Patricia L Hibberd1, Debra L Weiner. 1. Division of Clinical Research Resources, Tufts-New England Medical Center 35 Kneeland Street, Box 063, Boston, MA 02111, USA. phibberd@tufts-nemc.org
Abstract
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.
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.
Authors: Arthur E Frankel; Keith T Flaherty; George J Weiner; Robert Chen; Nilofer S Azad; Michael J Pishvaian; John A Thompson; Matthew H Taylor; Daruka Mahadevan; A Craig Lockhart; Ulka N Vaishampayan; Jordan D Berlin; David C Smith; John Sarantopoulos; Matthew Riese; Mansoor N Saleh; Chul Ahn; Eugene P Frenkel Journal: Oncologist Date: 2017-03-17