The File-Drawer Problem, Revisited

Abstract

It has been contended that drug companies have hidden, in the “file drawer,” the results of unsuccessful clinical trials while publishing the results of more successful trials ([1][1]). As others have pointed out, no one's interest (drug company, doctor, patient) is served by the marketing of ineffective drugs, but nevertheless, the scientific enterprise is set back when full results are not published. The remedy proposed is to make all clinical trials data available (“The old file-drawer problem,” D. Kennedy, Editorial, 23 July, p. [451][2]); indeed, some companies are already planning to post their clinical trials data. If there is minor mischief in the drug company file-drawer, there is major mischief with many epidemiology studies. Although there are legitimate reservations ([2][3]), why shouldn't epidemiologists also open their data sets ([3][4])? Arguably, the scientific need is greater than that for clinical trials. Whereas clinical trials test prespecified, well-defined hypotheses, in epidemiological investigations, hundreds to thousands of questions may be asked, but only those results that pass the minimal threshold of “statistically significant, P < 0.05” are reported. Statistical analyses are often not adjusted to reflect multiple testing, even though procedures are readily available ([4][5]). If hundreds to thousands of results are locked in the epidemiology file drawer, even readers who wish to make the adjustment for themselves cannot. The worst-case scenario is that the vast majority of results reported from epidemiology studies are false positives. To cite (but not single out) only one example of epidemiology file-drawer cases, antibiotic use was associated with breast cancer ([5][6]). The antibiotic-breast cancer association was culled from a very large search process. If analyses were adjusted to reflect the number of questions, there might well be no significant association. The central point, however, is that keeping these results in the file drawer prevents others from doing alternative analyses, and again the loser is the scientific enterprise. 1. 1.[↵][7] 1. L. Abboud , “Lilly plans broad access to results on its drug trials,” Wall Street J. , 3 Aug. 2004, pp. B1-B2. 2. 2.[↵][8] 1. E. Marshall , Science 290, 28 (2000). [OpenUrl][9][PubMed][10][Web of Science][11] 3. 3.[↵][12] 1. Board on Life Sciences , Sharing Publication-Related Data and Materials: Responsibilities of Authorship in the Life Sciences (National Academies Press, Washington, DC, 2003) (see [www.nap.edu/books/0309088593/html/][13]). 4. 4.[↵][14] 1. P. H. Westfall, 2. S. S. Young , Resampling-Based Multiple Testing (Wiley, New York, 1993). 5. 5.[↵][15] 1. C. M. Velicer 2. et al. , JAMA 29, 827 (2004). [OpenUrl][16] # Response {#article-title-2} I think most would disagree with Young's characterization of the unpublished clinical trials problem as “minor mischief.” His larger point, about epidemiological trials, is well taken—but forcing these out of hiding will be administratively difficult. Epidemiological studies undertaken in connection with some regulatory procedures or a court action can be subject to required disclosure. Many and probably most, however, are undertaken in pursuit of a problem that interests the investigator. It might be useful, as Young suggests, to have all that stuff out there. Alas, we don't have a process. [1]: #ref-1 [2]: /lookup/doi/10.1126/science.305.5683.451 [3]: #ref-2 [4]: #ref-3 [5]: #ref-4 [6]: #ref-5 [7]: #xref-ref-1-1 View reference 1. in text [8]: #xref-ref-2-1 View reference 2. in text [9]: {openurl}?query=rft.jtitle%253DScience%26rft.stitle%253DScience%26rft.issn%253D0036-8075%26rft.aulast%253DMarshall%26rft.auinit1%253DE.%26rft.volume%253D290%26rft.issue%253D5489%26rft.spage%253D28%26rft.epage%253D29%26rft.atitle%253DEthics.%2BEpidemiologists%2Bwary%2Bof%2Bopening%2Bup%2Btheir%2Bdata.%26rft_id%253Dinfo%253Apmid%252F11183141%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [10]: /lookup/external-ref?access_num=11183141&link_type=MED&atom=%2Fsci%2F306%2F5699%2F1133.4.atom [11]: /lookup/external-ref?access_num=000089724800008&link_type=ISI [12]: #xref-ref-3-1 View reference 3. in text [13]: http://www.nap.edu/books/0309088593/html/ [14]: #xref-ref-4-1 View reference 4. in text [15]: #xref-ref-5-1 View reference 5. in text [16]: {openurl}?query=rft.jtitle%253DJAMA%26rft.volume%253D29%26rft.spage%253D827%26rft.atitle%253DJAMA%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx