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Why Most Published Research Findings Are False

PLoS Med, Vol. 2, No. 8. (30 August 2005), e124.

X Abstract

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

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Theoretical analysis on the problems of interpreting research fingings

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Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true. Conflicts of interest and prejudice may increase bias, u. Conflicts of interest are very common in biomedical research [26], and typically they are inadequately and sparsely reported [26,27]. Prejudice may not necessarily have financial roots. Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings. Many otherwise seemingly independent, university-based studies may be conducted for no other reason than to give physicians and researchers qualifications for promotion or tenure. Such nonfinancial conflicts may also lead to distorted reported results and interpretations. Prestigious investigators may suppress via the peer review process the appearance and dissemination of findings that refute their findings, thus condemning their field to perpetuate false dogma. Empirical evidence on expert opinion shows that it is extremely unreliable [28].

Corollary 6: The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true. This seemingly paradoxical corollary follows because, as stated above, the PPV of isolated findings decreases when many teams of investigators are involved in the same field. This may explain why we occasionally see major excitement followed rapidly by severe disappointments in fields that draw wide attention. With many teams working on the same field and with massive experimental data being produced, timing is of the essence in beating competition. Thus, each team may prioritize on pursuing and disseminating its most impressive “positive” results. “Negative” results may become attractive for dissemination only if some other team has found a “positive” association on the same question. In that case, it may be attractive to refute a claim made in some prestigious journal. The term Proteus phenomenon has been coined to describe this phenomenon of rapidly alternating extreme research claims and extremely opposite refutations [29]. Empirical evidence suggests that this sequence of extreme opposites is very common in molecular genetics [29].


Claimed Research Findings May Often Be Simply Accurate Measures of the Prevailing Bias Top

As shown, the majority of modern biomedical research is operating in areas with very low pre- and post-study probability for true findings. Let us suppose that in a research field there are no true findings at all to be discovered. History of science teaches us that scientific endeavor has often in the past wasted effort in fields with absolutely no yield of true scientific information, at least based on our current understanding. In such a “null field,” one would ideally expect all observed effect sizes to vary by chance around the null in the absence of bias. The extent that observed findings deviate from what is expected by chance alone would be simply a pure measure of the prevailing bias.

For example, let us suppose that no nutrients or dietary patterns are actually important determinants for the risk of developing a specific tumor. Let us also suppose that the scientific literature has examined 60 nutrients and claims all of them to be related to the risk of developing this tumor with relative risks in the range of 1.2 to 1.4 for the comparison of the upper to lower intake tertiles. Then the claimed effect sizes are simply measuring nothing else but the net bias that has been involved in the generation of this scientific literature. Claimed effect sizes are in fact the most accurate estimates of the net bias. It even follows that between “null fields,” the fields that claim stronger effects (often with accompanying claims of medical or public health importance) are simply those that have sustained the worst biases.

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