Table 4.

Lessons concerning the analytic plan for nonadherence and cointerventions

(1) Commercial availability of study drug can make drop-in a serious problem because the use of commercial drug off protocol limits the capacity of the trial to observe a treatment effect. During trial execution, major efforts are required to reduce use of commercial drug, and an analytic plan needs to take account of drop-in.
(2A) Discontinuation of study drug is likely in a long-term trial in patients on dialysis, and generous estimates should be incorporated into power calculations.
(2B) Longer follow-up time does not necessarily increase study power.
(3) An analytic plan to take into account nonadherence must be prespecified. IPCW may be the best method to account for nonadherence, particularly if determinants of nonadherence are well established.
(4) It is necessary to take account of the effect of cointerventions that limit assessment of the trial’s main treatment effect. Depending on the nature of the intervention, it may be wise to censor follow-up time after the intervention or to incorporate the intervention into a composite end point (e.g., initiation of dialysis in a trial aiming to slow progression of CKD).
  • IPCW, Inverse probability of censoring weight.