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

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.

Independent Registries Are Cost-Effective Tools to Provide Mandatory Postauthorization Surveillance for Orphan Medicinal Products

“…The high prevalence of Fabry disease 9 in Canada has resulted in a high volume of data being available from 1 country, but we realize that this is not possible for most rare diseases. Other groups have proposed independent registries to facilitate international collaborative study of rare and ultrarare diseases, 8,[27][28][29][30][31] and our data demonstrate the advantages of independent registries relative to IFRs (higher data completeness and lower cost). A model of infrastructure that could support such collaboration has been proposed for Gaucher disease.…”

“…28,29 Databases have been designed to facilitate secure collaborative data collection at low cost 30 and have already been used successfully in inherited metabolic diseases. 31…”

Families’ healthcare experiences for children with inherited metabolic diseases: protocol for a mixed methods cohort study

“…IMDs typically follow one of three broad clinical course trajectories, with different implications for healthcare usage and experiences: (a) chronic and generally non-progressive; (b) acute episodes of severe illness with or without accompanying chronic multisystem sequelae and (c) progressive multisystem disease. Children with any of 30 priority IMDs included in an existing Canadian paediatric cohort study that will serve as one potential recruitment source54 55 are eligible for this study (table 1). Few of the IMDs included in that cohort study, however, are characterised as following trajectory (c).…”

Developments in evidence creation for treatments of inborn errors of metabolism

“…66,67 The CIMDRN recently has published lessons for consideration in future research initiatives for rare diseases based on their experience with the establishment of a comprehensive database for IEM. 68 Contact registries facilitate rapid implementation of studies by expediting recruitment and enrollment. 69,70 For example, the NIH-funded RDCRN has established a contact registry in which patients with the conditions studied by each of the participating consortia (several of which include IEM) can enroll.…”

“…In addition, several other recommendations have been developed to guide the establishment of rare disease patient registries including suggestions around registry governance, core data sets, information systems, data quality monitoring, and confidentiality 65,66 . The CIMDRN recently has published lessons for consideration in future research initiatives for rare diseases based on their experience with the establishment of a comprehensive database for IEM 67 …”