Issues for Masked Data Monitoring

  • O. Dale WilliamsEmail author
  • Katrina Epnere
Living reference work entry


The essential, primary purpose of a clinical trial is to provide a fair test for the comparison of treatments, drugs, strategies, etc. A challenge to this fairness is the appropriate utilization, or lack thereof, of masking or blinding. Masking generally refers to restricting knowledge as to the treatment group assignment for the individual or, in the case of a Data and Safety Monitoring Board (DSMB), to the summary of information comparing treatment groups. Fundamentally, masking is important to consider for those situations wherein knowledge of the treatment assignment could alter behavior or otherwise impact inappropriately on trial results. Masking may, however, while protecting against this bias, make it more difficult for the DSMB properly to protect trial participants from undue risk of adverse or serious adverse events. While there are several dimensions to this overall situation, this chapter addresses the important issue as to whether a trial’s DSMB should be fully aware of which treatment group is which as it reviews data summaries for an ongoing trial.


Data and safety monitoring board Data monitoring committee Masking Blinding Open report Closed report Interim analysis Risk/benefit 


  1. Anand SS, Wittes J, Yusuf S (2011) What information should a sponsor of a randomized trial receive during its conduct? Clin Trials 8(6):716–719CrossRefGoogle Scholar
  2. Bierer BE, Li R, Seltzer J, Sleeper LA, Frank E, Knirsch C, Aldinger CE, Lavine RJ, Massaro J, Shah A, Barnes M, Snapinn S, Wittes J (2016) Responsibilities of data monitoring committees: consensus recommendations. Ther Innov Regul Sci 50(5):648–659Google Scholar
  3. Buhr KA, Downs M, Rhorer J, Bechhofer R, Wittes J (2018) Reports to independent data monitoring committees: an appeal for clarity, completeness, and comprehensibility. Ther Innov Regul Sci 52(4):459–468Google Scholar
  4. Calis KA, Archdeacon P, Bain RP, Forrest A, Perlmutter J, DeMets DL (2017) Understanding the functions and operations of data monitoring committees: survey and focus group findings. Clin Trials 14(1):59–66CrossRefGoogle Scholar
  5. Chen-Mok M, VanRaden MJ, Higgs ES, Dominik R (2006) Experiences and challenges in data monitoring for clinical trials within an international tropical disease research network. Clin Trials 3(5):469–477CrossRefGoogle Scholar
  6. DeMets DL, Ellenberg SS (2016) Data monitoring committees—expect the unexpected. N Engl J Med 375(14):1365–1371CrossRefGoogle Scholar
  7. DeMets D, Califf R, Dixon D, Ellenberg S, Fleming T, Held P, Packer M (2004) Issues in regulatory guidelines for data monitoring committees. Clin Trials 1(2):162–169CrossRefGoogle Scholar
  8. Fleming TR, DeMets DL, Roe MT, Wittes J, Calis KA, Vora AN, Gordon DJ (2017) Data monitoring committees: promoting best practices to address emerging challenges. Clin Trials 14(2):115–123CrossRefGoogle Scholar
  9. Fleming TR, Ellenberg SS, DeMets DL (2018) Data monitoring committees: current issues. Clin Trials 15(4):321–328CrossRefGoogle Scholar
  10. Gordon VM, Sugarman J, Kass N (1998) Toward a more comprehensive approach to protecting human subjects. IRB: A Review of Human Subjects Research 20(1):1–5Google Scholar
  11. Holubkov R, Casper TC, Dean JM, Anand KJS, Zimmerman J, Meert KL, Nicholson C (2013) The role of the data and safety monitoring board in a clinical trial: the CRISIS study. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc 14(4):374Google Scholar
  12. Lewis RJ, Calis KA, DeMets DL (2016) Enhancing the scientific integrity and safety of clinical trials: recommendations for data monitoring committees. JAMA 316(22):2359–2360CrossRefGoogle Scholar
  13. Meinert CL (1998) Masked monitoring in clinical trials—blind stupidity? N Engl J Med 338:1381–1382CrossRefGoogle Scholar
  14. Neaton JD, Grund B, Wentworth D (2018) How to construct an optimal interim report: what the data monitoring committee does and doesn’t need to know. Clin Trials 15(4):359–365CrossRefGoogle Scholar
  15. Wittes J (1993) Behind closed doors: the data monitoring board in randomized clinical trials. Stat Med 12(5–6):419–424CrossRefGoogle Scholar
  16. Wittes J, Barrett-Connor E, Braunwald E, Chesney M, Cohen HJ, DeMets D, Walters L (2007) Monitoring the randomized trials of the Women’s health initiative: the experience of the data and safety monitoring board. Clin Trials 4(3):218–234CrossRefGoogle Scholar
  17. Greenberg Report (1967) Organization, Review, and administration of cooperative studies (Greenberg report): a report from the heart special project committee to the National Advisory Heart Council. Control Clin Trials. 1988 9:137–148Google Scholar

Online Documents

  1. Department of Health and Human Services, Office of Inspector General. (2013) Data and safety monitoring boards in NIH clinical trials: meeting guidance, but facing some issues.
  2. U.S. Department of Health and Human Services Food and Drug Administration, Center for Biologics Evaluation and Research (CBER)Center for Drug Evaluation, and Research (CDER) Center for Devices and Radiological Health (CDRH) (2016) Guidance for clinical trial sponsors establishment and operation of clinical trial data monitoring committee.
  3. European Medicines Agency Committee for medicinal products for human use (2005) Guideline on data monitoring committee.
  4. National Heart, Lung, and Blood Institute National Institutes of Health (2014) NHLBI policy for data and safety monitoring of extramural clinical studies. Scholar
  5. Clinical Trials Transformation Initiative (CTTI) (2016) CTTI recommendations: data monitoring committees. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MedicineUniversity of AlabamaBirminghamUSA
  2. 2.Statistics Collaborative Inc.WashingtonUSA

Section editors and affiliations

  • O. Dale Williams
    • 1
  1. 1.Department of MedicineUniversity of AlabamaBirminghamUSA

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