Maintaining confidentiality of interim data to enhance trial integrity and credibility

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. Clinical Trials 2008; 5: 157—167. http://ctj.sagepub.com