Evaluation of the quality of clinical data collection for a pan-Canadian cohort of children affected by inherited metabolic diseases: lessons learned from the Canadian Inherited Metabolic Diseases Research Network
Authors:   on behalf of the Canadian Inherited Metabolic Diseases Research Network, Tingley Kylie , Lamoureux Monica , Pugliese Michael , Geraghty Michael T. , Kronick Jonathan B. , Potter Beth K. , Coyle Doug , Wilson Kumanan , Kowalski Michael , Austin Valerie , Brunel-Guitton Catherine , Buhas Daniela , Chan Alicia K. J. , Dyack Sarah , Feigenbaum Annette , Giezen Alette , Goobie Sharan , Greenberg Cheryl R. , Ghai Shailly Jain , Inbar-Feigenberg Michal , Karp Natalya , Kozenko Mariya , Langley Erica , Lines Matthew , Little Julian , MacKenzie Jennifer , Maranda Bruno , Mercimek-Andrews Saadet , Mohan Connie , Mhanni Aizeddin , Mitchell Grant , Mitchell John J. , Nagy Laura , Napier Melanie , Pender Amy , Potter Murray , Prasad Chitra , Ratko Suzanne , Salvarinova Ramona , Schulze Andreas , Siriwardena Komudi , Sondheimer Neal , Sparkes Rebecca , Stockler-Ipsiroglu Sylvia , Trakadis Yannis , Turner Lesley , Van Karnebeek Clara , Vallance Hilary , Vandersteen Anthony , Walia Jagdeep , Wilson Ashley , Wilson Brenda J. , Yu Andrea C. , Yuskiv Nataliya , Chakraborty Pranesh 
Published: April 2020

Abstract
Background
The Canadian Inherited Metabolic Diseases Research Network (CIMDRN) is a pan-Canadian practice-based research network of 14 Hereditary Metabolic Disease Treatment Centres and over 50 investigators. CIMDRN aims to develop evidence to improve health outcomes for children with inherited metabolic diseases (IMD). We describe the development of our clinical data collection platform, discuss our data quality management plan, and present the findings to date from our data quality assessment, highlighting key lessons that can serve as a resource for future clinical research initiatives relating to rare diseases.

Methods
At participating centres, children born from 2006 to 2015 who were diagnosed with one of 31 targeted IMD were eligible to participate in CIMDRN’s clinical research stream. For all participants, we collected a minimum data set that includes information about demographics and diagnosis. For children with five prioritized IMD, we collected longitudinal data including interventions, clinical outcomes, and indicators of disease management. The data quality management plan included: design of user-friendly and intuitive clinical data collection forms; validation measures at point of data entry, designed to minimize data entry errors; regular communications with each CIMDRN site; and routine review of aggregate data.

Results
As of June 2019, CIMDRN has enrolled 798 participants of whom 764 (96%) have complete minimum data set information. Results from our data quality assessment revealed that potential data quality issues were related to interpretation of definitions of some variables, participants who transferred care across institutions, and the organization of information within the patient charts (e.g., neuropsychological test results). Little information was missing regarding disease ascertainment and diagnosis (e.g., ascertainment method – 0% missing).

Discussion
Using several data quality management strategies, we have established a comprehensive clinical database that provides information about care and outcomes for Canadian children affected by IMD. We describe quality issues and lessons for consideration in future clinical research initiatives for rare diseases, including accurately accommodating different clinic workflows and balancing comprehensiveness of data collection with available resources. Integrating data collection within clinical care, leveraging electronic medical records, and implementing core outcome sets will be essential for achieving sustainability.