Central monitoring in a randomized, open-label, controlled phase 3 clinical trial for a treatment-shortening regimen for pulmonary tuberculosis
Kia E Bryant, Yan Yuan, Melissa Engle, Ekaterina V Kurbatova, Cynthia Allen-Blige, Kumar Batra, Nicole E Brown, Kuo Wei Chiu, Howard Davis, Mascha Elskamp, Melissa Fagley, Pamela Fedrick, Kimberley N C Hedges, Kim Narunsky, Joanita Nassali, Mimi Phan, Ha Phan, Anne E Purfield, Jessica N Ricaldi, Kathleen Robergeau-Hunt, William C Whitworth, Erin E Sizemore, AIDS Clinical Trials Group, Tuberculosis Trials Consortium, Kia E Bryant, Yan Yuan, Melissa Engle, Ekaterina V Kurbatova, Cynthia Allen-Blige, Kumar Batra, Nicole E Brown, Kuo Wei Chiu, Howard Davis, Mascha Elskamp, Melissa Fagley, Pamela Fedrick, Kimberley N C Hedges, Kim Narunsky, Joanita Nassali, Mimi Phan, Ha Phan, Anne E Purfield, Jessica N Ricaldi, Kathleen Robergeau-Hunt, William C Whitworth, Erin E Sizemore, AIDS Clinical Trials Group, Tuberculosis Trials Consortium
Abstract
Introduction: With the growing use of online study management systems and rapid availability of data, timely data review and quality assessments are necessary to ensure proper clinical trial implementation. In this report we describe central monitoring used to ensure protocol compliance and accurate data reporting, implemented during a large phase 3 clinical trial.
Material and methods: The Tuberculosis Trials Consortium (TBTC) Study 31/AIDS Clinical Trials Group (ACTG) study A5349 (S31) is an international, multi-site, randomized, open-label, controlled, non-inferiority phase 3 clinical trial comparing two 4-month regimens to a standard 6 month regimen for treatment of drug-susceptible tuberculosis (TB) among adolescents and adults with a sample size of 2500 participants.
Results: Central monitoring utilized primary study data in a five-tiered approach, including (1) real-time data checks & topic-specific intervention reports, (2) missing forms reports, (3) quality assurance metrics, (4) critical data reports and (5) protocol deviation identification, aimed to detect and resolve quality challenges. Over the course of the study, 240 data checks and reports were programed across the five tiers used.
Discussion: This use of primary study data to identify issues rapidly allowed the study sponsor to focus quality assurance and data cleaning activities on prioritized data, related to protocol compliance and accurate reporting of study results. Our approach enabled us to become more efficient and effective as we informed sites about deviations, resolved missing or inconsistent data, provided targeted guidance, and gained a deeper understanding of challenges experienced at clinical trial sites.
Trial registration: This trial was registered with ClinicalTrials.gov (Identifier: NCT02410772) on April 8, 2015.
Keywords: Central monitoring; Clinical trial; Clinical trial quality assurance; Tuberculosis.
Conflict of interest statement
Competing interests
The authorship team members have declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Sanofi commercial interests did not influence the study design; the collection, analysis, or interpretation of data; the preparation of this manuscript; or the decision to submit this manuscript for publication. A Sanofi technical expert served on the protocol team.
Published by Elsevier Inc.
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Source: PubMed