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Practical Guide to Design Choice of Randomized Clinical Trials in Surgery

To identify the key insights or developments described in this article
1 Credit CME

Key elements in guiding the design choice of randomized clinical trials (RCTs) are the research question, the related hypothesis and appropriate methodology, ethics, feasibility, quality of evidence, and efficiency. The strength of RCTs is their internal validity, allowing for causal inference by attributing the observed outcomes to the type of treatment(s) and allowing the randomization to otherwise balance the study groups, thus addressing known and unknown potential confounders.1 RCTs offer high-quality evidence but are not always ethical, feasible, or necessary. If an RCT is feasible and possible,2 a choice has to be made between several options. The involvement of methodological and statistical experts will ensure success in the selection and implementation of the best design. In this article, we present the strengths and weaknesses of several RCT design options (Box).

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Article Information

Corresponding Author: Marcel G. W. Dijkgraaf, PhD, Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, the Netherlands (m.g.dijkgraaf@amsterdamumc.nl).

Published Online: October 26, 2022. doi:10.1001/jamasurg.2022.4889

Conflict of Interest Disclosures: Dr Haukoos reported personal fees from JAMA Surgery as Statistical Editor, Annals of Emergency Medicine as Research Methodology Editor, and American College of Emergency Physicians for serving as methodologist on the Clinical Policies Committee outside the submitted work. No other disclosures were reported.

References
1.
Campbell  DT , Stanley  JC . Chapter 5: experimental and quasi-experimental designs for research. In: Gage NL, ed.  Handbook of Research on Testing. Houghton Mifflin Co; 1963:1-34.
2.
Collins  R , Bowman  L , Landray  M , Peto  R .  The magic of randomization versus the myth of real-world evidence.   N Engl J Med. 2020;382(7):674-678. doi:10.1056/NEJMsb1901642PubMedGoogle ScholarCrossref
3.
Lies  SR , Zhang  AY .  Prospective randomized study of the effect of music on the efficiency of surgical closures.   Aesthet Surg J. 2015;35(7):858-863. doi:10.1093/asj/sju161PubMedGoogle ScholarCrossref
4.
Brophy  MT , Ferguson  RE . Point of Care clinical trials. In: Itani  KMF , Reda  DJ , eds.  Clinical Trials Design in Operative and Non Operative Invasive Procedures. Springer International Publishing; 2017:115-122. doi:10.1007/978-3-319-53877-8_13
5.
Hussey  MA , Hughes  JP .  Design and analysis of stepped wedge cluster randomized trials.   Contemp Clin Trials. 2007;28(2):182-191. doi:10.1016/j.cct.2006.05.007PubMedGoogle ScholarCrossref
6.
Chang  M .  Introductory Adaptive Trial Designs: a Practical Guide With R. CRC Press Taylor & Francis Group; 2015:1-10,123-130.
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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