Monitoring participant safety in phase I and II interventional trials: options and controversies.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Hibberd
Patricia L
PL
Division of Clinical Research Resources, Tufts-New England Medical Center 35 Kneeland Street, Box 063, Boston, MA 02111, USA. phibberd@tufts-nemc.org
Weiner
Debra L
DL
D000755:Anemia, Sickle Cell / Q000188:drug therapy; D026661:Clinical Trials Data Monitoring Committees; D017321:Clinical Trials, Phase I as Topic / Q000009:adverse effects / Q000191:economics / Q000379:methods* / Q000706:statistics & numerical data; D017322:Clinical Trials, Phase II as Topic / Q000009:adverse effects / Q000191:economics / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D009316:National Institutes of Health (U.S.); D009569:Nitric Oxide / Q000008:administration & dosage; D012109:Research Support as Topic; D012449:Safety; D014481:United States; D014486:United States Food and Drug Administration
D009569:Nitric Oxide