The IRD-PT is a clinical/genetic research registry. Its main goal is to create a national, web-based registry of IRDs in Portugal that allows to study their prevalence, genomic profile, genotype-phenotype correlations and natural history. Also, the registry may assist in the recruitment of participants for new treatments/clinical trials, and provide support for the establishment of disease-specific standards and care. The IRD-PT registry is included in the retina.pt platform (http://www.retina.com.pt), which was developed by the Portuguese Retina Study Group (GER, www.ger-portugal.com). The retina.pt registry deployed in 2017 to fulfil a vital component on patient-centered care for retinal diseases. It collects data on individuals diagnosed with retinal diseases, from several sites across Portugal, with over 1800 participants and over 30,000 consultations to date. The IRD-PT is a module interacting with the retina.pt core system. The core system provides a range of basic functions used for patient data management, while the IRD-PT module provides the user with the functionality to capture data for the specific purpose of IRDs.
Recruitment and Informed Consent
Both pediatric and adult patients with a genetic and/or clinical diagnosis of IRD living in Portugal and attending Ophthalmology clinics around the country are invited to participate. Participation in the registry is voluntary. Before enrollment, the participant (patient) or their legally authorized representative must provide informed consent for the collection, storage, and use of their personal health data. No costs or compensations are involved for participants or their family members as the data collected in the IRD-PT module refers to information routinely collected by the responsible physician. All included subjects are allowed to withdraw their consent at any time, without providing a reason. This does not impact their regular follow-up at the clinic.
Ethics and Regulations
The registry meets the necessary requirements for compliance with the General Data Protection Regulation (GDPR) of the European Union and all approvals were obtained prior to recruiting patients for the registry. Formal review and approval was obtained from the Portuguese Data Protection Authority (Comissão Nacional de Proteção de Dados – CNPD), HREC of Centro Hospitalar e Universitário de Coimbra (CHUC) and IRB of the Faculty of Medicine of the University of Coimbra (FMUC). All these independent entities ensured that the study protocol, governance, protections, and methods were ethical and appropriate. Furthermore, each participating core center needs to obtain approval from the respective Ethics Committee. Documentation of approval from each center is copied to the central governing office to ensure currency of approval is maintained.
All investigators (users) are mandated to sign the Investigator Declaration Form before obtaining credentials to use the registry. Both the project investigators and their institutions permit project-related monitoring, audits, and regulatory inspections, providing direct access to source data/documents. This may include, but is not limited to, review by HREC and institutional governance review bodies.
Proper handling of ethical, legal, social, and privacy issues must be a foundational component of the design, implementation, and long-term sustainability of a patient registry. As part of the retina.pt, the IRD-PT module was designed to provide maximum data security and patient anonymity. Several well-defined procedures were put in place to protect individual patient data within the registry study. Data security, integrity, and availability is monitored and regulated.
All data transmissions between the user and the server are encrypted using 128-bit encryption (Secure Sockets Layer). The data are stored and backed up on secure servers at Portugal Telecom – Altice, TEAR 3 certified Datacenter. Anonymity of users is also closely guarded. Individual users can only see their own data. However, users may find other centers with included data on a specific disease and ask for research collaborations within the platform. Users can withdraw their data from the registry at any time, without providing a reason.
Drop-down menus, pop-up explanatory notes, and tab-to-jump ensures rapid and user friendly data entry. Furthermore, retina.pt is a web-based application that is able to run on different server operating systems. Any device with Internet access and a recent browser can be used to interact with the application. Additional software on the user’s terminal is not required. When all mandatory fields have been filled, the User can “Finalize” the visit by pressing “Save”. The system has been designed in such a way that it will not allow a visit to be finalized unless all the mandatory fields have been filled and all numerical data fall within prespecified ranges. Additionally, the platform allows data to be automatically filled in by third party EHR applications with identically structured information, or the possibility of the user to generate a pdf document that can be printed/copied to the hospital EHR system. Moreover, storage and retrieval of clinical images is possible in the patient-specific page.
High quality data of rare diseases registries is considered to be one of the most important elements in the establishment and maintenance of a registry. Quality assurance includes quality improvement activities such as medical, clinical, and record audit and observational studies, to which the ethical principles of research apply.
Upon the development of the retina.pt platform, interoperability was a key issue. First, the registry has two available languages to choose from: Portuguese and English. Second, the age-related macular degeneration (AMD) module of retina.pt is already linked to the Fight Retinal Blindness! (FRB!) Project registry and efforts are in place to connect it to the International Consortium for Health Outcomes Measurement (ICHOM) AMD registry. Third, the platform is serving as the eCRF for an upcoming post-market authorization clinical trial. Rare diseases are a prime example of a research area that can strongly profit from coordination on a European and international scale. To allow interoperability of the IRD-PT module with other IRD registries across the world, all the diseases are coded accordingly to ICD9, ICD10, ICD11, and ORDO (ORPHA codes) numbers. Furthermore, the genes are coded according to the OGG and MIM, and patient signs and symptoms are coded according to HPO. This is in accordance with the eye-specific dataset of the Clinical Patient Management System (CPMS) of the ERN-EYE. Notably, ORDO, HPO, OGG and MIM are open-access, interoperable, community-driven, available in multiple languages and regularly updated.