Mice- Three Different Ones: Towards More Robust Preclinical Experiments


One of the most exciting and intellectually compelling talks thus far at the American Society of Gene Therapy meeting was Pedro Lowenstein’s.  A preclinical researcher who works on gene transfer approaches to brain malignancies (among other things), Lowenstein asked the question: why do so many gene transfer interventions that look promising in the laboratory fail during clinical testing? His answer: preclinical studies lack “robustness.”

In short,  first-in-human trials are typically launched on the basis of a pivotal laboratory study showing statistically significant differences between treatment and control arms. In addition to decrying the “p-value” fetish- in which researchers, journal editors, and granting agencies view “statistical significance” as having magical qualities- Lowenstein also urged preclinical researchers to test the “nuances” and “robustness” of their systems before moving into human studies.

He provided numerous provocative examples where a single preclinical study showed very impressive, “significant” effects on treating cancer in mice. When the identical intervention was tried with seemingly small variations (e.g. different mouse strains used, different gene promotors tried, etc.), the “significant effects” vanished.  In short, Lowenstein’s answer to the question of why so many human trials fail to recapitulate major effects seen in laboratory studies is: we aren’t designing and reviewing preclinical studies properly. Anyone (is there one?) who has followed this blog knows: I completely agree. This is an ethical issue in scientific clothing. (photo credit: Rick Eh, 2008)


    title = {Mice- Three Different Ones: Towards More Robust Preclinical Experiments},
    journal = {STREAM research},
    author = {Jonathan Kimmelman},
    address = {Montreal, Canada},
    date = 2009,
    month = may,
    day = 29,
    url = {http://www.translationalethics.com/2009/05/29/mice-three-different-ones-towards-more-robust-preclinical-experiments/}


Jonathan Kimmelman. "Mice- Three Different Ones: Towards More Robust Preclinical Experiments" Web blog post. STREAM research. 29 May 2009. Web. 04 Mar 2024. <http://www.translationalethics.com/2009/05/29/mice-three-different-ones-towards-more-robust-preclinical-experiments/>


Jonathan Kimmelman. (2009, May 29). Mice- Three Different Ones: Towards More Robust Preclinical Experiments [Web log post]. Retrieved from http://www.translationalethics.com/2009/05/29/mice-three-different-ones-towards-more-robust-preclinical-experiments/

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