Objective: Effectively evaluating disease-modifying effects in clinical trials has posed a problem for clinical trialists and drug development. One method that has been proposed to evaluate disease-modifying effects has been the re-randomization of active group participants to discontinue the intervention after a period sufficient to produce therapeutic effects. We aimed to determine if this design would permit inferences regarding disease modification in a trial evaluating Pegaptanib sodium, an intra-ocular injection, for the treatment of age-related macular degeneration.
Study design and setting: In two identically designed trials, 1,186 patients were randomized to receive 54 weeks of treatment. After 54 weeks, 1,053 were re-randomized to either stay on treatment or discontinue treatment. Patients were seen at multicenter outpatient clinics.
Results: We found that patients randomized to discontinue treatment after 54 weeks of treatment and followed for a further 48 weeks, were significantly different than the control group (sham) in loss of 15 letters of vision (Relative Risk 0.70, 95% Confidence Interval 0.57-0.88, P=0.002), indicating that treatment is disease modifying. This effect was consistent throughout our sensitivity analyses.
Conclusion: This trial is the first example of a clinical trial evaluating disease-modifying effects and this design should influence drug discovery to determine further therapeutic potential of pharmacologic interventions.