Active surveillance of the safety of Gadolinium-based contrast agent(s) in India

GBCAs are regarded as safe with few adverse events of usually mild to moderate severity. However, there are publications in the medical literature reporting that, following the administration of gadolinium-based contrast agents (GBCAs), traces of gadolinium can be retained for months or years in several organs. To date, clinical consequences of gadolinium retention have not been established in patients with normal renal function.Further, there were adverse reaction reports from post-marketing surveillance that reported adverse events with variable onset and duration, without an established causal link to gadolinium retention. Reported events include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems. Active surveillance will be achieved by GBCA brand specific recruitment and follow-up of consecutive GBCA naïve patients who agree to participate.At first contact, patients determined to require GBCA-enhanced MRI will be asked for permission to be contacted by phone 6 (±2) weeks after the MRI scan. Sentinel sites will keep a log of questionnaires for all eligible patients. Patients will be informed about the active surveillance by site personnel. For patients who agreed to participate, GBCA administration will be documented by site personnel. In follow-up phone calls after 6 (±2) weeks, each patient who consented will be asked by open, non-directing questions about adverse experience after exposure to the GBCA. Up to two attempts will be made to contact a patient.After each patient contact, the questionnaire will immediately be reviewed for reported adverse events. The MA holder will be notified immediately about any adverse event by a copy of the questionnaire and, if available, supportive documents. Adverse event reports will be handled by the MAH as solicited post-marketing reports and reported in line with regulatory requirements. After completion, questionnaires will be forwarded to the MAH for preparation of a final report and archiving. Each MAH will prepare a GBCA brand specific final report within 6 months after the last scheduled interview. The report will present descriptive statistics, stratified by sentinel site and counts of adverse event reports. In addition, the GBCA brand specific report will summarize adverse experience by MedDRA system organ classes and MedDRA preferred terms, by case and event seriousness, by reporter and company assessment of causal relationship, by latency (i.e., interval between injection of GBCA and onset of adverse event), by duration, by outcome, by number of GBCA administrations (confounded cases), and by expectedness (India).