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This article describes vignettes concerning interactions with Data Safety Monitoring Boards during the design and monitoring of some clinical trials with an adaptive design. Most reflect personal experiences by the author.

Background: Any therapeutic intervention carries with it the potential for benefit and harm. Generally, benefit is far more common than risk; however, risk aversion drives many of the treatment decisions made by patients and their physicians. Objective: To provide guidelines to help clinicians improve their understanding of causality and the interpretation of harm. Methods: A group of dermatologists involved in data safety monitoring boards, clinical trial investigators, and a clinical epidemiologist identified the need for practical advice on how to understand and explain causality and harm and combined to share their knowledge. Results: An explanation of how data are collected and the environment that shapes the data seen by clinicians is presented. The article spans an overview of the regulatory environment that informs trial design for regulatory approval to a description of types of designs that inform safety and techniques, such as the rule of three, to provide guidance to clinicians in interpreting the data. Conclusion: Communicating the potential for harm to patients is critical. Placing the potential for rare and serious risks into perspective for the patient is as important as discussing the potential benefits of medication.

Background Models for the structure and procedures of data and safety monitoring boards (DSMBs) continue to evolve in response to issues of new and of old concern. Some authors have called for an open dialogue on these questions through publication of the experiences of DSMBs in addressing them. Purpose The goal of this paper is to add to the current discussion about acceptable models for establishing, serving on, and reporting to monitoring committees, particularly those that oversee multiple studies in less developed countries. The paper seeks to do so by describing the establishment and subsequent operation of one such multi-trial DSMB over a five-year period. This DSMB was formed to monitor trials conducted by members of the International Centers for Tropical Disease Research (ICTDR) network of the National Institute of Allergy and Infectious Diseases (NIAID). Methods The operational model and experiences are summarized by the authors, who had immediate responsibilities for directing the DSMB's activities. Results The board played an active, traditional role in assuring that patient safety was maintained and that current standards for clinical research were met. In addition, both NIAID and the board members viewed education of investigators to be an important role for the board to play in this particular setting. This affected the threshold for identifying which trials would be monitored, and it impacted several procedures adopted by the board. Limitations This report reflects the observations of those involved in managing the DSMB, including comments offered by the DSMB and by investigators, but not data gathered in a systematic way. Conclusions The operational model described here has allowed the DSMB to fulfill its role in the oversight of the trials. We hope that the ideas we present may help others facing similar situations and may stimulate further critical thinking about DSMB structure and function.