title: The impact of clinical trial monitoring approaches on data integrity and cost--a review of current literature.
abstract: OBJECTIVE
  Monitoring is a costly requirement when conducting clinical trials. New regulatory guidance encourages the industry to consider alternative monitoring methods to the traditional 100 % source data verification (SDV) approach. The purpose of this literature review is to provide an overview of publications on different monitoring methods and their impact on subject safety data, data integrity, and monitoring cost.
  
  
  METHODS
  The literature search was performed by keyword searches in MEDLINE and hand search of key journals. All publications were reviewed for details on how a monitoring approach impacted subject safety data, data integrity, or monitoring costs.
  
  
  RESULTS
  Twenty-two publications were identified. Three publications showed that SDV has some value for detection of not initially reported adverse events and centralized statistical monitoring (CSM) captures atypical trends. Fourteen publications showed little objective evidence of improved data integrity with traditional monitoring such as 100 % SDV and sponsor queries as compared to reduced SDV, CSM, and remote monitoring. Eight publications proposed a potential for significant cost reductions of monitoring by reducing SDV without compromising the validity of the trial results.
  
  
  CONCLUSIONS
  One hundred percent SDV is not a rational method of ensuring data integrity and subject safety based on the high cost, and this literature review indicates that reduced SDV is a viable monitoring method. Alternative methods of monitoring such as centralized monitoring utilizing statistical tests are promising alternatives but have limitations as stand-alone tools. Reduced SDV combined with a centralized, risk-based approach may be the ideal solution to reduce monitoring costs while improving essential data quality.
authors.affiliation: Nordic Bioscience Clinical Development A/S, Herlev Hovedgade 205-207, 2730, Herlev, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Olsen
authors.affiliation: Nordic Bioscience Clinical Development A/S, Herlev Hovedgade 205-207, 2730, Herlev, Denmark.
authors.forename: Asger Reinstrup
authors.initials: AR
authors.lastname: Bihlet
authors.affiliation: Nordic Bioscience Clinical Development A/S, Herlev Hovedgade 205-207, 2730, Herlev, Denmark.
authors.forename: Faidra
authors.initials: F
authors.lastname: Kalakou
authors.affiliation: Nordic Bioscience Clinical Development A/S, Herlev Hovedgade 205-207, 2730, Herlev, Denmark. jra@Nordicbioscience.com.
authors.forename: Jeppe Ragnar
authors.initials: JR
authors.lastname: Andersen
mesh_terms: D026661:Clinical Trials Data Monitoring Committees / Q000191:economics* / Q000592:standards*; D002986:Clinical Trials as Topic / Q000191:economics* / Q000592:standards*; D016208:Databases, Factual / Q000191:economics* / Q000592:standards*; D006801:Humans
keywords: Centralized monitoring; Clinical trial monitoring; Remote monitoring; Risk-based monitoring; Source data verification; Statistical monitoring