Literature DB >> 18375654

Maintaining confidentiality of interim data to enhance trial integrity and credibility.

Thomas R Fleming1, Katrina Sharples, John McCall, Andrew Moore, Anthony Rodgers, Ralph Stewart.   

Abstract

BACKGROUND: For clinical trials of interventions that could affect mortality or major morbidity, Data Monitoring Committees have an important role in safeguarding patient interests and enhancing trial integrity and credibility. In trials overseen by an independent DMC it is widely recognized that interim data should remain confidential to the DMC and to the statistical group preparing reports. However, we have found that the principle of confidentiality is not always followed in practice, particularly where the interim data include complete results on a short-term outcome measure.
PURPOSE: To discuss the reasoning and evidence supporting the principle of confidentiality of interim data with emphasis on the setting where the interim data include complete results on a short-term outcome.
METHODS: We review the reasons why wider access to interim data can increase the risk of false positive or false negative conclusions and discuss the types of harm which can occur. We provide illustrations and insights from recent experiences and discuss the level of consensus in the research community.
RESULTS: The arguments in favor of early release of interim data include the need to provide reliable data in a timely manner to patients and physicians, the potential to increase the enthusiasm of trial investigators, and to restore equipoise. However interim data, even where these include complete results on a short-term outcome measure, provide an unreliable and biased assessment of the overall benefit-to-risk profile of the trial treatments. Pre-judgment based on over-interpretation of such interim data can affect recruitment, treatment delivery, and follow-up, risking the ability of the trial to achieve its goals.
CONCLUSIONS: In order to preserve the integrity of a trial and safeguard the interests of patients, interim data, including complete data on short-term outcomes, should remain confidential to the DMC and the statistical group responsible for preparing interim reports until the trial has achieved its primary objectives.

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Mesh:

Year:  2008        PMID: 18375654      PMCID: PMC2703711          DOI: 10.1177/1740774508089459

Source DB:  PubMed          Journal:  Clin Trials        ISSN: 1740-7745            Impact factor:   2.486


  25 in total

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3.  Surrogate endpoints and FDA's accelerated approval process.

Authors:  Thomas R Fleming
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4.  Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial.

Authors:  Ruben Veldkamp; Esther Kuhry; Wim C J Hop; J Jeekel; G Kazemier; H Jaap Bonjer; Eva Haglind; Lars Påhlman; Miguel A Cuesta; Simon Msika; Mario Morino; Antonio M Lacy
Journal:  Lancet Oncol       Date:  2005-07       Impact factor: 41.316

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Authors:  K McPherson
Journal:  N Engl J Med       Date:  1974-02-28       Impact factor: 91.245

6.  A multiple testing procedure for clinical trials.

Authors:  P C O'Brien; T R Fleming
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7.  A randomized, placebo-controlled trial of the safety and efficacy of oral ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected individuals. Terry Beirn Community Programs for Clinical Research on AIDS.

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8.  Preliminary data release for randomized clinical trials of noninferiority: a new proposal.

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Authors:  Stevo Julius; Sverre E Kjeldsen; Michael Weber; Hans R Brunner; Steffan Ekman; Lennart Hansson; Tsushung Hua; John Laragh; Gordon T McInnes; Lada Mitchell; Francis Plat; Anthony Schork; Beverly Smith; Alberto Zanchetti
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10.  A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. The Terry Beirn Community Programs for Clinical Research on AIDS.

Authors:  D I Abrams; A I Goldman; C Launer; J A Korvick; J D Neaton; L R Crane; M Grodesky; S Wakefield; K Muth; S Kornegay
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  17 in total

1.  Should sponsors and DSMBs share interim results across trials?

Authors:  Seema K Shah; Liza Dawson; Dennis O Dixon; Reidar K Lie
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2.  The Adaptive designs CONSORT Extension (ACE) statement: a checklist with explanation and elaboration guideline for reporting randomised trials that use an adaptive design.

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4.  Enhancing trial integrity by protecting the independence of data monitoring committees in clinical trials.

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5.  Clinical trials: discerning hype from substance.

Authors:  Thomas R Fleming
Journal:  Ann Intern Med       Date:  2010-09-21       Impact factor: 25.391

6.  Data monitoring committees: Promoting best practices to address emerging challenges.

Authors:  Thomas R Fleming; David L DeMets; Matthew T Roe; Janet Wittes; Karim A Calis; Amit N Vora; Alan Meisel; Raymond P Bain; Marvin A Konstam; Michael J Pencina; David J Gordon; Kenneth W Mahaffey; Charles H Hennekens; James D Neaton; Gail D Pearson; Tomas Lg Andersson; Marc A Pfeffer; Susan S Ellenberg
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7.  Protecting the confidentiality of interim data: addressing current challenges.

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