The WISDOM Study: breaking the deadlock in the breast cancer screening debate.

There are few medical issues that have generated as much controversy as screening for breast cancer. In science, controversy often stimulates innovation; however, the intensely divisive debate over mammographic screening has had the opposite effect and has stifled progress. The same two questions-whether it is better to screen annually or bi-annually, and whether women are best served by beginning screening at 40 or some later age-have been debated for 20 years, based on data generated three to four decades ago. The controversy has continued largely because our current approach to screening assumes all women have the same risk for the same type of breast cancer. In fact, we now know that cancers vary tremendously in terms of timing of onset, rate of growth, and probability of metastasis. In an era of personalized medicine, we have the opportunity to investigate tailored screening based on a woman's specific risk for a specific tumor type, generating new data that can inform best practices rather than to continue the rancorous debate. It is time to move from debate to wisdom by asking new questions and generating new knowledge. The WISDOM Study (Women Informed to Screen Depending On Measures of risk) is a pragmatic, adaptive, randomized clinical trial comparing a comprehensive risk-based, or personalized approach to traditional annual breast cancer screening. The multicenter trial will enroll 100,000 women, powered for a primary endpoint of non-inferiority with respect to the number of late stage cancers detected. The trial will determine whether screening based on personalized risk is as safe, less morbid, preferred by women, will facilitate prevention for those most likely to benefit, and adapt as we learn who is at risk for what kind of cancer. Funded by the Patient Centered Outcomes Research Institute, WISDOM is the product of a multi-year stakeholder engagement process that has brought together consumers, advocates, primary care physicians, specialists, policy makers, technology companies and payers to help break the deadlock in this debate and advance towards a new, dynamic approach to breast cancer screening

Withdrawal of inhaled glucocorticoids and exacerbations of COPD.

This is the final version of the article. It first appeared from Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa1407154BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. CONCLUSIONS: In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).Supported by Boehringer Ingelheim Pharma