Clinical research is undergoing a revolution in light of new demands for speed and opportunities from a technological standpoint. These trends have given rise to a debate about the quality and clinical meaning of traditional methods of investigations versus modern types of clinical studies to collect real world evidence. This debate at the 3rd annual Medical Affairs Innovation Olympics #MAIO2024 in a unique and exciting format with a live poll at the conclusion, features an animated discussion from three speakers: Rashad Massoud, MD, MPH, CEO of Rashad Massoud Associates, LLC., globally recognized healthcare quality expert, physician, formerly visiting faculty at the T.H. Chan School of Public Health; Suzanne Pavon (moderator), Doctor of Pharmacy, Board Member at Iethico, former Vice President of Pharmacovigilance and Quality at Argenx; and Sana Syed, Senior Medical Director - Clinical Lead at Sanofi and public health expert formerly at T.H. Chang School of Public Health.

Debate Objectives: ● To discuss the utility of RCTs in research and learning ● To discuss the challenges in translating RCT findings into the real-world environment ● To review the utility of the RCT approach to facilitate real world implementation ● To review the impact of the RCT approach for impact and limitations ● To discuss alternative research methods for research and learning ● To conclude with the research approaches that fit best for clinical trials and the real world; indicating a need for an adaptive, dual approach. 0:00 Alloutcoach Intro Music

0:09 Episode Highlight

3:09 Innovation Olympics Introduction

4:44 Debate Rules & Introduction

6:30 RCTs are the Gold Standard for Research and Learning - For the Motion - Sana Syed 8:12 The Scientific Method - Standard RCT Design 9:46 Rare Disease Case Study 11:38 Translating Biology vs Translating Real World Factors 14:34 Diversity of patients critical for data to represent populations 18:50 RCTs are NOT the Gold Standard for Research: Against the Motion - Rashad Massoud 20:27 Properties of an RCT 21:19 Other Research Questions to Eliminate Other Factors that may influence the results 24:13 Access Questions and Outcomes of Interest - Discovery and Delivery

24:48 Agency for Healthcare Research and Quality (AHRQ) - ~17 yrs to translate data into real world 26:33 Efficacy vs. Effectiveness Research 31:02 Concluding Remarks - case study in which RCT designs are not beneficial 35:30 Question: Health Avatar and AI to create real and virtual control arm Using virtual control arm using real world databases using Bayesian statistical methods 39:23 Case study to emphasize Harnessing Tacit knowledge 42:02 Comment: Weaknesses in generating data we can translate into populations 43:44 Question: Are we creating RCTs from virtual patients or classical RCT design? 47:34 Final Comments - For the Motion, Sana Syed Clinical Studies and Scientific Method - adjustments in diverse patient recruitment tactics

49:31 Final Comments - Against the Motion, Rashad Massoud

53:14 Live Voting Results