FOR-DMD: Recruitment and Retention Challenges Addressing the Challenges Benefits vs risks of corticosteroids? Why invest so much to study a treatment of established (short term) benefit? Corticosteroids vs curative new treatment? Does FOR-DMD preclude participation in another study? Can subjects leave FOR-DMD to enter another study? presentations/2010/Freiburg 2010

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 This slide has the Slide Design template “content” applied. The first level bullet has been set up with a “null” character to make it appear unbulleted and still allow automatic bullets for subsequent levels. The second through fifth levels have bullets: from the left margin, tab once (or click the “increase indent” button) and the second level bullet will appear; further tabbing increases the indent and produces the corresponding bullet. presentations/2010/Freiburg 2010

No standard treatment (31 regimens) 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) This slide has the Slide Design template “content” applied. The first level bullet has been set up with a “null” character to make it appear unbulleted and still allow automatic bullets for subsequent levels. The second through fifth levels have bullets: from the left margin, tab once (or click the “increase indent” button) and the second level bullet will appear; further tabbing increases the indent and produces the corresponding bullet. presentations/2010/Freiburg 2010

Heterogeneous Steroid Regimens: A Challenge for New Therapeutic Approaches Different benefits from different agents? Varying time courses of benefit Improved in 10-90 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. This slide has the Slide Design template “content” applied. The first level bullet has been set up with a “null” character to make it appear unbulleted and still allow automatic bullets for subsequent levels. The second through fifth levels have bullets: from the left margin, tab once (or click the “increase indent” button) and the second level bullet will appear; further tabbing increases the indent and produces the corresponding bullet. presentations/2010/Freiburg 2010

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 This slide has the Slide Design template “content” applied. The first level bullet has been set up with a “null” character to make it appear unbulleted and still allow automatic bullets for subsequent levels. The second through fifth levels have bullets: from the left margin, tab once (or click the “increase indent” button) and the second level bullet will appear; further tabbing increases the indent and produces the corresponding bullet. presentations/2010/Freiburg 2010

Does FOR-DMD preclude participation in another study? Yes Can subjects leave FOR-DMD to enter another study? Yes This slide has the Slide Design template “content” applied. The first level bullet has been set up with a “null” character to make it appear unbulleted and still allow automatic bullets for subsequent levels. The second through fifth levels have bullets: from the left margin, tab once (or click the “increase indent” button) and the second level bullet will appear; further tabbing increases the indent and produces the corresponding bullet. presentations/2010/Freiburg 2010

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