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For sample size determination, it is anticipated that approximately 80% of patients receiving Timolol will experience visual field loss progression at 3 months post laser PI. With the hope that the proportion of Brimonidine treated patients having visual field loss progression will be reduced to 40%, a two‐sided test, with 5% level of significance and power of 90% would require recruitment of 30 patients in each arm (Machin, Campbell, Fayers & Pinol, 1997¹).

It is anticipated that after randomisation, 10% of the AACG patients may not respond to the initial medical treatment, and will require surgery instead of laser PI, and thus will not continue in the trial. After PI, it is expected that a further 10% of patients may not complete the trial and may withdraw from the study (see Withdrawal from Treatment). Taking into consideration the patients expected to fall out at each stage, we thus require approximately 80 AACG patients (40 patients per treatment group) for the trial.

¹Now updated as Machin, Campbell, Tan and Tan (2018).

In this example, the protocol takes note of patient losses due to a relatively large proportion expected to need surgery (rather than laser peripheral iridotomy, PI) and compensates by adjusting upwards the number of patients to recruit. They do not stipulate; however, how these patients will be dealt with in the final analysis and reporting. One option is to regard all these as failures when calculating the proportions in each group with visual field loss at 3 months post PI.

An alternative design possibility would have been to randomise patients after successful PI, so as to avoid recruiting patients who will provide little information on the relative merits of Timolol and Brimonidine. However, the design team may have discussed this (as well as other options) and rejected this for good reasons.