I haven't had the chance to read this closely, but it looks pretty good.
Why Most Published Research Findings Are False
PLoS Medicine 2(8): e124
John P. A. Ioannidis
Summary: 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.
Most Published Research Findings Are False—But a Little Replication Goes a Long Way
Ramal Moonesinghe, Muin J. Khoury, A. Cecile J. W. Janssens
"We know there is a lot of lack of replication in research findings, most notably in the field of genetic associations [1–3]. For example, a survey of 600 positive associations between gene variants and common diseases showed that out of 166 reported associations studied three or more times, only six were replicated consistently . Lack of replication results from a number of factors such as publication bias, selection bias, Type I errors, population stratification (the mixture of individuals from heterogeneous genetic backgrounds), and lack of statistical power .
In a recent article in PLoS Medicine, John Ioannidis quantified the theoretical basis for lack of replication by deriving the positive predictive value (PPV) of the truth of a research finding on the basis of a combination of factors. He showed elegantly that most claimed research findings are false . One of his findings was that the more scientific teams involved in studying the subject, the less likely the research findings from individual studies are to be true. The rapid early succession of contradictory conclusions is called the “Proteus phenomenon” . For several independent studies of equal power, Ioannidis showed that the probability of a research finding being true when one or more studies find statistically significant results declines with increasing number of studies."
and in the conclusion:
"In summary, while we agree with Ioannidis that most research findings are false, we clearly demonstrate that replication of research findings enhances the positive predictive value of research findings being true. While this is not unexpected, it should be encouraging news to researchers in their never-ending pursuit of scientific hypothesis generation and testing. Nevertheless, more methodologic work is needed to assess and interpret cumulative evidence of research findings and their biological plausibility. This is especially urgent in the exploding field of genetic associations."