2.1. CureGN study design

Enrollment began in 2014 with a target of 2400 participants, and over time has included 67 to 70 clinical sites managed by four Participating Clinical Center (PCC) networks. Now in its second funding cycle (CureGN-2) the scope of data and sample collection is comprehensive, and includes hundreds of clinical data values, including demographics, medical history, medications, family history, and laboratory data. Patient or parent-proxy reported Outcomes (PROs) applied selected PRO Measurement Information System measures as well as newly developed content, and were administered during in-person visits, twice in year one and annually thereafter. Study coordinators enter the data for all of these measures using a flexible in-house data entry platform (GN-Link) that includes real-time reports, task and completeness reminders, and alerts for lab data outside the expected range, using logic that reduces coordinator burden while ensuring that relevant questions are asked. Entry within 30 days of a patient visit or phone call is expected.

Biospecimens (serum, plasma, urine, Deoxyribonucleic Acid [DNA], and Ribonucleic Acid [RNA]) are collected and shipped for storage in the National Institutes of Health (NIH) central biorepository. Additional genetic data (peripheral blood leukocyte gene expression and blood whole genome sequencing [WGS] data sets) are currently generated and will be submitted to National Center for Biotechnology Information (NCBI) data repository for access by the research community after completion of quality control measures. Pathology materials (scans of biopsy reports, glass slides, and electron microscopy [EM] and immunofluorescence [IF] jpeg images) are sent to the NIH Image Coordinating Center, where glass slides are scanned into whole slide images (WSI). All digital materials are uploaded and stored in the CureGN digital pathology repository (DPR). All patients provided written informed consent to participate; the study was carried out in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of each site and the Data Coordinating Center.

Patient follow-up in CureGN-1 included two in-person study visits in the first year and one in-person and two additional visits (by phone, email, or in-person) each subsequent year, during a disease flare or relapse when possible. Subjects are followed for kidney disease activity, progression, and non-renal complications of disease or treatment, including infection, malignancy, and cardiovascular and thromboembolic events. Patients in CureGN-1 could continue into CureGN-2 with re-consent. CureGN-2 includes one in-person study visit each year, and two additional visits (by phone, email, or other modality) for those in the study for years one to three. Starting in year four, one in-person and one additional visit are completed each year.

Initial coordinator training is provided by the Data Coordinating Center (DCC) at the beginning of the study phase via webinars. To improve uniformity across sites, quarterly Town Halls are held to continue coordinators’ education in CureGN. Topics addressed during Town Halls include updates to the GN-Link database, changes in processes, and special guest presenters providing information and tips regarding topics relevant to coordinators day-to-day activities. The trainings and Town Halls are recorded and posted on the study website for coordinators to access. Also included on the study website are the Manual of Operations, GN-Link User Manual, and other reference documents. The PCC lead coordinators use the videos and documents as training aids for new coordinators and as refresher trainings for established coordinators. We note that each PCC lead coordinator is funded by the grant to manage their own site as well as to assist their participating site coordinators. Effort for the participating site coordinators is covered in the per-visit reimbursement schedule, which is limited by NIDDK budget constraints.