The validity of a systematic review depends on the methods used to conduct the review. If there is a systematic bias, such that studies with statistically significant or positive findings are more likely to be published and included in systematic reviews than trials with non-significant findings, then the validity of a review's conclusions can be threatened.
This methodology review identified five studies that investigated the extent to which the publication of clinical trials (such as those approved by an ethics review board) is influenced by the statistical significance or direction of a trial's results. These studies showed that trials with positive findings (defined either as those that were statistically significant (P < 0.05), or those findings perceived to be important or striking, or those indicating a positive direction of treatment effect), had nearly four times the odds of being published compared to findings that were not statistically significant (P ≥ 0.05), or perceived as unimportant, or showing a negative or null direction of treatment effect. This corresponds to a risk ratio of 1.78 (95% CI 1.58 to 1.95), assuming that 41% of negative trials are published.Two studies found that trials with positive findings also tended to be published more quickly than trials with negative findings. The size of the trial (assessed in three studies) and the source of funding, academic rank, and sex of the principal investigator (assessed in one study) did not appear to influence whether a trial was published.
These results provide support for mandating that clinical trials are registered before recruiting participants so that review authors know about all potentially eligible studies, regardless of their findings. Those carrying out systematic reviews should ensure they assess the potential problems of publication bias in their review and consider methods for addressing this issue by ensuring a comprehensive search for both published and unpublished trials.