Finding Skew: Informed Consent and Bias in Clinical Trials

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Clinical researchers have long claimed that patients who enter clinical trials are better off medically than those who don’t. I’m open to the notion that patients might derive personal meaning from trial participation, but I’ve always been dubious of the suggestion that trial participation in itself is therapeutically beneficial–above and beyond drugs received– in part because this has never been demonstrated in a convincing way. I’ve also worried about the way the “trial effect” has been occasionally mobilized to recruit patients, or to apologize for studies of dubious design. Last, I’ve worried about the ethical implications of the prospect that, in order to receive top quality care, patients should be enrolling in (or have access to) clinical trials.


One reason I have been skeptical of the “trial effect” is that trials do not enroll a random sample of patients. Ethical research requires informed consent, and if patients who consent to trials have different characteristics than those who decline, it seems plausible that they will have different medical courses. UK researchers led by Andrew Clark recently put this thesis to the test (Eur J Heart Failure; also reported in the December issue of Nature Medicine). In their study, they asked a large sample of patients whether they were willing to enter a clinical trial. They then followed the clinical course of patients who declined, and compared them with patients who consented to participation but were never enrolled in a clinical trial. They found that patients who accepted enrollment had better clinical outcomes- even when factors like age, other sicknesses, or drug use.

The finding raises a number of interesting questions about tensions between study validity and informed consent. It does not suggest that we should relax consent standards to reduce bias- though some may be tempted to view the study in this way. It does, however, raise questions about how findings in clinical trials should be interpreted when applying them in real clinical settings. And it provides another problem for those who are attached to the position that trial participation is, in itself, therapeutic. (photo credit: funkandjazz, Skew, 2007)

BibTeX

@Manual{stream2009-76,
    title = {Finding Skew: Informed Consent and Bias in Clinical Trials},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = dec,
    day = 4,
    url = {https://www.translationalethics.com/2009/12/04/finding-skew-informed-consent-and-bias-in-clinical-trials/}
}

MLA

Jonathan Kimmelman. "Finding Skew: Informed Consent and Bias in Clinical Trials" Web blog post. STREAM research. 04 Dec 2009. Web. 22 Oct 2021. <https://www.translationalethics.com/2009/12/04/finding-skew-informed-consent-and-bias-in-clinical-trials/>

APA

Jonathan Kimmelman. (2009, Dec 04). Finding Skew: Informed Consent and Bias in Clinical Trials [Web log post]. Retrieved from https://www.translationalethics.com/2009/12/04/finding-skew-informed-consent-and-bias-in-clinical-trials/


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 = {https://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. 22 Oct 2021. <https://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 https://www.translationalethics.com/2008/10/06/stairing-at-method-in-preclinical-studies/


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