Noninferiority trials have serious inherent limitations , the main one being that (unlike in a superiority trial), given a finding of noninferiority, it is impossible to distinguish between true equivalence and poor execution or faulty pretrial a priori assumptions regarding expectations of benefit and event rates. In this particular trial, a 15% absolute difference in the primary outcome was arguably too large to use as a noninferiority threshold. That threshold implies acceptance of 1 additional COPD exacerbation for each 7 patients treated. If a superiority trial showed a week's extra steroids prevented 1 COPD exacerbation for 10 or even 20 patients treated (, a 5-10% noninferiority margin), I think many doctors and patients would endorse longer-course prednisone. This trial (as designed) would fail to detect that.
To determine the onset of menopause in women receiving oral contraceptives, levels of follicle-stimulating hormone (FSH) must be measured to identify the rise that occurs in response to ovarian failure. Evaluation of the FSH level on the sixth day of the placebo week during oral contraceptive use can help define the best time to change to traditional estrogen replacement therapy ( Table 2 ) . When the FSH level is in the menopausal range, the change can be made from low-dose oral contraceptive pills to traditional estrogen replacement therapy. 20 – 22 In some postmenopausal women, FSH measurements do not reliably increase even after two weeks without oral contraceptives. In these women, estradiol levels will usually indicate a menopausal status. One small study 20 of 12 women showed that a combination of FSH level and serum estradiol reliably predicted menopause and an appropriate time to begin hormone replacement therapy.