A new controlled clinic trial showed that Sildenafil, a phosphodiesterase-5 inhibitor, commonly known as Viagra, had no benefit for the advanced IPF patients. The trial enrolled 180 patients. The study was published in N Engl J Med. 2010 Aug 12;363(7):620-8.
Recently, Dr. Rossi and Dr. Seccia of University of Padua, Padua, Italy, suggested that the conclusion of the study represents an example of a type II statistical error.
"The primary outcome was the proportion of patients who improved at least 20% on the 6-minute walk distance after 12 weeks of receiving sildenafil, as compared with placebo. The investigators based their power calculation on a study involving 14 patients in which there was no increase among those who had a baseline 6-minute walk distance that was similar to the walk distance for patients in STEP-IPF. Thus, we think that the investigators' power calculation was undersized for the primary outcome. A potential benefit for sildenafil is suggested by patients' improvement in several less variable secondary outcomes."
Dr. Flaherty replied that "we agree with Rossi and Seccia that our study was underpowered to detect response rates of 20% versus 10% for patients in the sildenafil group, as compared with those in the placebo group". A sample size of approximately 580 patients would have been required for the study to be adequately powered to detect response rates of 20% versus 10%. On the basis of our preliminary data and discussions about clinically meaningful effects, we powered the study for response rates of 30% versus 10%. As noted by Rossi and Seccia, the positive response in several secondary end points provides some evidence for a benefit of sildenafil for the treatment of patients with advanced idiopathic pulmonary fibrosis, even though there was no significant between-group difference in the primary end point.
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