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Monitoring Participant Safety in Phase I and II Interventional Trials: Options and Controversies
  1. Patricia L. Hibberd,
  2. Debra L. Weiner
  1. From the Division of Clinical Research Resources (P.L.H.), Tufts-New England Medical Center, and the Department of Medicine (P.L.H.), Tufts University School of Medicine, Boston, MA; and Emergency Medicine (D.L.W.), Children's Hospital Boston, and the Department of Pediatrics (D.L.W.), Harvard Medical School, Boston, MA.
  2. Support was provided through the General Clinical Research Center, funded by the Division of Research Resources of the National Institutes of Health under grant MO1-RR00054.
  3. Address correspondence to: Dr. Patricia L. Hibberd, Division of Clinical Research Resources, Tufts-New England Medical Center, 35 Kneeland Street, Box 063, Boston, MA 02111; e-mail: phibberd{at}


Background The need for phase I and II clinical trials to have a data and safety monitoring plan (DSMP) is widely accepted; however, whether and/or when these trials should also have oversight by a data and safety monitoring board (DSMB) is controversial. Monitoring requirements also depend on whether the study is funded by the National Institutes of Health, funded and/or monitored by the US Food and Drug Administration (FDA), or funded by industry. However, there is little guidance about when and how to constitute a DSMB for phase I and II clinical trials.

Objectives The objectives of this article are to suggest guidelines for when and how to constitute a DSMB for phase I and II studies and to highlight the similarities and differences between DSMBs monitoring phase I and II versus phase III clinical studies. We highlight the utility of these guidelines in the safety monitoring of a mechanism of disease-based study of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease that was funded and regulated by the FDA.

Conclusion The goal of DSMPs regardless of the phase of the clinical trial is to protect participant safety and ensure the integrity and validity of the data. A DSMB can ensure that risks and data are evaluated in a timely, efficient, and unbiased manner. We describe “risk-based” guidelines to determine situations in which a DSMB may be an appropriate addition to a DSMP for phase I and II clinical trials. We also address the roles and responsibilities of the DSMB for these studies.

Key Words
  • data and safety monitoring
  • phase I clinical trials
  • phase II clinical trials
  • risk assessment

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