Achieving Clinically Meaningful Outcomes in Research Trials

1. Achieving Clinically Meaningful Outcomes in Research Trials ASCO March 17, 2014

2. Goals • To help investigators develop randomized phase III trials that: • are likely to impact clinical care in the era of molecularly targeted therapy • focus on patient impact, rather than statistical significance • To inspire patient advocates who are participating in peer review programs, IRBs, and protocol or design committees to demand more from trials • To assist clinical trial sponsors and investigators with making decisions when weighing research and funding priorities

3. Process for Defining Clinically Meaningful Outcomes • Working Groups for pancreas, breast, lung, and colon cancers included oncologists, patients/ advocates, statisticians, industry and FDA oncologists • Comments received from patients, oncologists, ASCO volunteers, and the public • Recommendations considered patient population, endpoints, current standards of care and meaningful increases to expected outcomes

4. Key Decisions When Defining Meaningful Outcomes • Outcomes must be aspirational yet achievable • Outcome recommendations that are too prescriptive could cause unintended consequences • Toxicity must be considered - greater toxicity acceptable for greater gains • Multiple parameters define a clinically meaningful outcome • OS with significant improvement in 2 yr survival (tail of curve) • QOL not the same in all cancers • Must be cancer specific • Recs are intended as desired goals for clinical trial design (not for regulatory or reimbursement purposes)

5. Recommendations for Meaningful Outcomes • Minimum meaningful incremental improvement is an HR of ≤0.8 and median OS improvement from 2.5 to 6 months • New regimens that are substantially more toxic than current standards should also produce the greatest increments in OS