Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy

http://032912b.membershipsoftware.org/libdocuments/Antidepressants_meta-analysis.pdf


This paper shows that negative results of trials are often withheld, when the results of drugs are 
completely random compared to placebo this can make the drug appear to be working.

Selective Publication of Antidepressant

Trials and Its Influence on Apparent Efficacy

Erick H. Turner, M.D., Annette M. Matthews, M.D., Eftihia Linardatos, B.S.,

Robert A. Tell, L.C.S.W., and Robert Rosenthal, Ph.D.

From the Departments of Psychiatry

(E.H.T., A.M.M.) and Pharmacology

(E.H.T.), Oregon Health and Science Uni

-

versity; and the Behavioral Health and

Neurosciences Division, Portland Veter

-

ans Affairs Medical Center (E.H.T., A.M.M.,

R.A.T.)

—

both in Portland, OR; the De

-

partment of Psychology, Kent State Uni

-

versity, Kent, OH (E.L.); the Department

of Psychology, University of California–

Riverside, Riverside (R.R.); and Harvard

University, Cambridge, MA (R.R.). Address

reprint requests to Dr. Turner at Portland

VA Medical Center, P3MHDC, 3710 SW

US Veterans Hospital Rd., Portland, OR

97239, or at turnere@ohsu.edu.

N Engl J Med 2008;358:252-60.

Copyright © 2008 Massachusetts Medical Society.

A B S T R A C T

BACKGROUND

Evidence-based medicine is valuable to the extent that the evidence base is complete

and unbiased. Selective publication of clinical trials — and the outcomes within

those trials — can lead to unrealistic estimates of drug effectiveness and alter the

apparent risk–benefit ratio.

METHODS

We obtained reviews from the Food and Drug Administration (FDA) for studies of

12 antidepressant agents involving 12,564 patients. We conducted a systematic lit

-

erature search to identify matching publications. For trials that were reported in the

literature, we compared the published outcomes with the FDA outcomes. We also

compared the effect size derived from the published reports with the effect size de

-

rived from the entire FDA data set.

RESULTS

Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were

not published. Whether and how the studies were published were associated with

the study outcome. A total of 37 studies viewed by the FDA as having positive results

were published; 1 study viewed as positive was not published. Studies viewed by the

FDA as having negative or questionable results were, with 3 exceptions, either not

published (22 studies) or published in a way that, in our opinion, conveyed a posi

-

tive outcome (11 studies). According to the published literature, it appeared that

94% of the trials conducted were positive. By contrast, the FDA analysis showed that

51% were positive. Separate meta-analyses of the FDA and journal data sets showed

that the increase in effect size ranged from 11 to 69% for individual drugs and was

32% overall.

CONCLUSIONS

We cannot determine whether the bias observed resulted from a failure to submit

manuscripts on the part of authors and sponsors, from decisions by journal editors

and reviewers not to publish, or both. Selective reporting of clinical trial results may

have adverse consequences for researchers, study participants, health care profes

-

sionals, and patients