Central monitoring in a randomized, open-label, controlled phase 3 clinical trial for a treatment-shortening regimen for pulmonary tuberculosis.


Bryant KE(1), Yuan Y(2), Engle M(3), Kurbatova EV(2), Allen-Blige C(4), Batra K(4), Brown NE(2), Chiu KW(4), Davis H(4), Elskamp M(5), Fagley M(2), Fedrick P(4), Hedges KNC(6), Narunsky K(7), Nassali J(8), Phan M(9), Phan H(10), Purfield AE(11), Ricaldi JN(2), Robergeau-Hunt K(12), Whitworth WC(2), Sizemore EE(2); AIDS Clinical Trials Group; Tuberculosis Trials Consortium.
Author information:
(1)U.S. Centers for Disease Control & Prevention, Atlanta, GA, United States of America. Electronic address: [Email]
(2)U.S. Centers for Disease Control & Prevention, Atlanta, GA, United States of America.
(3)Audie L. Murphy Veterans Affairs Medical Center, University of Texas Health Science Center, San Antonio, TX, United States of America.
(4)Peraton, Herndon, VA, United States of America.
(5)Columbia University Irving Medical Center, New York, NY, United States of America.
(6)U.S. Centers for Disease Control & Prevention, Atlanta, GA, United States of America; Peraton, Herndon, VA, United States of America.
(7)University of Cape Town Lung Institute, Cape Town, South Africa.
(8)Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda.
(9)Northrop Grumman Corporation, San Diego, CA, United States of America.
(10)Vietnam National Tuberculosis Program, University of California San Francisco Research Collaboration, Hanoi, Viet Nam.
(11)U.S. Centers for Disease Control & Prevention, Atlanta, GA, United States of America; US Public Health Service Commissioned Corps, Rockville, MD, United States of America.
(12)Westat, Rockville, MD, United States of America.


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.