Pragmatic Randomized Clinical Trials. Using Primary Data Collection and Electronic Health Records

Table of Contents

Acknowledgements
Preface
Robert Califf and Joe Selby

I: Introduction
1. Introduction to pRCTs
Cynthia J. Girman and Mary Elizabeth Ritchey
2. The Efficacy-Effectiveness Gap
Rolf H.H. Groenwold
3. Studies for labeling vs reimbursement
Robert Epstein

II: Patient Voice and Stakeholder Feedback
4. Stakeholder Engagement in pRCT Design and Conduct
Thomas Concannon
5. Patient Voice in Clinical Trial Programs in Industry
Jeanne M. Regnante

III: Design & Analysis
6. What is the research question?
Elizabeth A. Suarez and Soko Setoguchi
7. Feasibility assessment for use of EHR
Mary Elizabeth Ritchey
8. Important design considerations in pRCTs
Kevin Thorpe
9. Randomization and Blinding Randomization at what unit? Blinding of who and what?
Jennifer Christian
10. Cluster Randomized Trials
Katherine Harris
11. Design and Analytic Approaches to Minimize Bias and Confounding
Michele Jonsson Funk
12. Sensitivity analyses
Elizabeth A. Suarez and Cynthia J. Girman
13. Methodology and Reporting Guidelines
Aisling Caffrey
14. Unmeasured Confounding with and without randomization
Phyo Than Htoo and Til Sturmer

IV: Operational Aspects
15. Validation of Electronic Health Record and Patient-Reported Outcomes
Vincent Lo Re III
16. Special Considerations in EHR
Leah McGrath and Jenna Wong
17. Distributed Networks of Electronic Health Record Data
Catherine A. Panozzo
18. International and global issues differences in medical practice
Ju-Young (Judy) Shin, Kenneth Man and Wei Zhou

V: Privacy and Ethics
19. Considerations for Protecting Research Participants
Aisling Caffrey

VI: Interpretation, Limitations, and Strengths
20. Replication and reproducibility
Kristy Iglay and Mary Elizabeth Ritchey

VII: Dissemination
21. Communicating results to patients for shared decision-making
Wendy Camelo Castillo
22. Communicating Results of pRCTs to the Medical Community
Joe Selby and Timothy Carey
23. Communicating to regulatory agencies
Larry D. Alphs

VIII: Special Considerations on Interventions
24. Biologics
Jaclyn L. F. Bosco and Priscilla Velentgas
25. Medical Devices
Mary Elizabeth Ritchey
26. Rare Diseases
Cunlin Wang and Lina Titievsky
27. Behavioral Interventions
Andrea Troxel

IX: Case Studies
28. Examples from Primary Data Collection
Kourtney J. Davis and Jeanne Marie Pimenta
29. Examples from Electronic Health Records and Administrative Claims Data
Ehab Hasan
30. Use of Pragmatic Randomized Clinical Trials in Reimbursement Decisions
Kati Copley-Merriman

X: Conclusions
31. Concluding remarks
Cynthia J. Girman, Mary Elizabeth Ritchey and Elizabeth A. Suarez

Authors

Cynthia J. Girman Founder and President; Real World Evidence, Pharmacoepidemiology and Patient Outcomes; CERobs Consulting, LLC; Wrightsville Beach, NC USA. Cynthia Girman, DrPH, FISPE, is founder and President of CERobs Consulting, LLC, which provides consulting services to the pharmaceutical and healthcare industry on study design and scientific methods for real world observational studies, comparative effectiveness research and pragmatic randomized clinical trials. Dr. Girman is a seasoned epidemiologist with strong interest in biostatistical and observational methods, and the bulk of her 40+ year career has been in the pharmaceutical industry. Her undergraduate and doctoral training was at UNC and her MS in Applied Statistics and Computer Science is from Villanova University. She has led multi-institution academic collaborations, published extensively and reviewed for numerous peer-reviewed medical journals. As Adjunct Professor of Epidemiology at the University of North Carolina (UNC) Gillings School of Global Public Health, she collaborates on methodology research, gives guest classroom lectures and mentors numerous doctoral candidate graduate research assistants and post-doctoral fellows. Dr. Girman was an elected Board member 2015-2020 and is a fellow of the International Society for Pharmacoepidemiology (ISPE) and she annually teaches in the pragmatic randomized clinical trials (pRCT) pre-conference course. In September 2014, Dr. Girman was the first industry member nominated to the Patient-Centered Outcomes Research Institute (PCORI) Methodology Committee, on which she actively contributes along with their Clinical Trials Advisory Panel. Currently, Dr. Girman consults on study design, protocol development and analytic methods for real world evidence, such as registries, post-authorization safety studies, natural history studies, comparative effectiveness research, pragmatic randomized clinical trials, and external control groups for rare diseases. She also consults on endpoint strategies for randomized clinical trials, including patient reported outcomes, clinician assessments and expert review panels, as well as patient engagement and qualitative research. Mary E. Ritchey Principal and Owner, Med Tech Epi, LLC, Philadelphia, PA USA; Associate Research Professor, Center for Pharmacoepidemiology and Treatment Sciences, Rutgers University, New Brunswick, NJ USA; Senior Executive Pharmacoepidemiologist, Real World Evidence, Pharmacoepidemiology and Patient Outcomes, CERobs Consulting, LLC; Wrightsville Beach, NC USAPrincipal and Owner, Med Tech Epi, LLC, Philadelphia, PA USA; Associate Research Professor, Center for Pharmacoepidemiology and Treatment Sciences, Rutgers University, New Brunswick, NJ USA; Senior Executive Pharmacoepidemiologist, Real World Evidence, Pharmacoepidemiology and Patient Outcomes, CERobs Consulting, LLC; Wrightsville Beach, NC USA. Mary E Ritchey, PhD, FISPE is Principal and Owner, Med Tech Epi, LLC a consulting group which provides real-world evidence strategy development, study design and implementation for medical devices, biotech, and medicines. She is an Associate Research Professor in the Center for Pharmacoepidemiology and Treatment Sciences at Rutgers University and a Senior Executive Pharmacoepidemiologist for CERobs Consulting, LLC. Dr. Ritchey obtained her masters and doctorate degrees in epidemiology from University of North Carolina Gillings School of Global Public Health. She is a Fellow and board member (2019-2022) of the International Society of Pharmacoepidemiology (ISPE), a member of the Medical Device Epidemiology (MDEpiNet) Scientific Oversight Committee, and Associate Editor for Pharmacoepidemiology and Drug Safety. Her career spans more than 15 years in government, industry, consulting, and academia focused on better understanding medical product safety and effectiveness when used in actual clinical practice. She is adept with scientific, technical, and logistical aspects of feasibility, utilization, safety, and effectiveness real-world studies for postmarketing requirements, labeling expansion, clinical trial support studies, and pragmatic clinical trials. She enjoys engaging with clinical and research teams to gather knowledge, generate evidence, inform decision-makers, and communicate meaningful results to regulators, payers, clinicians, and patients.