Estimating treatment effect with clinical interpretation from a comparative clinical trial with an end point subject to competing risks

TY - JOUR

T1 - Estimating treatment effect with clinical interpretation from a comparative clinical trial with an end point subject to competing risks

AU - Zhao, Lihui

AU - Tian, Lu

AU - Claggett, Brian

AU - Pfeffer, Marc

AU - Kim, Dae Hyun

AU - Solomon, Scott

AU - Wei, Lee Jen

N1 - Funding Information: Author Affiliations: Department of Preventive Medicine, Northwestern University, Chicago, Illinois (Zhao); Stanford Medical School, Stanford University, Stanford, California (Tian); Division of Cardiovascular, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts (Claggett, Pfeffer, Solomon); Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts (Kim); Department of Biostatistics, Harvard University, Boston, Massachusetts (Wei). Corresponding Author: Lee-Jen Wei, PhD, Department of Biostatistics, Harvard University, 655 Huntington Ave, Boston, MA 02115 (wei@hsph.harvard.edu). Accepted for Publication: January 18, 2018. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Pfeffer reports receiving personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, DalCor, Gilead, GlaxoSmithKline, Janssen, Lilly USA, The Medicines Company, Merck, Novo Nordisk, Relypsa, Thrasos, Genzyme, and Teva and grants and personal fees from Novartis and Sanofi. He also holds a patent with Novartis for the use of inhibitors of renal artery stenosis in patients with myocardial infarction. Dr Kim reports receiving grant support from the National Institute on Aging and personal fees from Alosa Health. No other disclosures were reported. Published Online: March 14, 2018. doi:10.1001/jamacardio.2018.0127 Author Contributions: Drs Wei, Claggett, and Tian had full access to the data from the β-Blocker Evaluation of Survival Trial and had full responsibility for the integrity of data and the accuracy of data analysis. Drs Zhao and Tian equally contributed to this work and are co-first authors, and Drs Solomon and Wei have equally contributed to this work and are co-last authors. Concept and design: Zhao, Tian, Solomon, Wei. Acquisition,analysis,orinterpretationofdata:Zhao,Tian,Claggett,Pfeffer,Kim,Wei. Drafting of the manuscript: Zhao, Tian, Claggett, Wei. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Zhao, Tian. Obtained funding: Shao, Tian, Solomon, Wei. Supervision: Solomon, Wei. Funding/Support: This work was partially supported by grants and contracts from the National Institutes of Health. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Additional Contributions: We thank Michael Pencina, PhD, Duke Clinical Research Institute, and 3 reviewers for their constructive suggestions/ comments on the article. They were not compensated for their contributions. 1. Royston P, Parmar MK. Restricted mean survival time: an alternative to the hazard ratio for the design and analysis of randomized trials with a time-to-event effect. BMC Med Res Methodol. 2013;13(1):152. 2. Uno H, Wittes J, Fu H, et al. Alternatives to hazard ratios for comparing the efficacy or safety of therapies in noninferiority studies. Ann Intern Med. 2015; 163(2):127-134. 3. Kim DH, Uno H, Wei LJ. Restricted mean survival time as a measure to interpret clinical trial results. JAMA Cardiol. 2017;2(11):1179-1180. 4. Eichhorn EJ, Domanski MJ, Krause-Steinrauf H, Bristow MR, Lavori PW; Beta-Blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001; 344(22):1659-1667. 5. Lau B, Cole SR, Gange SJ. Competing risk regression models for epidemiologic data. Am J Epidemiol. 2009;170(2):244-256. 6. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496-509. doi:10.1080 /01621459.1999.10474144 Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2018/4

Y1 - 2018/4

UR - http://www.scopus.com/inward/record.url?scp=85046020026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046020026&partnerID=8YFLogxK

U2 - 10.1001/jamacardio.2018.0127

DO - 10.1001/jamacardio.2018.0127

M3 - Letter

C2 - 29541747

AN - SCOPUS:85046020026

VL - 3

SP - 357

EP - 358

JO - JAMA Cardiology

JF - JAMA Cardiology

SN - 2380-6583

IS - 4

ER -