Here is the design of a clinical trial:

Official Title: Glucocorticoid Withdrawal and Glucocorticoid-induced Adrenal Insufficiency: a Randomized Controlled Multicenter Trial

Included conditions:
- Inflammatory Disorder
- Autoimmune

Study Armgroups:
- {'label': 'Placebo arm (intervention arm)', 'type': 'PLACEBO_COMPARATOR', 'description': 'Stop glucocorticoid treatment; administer placebo matching the verum preparation in weekly intervals.', 'interventionNames': ['Other: Placebo Arm']}
- {'label': 'Verum group (control/standard arm)', 'type': 'ACTIVE_COMPARATOR', 'description': 'If patient is on \\> 7.5 mg prednisone-equivalent daily: administer 7.5 mg q.d. for 7 days, then 5 mg q.d. for 7 days, then 2.5 mg q.d. for 7 days, then 2.5 mg q.d. every second day, then stop. If patient on 7.5 mg q.d.: maintain for 7 days, then taper as above.', 'interventionNames': ['Drug: Prednisone']}

Interventions:
- {'type': 'DRUG', 'name': 'Prednisone', 'description': 'The control intervention (standard treatment) consists of prednisone treatment in decreasing doses, starting with 7.5 mg q.d. and reducing the dose every 7 days, such that prednisone treatment is stopped after a total of 4 weeks.', 'armGroupLabels': ['Verum group (control/standard arm)']}
- {'type': 'OTHER', 'name': 'Placebo Arm', 'description': 'The experimental intervention consists of stopping glucocorticoid treatment abruptly and administering matching placebo over 4 weeks.', 'armGroupLabels': ['Placebo arm (intervention arm)']}

Primary Outcomes:
- {'measure': 'Time to any incidence', 'description': 'Time to first occurrence of hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis (defined as glucocorticoid-responsive hypotension or shock with or without accompanying symptoms and signs such as weakness, apathy, nausea, vomiting, abdominal pain, hypothermia, hyponatremia \\[serum sodium \\< 135 millimole (mM)\\], hyperkalemia \\[serum potassium \\> 5 mM\\], hypoglycemia \\[plasma glucose \\< 3.5 mM\\]); whichever occurs first.', 'timeFrame': 'up to 6 months'}

Please estimate the sample size based on the assumption: 
Patients are randomized in a 1:1 ratio. All patients are followed for 6 months, with a 10% dropout rate. The significance level is 5%. The power is estimated to be 80%.
Sample size
          To assess the primary outcome measure, a Cox proportional hazards regression model will be fitted to the data. Noninferiority will be concluded if the two-sided 95% confidence interval of the hazard ratio between the experimental and the control arm lies entirely below the critical hazard ratio defined as

HR=Î»eÎ»e=âlog(Ïet)tâlog(Ïct)t=âlog(Ïet)âlog(Ïct)=âlog(Ïctâm)âlog(Ïct)

where Î»e and Î»c are the hazard rates in the experimental and control arms, t is a fixed point of time, Ïet and Ïct are the proportions of event-free patients at time t, and m is the noninferiority margin expressed as the additional proportion of patients having had an event in the experimental arm, assuming that the occurrence of events follows an exponential distribution. Noninferiority will be concluded if the upper limit of the two-sided 95% confidence interval of the hazard ratio lies below the critical hazard ratio.
          For the sample size estimation, the following assumptions were made:
          
            
              Patients are randomized to the control and experimental arms in a 1:1 ratio.
            
            
              After inclusion, all patients are followed for 6 months. Patients without an event within 6 months are considered right-censored and are not followed any further even though the trial might be ongoing.
            
            
              10% of patients will drop out within the 6 months follow-up period. The drop-out events are distributed uniformly over this period.
            
            
              The event rate within the 6 months follow-up period, i.e., the proportion of patients with an event, is 40%, both for the control and the experimental arms. We estimated this overall figure based on expected relapse rates for the various eligible diseases, as indicated by clinical experts and published data, e.g. in COPD or inflammatory bowel disease. Our estimation is conservative since the other components of the combined primary outcome will contribute to the event rate.
            
            
              The survival curves in the control and experimental arms follow the same exponential distribution. The rate parameter of the exponential distribution is chosen so that the corresponding cumulative distribution function value at 6 months equals the assumed event rate.
            
            
              The noninferiority margin is defined as an absolute increase of the event rate by 13% over 6 months. We used a modified Delphi approach to determine this margin. 10 experienced clinicians board-certified in internal medicine and/or rheumatology, gastroenterology, and endocrinology were individually asked to define the maximum increase in outcome events they would accept for the benefit of rapid glucocorticoid stop and gain of high-quality scientific data in the area of steroid withdrawal. Assuming an event rate of 40% in the standard treatment arm, the mean tolerable increase under experimental treatment was 13.6% (range, 5 to 20%; median, 13%).
            
            
              The significance level is 5%.
            
          
          For each combination of the noninferiority margins 7.5%, 7.6%, â¦, 17.5%, and the sample sizes n = 200, 210, â¦, 1200, 999 individual data sets were simulated based on the above assumptions. A Cox proportional hazards regression model was fitted to each data set, and the hazard ratios for the experimental vs. the control arm with the associated 95% confidence interval were estimated. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the hazard ratio was below the critical hazard ratio (see above equation). The power was estimated as the proportion of positive conclusions divided by the total number of the 999 iterations per parameter combination. To achieve a power of 80%, 573 patients (95% CI, 565 to 580) need to be included, assuming an event rate of 40% over the 6 months follow-up period and setting the noninferiority margin to 13%. The critical hazard ratio for this noninferiority scenario is 1.478.
          The sample size of n = 573 is a conservative estimation, since the assumed drop-out rate of 10% is relatively high.