M01: Antiinflammatory and antirheumatic products

Pain needs a fitted placebo time course. In oral osteoarthritis trials the WOMAC placebo response is large and reaches 90% of its maximum only after 5 to 7 weeks [1]. In an acute postoperative model, pain relief was fitted as a function of ketorolac concentration (E_max), a subject random effect and time, the last capturing the waxing and waning of placebo [2].

Remedication is informative dropout. Patients remedicate when relief is insufficient, with a probability driven by the observed level of pain relief and rising with time, and ignoring that informative dropout biases the drug effect [2,3].