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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Med. | doi: 10.3389/fmed.2019.00147


 Carla M. Torre1, 2*, Maria Cary2, Fábio C. Borges3, Paula S. Ferreira1, 4, Joana Alarcão5,  Hubert G. Leufkens6, João Costa4, 5 and  Ana P. Martins1
  • 1Faculty of Pharmacy, University of Lisbon, Portugal
  • 2Independent researcher, Portugal
  • 3Portuguese Institute of Oncology Francisco Gentil, Portugal
  • 4Other, Portugal
  • 5Center for Evidence-Based Medicine, Faculty of Medicine, University of Lisbon, Portugal
  • 6Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Netherlands

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 a 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 analysed descriptively. The methodological quality of selected studies was assessed using the modified Downs and Black checklist.
Results: From 1400 screened citations, we identified 86 papers, corresponding to 69 different studies. 70% 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 10479 (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.

Keywords: Adverse Drug Reaction Reporting Systems, Clinical practice pattern, Drug Monitoring, Pharmacovigilance, Systematic review

Received: 20 Apr 2019; Accepted: 12 Jun 2019.

Edited by:

Steffen Thirstrup, NDA Advisory Services ltd, United Kingdom

Reviewed by:

Lise Aagaard, Havemann Ltd., Denmark
Brian D. Edwards, NDA Group, United Kingdom  

Copyright: © 2019 Torre, Cary, Borges, Ferreira, Alarcão, Leufkens, Costa and Martins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Carla M. Torre, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal,