Filing Cabinet Syndrome: The Effect of Nonpublication of Preclinical Research

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Much has already been said about Filing Cabinet syndrome in medical research: the tendency of researchers to publish exciting results from clinical trials, and to stash null or negative findings safely away from public view in a filing cabinet. Nonpublication distorts the medical literature, because it prevents medical practitioners from accessing negative information about drugs. Recall that, back in 2004, attorney-general Eliot Spitzer sued Glaxo Smithkline for suppressing trial results that showed elevated risk of suicide for adolescents taking the antidepressant drug Paxil; this and several similar episodes led FDA, major medical journals, World Health Organization, World Medical Association, and others to require researchers to register clinical trials before they enroll any patients.


Yet important gaps remain. In the March 2010 issue of PLoS Biology, Emily S. Sena and coauthors provide the most detailed analysis yet of one of these gaps: nonpublication of preclinical (animal) studies. They aggregated results of 16 systematic reviews of preclinical studies involving acute ischaemic stroke, and used statistical methods to estimate the degree of publication bias, and the likely effect of publication bias on measured disease responses. Among other things, they found that 16% of animal experiments were not published, leading to a 31% overstatement of efficacy. The authors note: “we estimate that for the interventions described here, experiments involving some 3,600 animals have remained unpublished. We consider this practice to be unethical.”

The authors urge that central registries of preclinical studies be established and maintained– a call that is not likely to go heeded anytime soon by companies that have much at stake in the secrecy in preclinical research. But their proposal ought to be taken seriously by anyone committed not only to respecting animals used in medical research, but also protecting the welfare of human beings who might enroll in possibly unwarranted clinical research. (photo credit: amy allcock 2009)

BibTeX

@Manual{stream2010-66,
    title = {Filing Cabinet Syndrome: The Effect of Nonpublication of Preclinical Research},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2010,
    month = may,
    day = 11,
    url = {http://www.translationalethics.com/2010/05/11/filing-cabinet-syndrome-the-effect-of-nonpublication-of-preclinical-research/}
}

MLA

Jonathan Kimmelman. "Filing Cabinet Syndrome: The Effect of Nonpublication of Preclinical Research" Web blog post. STREAM research. 11 May 2010. Web. 21 Oct 2020. <http://www.translationalethics.com/2010/05/11/filing-cabinet-syndrome-the-effect-of-nonpublication-of-preclinical-research/>

APA

Jonathan Kimmelman. (2010, May 11). Filing Cabinet Syndrome: The Effect of Nonpublication of Preclinical Research [Web log post]. Retrieved from http://www.translationalethics.com/2010/05/11/filing-cabinet-syndrome-the-effect-of-nonpublication-of-preclinical-research/


STAIRing at Method in Preclinical Studies

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Medical research, we all know, is highly prone to bias. Researchers are, after all, human in their tendencies to mix desire with assessment. So too are trial participants. Since the late 1950s, epidemiologists have introduced a number of practices to clinical research designed to reduce or eliminate sources of bias, including randomization of patients, masking (or “blinding”) of volunteers and physician-investigators, and statistical analysis.


In past entries, I have rallied for extending such methodological rigor to preclinical research. This has three defenses. First, phase 1 human trials predicated on weak preclinical evidence are insufficiently valuable to justify their execution. Second, methodologically weak preclinical research is an abuse of animals. Third, publication of methodologically weak studies is a form of “publication pollution.”

Two recent publications underscore the need for greater rigor in preclinical studies. The first is a paper in the journal Stroke (published online August 14, 2008; also reprinted in Journal of Cerebral Blood Flow and Metabolism). Many of the paper’s authors have doggedly pursued the cause of preclinical methodological rigor in stroke research by publishing a series of meta-analyses of preclinical studies in stroke. In this article, Malcolm Macleod and co-authors outline eight practices that journal editors and referees should look for in reviewing preclinical studies. Many are urged by STAIR (Stroke Therapy Academic Industry Roundtable)– a consortium organized in 1999 to strengthen the quality of stroke research.

Their recommendations are:

1- Animals (precise species, strain, and details should be provided)
2- Sample-size calculation
3- Inclusion and exclusion criteria for animals
4- Randomization of animals
5- Allocation concealment
6- Reporting of animals concealed from analysis
7- Masked outcome assessment
8- Reporting interest conflicts and funding

There’s an interesting, implicit claim in this paper: journal editors and referees partly bear the blame for poor methodological quality in preclinical research. In my next post, I will turn to a related news article about preclinical studies in Amyotrophic Lateral Sclerosis. (photo credit: 4BlueEyes, 2006)

BibTeX

@Manual{stream2008-132,
    title = {STAIRing at Method in Preclinical Studies},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2008,
    month = oct,
    day = 6,
    url = {http://www.translationalethics.com/2008/10/06/stairing-at-method-in-preclinical-studies/}
}

MLA

Jonathan Kimmelman. "STAIRing at Method in Preclinical Studies" Web blog post. STREAM research. 06 Oct 2008. Web. 21 Oct 2020. <http://www.translationalethics.com/2008/10/06/stairing-at-method-in-preclinical-studies/>

APA

Jonathan Kimmelman. (2008, Oct 06). STAIRing at Method in Preclinical Studies [Web log post]. Retrieved from http://www.translationalethics.com/2008/10/06/stairing-at-method-in-preclinical-studies/


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