Intensive Monitoring Studies for Assessing Medicines: A Systematic Review

Carla Torre, Maria Cary, Fábio Cardoso Borges, Paula S. Ferreira, Joana Alarcão, Hubert G. Leufkens, João Costa, Ana Paula Martins

Introduction: Intensive monitoring (IM) is one of the methods of post-marketing active surveillance based upon event monitoring, which has received interest in the current medicines regulatory landscape. For a specific period of time, IM involves primary data collection and is actively focused on gathering longitudinal information, mainly safety, since the first day of drug use. Objectives: To describe IM systems and studies' data published over 11-years period (2006-2016). Specifically, we reviewed study population/event surveillance, methodological approaches, limitations, and its applications in the real-world evidence generation data. Methods: We completed a systematic search of MEDLINE and EMBASE to identify studies published from 2006 to 2016, that used IM methodology. We extracted data using a standardized form and results were analyzed descriptively. The methodological quality of selected studies was assessed using the modified Downs and Black checklist. Results: From 1,400 screened citations, we identified 86 papers, corresponding to 69 different studies. Seventy percent of reviewed studies corresponded to established IM systems, of which, more than half were prescription event monitoring (PEM) and modified-PEM. Among non-established IM systems, vaccines were the most common studied drugs (n = 14). The median cohort size ranged from 488 (hospitals) to 10,479 (PEM) patients. Patients and caregivers were the event data source in 39.1% of studies. The mean overall quality score was similar between established and non-established IM. Conclusions: Over the study period, IM studies were implemented in 26 countries with different maturity levels of post-marketing surveillance systems. We identified two major limitations: only 20% of studies were conducted at hospital-level, which is a matter of concern, insofar as healthcare systems are facing a lack of access to new medicines at ambulatory care level. Additionally, IM access to data of drug exposure cohorts, either at identification or at follow-up stages, could somehow constitute a barrier, given the complexity of managerial, linkable, and privacy data issues.