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Are we taking the right approach in planning chemoprevention studies?

Nature Clinical Practice Oncology volume 3, pages 464–465 (2006)Cite this article

Evidence gained in randomized controlled trials (RCTs) is considered superior to that gained in association epidemiological studies, such as cohort or case–control studies. Association studies are prone to methodological bias, which is assumed to be overcome by proper randomization of the study population. The decision to embark on an RCT usually relies on preliminary data from human association studies supported by biological data from other types of studies and is not made lightly. RCTs require years of intervention and follow-up and are hence costly.

RCTs have failed to validate several epidemiological hypotheses for cancer prevention. For example, β-carotene, shown in many epidemiological studies to be associated with reduced incidence of many cancers, among them lung cancer,1 was found in RCTs to increase the probability of lung cancer in smokers.2,3 Fiber supplementation in the diet, shown in association studies to reduce the risk of colorectal cancer,4 failed to reduce colorectal adenoma formation.5 In contrast to a recent study showing an inverse association between use of statins and colorectal cancer,6 historical RCTs of effects of statins in populations at risk for cardiovascular disease failed to confirm such a cancer-preventive effect.7 This seemingly repeated failure of RCTs to confirm associations identified by epidemiology datasets and biological inferences might be explained by deficiencies in the design and conduct of the observational association studies, as well as deficiencies in the design of the randomized chemoprevention trials.

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Authors and Affiliations

  1. Chairman of the Department of Community Medicine and Epidemiology at Carmel Medical Center and B Rappaport Faculty of Medicine of the Technion in Haifa, Israel

    Gad Rennert

  2. CHS National Israeli Cancer Control Center,

    Gad Rennert

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  1. Gad Rennert
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Correspondence to Gad Rennert.

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The author declares no competing financial interests.

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Rennert, G. Are we taking the right approach in planning chemoprevention studies?. Nat Rev Clin Oncol 3, 464–465 (2006). https://doi.org/10.1038/ncponc0535

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