Michelle Ghert, MD, FRCSC Center for Evidence-Based Orthopaedics McMaster University

1. International Randomized Trials in Orthopaedic Oncology: Joining Forces and Shifting the Paradigm Michelle Ghert, MD, FRCSC Center for Evidence-Based Orthopaedics McMaster University

3. Disclosure • Committee Chair: Orthopaedic Research Society • Committee Member: Musculoskeletal Tumor Society • Grand Funding: OREF, MSTS, PSI, CCSRI, MSA • Private Funding: Manherz Family Donation

4. Overview • Learning Process • Take Home Points: • Trials require: 1. The right question 2. Centralized infrastructure 3. Collaborative network

5. Where the Process Started

6. Strong Pull to 'The Dark Side’

7. First ever Department of Clinical Epidemiology Chairman: Dr. David Sackett Dr. David Sackett M.S. from Harvard Epidemiology Mentor Dr. Gordon Guyatt Coined the term “Evidence-Based Medicine” Mentor Dr. Mohit Bhandari Unparalleled transformation in orthopaedic research Prospective international randomized controlled trials Mentor

8. Clinical Epidemiology: Absorbed through osmosis

9. “Elephant in Paris” moment CTOS 2010

10. Will it work? • Trials require: 1. The right question 2. Centralized infrastructure 3. Collaborative network

11. Challenges to Prospective Research

12. Current Evidence in Orthopaedic Oncology

13. SPRINT Trial

14. SPRINT trial: 1339 patients, 95% follow-up • FLOW trial: 2500 patients recruited, target 2520 • FAITH trial: 990 patients, target 1000 • TRUST trial: 500 patients, target 1000 • HEALTH trial: 358 patients, target 1400 • INORMUS and PRAISE cohorts: 7900 patients • Collaboration with over 150 centers around the world

15. Preliminary Steps for a Surgical Trial • Find an important question • Systematic review • Survey the field • Publish a protocol • Apply for funding

16. 22 year-old male with sarcoma right femur

24. 58year-old female

28. Clinical Question: PICO Population Intervention Comparison Outcome

29. Preliminary Steps for a Surgical Trial • Find a question important to your field • Systematic review • Survey the field for practice and opinion • Publish a protocol • Apply for funding

32. Preliminary Steps for a Surgical Trial • Find an important question • Systematic review • Survey the field • Publish a protocol • Apply for funding

36. Preliminary Steps for a Surgical Trial • Find an important question • Systematic review • Survey the field • Publish a protocol • Apply for funding

37. Study Design Standard pre-op and intra-op antibiotics AND 24 hours post op antibiotics Follow-up one year Follow-up one year Patient screened and eligible and provides informed consent Randomization Standard pre-op and intra-op antibiotics AND 5 days post op antibiotics

40. Sample Size Calculation • Infection rate: 10% • Superiority of long-term antibiotics: • threshold of 5% for inferiority • Estimated sample size of 920

42. Preliminary Steps for a Surgical Trial • Find an important question • Systematic review • Survey the field • Publish a protocol • Apply for funding

43. Writing Grants

44. Research Funding: Pilot (vanguard phase)

45. What you need to run RCTs • Trials require: 1. The right question √ 2. Centralized infrastructure 3. Collaborative network

46. What you need to run RCTs • Trials require: 1. The right question √ 2. Centralized infrastructure 3. Collaborative network

47. Methods Center Nominated Principal Investigator Co-Investigators Senior Biostatistician Study Coordinator Administrative Assistants Statistician Graduate Students Data Manager Research Assistants

48. Central Source of Information

49. Newsletter and website

50. Budgeting and Contracts