Bias in Clinical Trials

1. Where Bias Can Be Introduced

1.5. At Time of Reporting

Publication bias refers to the fact that positive results are more likely to be published (rapidly) than negative results. Researchers may not be interested or less motivated in publishing negative trial results, fearing that such findings may negatively reflect on their professional abilities, the image of their company (institution) and perhaps their new medicine. Hence positive results are more likely to be submitted rapidly for publication than negative results.

Publication bias is detrimental since it is preventing access to clinical trial results. Beyond single trial results, the efficacy and safety profile of a treatment needs to be assessed globally taking into account all the data and the results available from clinical trials investigating that treatment. Researchers planning new experimentation may be limited by the information available in published results. Negative results may inform about the lack of efficacy of a treatment and the absence of justification for continuing with further development. The conclusions of a meta-analysis may be flawed if based only on published data.

Initiatives are ongoing for reducing publication bias. One of them is to promote the registration of clinical trials for medicines. For instance, the International Committee of Medical Journal Editors (ICMJE) will not publish trials that are not registered in public registries such as, created and operated by the US National Institutes of Health (NIH). With such registries, researchers know what the existing clinical trials are, even if their results were never published, and may contact the trial sponsor in order to gain access to the results.

Despite these measures, publication bias has not been completely eliminated. While trial registries provide medical researchers with information about unpublished trials, researchers may be left to only speculate as to the results of these trials. Various organisations are currently engaged in initiatives to encourage or require the registration and disclosure of clinical trial information. In Europe, EudraCT, the European Clinical Trials Database of the European Medical Agency collects information on all clinical trials of medicines performed in Europe. As of July 2014, this database also makes trial summary results available to the public. The World Health Organisation (WHO), through its International Clinical Trials Registry Platform (ICTRP), is setting international standards for registering and reporting on all clinical trials. In the US, the registry is doing similarly.

Reducing publication bias will also occur by increasing the willingness of scientific journals to publish trials with negative results. Manuscripts should be reviewed on the basis of the quality of the methodology used, not on the apparent success of the trial. In addition, funding agencies should take a more active role in the dissemination of clinical trials they fund.