Statistical analysis
SECONDARY, STILL
The primary analysis was a comparison of the accuracy of MTO and AVS. Each test was deemed accurate if it recommended surgery and surgery resulted in a cure (according to each PASO criterion), or if the test did not indicate surgery and surgery did not result in a cure. Since surgery was almost exclusively undertaken when one or both tests indicated that surgery was required, for those patients for whom neither test indicated surgery, both tests were treated in the analysis as having equal accuracy. Only in those patients for whom the two tests gave conflicting recommendations was it possible to determine which of the two test was accurate and which was not.The difference in accuracy between the two tests was estimated among those who underwent surgery using the Newcombe–Wilson score method for paired binary data and tested using an exact McNemar test.The sample size for the study was estimated from a table of all permutations of outcomes from each investigation and surgery, in which the frequency of each outcome reflected experience at participating centers (Supplementary Table The sample size was revised in November 2019 when it became apparent that the use of two investigations increased the proportion of participants with detectable unilateral PA, from the expected 50% to 66%. The dropout rate was much lower than 10%. The resulting smaller proportion of participants managed medically risked inadequate power for several secondary analyses (comparison of baseline characteristics and outcomes in the surgical and medical groups, and whether outcomes were sustained with time). The recalculated overall number of recruits anticipated to maintain the size of the medical group, and duration of follow-up, was 150. Still allowing for a 10% dropout rate, the revised total sample size was calculated to be 165.Rather than reduce the margin of superiority of which increased numbers would permit detection, the larger sample size permitted declaration of a non-inferiority margin. A total of 150 completed patients, with at least 75 proceeding to surgery, would have 90% power to demonstrate non-inferiority of MTO versus AVS within a non-inferiority margin of −17%. The addition of this non-inferiority margin is specified in the protocol and statistical analysis plan and was published on clinicaltrials.gov after approval by the Dulwich Ethics Research Committee and Medicines and Healthcare products Regulatory Agency.We had a qualitative and quantitative basis for the 17% margin. Regulatory advice is that bounds in equivalence and non-inferiority studies reflect ‘the largest difference that is clinically acceptable, so that a difference bigger than this would matter in practice’The full analysis set was defined as all patients who had both investigations. Because of pandemic-associated interruptions to the study, particularly the availability of laparoscopic adrenalectomy, the study was censored when more than 75 patients had undergone surgery and at least one evaluable outcome visit. The analysis is reported for the 128 patients who had reached a primary outcome visit either 6 months post-unilateral adrenalectomy (including five for whom data from their most recent, 3-month visit was carried forward) or 9–12 months after their baseline visit in the medically treated patients.A benefit of the delayed completion of MATCH was that the 25-participant extension could be revised to include a within-patient comparison of MTO and AVS with an 