Formulating Decision Rules for an Adaptive Long-Term Disease Modifying Trial in Osteoarthritis
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*Michael J Brown, Pfizer Global Research and Development 

Keywords: Adaptive Design, Longitudinal Analysis, Simulation

Clinical trials to assess disease modifying effect in osteoarthritis typically require at least two years of treatment and utilize a primary endpoint of radiographic joint space narrowing (JSN) of the knee. Clinical trials must be large and long in order to develop sufficient evidence that a drug is impacting the disease. There is reasonable risk that there will be a lack of sensitivity due to high variability or a low placebo progression rate. An adaptive trial was deisgned to allow for 1)an increase in the length of follow-up from 24 to 30 months if there was evidence of high measurement variability; 2) to stop if the placebo rate was too low or 3) stop for evidence that the drug did not have sufficient efficacy. Using simulation the design and adaptation guidelines were assessed. We present the outcome of those assessments and discuss general issues related to the process.