Monitoring Drug Safety in Rheumatoid Arthritis Prevention Trials.

ABSTRACT

This commentary discusses issues particular to drug safety monitoring in prevention trials. Although the general approach to safety assessment applies across all clinical trials, prevention trials pose special challenges given that the patient population is currently asymptomatic or experiencing only mild symptoms of the targeted disease. This sways the risk-benefit analysis balance toward minimal acceptable risk. Definition of the predisease state with validated biomarkers or other assessment tools is essential. The timing and required length of exposure to the disease intervention to produce an effect requires special methodologic considerations. In addition, prevention trials generally have a longer duration with higher dropout rates. As a result, there is an enhanced focus on lessening patient burden in regard to data collection and finding ways to minimize the safety signal to noise ratio to enable product causality assessment. To meet these challenges, clinical safety monitoring in prevention trials involves 3 essential steps: safety planning, systematic data collection and evaluation, and transparent communication of safety information. We discuss some of these issues using historical experience with primary prevention cardiovascular trials and then focus on unique issues surrounding patient populations at risk for rheumatoid arthritis.