Question: Please explain the difference in an easy to understand way of a negative vs a positive study given the example below. In a blinded randomized
Please explain the difference in an easy to understand way of a negative vs a positive study given the example below.
In a blinded randomized clinical trial of 804 men with heart failure, investigators compared treatment with enalapril (an angiotensin-converting enzyme [ACE] inhibitor) to treatment with a combination of hydralazine and nitrates.6 In the follow-up period, which ranged from 6 months to 5.7 years, 132 of 403 patients (33%) assigned to receive enalapril died, as did 153 of 401 patients (38%) assigned to receive hydralazine and nitrates. The P value associated with the difference in mortality is .11. Looking at this study as an exercise in hypothesis testing and adopting the usual 5% risk of obtaining a false-positive result, we would conclude that chance remains a plausible explanation for the apparent differences between groups. We would classify this as a negative study (ie, we would conclude that no important difference existed between the treatment and control groups). The investigators also conducted an additional analysis that compared the time pattern of the deaths occurring in both groups. This survival analysis, which generally is more sensitive than the test of the difference in proportions (see Chapter 8, Does Treatment Lower Risk? Understanding the Results), had a nonsignificant P value of .08, a result that leads to the same conclusion as the simpler analysis that focused on relative proportions at the end of the study. The authors also tell us that the P value associated with differences in mortality at 2 years (a point predetermined to be a major end point of the trial) was significant at .016. At this point, one might excuse clinicians who feel a little confused. Ask yourself, is this a positive trial, dictating use of an ACE inhibitor instead of the combination of hydralazine and nitrates, or is it a negative study, showing no difference between the 2 regimens and leaving the choice of drugs open?
Guyatt, Gordon; Guyatt, Gordon; Guyatt, Gordon; Rennie, Drummond; Rennie, Drummond; Rennie, Drummond; Meade, Maureen O.; Meade, Maureen O.; Meade, Maureen O.; Cook, Deborah J.; Cook, Deborah J.; Cook, Deborah J.. Users' Guides to the Medical Literature: Essentials of Evidence-Based Clinical Practice, Third Edition (Uses Guides to Medical Literature) (pp. 196-197). McGraw-Hill Education. Kindle Edition.
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