Abstract
Background
There is little information available about the impact that FDA guidances have on the clinical trial enterprise.
Objective
To estimate the impact of the FDA’s Guidance for Industry, “The Establishment and Operation of Clinical Trial Data Monitoring Committees for Clinical Trial Sponsors.”
Methods
An economic model was developed to measure the costs and potential savings associated with the change in data monitoring committee (DMC) usage since issuance of the DMC guidance for industry-sponsored clinical trials. To establish the change in use following the issuance of the DMC guideline, a literature search was conducted among high-impact medical journals during publication year 2010 and compared to a similar analysis conducted during publication year 2000. Costs were obtained for DMCs and applicable clinical trials. The results were applied to an analysis of ClinicalTrials.gov completed trials during 2007 to 2013.
Results
Review of 4200 manuscripts from publication year 2010 was compared to a similar literature search of publication year 2000. The mention of DMCs in industry-sponsored randomized controlled trials from high-impact journals increased from 24% to 47% (risk ratio = 1.9, P <.0001). This increased rate of DMCs is associated with an increase of 1045 DMCs for industry-sponsored phase 2 and 3 interventional trials that were commenced and completed from 2007 to 2013 and were listed in ClinicalTrials.gov. The increased cost due to these additional DMCs was approximately US$231 million, and the savings associated with early termination of clinical trials due to these DMCs was approximately US$428 million.
Conclusion
The DMC guidance has had a net positive economic impact on the clinical trial enterprise. However, noneconomic factors need to be evaluated. ClinicalTrials.gov could be further leveraged to explore further noneconomic benefits and costs of DMCs.
Similar content being viewed by others
References
US Food and Drug Administration. Guidance and regulation. http://www.fda.gov/Food/GuidanceRegulation. Accessed December 9, 2014.
Hirshberg B, Katz A. Cardiovascular outcome studies with novel antidiabetes agents: scientific and operational considerations. Diabetes Care. 2013;36 (suppl 2):S253–S258.
US Food and Drug Administration. Economic impact analyses of FDA regulations. http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/. Accessed December 9, 2014.
Bouvy J, Koopmanschap M, Shah R, Schellekens H. The cost-effectiveness of drug regulation: the example of thorough QT/QTc studies. Clin Pharmacol Ther. 2012;91 (2):281–288.
Pasquali S, Lam W, Chiswell K, Kemper A, Li J. Status of the pediatric clinical trials enterprise: an analysis of the US ClinicalTrials.gov Registry. Pediatrics. 2012;130 (5):e1269–e1277.
US Food and Drug Administration. The establishment and operation of clinical trial data monitoring committees for clinical trial sponsors. http://www.fda.gov/regulatoryinformation/guidances/ucm127069.htm. Published March 2006. Accessed December 9, 2014.
Department of Health and Human Services. Institutional review boards: a time for reform. https://oig.hhs.gov/oei/reports/oei-01-97-00193.pdf. Accessed December 9, 2014.
Wadman M. FDA says study overestimated non-compliance with data-reporting laws. Nature. May 1, 2012.
US National Institutes of Health. ClinicalTrials.gov. Histories, policies, and laws. http://ClinicalTrials.gov/ct2/about-site/history. Accessed November 2015.
DeAngelis C, Drazen J, Frizelle F, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. JAMA. 2004;292 (11):1363–1364.
Sydes M, Altman D, Babikera A, Parmar M, Spiegelhalter D; DAMOCLES Group. Reported use of data monitoring committees in the main published reports of randomized controlled trials: a cross-sectional study. Clin Trials. 2004;1(1):48–59.
Berndt E, Cockburn I. Price indexes for clinical trial research: a feasibility study. http://www.bls.gov/opub/mlr/2014/article/pdf/price-indexes-for-clinical-trial-research-a-feasibility-study.pdf. Accessed December 9, 2014.
Bussom D, Winter L. Data monitoring committees: implementation and sourcing model options. http://www.appliedclinicaltrialsonline.com/appliedclinicaltrials/Online+Extras/Data-Monitoring-Committees-Implementation-and-Sour/ArticleStandard/Article/detail/835338?contextCategoryId=47497. Published 2014. Accessed December 9, 2014.
Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A. Characteristics of clinical trials registered in ClinicalTrials.gov, 2007–2010. JAMA. 2012;307:1838–1847.
Thomson Reuters. Science citation reports 2010 (impact factor) by Journal Citation Reports. http://www.rcmishra.com/research-tools/impact-factor-2010-journal-citation-reports-by-thomson-reutors. Accessed November 2015.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Seltzer, J. An Estimate of the Benefit-Cost Impact of the FDA Guidance on Data Monitoring Committees. Ther Innov Regul Sci 49, 698–705 (2015). https://doi.org/10.1177/2168479015573586
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1177/2168479015573586