A high proportion of published studies of the outcomes and adverse side effects of phase III clinical trials of breast cancer treatments contain spin and bias. In addition, a third of all trials that failed to show a statistically significant benefit for the treatment under investigation included reports that focused on other, less important outcomes in order to positively influence the interpretation of the results, according to a recent study.
Two-thirds of the reports were biased in the way that adverse effects of the treatment were reported, with grade III or IV adverse events poorly reported. This was particularly the case in trials that showed a significant benefit for the treatment under investigation. Only 32% of articles gave details of the frequency of grade III or IV toxicities in their abstracts.
The researchers identified all randomized, controlled, phase III clinical trials for breast cancer therapies that had been published between January 1995 and August 2011. Out of a total of 568 articles, 164 were eligible for inclusion in their analysis. Phase III trials usually evaluate the efficacy and/or the best dose for a particular therapy that has already been tested in earlier, small trials, and they usually involve more patients than phase I or II trials. Often, they are the final stage that a drug or other therapy has to pass before the treatment can be licensed for use in patients in normal clinical practice, outside of the trial setting.
Ian Tannock, MD, PhD, and colleagues defined bias as inappropriate reporting of the primary end point and toxicity, with emphasis on reporting of these outcomes in the abstract. They defined spin as the use of words in the concluding statement of the abstract to suggest that a trial with a negative primary end point was positive based on some apparent benefit shown in one or more secondary end points.
They found that 54 (33%) trials were reported as positive, based on secondary end points, despite not finding a statistically significant benefit in the primary end point. ”These reports were biased and used spin in attempts to conceal that bias,” wrote the authors. They found that 58% of 92 trials that showed no benefit for patients from the experimental therapy (negative primary end point) used secondary end points to suggest benefit from the treatment.
A total of 110 (67%) of papers reported adverse side effects of the experimental therapy in a biased manner. If a trial showed a benefit for the treatment (a positive primary end point), toxicities were more likely to be underreported.
The source of funding for trials, industry or academic, was not associated with bias or spin in reporting of results and toxicities.
This research was published in Annals of Oncology (2013; doi:10.1093/annonc/mds636).