http://www.biomedcentral.com/1471-2377/7/6
Assumptions
The existing evidence does not allow precise estimates of improvement with the trial treatments. However the available data suggests that at one year follow up, 50 to 63% of participants with CFS/ME had a positive outcome, by intention to treat, in the three RCTs of rehabilitative CBT [18,25,26], with 69% improved after an educational rehabilitation that closely resembled CBT [43]. This compares to 18 and 63% improved in the two RCTs of GET [23,24], and 47% improvement in a clinical audit of GET [56]. Having usual rather than specialist medical care allowed 6% to 17% to improve by one year in two RCTs [18,25]. There are no previous RCTs of APT to guide us [11,12], but we estimate that APT will be at least as effective as the control treatments of relaxation and flexibility used in previous RCTs, with 26% to 27% improved on primary outcomes [23,26]. We propose that a clinically important difference would be between 2 and 3 times the improvement rate of SSMC.
Power analyses
Our planned intention to treat analyses will compare APT against SSMC alone, and both CBT and GET against APT. Assuming ? = 5% and a power of 90%, we require a minimum of 135 participants in the SSMC alone and APT groups, 80 participants in the GET group and 40 in the CBT group [57]. However these last two numbers are insufficient to study predictors, process, or cost-effectiveness. We will not be able to get a precise estimate of the difference between CBT and GET, though our estimates will be useful in planning future trials. As an example, to detect a difference in response rates of 50% and 60%, with 90% power, would require 520 participants per group; numbers beyond a realistic two-arm trial. Therefore, we will study equal numbers of 135 participants in each of the four arms, which gives us greater than 90% power to study differences in efficacy between APT and both CBT and GET. We will adjust our numbers for dropouts, at the same time as designing the trial and its management to minimise dropouts. Dropout rates were 12 and 33% in the two studies of GET [23,24] and 3, 10, and 40% in the three studies of rehabilitative CBT [18,25,26]. On the basis of our own previous trials, we estimate a dropout rate of 10%. We therefore require approximately 150 participants in each treatment group, or 600 participants in all. Calculation of the sample size required to detect economic differences between treatment groups requires data of cost per change in outcome, which is not currently available.
