title: Risk based monitoring (RBM) tools for clinical trials: A systematic review.
abstract: In November 2016, the Integrated Addendum to ICH-GCP E6 (R2) will advise trial sponsors to develop a risk-based approach to clinical trial monitoring. This new process is commonly known as risk based monitoring (RBM). To date, a variety of tools have been developed to guide RBM. However, a gold standard approach does not exist. This review aims to identify and examine RBM tools.
  
  
  
  Review of published and grey literature using a detailed search-strategy and cross-checking of reference lists. This review included academic and commercial instruments that met the Organisation for Economic Co-operation and Development (OECD) classification of RBM tools.
  
  
  
  Ninety-one potential RBM tools were identified and 24 were eligible for inclusion. These tools were published between 2000 and 2015. Eight tools were paper based or electronic questionnaires and 16 operated as Service as a System (SaaS). Risk associated with the investigational medicinal product (IMP), phase of the clinical trial and study population were examined by all tools and suitable mitigation guidance through on-site and centralised monitoring was provided.
  
  
  
  RBM tools for clinical trials are relatively new, their features and use varies widely and they continue to evolve. This makes it difficult to identify the "best" RBM technique or tool. For example, equivalence testing is required to determine if RBM strategies directed by paper based and SaaS based RBM tools are comparable. Such research could be embedded within multi-centre clinical trials and conducted as a SWAT (Study within a Trial).
authors.affiliation: Dept. Epidemiology and Public Health, University College Cork, Ireland. Electronic address: carolinehurley@ucc.ie.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hurley
authors.affiliation: Dept. Epidemiology and Public Health, University College Cork, Ireland; Health Research Board - Clinical Research Facility, University College Cork, Ireland.
authors.forename: Frances
authors.initials: F
authors.lastname: Shiely
authors.affiliation: Centre for Global Health, Trinity College Dublin, Ireland.
authors.forename: Jessica
authors.initials: J
authors.lastname: Power
authors.affiliation: Centre for Public Health, Queen's University Belfast, Ireland.
authors.forename: Mike
authors.initials: M
authors.lastname: Clarke
authors.affiliation: Health Research Board - Clinical Research Facility, University College Cork, Ireland.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Eustace
authors.affiliation: Health Research Board - Clinical Research Facility, University College Cork, Ireland.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Flanagan
authors.affiliation: Dept. Epidemiology and Public Health, University College Cork, Ireland.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Kearney
mesh_terms: D026661:Clinical Trials Data Monitoring Committees; D002986:Clinical Trials as Topic; D006801:Humans; D012306:Risk
keywords: Clinical trial; Risk based monitoring