Bryan R. Luce, PhD; Jason T. Connor, PhD; Kristine R. Broglio, MS; C. Daniel Mullins, PhD; K. Jack Ishak, PhD; Elijah Saunders, MD; Barry R. Davis, MD, PhD; on behalf of the RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials) Investigators (*)
Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the official views of the Patient-Centered Outcomes Research Institute; National Heart, Lung, and Blood Institute (NHLBI); or the National Institutes of Health (NIH).
Acknowledgment: The authors thank the NHLBI for their generous financial support and the ALLHAT Steering Committee for their moral support and guidance.
Financial Support: The RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials) project was supported by the NHLBI (award 1RC4HL106363-01).
Disclosures: Dr. Luce reports work with United BioSource Corporation (subcontractor of the University of Maryland for the NIH grant that funded this study) during the conduct of the study; he also reports that Untied BioSource Corporation received contracts from various pharmaceutical companies that could have had a passing interest in this NIH-funded manuscript. Dr. Connor reports grants from the NHLBI during the conduct of the study. Ms. Broglio reports grants from the NHLBI (grant 1RC4HL106363-01 to Berry Consultants) during the conduct of the study. Dr. Mullins reports grants from NHLBI during the conduct of the study. He also reports grants and personal fees from Amgen, Bayer, and Pfizer; and personal fees from Bristol-Myers Squibb, Daiichi Sankyo, Genentech, and Janssen (Johnson & Johnson) outside of the study. Dr. Ishak reports grants from the NHLBI (to Evidera) during the conduct of the study; he is also an employee of Evidera. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0823.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Requests for Single Reprints: Bryan R. Luce, PhD, Department of Pharmacy, University of Washington, H172 Health Science Building, 1959 Northeast Pacific Street, Seattle, WA 98195; e-mail, email@example.com.
Current Author Addresses: Dr. Luce: Department of Pharmacy, University of Washington, H172 Health Science Building, 1959 Northeast Pacific Street, Seattle, WA 98195.
Dr. Connor: Berry Consultants, 8290 Southwest 180th Street, Miami, FL 33157.
Ms. Broglio: Berry Consultants, 4301 Westbank Drive, Building B, Suite 140, Austin, TX 78746.
Dr. Mullins: Pharmaceutical Health Services Research Department, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD 21201.
Dr. Ishak: Department of Biostatistics, Evidera, 7575 Trans-Canada Highway, Suite 500, Saint-Laurent, Quebec H4T 1V6, Canada.
Dr. Davis: Department of Biostatistics, The University of Texas School of Public Health, 1200 Pressler Street, Room W916, Houston, TX 77030.
Author Contributions: Conception and design: B.R. Luce, J.T. Connor, C.D. Mullins, K.J. Ishak, E. Saunders.
Analysis and interpretation of the data: B.R. Luce, J.T. Connor, K.J. Ishak, B.R. Davis.
Drafting of the article: B.R. Luce, J.T. Connor, K.R. Broglio, C.D. Mullins, K.J. Ishak.
Critical revision of the article for important intellectual content: B.R. Luce, J.T. Connor, K.R. Broglio, C.D. Mullins, K.J. Ishak, B.R. Davis.
Final approval of the article: B.R. Luce, J.T. Connor, K.R. Broglio, C.D. Mullins, K.J. Ishak, B.R. Davis.
Provision of study materials or patients: B.R. Davis.
Statistical expertise: J.T. Connor, K.R. Broglio, K.J. Ishak, B.R. Davis.
Obtaining of funding: B.R. Luce, J.T. Connor, C.D. Mullins, E. Saunders.
Administrative, technical, or logistic support: J.T. Connor, C.D. Mullins.
Collection and assembly of data: J.T. Connor, B.R. Davis.
Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs.
To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research.
Virtual execution of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design.
Comparative effectiveness trial of antihypertensive medications.
Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data.
Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions.
The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier.
This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered.
In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better-performing groups.
National Heart, Lung, and Blood Institute.
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Luce BR, Connor JT, Broglio KR, Mullins CD, Ishak KJ, Saunders E, et al. Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution. Ann Intern Med. 2016;165:431-438. doi: 10.7326/M15-0823
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Published: Ann Intern Med. 2016;165(6):431-438.
Published at www.annals.org on 7 June 2016
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