title: Data monitoring committees: Promoting best practices to address emerging challenges.
abstract: OBJECTIVE
  Data monitoring committees are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of data monitoring committees from sponsors and investigators is essential in achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten data monitoring committees' independence and effectiveness.
  
  
  METHODS
  An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary data monitoring committees.
  
  
  CONCLUSIONS
  Prospective data monitoring committee members need better training. Options could include didactic instruction as well as apprenticeships to provide real-world experience. Data monitoring committee members should be protected against legal liability arising from their service. While avoiding breaches in confidentiality of interim data remains a high priority, data monitoring committees should have access to unblinded efficacy and safety data throughout the trial to enable informed judgments about risks and benefits. Because overly rigid procedures can compromise their independence, data monitoring committees should have the flexibility necessary to best fulfill their responsibilities. Data monitoring committee charters should articulate principles that guide the data monitoring committee process rather than list a rigid set of requirements. Data monitoring committees should develop their recommendations by consensus rather than through voting processes. The format for the meetings of the data monitoring committee should maintain the committee's independence and clearly establish the leadership of the data monitoring committee chair. The independent statistical group at the Statistical Data Analysis Center should have sufficient depth of knowledge about the study at hand and experience with trials in general to ensure that the data monitoring committee has access to timely, reliable, and readily interpretable insights about emerging evidence in the clinical trial. Contracts engaging data monitoring committee members for industry-sponsored trials should have language customized to the unique responsibilities of data monitoring committee members rather than use language appropriate to consultants for product development. Regulatory scientists would benefit from experiencing data monitoring committee service that does not conflict with their regulatory responsibilities.
authors.affiliation: 1 Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.affiliation: 2 University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: DeMets
authors.affiliation: 3 Duke Clinical Research Institute (DCRI), Duke University Medical Center, Durham, NC, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: 4 Statistics Collaborative, Inc., Washington, DC, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.affiliation: 5 Center for Drug Evaluation and Research (CDER), FDA, Silver Spring, MD, USA.|6 National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD, USA.
authors.forename: Karim A
authors.initials: KA
authors.lastname: Calis
authors.affiliation: 3 Duke Clinical Research Institute (DCRI), Duke University Medical Center, Durham, NC, USA.
authors.forename: Amit N
authors.initials: AN
authors.lastname: Vora
authors.affiliation: 7 University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Meisel
authors.affiliation: 8 Merck Research Laboratories, North Wales, PA, USA.
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Bain
authors.affiliation: 9 Tufts Medical Center, Boston, MA, USA.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.affiliation: 3 Duke Clinical Research Institute (DCRI), Duke University Medical Center, Durham, NC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.affiliation: 10 National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Gordon
authors.affiliation: 11 Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: 12 Florida Atlantic University, Boca Raton, FL, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hennekens
authors.affiliation: 13 University of Minnesota, Minneapolis, MN, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.affiliation: 10 National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, MD, USA.
authors.forename: Gail D
authors.initials: GD
authors.lastname: Pearson
authors.affiliation: 14 AstraZeneca, Mölndal, Sweden.
authors.forename: Tomas Lg
authors.initials: TL
authors.lastname: Andersson
authors.affiliation: 15 Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pfeffer
authors.affiliation: 16 University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Ellenberg
mesh_terms: D026661:Clinical Trials Data Monitoring Committees; D003219:Confidentiality; D006801:Humans; D007341:Insurance; D017410:Practice Guidelines as Topic
keywords: Independence; apprenticeship; charter; confidentiality; experience; indemnification; operating principles; regulatory; training