Spin and bias in published studies of breast cancer trials
The first author of the study, Dr Francisco Vera-Badillo, clinical research fellow at the Princess Margaret, said: “We found a high incidence of biased reporting of the outcomes of clinical trials. In those with outcomes that were either negative or did not show a statistically significant benefit, spin was used frequently to influence positively the interpretation of the results, by focusing on apparent benefits from secondary endpoints.
“Where trials showed a positive outcome, the toxicities were less likely to be reported. A possible explanation for this could be that the investigators, sponsors or both, prefer to focus on the efficacy of the experimental treatment and downplay toxicity to make the results look more attractive.”
The source of funding for trials (industry or academic) was not associated with bias or spin in the reporting of results and toxicities.
A new study could change exercise recommendations for breast cancer survivors to give them the freedom to pursue a wider range of physical activities after treatment, experts say.
Breast cancer survivors for years have been told not to lift weights for fear of developing an incurable condition called lymphedema, a complication of cancer surgery that can cause painful swelling in the arm. To prevent the disabling condition, women have been told to virtually “put their arm in a box,” says Jennifer Ligibel of Boston’s Dana-Farber Cancer Institute.
But that can allow bones and muscles to weaken, Ligibel says. So when a woman needs to lift something heavy, she may injure herself and cause a flare-up of lymphedema.
Up to 70% of breast cancer survivors experience some symptoms of lymphedema, although many cases are mild, a study in today’s New England Journal of Medicine shows. The new findings show that women with lymphedema who follow a carefully designed strength-training program can build muscle while cutting the risk of painful flare-ups in half.
“For many years, we’ve told women not to lift anything heavier than a handbag,” says Anna Schwartz, an affiliate professor of nursing at the University of Washington and author of Cancer Fitness, who was not involved in the study. “This is the first really well-designed study that demonstrates that women can do a lot more than we thought.”
Doctors studied 141 lymphedema patients who had an average age in the mid-50s and assigned half to a structured weight-lifting class at the YMCA. By the end of the course, the exercisers could bench-press an average of 53 pounds - a 29% improvement, says study co-author Kathryn Schmitz of the University of Pennsylvania School of Medicine.
After one year, 14% of the exercisers experienced a flare-up in their lymphedema, compared with 29% of the non-exercisers, says the study, funded partly by the National Institutes of Health.
In order to be published in most academic journals, it is now compulsory to register clinical trials before they start. Many countries register them on either the USA registry (ClinicalTrials.gov) or the European registry (clinicaltrialsregister.eu). Some of the studies analysed for the Annals of Oncology paper started before registration became compulsory. However, for those that were registered, the researchers found that some changed the primary endpoint between registration and the report of the outcomes being published. “Among these trials, there was a trend towards change of the primary endpoint being associated with positive results, suggesting that it may be a strategy to make a negative trial appear positive,” write the authors. “Trial registration does not necessarily remove bias in reporting outcomes, although it does make it easier to detect.”
Breast cancer is the second leading cause of cancer death in women in the United States, with approximately 200,000 cases diagnosed each year. Depending on the extent of the cancer, some women may benefit from adjuvant therapy. Adjuvant therapy is a treatment that is added to increase the effectiveness of a primary therapy. Adjuvant therapy may include chemotherapy, radiation therapy, biologic therapy or hormonal therapy. These adjuvant treatments can be administered alone or in combination after surgery to increase the chances of curing the cancer or prolonging a remission.
Adjuvant therapy is often associated with side effects such as fatigue, nausea, anxiety and depression. As a result, women often discontinue physical activity in an effort to cope with the side effects. However, this inactivity can actually sometimes exacerbate their condition, causing a decline in physical functioning.
Researchers at the Ottawa Regional Cancer Centre conducted a study to evaluate the effects of exercise on physical functioning and quality of life during adjuvant therapy. The study included 123 women with stages I and II breast cancer who were divided into three groups: usual care, self-directed exercise intervention, and supervised exercise intervention. Participants in the usual care group received general advice from their oncologist regarding the benefits of exercise. The self-directed exercise participants received a home exercise plan and were asked to exercise 5 times a week for 26 weeks. The supervised exercise group participated in a supervised exercise program 3 times a week for 26 weeks. The exercise consisted of moderate-level aerobic activity such as brisk walking.
Both the self-directed exercisers and the supervised exercisers experienced a significant improvement in physical functioning and aerobic capacity. These groups of women were able to participate in physical activity while undergoing adjuvant therapy, without any reported adverse effects from the activity. The researchers evaluated the data for all women and also evaluated the data based on whether participants were receiving chemotherapy. Of the 123 women, 83 were receiving chemotherapy. While both exercising groups experienced improved physical functioning and aerobic capacity, these gains were slightly lower in women receiving chemotherapy.
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Notes:
[1] “Bias in reporting of endpoints of efficacy and toxicity in randomized clinical trials for women with breast cancer”, by F.E. Vera-Badillo, R. Shapiro, A. Ocana, E. Amir, I.F. Tannock.
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Emma Mason
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European Society for Medical Oncology