Abstract
Chronic pain trials commonly allow auxiliary pain medications such as rescue and concomitant analgesics in addition to the randomized treatment. Changes in auxiliary pain medications after randomization represent intercurrent events that may affect either the interpretation or the existence of the measurements associated with the clinical question of interest, complicating the assessment of treatment efficacy. In chronic pain trials, pain intensity typically varies and patients may take the auxiliary medications 1 day but not the next or increase and decrease the dosages temporarily while continuing their randomized study medication. This distinctive feature of auxiliary pain medications as an intercurrent event has received little attention in the literature. Further clarifications on how to manage these issues are therefore pressing. Here we provide perspectives on issues related to auxiliary pain medication-related intercurrent events in randomized controlled chronic pain trials considering the strategies suggested in the E9(R1) addendum to the ICH guideline on statistical principles for clinical trials.