Use of the false discovery rate for evaluating clinical safety data

Mehrotra, Devan V.; Heyse, Joseph F.
June 2004
Statistical Methods in Medical Research;Jun2004, Vol. 13 Issue 3, p227
Academic Journal
journal article
Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed 'Double FDR' approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term 'Double FDR'.


Related Articles

  • The effect of correlation structure on treatment contrasts estimated from incomplete clinical trial data with likelihood-based repeated measures compared with last observation carried forward ANOVA. Mallinckrodt, Craig H; Kaiser, Christopher J; Watkin, John G; Molenberghs, Geert; Carroll, Raymond J // Clinical Trials;2004, Vol. 1 Issue 6, p477 

    Valid analyses of longitudinal data can be problematic, particularly when subjects dropout prior to completing the trial for reasons related to the outcome. Regulatory agencies often favor the last observation carried forward (LOCF) approach for imputing missing values in the primary analysis of...

  • Comment from Sarah Sleet - Chief Executive - Coeliac UK.  // Foods Matter (USA);Nov2008, p5 

    The author comments on the results of the clinical trials for the treatment of coeliac disease. She states that she is interested in the fact that there is a potential in the results of the trials, however, it is important to stress that there is still no pill and that a vaccine in not yet...

  • How might acupuncture work? A systematic review of physiologic rationales from clinical trials. Moffet, Howard H. // BMC Complementary & Alternative Medicine;2006, Vol. 6, p25 

    Background: Scientific interest in acupuncture has led numerous investigators to conduct clinical trials to test the efficacy of acupuncture for various conditions, but the mechanisms underlying acupuncture are poorly understood. Methods: The author conducted a PubMed search to obtain a fair...

  • Malaria: Joint attack on malaria. Ellis, Clare // Nature Reviews Microbiology;Sep2004, Vol. 2 Issue 9, p689 

    The article reports on the success of the study conducted by a group of international scientists that to develop a new antimalarial drug. The team, that is consists of researchers from universities and medical-related institutions worldwide, aims to identify a new synthetic peroxide antimalarial...

  • ENHANCE: Imaging study did not show clinical benefit. Raible, Eric // Cardiology Today;Feb2008, Vol. 11 Issue 2, p19 

    The article provides information on the initial result of the Effect of Combination Ezetimibe and High-Dose Simvastatin versus Simvastatin Alone on Patients with Heterozygous Familial Hypercholesterolemia (ENHANCE) clinical trial. Result shows that ezetimibe drug failed to reduce the risk of...

  • Adding Ancillaries: Clinical trials. Weiss, Barbara // Medical Economics;1/6/2006, Vol. 83 Issue 1, p53 

    The article presents the factors to be considered when planning to conduct a clinical trial. Study drugs must be stored in a secure place like a lockable cabinet. Designating a room as the study coordinator's office is also important. A good and competent clinical research coordinator is a must...

  • News in brief . . .  // Reactions Weekly;6/18/2005, Issue 1056, p2 

    Presents updates on issues and events concerning medical researches in the U.S. as of June 2005. Reason for the temporary suspension of the clinical trial for the AV 1101 drug; Recommendations of Bristol-Myers Squibb for pregnant women taking the Sustiva drug; Postponement of the patient...

  • Asking about condom use: a key to individualized care when screening for chlamydia. Carré, H.; Lindström, R.; Boman, J.; Janlert, U.; Lundqvist, L.; Nylander, E. // International Journal of STD & AIDS;Aug2011, Vol. 22 Issue 8, p436 

    Chlamydia trachomatis (CT) infection has been a target for both selective and national screening programmes, and Sweden has an opportunistic approach. A national plan of action states that risk groups should be identified and offered risk reduction counselling. Patients attending a drop-in...

  • Promising SARS Vaccine. Hampton, Tracy // JAMA: Journal of the American Medical Association;8/25/2004, Vol. 292 Issue 8, p916 

    Reports on a promising nasal spray vaccine for SARS. How the experimental vaccine was designed by the National Institute of Allergy and Infectious Diseases; Belief the spray is ready for clinical trials; Evidence that the vaccine strain has been shown safe in children.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics