FOR-DMD: Recruitment and Retention Challenges Addressing the Challenges 1.Benefits vs risks of corticosteroids? 2.Why invest so much to study a treatment of established (short term) benefit? 3.Corticosteroids vs curative new treatment? 4.Does FOR-DMD preclude participation in another study? 5.Can subjects leave FOR-DMD to enter another study?

2 Benefits vs risks of corticosteroids? No longer equipoise concerning corticosteroids vs placebo (study sections X3; FOR-DMD investigators; CINRG Network; Cochrane, AAN reviews) Long-term data, albeit uncontrolled New trials are “permitting” corticosteroids

3 Why invest so much to study a treatment of established (short term) benefit? No standard treatment (31 regimens) No standards of side effect prevention/long-term treatment of DMD Heterogeneity of regimens may defeat and unquestionably complicates new treatment evaluations (e.g., PTC 124)

4 Heterogeneous Steroid Regimens: A Challenge for New Therapeutic Approaches Different benefits from different agents? Varying time courses of benefit Improved in days Plateau in 3-12 mos Decline in 18-? mos Worsen off treatment in ? Effect of variation on study power Adverse effects differ Different drug interactions.

5 Corticosteroids vs curative new treatment? No proposed new treatment likely curative Few new treatments applicable to all DMD People underestimate the benefit of corticosteroids 30% longer ambulation 30% longer off ventilator Survive? (Better than pacemakers, defibrillators, all cancer chemotherapy

6 Does FOR-DMD preclude participation in another study? Yes Can subjects leave FOR-DMD to enter another study? Yes

This trial will also establish standards of care in 41 centers and 11 countries. 7