Advertisement

A benefit-risk Model to Facilitate DMC-sponsor Communication and Decision Making

  • Andreas SashegyiEmail author
Statistics

Abstract

In drug development, independent data monitoring committees (DMCs) are routinely engaged by clinical trial sponsors to monitor patient safety. Transferring the obligation of interim data monitoring to an independent party helps ensure trial integrity by allowing the sponsor to remain blinded to emerging treatment results. But it also poses a dilemma: after each interim analysis, the DMC makes a recommendation to the sponsor regarding the continuation or modification of the ongoing trial, on the basis of which the sponsor must make a decision. Yet the unblinded results, which alone are the ideal basis for decision making, are only seen by the DMC and by design are withheld from the sponsor. We propose application of a multiattribute benefit-risk model to enable more informed decision making. The model provides an assessment of the emerging benefits and risks of active therapy versus control, based on an evaluation of attributes prespecified by the sponsor. While revealing no specific study outcomes, it allows an appreciation of the direction and magnitude of differentiation between treatment groups in terms of benefit and risk, enabling conversations around scenarios that would lead to this kind of assessment. The model also reflects uncertainty in the evaluation of benefits and risks, an essential feature in the analysis of interim data. This type of assessment may be leveraged to provide meaningful context accompanying the textual recommendation of a DMC to enable more informed decision making, while upholding the sponsor’s commitment to remain blinded to particular study results.

Keywords

Data monitoring committee Multiattribute model Beneft-risk Blinding 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ellenberg S. Fleming T, DeMets D. Data Monitoring Committees in Clinical Trials: A Practical Perspective. West Sussex, UK: Wiley; 2002.CrossRefGoogle Scholar
  2. 2.
    CHMP. Guideline on data monitoring committees. 2005. http://www.emea.europa.eu/pdfs/human/ewp/587203en.pdf (accessed February 3, 2011).Google Scholar
  3. 3.
    Food and Drug Administration. Guidance for clinical trial sponsors: establishment and operation of clinical trial data monitoring committees. 2002. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm127073.pdf (accessed February 3, 2011).Google Scholar
  4. 4.
    DeMets DL. Pocock SJ, Julian DG. The agonizing negative trend in monitoring of clinical trials. Lancet. 1999;354:1983–1988.CrossRefGoogle Scholar
  5. 5.
    Sashegyi AI. Role of the data monitoring committee and sponsor in monitoring adaptive designs. Pharm Outsourcing. 2010;11:28–31.Google Scholar
  6. 6.
    Mussen F. Salek S, Walker S. A quantitative approach to benefit-risk assessment of medicines— part 1: the development of a new model using multi-criteria decision analysis. Pharmacoepidemiol Drug Saf. 2007;16:S2–S15.CrossRefGoogle Scholar
  7. 7.
    Felli JC. Noel RA, Cavazzoni PA. A multiattribute model for evaluating the benefit-risk profiles of treatment alternatives. Med Decis Making. 2009; 29:105–115.CrossRefGoogle Scholar

Copyright information

© Drug Information Association, Inc 2011

Authors and Affiliations

  1. 1.Research Advisor, Decision Sciences Lilly Corporate CenterEli Lilly and CompanyIndianapolisUSA

Personalised recommendations