HALT-PKD Trials

Building a Homegrown Data Management System: Perspectives from the HALT-PKD Trials Assistant Professor of Medicine, Biostatistics, and Clinical & Translational Sciences Center for Research on Health Care Data Center University of Pittsburgh School of Medicine May 18, 2015

1 Overview of HALT-PKD 2 On the fly fixes Outcome Adjudication 3 Conclusions

Overview Autosomal Dominant Polycystic Kidney Disease (ADPKD) 4th leading cause of end-stage renal disease (ESRD). Kidney cyst growth = increased kidney volume, activation of the RAAS, hypertension, and renal failure. No evidence BP control or RAAS blockade slows the progression of renal disease.

HALT-PKD Trials Study A: Participants & Trial Design 558 young (15-49 yrs) and healthy (egfr > 60) participants Randomized in 2x2 design to: ACE-I + ARB or ACE-I alone standard (120-130/70-80 mmhg) or low (95-110/60-75 mmhg) BP Study B: Participants & Trial Design 486 slightly older (18-64 yrs) participants with moderately advanced disease (egfr 20-60). Randomized to: ACE-I + ARB or ACE-I alone

HALT-PKD Consortium Map HALT%PKD%Clinical%Catchment%Zones% U. Colorado Mayo U. Kansas CCF Pitt (DCC) Tufts BIDMC Emory

Data Coordinating Center Transition of DCC DCC originally housed at another institution In 2009, transfered to CRHC-DC Personnel PI: Charity Moore, PhD Co-I & Lead Statistician: Kaleab Abebe, PhD Lead Research Coordinator: Susan Spillane, RN, CCRP Statisticians: Diane Comer, Jie Li, Elan Cohen Systems Analysts: Joe Weiss, Terry Sefcik, Linda Quinn, Shelly Rowe

Data Coordinating Center Responsibilities Aim 1 To serve as the HALT-PKD DCC by collaborating with study investigators, managing protocol and regulatory compliance, facilitating the transfer of data, and supporting HALT-PKD activities for quality control, endpoint adjudication, and blood pressure management. Aim 2 Maintain the Web-based data management system that incorporates data tracking, entry, quality control, and report generation. Aim 3 Conduct interim and final statistical analyses to support the aims of the study including the primary analyses for Study A and Study B.

electronic System for Data Management (esysdm) Web-based data entry and tracking system; data stored on SQL server Facilitates automatic import of centralized laboratory results Allows real-time reporting of visit completeness, follow-up tracking, drug dosage, specimen inventory, and blood pressure reports. On the fly fixes During the course of the study, there were 2 major changes the DCC had to make: Integration of outcome adjudication process into web-based system Creation of an electronic regulatory management system

Outcome Adjudication 1 Overview of HALT-PKD 2 On the fly fixes Outcome Adjudication 3 Conclusions

Outcome Adjudication Overview All-cause and CV-related hospitalizations are secondary outcomes for both Study A & B. All AEs reviewed during monthly QC call Need to adjudicate hospitalization based on discharge summary information

Outcome Adjudication Hospitalization adjudication portal 1.0

Outcome Adjudication Hospitalization adjudication portal 2.0

Overview In 2012, the need for a centralized Regulatory system was identified. Design and implementation of Sharepoint MRF system was completed while writing the closeout protocol. ICH E6 Good Clinical Practice as a guidance for what to include.

SHARED FILES SITE SPECIFIC FILES

1 Overview of HALT-PKD 2 On the fly fixes Outcome Adjudication 3 Conclusions

Take Home Messages Hospital Adjudication Outcomes that require adjudication must have secure, systematic, and reproducible review to ensure the integrity of their results. Develop a standardized regulatory file system with guidance/justification for required documentation at the initiation of clinical trial activities promotes regulatory compliance educational tool for regulatory-naive coordinators aids in remote monitoring of multi-centered trials

Acknowledgements

Acknowledgements Susan Spillane, RN, CCRP Diane Comer, Jie Li, Elan Cohen Joe Weiss, Terry Sefcik, Linda Quinn, Shelly Rowe