Randomized controlled trials (RCTs) are widely considered the gold standard for inference on the comparative effects of 2 or more treatment strategies. Randomization is the most powerful technique available in causal inference, and the controlled setting of carefully designed experiments is a necessity in evaluating most treatments. Still, as currently designed, conducted, and analyzed, clinical trials are not without limitations and might be susceptible to some of the biases present in observational studies (1, 2). Strict inclusion and exclusion criteria, as well as trials often being conducted “in parallel” with regular clinical care, have led to concerns that the enrolled ...
References
- 1.
Hernán MA ,Hernández-Díaz S ,Robins JM . Randomized trials analyzed as observational studies. Ann Intern Med. 2013;159:560-2. [PMID: 24018844] AbstractGoogle Scholar - 2.
Mansournia MA ,Higgins JP ,Sterne JA ,Hernán MA . Biases in randomized trials: a conversation between trialists and epidemiologists. Epidemiology. 2017;28:54-9. [PMID: 27748683] CrossrefMedlineGoogle Scholar - 3.
Goldstein BA ,Bhavsar NA ,Phelan M ,Pencina MJ . Controlling for informed presence bias due to the number of health encounters in an electronic health record. Am J Epidemiol. 2016;184:847-55. [PMID: 27852603] CrossrefMedlineGoogle Scholar - 4.
Sherman RE ,Anderson SA ,DalPan GJ ,Gray GW ,Gross T ,Hunter NL ,et al . Real-world evidence—what is it and what can it tell us? N Engl J Med. 2016;375:2293-7. [PMID: 27959688] CrossrefMedlineGoogle Scholar - 5.
Lauer MS ,D'Agostino RB . The randomized registry trial—the next disruptive technology in clinical research? N Engl J Med. 2013;369:1579-81. [PMID: 23991657] doi:10.1056/NEJMp1310102 CrossrefMedlineGoogle Scholar - 6.
Jones WS ,Roe MT ,Antman EM ,Pletcher MJ ,Harrington RA ,Rothman RL ,et al . The changing landscape of randomized clinical trials in cardiovascular disease. J Am Coll Cardiol. 2016;68:1898-1907. [PMID: 27765193] doi:10.1016/j.jacc.2016.07.781 CrossrefMedlineGoogle Scholar - 7.
Pencina MJ ,Peterson ED . Moving from clinical trials to precision medicine: the role for predictive modeling [Editorial]. JAMA. 2016;315:1713-4. [PMID: 27115375] doi:10.1001/jama.2016.4839 CrossrefMedlineGoogle Scholar - 8.
Mansournia MA ,Etminan M ,Danaei G ,Kaufman JS ,Collins G . Handling time varying confounding in observational research. BMJ. 2017;359:j4587. [PMID: 29038130] doi:10.1136/bmj.j4587 CrossrefMedlineGoogle Scholar - 9.
Lopes RD ,Rordorf R ,DeFerrari GM ,Leonardi S ,Thomas L ,Wojdyla DM ,et al ;ARISTOTLE Committees and Investigators . Digoxin and mortality in patients with atrial fibrillation. J Am Coll Cardiol. 2018;71:1063-74. [PMID: 29519345] doi:10.1016/j.jacc.2017.12.060 CrossrefMedlineGoogle Scholar - 10.
Li F ,Morgan KL ,Zaslavsky AM . Balancing covariates via propensity score weighting. J Am Stat Assoc. 2017;113:390-400. CrossrefGoogle Scholar
Author, Article, and Disclosure Information
Duke University School of Medicine, Durham, North Carolina (M.J.P.)
Duke Clinical Research Institute, Durham, North Carolina (F.W.R.)
Boston University, Boston, Massachusetts (R.B.D.)
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1093.
Corresponding Author: Michael J. Pencina, PhD, Duke University School of Medicine, 2400 Pratt Street, Duke Box 3850, Durham, NC 27710; e-mail, michael.
Current Author Addresses: Dr. Pencina: Duke University School of Medicine, 2400 Pratt Street, Duke Box 3850, Durham, NC 27710.
Dr. Rockhold: Duke Clinical Research Institute, 2400 Pratt Street, Duke Box 3850, Durham, NC 27710.
Dr. D'Agostino: Boston University, 111 Cummington Mall, Boston, MA 02215.
Author Contributions: Conception and design: M.J. Pencina, F.W. Rockhold, R.B. D'Agostino.
Analysis and interpretation of the data: M.J. Pencina, F.W. Rockhold, R.B. D'Agostino.
Drafting of the article: M.J. Pencina.
Critical revision for important intellectual content: F.W. Rockhold, R.B. D'Agostino.
Final approval of the article: M.J. Pencina, F.W. Rockhold, R.B. D'Agostino.
Statistical expertise: M.J. Pencina, F.W. Rockhold, R.B. D'Agostino.
This article was published at Annals.org on 24 July 2018.
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
*All comments submitted after October 1, 2021 and selected for publication will be published online only.