Bias and Spin in Reporting of Breast Cancer Trials

Zosia Chustecka

January 15, 2013

Clinical trial investigators are often biased in their reporting of results from breast cancer studies, and they use spin to emphasize secondary results when the primary end point is not significant. These are the conclusions of study published online January 9 in the Annals of Oncology.

A team led by Ian Tannock, MD, PHD, Dsc, professor of medical oncology at the Princess Margaret Hospital and University of Toronto, in Ontario, Canada, reviewed 164 breast cancer clinical trials published from 1995 to 2011.

They found bias in the reporting of the primary end point in 33% of those studies and bias in the reporting of toxicity in 67%.

In addition, "spin was used frequently to influence, positively, the interpretation of negative trials, by emphasizing the apparent benefit of a secondary end point," the researchers write.

Spin and bias were used to suggest efficacy in 59% of trials that had no significant difference in their primary end point, Dr. Tannock and colleagues report.

The results for breast cancer trials are similar to those previously reported in other areas of medicine, they note.

"This problem isn't at all unique to breast cancer and isn't surprising," according to Kathy D. Miller, MD, associate professor of medicine at Indiana University in Indianapolis, who writes the Medscape Miller on Oncology blog.

Dr. Miller, who has been involved in many large breast cancer trials, told Medscape Medical News that "we put a tremendous amount of effort and time into each trial — the bias to look for the positive is one we all share."

Biased Reporting Prevalent

Of the 164 randomized clinical trials analyzed, 148 were for systemic therapy, 11 were for radiation therapy, and 5 were for surgical therapy. About half of the trials were conducted in the adjuvant setting, and about half evaluated an experimental therapy in women with metastatic breast cancer.

One third of these trials (32.9%) were reported as positive, despite not having a statistically significant difference in the primary end point, the Dr. Tannock and colleagues explain. "These reports were biased and used spin in an attempt to conceal that bias," they add.

Two thirds of the trials (67.1%) were biased in their reporting of toxicity. The researchers rated the reporting of toxicity on a hierarchical scale, ranging from 1 (excellent) to 7 (very poor). They looked at whether grade 3 and 4 toxicities were reported in the concluding statement of the abstract, appeared anywhere in the abstract, appeared in the results section of the paper, appeared only in table form, appeared only in the discussion section, or did not appear at all.

Of the 164 trials, 34 were rated 7, 55 were rated 6, and 21 were rated 5.

"We found that bias in the reporting of toxicity was higher when the trial had a significant P value for the difference in the primary end point between experimental and control arms," the researchers note. "A possible explanation for this finding may be that investigators and/or sponsors then focus on efficacy as the basis of registration and downplay the toxicity to make the results more attractive," they add.

Interestingly, industry funding was not associated with bias in the reporting of the primary end point or toxicity. Of the trials analyzed for the review, 67% were sponsored by industry.

The incidence of bias found in this analysis was "higher that we expected," Dr. Tannock told Medscape Medical News.

"Clinicians should read articles critically," he advised. Bias in the reporting of efficacy and toxicity remains prevalent, so clinicians, journal editors, and regulators "should apply a critical eye to trial reports and be wary of the possibility of biased reporting," he explained.

Dr. Tannock suggested that "journal editors should have a checklist to ensure that the abstract ends with a statement about the primary end point and a sentence summarizing major toxicity differences between the arms."

Registration of clinical trials is now mandatory, the researchers note. However, because ClinicalTrials.gov was only established in 2002, just 18% of the 164 trials analyzed were registered.

"Trial registration does not necessarily remove bias in reporting outcome, although it makes it easier to detect," they add.

Dr. Tannock and coauthors has disclosed no relevant financial relationships. Dr. Miller reports serving as a speaker for Genentech and Roche.

Ann Oncol. Published online January 9, 2013. Abstract

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