Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial

Abstract

Introduction and hypothesis

Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months.

Methods

ESTEEM is a multisite, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure, and need for additional treatment.

Results

The final study design was implemented in November 2013 across eight clinical sites in the Pelvic Floor Disorders Network. As of 27 February 2016, 433 total/472 targeted participants had been randomized.

Conclusions

We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision making.

Appendix: Pelvic Floor Disorders Network contributors

Cleveland Clinic

Mathew D. Barber, Principal Investigator

J. Eric Jelovsek, Co-Investigator

Marie Fidela R. Paraiso, Co-Investigator

Mark D. Walters, Co-Investigator

Beri Ridgeway, Co-Investigator

Brooke Gurland, Co-Investigator

Massarat Zutshi, Co-Investigator

Geetha Krishnan, Research Nurse Clinician

Ly Pung, Research Nurse

Annette Graham, Research Nurse Clinician

Alpert Medical School of Brown University-Women & Infant’s Hospital of Rhode island

Vivian W. Sung, Principal Investigator

Deborah L. Myers, Co-Investigator

Charles R. Rardin, Co-Investigator

Cassandra Carberry, Co-Investigator

B. Star Hampton, Co-Investigator

Kyle Wohlrab, Co-Investigator

Ann S. Meers, Research Nurse Coordinator

Duke University

Anthony Visco, Principal Investigator

Cindy Amundsen, Co-Investigator

Alison Weidner, Co-Investigator

Nazema Siddiqui, Co-Investigator

Ingrid Harm-Ernandes, Interventionist

Jennifer Maddocks, Interventionist

Shantae McLean, Research Coordinator

University of Alabama at Birmingham

Holly Richter, Primary Investigator

Alayne Markland, Co-Investigator

R. Edward Varner, Co-Investigator

Robert Holley, Co-Investigator

L. Keith Lloyd, Co-Investigator

Tracy S. Wilson, Co-Investigator

Alicia Ballard, Co-Investigator

Jeannine McCormick, Research Nurse Clinician

Velria Willis, Research Nurse Coordinator

Nancy Saxon, Research Nurse Coordinator

Kathy Carter, Research Nurse

Julie Burge, Research Coordinator

NIH Project Scientist

Susan Meikle, Primary Investigator

University of California, San Diego

Charles Nager, Principal Investigator

Michael Albo, Co-Investigator

Emily Lukacz, Co-Investigator

Cindy Furey, Interventionist

Patricia Riley, Interventionist

JoAnn Columbo, Research Coordinator

Sherella Johnson, Research Coordinator

Kaiser Permanente–San Diego

Shawn Menefee, Co-Investigator

Karl Luber, Co-Investigator

Keisha Dyer, Co-Investigator

Gouri Diwadkar, Co-Investigator

Jasmine Tan-Kim, Co-Investigator

University of New Mexico

Rebecca G. Rogers, Primary Investigator

Yuko Komesu, Co-Investigator

Gena Dunivan, Co-Investigator

Peter Jeppson, Co-Investigator

Sara Cichowski, Co-Investigator

Christy Miller, Interventionist

Barbara White, Interventionist

Sue Lee, Research Coordinator

Julia Middendorf, Research Nurse

RTI

Dennis Wallace, Primary Investigator

Marie G. Gantz, Co-Investigator

University of Pennsylvania

Lily Arya, Principal Investigator

Ariana Smith, Co-Investigator

Heidi Harve, Co-Investigator

Uduak Umoh Andy, Co-Investigator

Pamela Levin, Co-Investigator

Diane K. Newman, Co-Investigator

Mary Wang, Interventionist

Donna Thompson, Interventionist

Teresa Carney, Interventionist

Michelle Kingslee, Research Coordinator

Lorraine Flick, Research Nurse

University of Pittsburgh

Halina Zyczynski, Principle Investigator

Pam Moalli, Co-Investigator

Gary Sutkin, Co-Investigator

Jonathan Shepherd, Co-Investigator

Michael Bonidie, Co-Investigator

Steven Abo, Co-Investigator

Janet Harrison, Co-Investigator

Lori Geraci, Research Coordinator

Judy Gruss, Research Coordinator

Karen Mislanovich, Research Coordinator

Ellen Eline, Interventionist

Beth Klump, Interventionist