Randomized Controlled Trials
Open accessAbstract
Randomized controlled trials (RCTs) are considered the highest level of evidence to establish causal associations in clinical research. There are many RCT designs and features that can be selected to address a research hypothesis. Designs of RCTs have become increasingly diverse as new methods have been proposed to evaluate increasingly complex scientific hypotheses. This article reviews the principles and general concepts behind many common RCT designs and introduces newer designs that have been proposed, such as adaptive and cluster randomized trials. A focus on the many choices for randomization within an RCT is described, along with their potential tradeoffs. To illustrate their diversity, examples of RCTs from the literature are provided. Statistical considerations, such as power and type I error rates, are discussed with the intention of providing practical guidance about how to specify study hypotheses that address the scientific question while being statistically appropriate. Finally, the freely available Consolidated Standards of Reporting Trials guidelines and US Food and Drug Administration guidance documents are introduced, along with a set of guidelines one should consider when planning an RCT or reviewing RCTs submitted for publication in peer-reviewed academic journals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Simple randomization does not guarantee the control of important variables to be considered for both treatment groups, as occurs in stratified randomization.
“In addition, simple randomization does not guarantee the control of important variables to be considered for both treatment groups, as occurs in stratified randomization 3 , 35 .”
From Global mapping of randomized controlled trials in dentistry (2024) · cites this paper as [3]
RCTs are the basis for clinical decision-making.
“RCTs are the basis for clinical decision-making.”
From Global mapping of randomized controlled trials in dentistry (2024) · cites this paper as [3]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting
Hemming, K., Haines, T. P., Chilton, P. J., Girling, A. J., & Lilford, R. J. (2015) · BMJ · doi:10.1136/bmj.h391 · Cited by 1,410 · see citing works
The Predictive Approaches to Treatment effect Heterogeneity (PATH) statement
Kent, D. M., Paulus, J. K., van Klaveren, D., D'Agostino, R., Goodman, S., Hayward, R., Ioannidis, J. P. A., Patrick-Lake, B., Morton, S., Pencina, M., et al. (2020) · Annals of Internal Medicine · doi:10.7326/m18-3667 · Cited by 469 · see citing works
Properties of permuted-block randomization in clinical trials
Matts, J. P., & Lachin, J. M. (1988) · Controlled Clinical Trials · doi:10.1016/0197-2456(88)90047-5 · Cited by 321 · see citing works
Flagged first, then by citations
Research works printed but not linked: 21
- The periodic health examination. Canadian Task Force on the Periodic Health Examination. Can Med Assoc J. 1979;121(9):1193- 1254.
- Hemming K, Eldridge S, Forbes G, Weijer C, Taljaard M. How to design efficient cluster randomised trials. BMJ. 2017;358:j3064.
- Hobbs BP, Berry DA, Coombes KR. Biostatistics and bioinformatics in clinical trials. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology, Sixth Edition. Philadelphia, PA: Elsevier; 2020. 284-295.e2.
- Hobbs BP, Lee JJ. Adaptive trial designs. In: Crowley J, Hoering A, eds. Handbook of Statistics in Clinical Oncology. Third Edition. Boca Raton, FL: Taylor & Francis/CRC Press; 2012:265-292.
- Renfro LA, Sargent DJ. Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples. Ann Oncol. 2017;28(1):34-43.
- Woodcock J, LaVange LM. Master protocols to study multiple therapies, multiple diseases, or both. N Engl J Med. 2017;377(1):62- 70.
- Hobbs BP, Chen N, Lee JJ. Controlled multi-arm platform design using predictive probability. Stat Methods Med Res. 2018;27(1):65- 78.
- Pépin JL, Jullian-Desayes I, Sapéne M, et al. Multimodal remote monitoring of high cardiovascular risk patients with OSA initiating CPAP: a randomized trial. Chest. 2019;155(4):730-739.
- Tanner NT, Yarmus L, Chen A, et al. Standard bronchoscopy with fluoroscopy vs thin bronchoscopy and radial endobronchial ultrasound for biopsy of pulmonary lesions: a multicenter, prospective, randomized trial. Chest. 2018;154(5):1035-1043.
- Furian M, Lichtblau M, Aeschbacher SS, et al. Efficacy of dexamethasone in preventing acute mountain sickness in COPD patients: randomized trial. Chest. 2018;154(4):788-797.
- Semler MW, Janz DR, Russell DW, et al. A multicenter, randomized trial of ramped position vs sniffing position during endotracheal intubation of critically ill adults. Chest. 2017;152(4):712-722.
- Alansari K, Sayyed R, Davidson BL, Al Jawala S, Ghadier M. IV magnesium sulfate for bronchiolitis: a randomized trial. Chest. 2017;152(1):113-119.
- Kim ES, Bruinooge SS, Roberts S, et al. Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. J Clin Oncol. 2017;35(33):3737-3744.
- Van Spall HGC, Toren A, Kiss A, Fowler RA. Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review. JAMA. 2007;297(11): 1233-1240.
- Hobbs BP, Thall PF, Lin SH. Bayesian group sequential clinical trial design using total toxicity burden and progression-free survival. J R Stat Soc Ser C Appl Stat. 2016;65(2):273-297.
- Dunn OJ. Multiple comparisons among means. J Am Stat Assoc. 1961;56(293):52-64.
- Sidák Z. Rectangular confidence regions for the means of multivariate normal distributions. J Am Stat Assoc. 1967;62(318):626-633.
- Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat. 1979;6(2):65-70.
- Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31(1):103-115.
- Thall PF, Wathen JK. Practical Bayesian adaptive randomisation in clinical trials. Eur J Cancer. 2007;43(5):859-866.
- Lee JJ, Xuemin G, Suyu L. Bayesian adaptive randomization designs for targeted agent development. Clin Trials. 2010;7(5): 584-596.
Cited by
Sorted by citations
Schönenberger, C. M., Griessbach, A., Taji Heravi, A., Gryaznov, D., Gloy, V. L., Lohner, S., Klatte, K., Ghosh, N., Lee, H., Mansouri, A., et al. (2022) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2022.05.014 · Cited by 17 · see citing works
Global mapping of randomized controlled trials in dentistry
Prado, M. C., Dotto, L., Agostini, B., & Sarkis-Onofre, R. (2024) · Brazilian Dental Journal · doi:10.1590/0103-644020246233 · Cited by 1 · see citing works
- Authors
- Zabor, E. C., Kaizer, A. M., & Hobbs, B. P.
- Affiliations
- Cleveland Clinic (US)
- Colorado School of Public Health (US)
- Corresponding author
- Zabor, Emily C.
- Venue
- Chest
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 158
- Issue
- 1
- Pages
- S79-S87
- ISSN
- 0012-3692 (ISSN-L)
- PMC
- PMC8176647
- OpenAlex
- W3038343580
- Cited by
- 294
- References
- 3
- Citations by year
- 2026: 72 · 2025: 94 · 2024: 78 · 2023: 33 · 2022: 12 · 2021: 5
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CHEST Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cleveland Clinic
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Keywords
- randomized controlled trials, adaptive design, randomization methods, statistical power, type I error rate, CONSORT guidelines, FDA guidance, trial reporting quality
- MeSH terms
- Humans, Research Design, Randomized Controlled Trials as Topic, Guidelines as Topic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
