB members reported near-ideal willingness to reverse earlier decisions, investigators rated this capacity far from ideal. Investigators rated IRB members' knowledge about procedures and policy as nearly ideal, but IRB members themselves rated this aspect far from ideal. Noteworthy site-level differences in the ratings of IRB functions and activities were also identified.ConclusionsAlthough these VA IRBs perform well in some areas, these data support the need for ongoing quality improvement. The described method of administering and analyzing the IRB-RAT may help identify and monitor site- and activity- specific initiatives for quality improvement.

Project description:BackgroundTo improve the implementation of clinical trial interventions, there is a need to facilitate communication between key stakeholders and research teams. Community Advisory Boards (CAB) bring together a range of stakeholders not historically included in the research process to inform and work collaboratively with research teams.ObjectiveTo describe our procedures and processes for (1) integration of a CAB into a pragmatic clinical trial of a telehealth-delivered group mindfulness program for persons with chronic low back pain (cLBP) within primary care, and (2) for the rapid uptake and implementation of CAB recommendations.MethodsThe CAB we convened includes persons with cLBP who have undergone the mindfulness intervention, health care system leadership, advocacy groups, and mindfulness experts. The CAB members underwent a two hour initial training that introduced the research process and the CAB's role as research partners. The CAB met monthly for 1 hour. We used the Lighting Report method to summarize meetings and share feedback with the research team.ResultsThe recommendations of the CAB during the first year they met were divided into recruitment, informed consent, and survey recommendations. The study website also was overhauled based on recommendations, including a more engaging first page with rotating images of nature and testimonials. The language on the website was edited to be more concise and participant-friendly. The CAB recommended talking points to discuss with participants during screening or informed consent about the benefits of participating in research.ConclusionWe established a CAB that represented diverse perspectives, organizations, and experience with cLBP and mindfulness. The differing perspectives of the CAB resulted in recommendations that the research team itself would not have decided on their own. The Lightning Reports were also an effective way to efficiently communicate the CAB recommendations to the research team.

Project description:BackgroundThe appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy.MethodsUsing an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis.ResultsA total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]).ConclusionsIn this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Project description:BACKGROUND:Pragmatic randomized clinical trials are essential to determine the effectiveness of interventions in "real-world" clinical practice. These trials frequently use a cluster-randomized methodology, with randomization at the site level. Despite policymakers' increased interest in supporting pragmatic randomized clinical trials, no studies to date have reported on the unique recruitment challenges faced by cluster-randomized pragmatic trials. We investigated key challenges and successful strategies for hospital recruitment in the Comprehensive Post-Acute Stroke Services (COMPASS) study. METHODS:The COMPASS study is designed to compare the effectiveness of the COMPASS model versus usual care in improving functional outcomes, reducing the numbers of hospital readmissions, and reducing caregiver strain for patients discharged home after stroke or transient ischemic attack. This model integrates early supported discharge planning with transitional care management, including nurse-led follow-up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7-14 days involving a functional assessment and neurological examination. We present descriptive statistics of the characteristics of successfully recruited hospitals compared with all eligible hospitals, reasons for non-participation, and effective recruitment strategies. RESULTS:We successfully recruited 41 (43%) of 95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non-participation included: insufficient staff or financial resources (n?=?33, 61%), lack of health system support (n?=?16, 30%), and lack of support of individual decision-makers (n?=?11, 20%). Successful recruitment strategies included: building and nurturing relationships, engaging team members and community partners with a diverse skill mix, identifying gatekeepers, finding mutually beneficial solutions, having a central institutional review board, sharing published pilot data, and integrating contracts and review board administrators. CONCLUSIONS:Although we incorporated strategies based on the best available evidence at the outset of the study, hospital recruitment required three times as much time and considerably more staff than anticipated. To reach our goal, we tailored strategies to individuals, hospitals, and health systems. Successful recruitment of a sufficient number and representative mix of hospitals requires considerable preparation, planning, and flexibility. Strategies presented here may assist future trial organizers in implementing cluster-randomized pragmatic trials. TRIAL REGISTRATION:Clinicaltrials.gov, NCT02588664 . Registered on 23 October 2015.

Dataset Information

Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial.

Background

Main text

Conclusion

Publications

Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial.

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