Skip to main content

Main menu

  • Home
  • COVID-19
    • Articles & podcasts
    • Blog posts
    • Collection
    • News
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
    • Career Ad Discount
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2021
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN

User menu

Search

  • Advanced search
CMAJ
  • CMAJ JOURNALS
    • CMAJ Open
    • CJS
    • JAMC
    • JPN
CMAJ

Advanced Search

  • Home
  • COVID-19
    • Articles & podcasts
    • Blog posts
    • Collection
    • News
  • Content
    • Current issue
    • Past issues
    • Early releases
    • Collections
    • Sections
    • Blog
    • Infographics & illustrations
    • Podcasts
  • Authors
    • Overview for authors
    • Submission guidelines
    • Submit a manuscript
    • Forms
    • Editorial process
    • Editorial policies
    • Peer review process
    • Publication fees
    • Reprint requests
  • CMA Members
    • Overview for members
    • Earn CPD Credits
    • Print copies of CMAJ
    • Career Ad Discount
  • Subscribers
    • General information
    • View prices
  • Alerts
    • Email alerts
    • RSS
  • JAMC
    • À propos
    • Numéro en cours
    • Archives
    • Sections
    • Abonnement
    • Alertes
    • Trousse média 2021
  • Visit CMAJ on Facebook
  • Follow CMAJ on Twitter
  • Follow CMAJ on Pinterest
  • Follow CMAJ on Youtube
  • Follow CMAJ on Instagram
Controversy

Why Sackett‚s analysis of randomized controlled trials fails, but needn‚t

Stanley H. Shapiro and Kathleen Cranley Glass
CMAJ October 03, 2000 163 (7) 834-835;
Stanley H. Shapiro
Dr. Shapiro is with the Department of Epidemiology & Biostatistics, McGill University, and the Randomized Clinical Trials Unit, Sir Mortimer B. Davis‐Jewish General Hospital, Montreal, Que. Dr. Glass is with the Biomedical Ethics Unit and the Departments of Human Genetics and Pediatrics, McGill University, and the Montreal Children‚s Hospital, Montreal, Que. Both are members of the Clinical Trials Research Group, McGill University, Montreal, Que.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen Cranley Glass
Dr. Shapiro is with the Department of Epidemiology & Biostatistics, McGill University, and the Randomized Clinical Trials Unit, Sir Mortimer B. Davis‐Jewish General Hospital, Montreal, Que. Dr. Glass is with the Biomedical Ethics Unit and the Departments of Human Genetics and Pediatrics, McGill University, and the Montreal Children‚s Hospital, Montreal, Que. Both are members of the Clinical Trials Research Group, McGill University, Montreal, Que.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Responses
  • Metrics
  • PDF
Loading

Randomized clinical trials play a pivotal role in answering questions about the superiority of competing treatments. They are initiated not because a particular investigator is unsure of the treatment of choice, but because there is sufficient uncertainty in the medical and scientific community to warrant mounting a trial. Of course, the commitment of enrolling physicians and patients in a trial is critical to its success, and we agree with Dave Sackett‚s recent comments1 about the importance of ”coal-face commitment.”

The idea that an individual physician must be in a state of complete indifference with regard to two alternative treatments in order to randomly assign patients to those treatments was challenged years ago as untenable by Benjamin Freedman.2 Sackett makes that observation again, although the solution he proposes is not consistent with Freedman‚s.

Sackett and others3 take the view that a physician must be substantially uncertain about the merits of a treatment to ethically recommend enrolment for a patient. We do not contest the physician‚s obligation to serve the best interests of each patient; comorbidity or other reasons might make enrolment in one or both of the trial arms undesirable for any particular patient. However, fulfilling that obligation requires not only clinical skill and an understanding of each patient‚s situation, but up-to-date knowledge of the best therapeutic strategies available. Physicians cannot develop this knowledge in isolation, but must rely on the collective judgement of the medical community as a whole.

The uncertainty or certainty of any individual physician about the relative merits of a treatment is irrelevant to the moral basis of a trial. Rather, the ethical basis for a clinical trial arises from the uncertainty that rests with the expert clinical community as a whole: this is the state of clinical equipoise described by Freedman.4 Consider a situation in which there was no individual physician uncertainty, with half the physicians considering treatment A preferable, and half preferring B. A consequence of Sackett‚s position would be that a randomized trial could not move forward: physicians could not, in good conscience, enrol any patients. Yet it is just this state of (un)certainty that calls out for evidence as to which is the better treatment. It is important for the individual physician to set aside his or her opinion, bias or ”certainty” in deference to the reasoned uncertainty that exists within the larger community of experts. When clinical equipoise exists one could argue that physicians have an obligation to inform patients of the existence of relevant clinical trials.

A trial that is in clinical equipoise does not sacrifice the welfare of current patients for the sake of future patients. Neither investigators nor enrolling physicians should ask patients to forgo what is known to be a better or more appropriate treatment to enter a clinical trial. Clinical equipoise ensures that the physician‚s obligation to the patient is not breached because it requires that the only trials that go forward are those for which the superior treatment is unknown; that is, there is a lack of consensus in the expert community as to the superior treatment. It provides a basis for assessing whether a trial is ethical, with regard to both its initiation and its continuation. That decision is not idiosyncratic, but collective. Although the decision as to whether to offer enrollment in a trial will of course rest with the enrolling physicians, they need not feel that they can only maintain ”coal-face commitment” if they personally are uncertain as to the preferred treatment for an individual patient. To the extent the uncertainty principle promotes that view, it does a disservice by creating unnecessary tension.

In arguing that equipoise is incapable of application, Sackett confuses theoretical equipoise (which requires that the evidence supporting 2 treatments be exactly balanced) with clinical equipoise (which requires only a lack of consensus within the expert community). His claim that equipoise is almost never possessed by investigators or explored by ethics committees is surprising from one who has spent so much time advancing an evidence-based approach. The Tri-Council Policy Statement5 begins its section on clinical trials with a discussion of clinical equipoise, and most research ethics boards that we are familiar with consider clinical equipoise an integral part of the ethics review process.

Giving undue weight to a physician‚s possibly uninformed views, as the uncertainty principle allows, is not consistent with an evidence-based approach to health care. The collective judgement of the medical community relies on the informed views of its members as a whole. Sackett‚s analysis takes into account the individual physician, but fails to locate that individual within the larger community of which he or she is a part. He briefly considers a group version of the uncertainty principle. However, this seems to be a bit like trying to reinvent the (clinical equipoise) wheel.

Although there is much of value in Sackett‚s discussion of randomized controlled trials, his comments on equipoise perpetuate misconceptions rather than helping to remedy them.

Footnotes

  • 𝛃 An invited response from Dr. Sackett appears on page 835.

    Acknowledgement: This work is supported by an operating grant from the Social Sciences and Humanities Research Council of Canada and the Medical Research Council of Canada.

    Competing interests: None declared.

References

  1. 1.↵
    Sackett DL. Why randomized controlled trials fail but needn‚t. CMAJ 2000; 162(9):1311-4. Avaialable: www.cma.ca/cmaj/vol-162/issue-9/1301.htm
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    Freedman, B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317(3):141.
    OpenUrlCrossRefPubMed
  3. 3.↵
    Peto R, Baignent C. Trials: the next 50 years. BMJ 1998;317:1170.
    OpenUrlFREE Full Text
  4. 4.↵
    Weijer C, Shapiro SH, Glass KC. Why clinical equipoise, and not the uncertainty principle, is the moral underpinning of the RTC. BMJ. In press.
  5. 5.↵
    Tri-Council policy statement: ethical conduct for research involving humans. Ottawa: Medical Research Council, Natural Sciences and Engineering Research Council, Social Sciences and Humanities Research Council; 1998. Available: www.sshrc.ca/english/programinfo/policies/ethics.htm (accessed 2000 Sept 7).
PreviousNext
Back to top

In this issue

CMAJ
Vol. 163, Issue 7
3 Oct 2000
  • Table of Contents
  • Index by author
  • Canadian Adverse Drug Reaction Newsletter (879-886)

Article tools

Print
Download PDF
Article Alerts
To sign up for email alerts or to access your current email alerts, enter your email address below:
Email Article

Thank you for your interest in spreading the word on CMAJ.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Why Sackett‚s analysis of randomized controlled trials fails, but needn‚t
(Your Name) has sent you a message from CMAJ
(Your Name) thought you would like to see the CMAJ web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Why Sackett‚s analysis of randomized controlled trials fails, but needn‚t
Stanley H. Shapiro, Kathleen Cranley Glass
CMAJ Oct 2000, 163 (7) 834-835;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
‍ Request Permissions
Share
Why Sackett‚s analysis of randomized controlled trials fails, but needn‚t
Stanley H. Shapiro, Kathleen Cranley Glass
CMAJ Oct 2000, 163 (7) 834-835;
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Footnotes
    • References
  • Responses
  • Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • Uncertainty about clinical equipoise
  • Uncertainty about clinical equipoise
  • Uncertainty about clinical equipoise
  • Equipoise, a term whose time (if it ever came) has surely gone
  • Google Scholar

More in this TOC Section

  • The 2003 Canadian recommendations for dyslipidemia management: Revisions are needed
  • Rebuttal
  • The analysis by Manuel and colleagues creates controversy with headlines, not data
Show more Controversy

Similar Articles

Content

  • Current issue
  • Past issues
  • Collections
  • Sections
  • Blog
  • Podcasts
  • Alerts
  • RSS
  • Early releases

Information for

  • Advertisers
  • Authors
  • Reviewers
  • CMA Members
  • Media
  • Reprint requests
  • Subscribers

About

  • General Information
  • Journal staff
  • Editorial Board
  • Governance Council
  • Journal Oversight
  • Careers
  • Contact
  • Copyright and Permissions

Copyright 2021, Joule Inc. or its licensors. All rights reserved. ISSN 1488-2329 (e) 0820-3946 (p)

All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association or its subsidiaries.

To receive any of the resources on this site in an accessible format, please contact us at cmajgroup@cmaj.ca.

Powered by HighWire