title: Risk analysis and risk adapted on-site monitoring in noncommercial clinical trials.
abstract: BACKGROUND
  The concept of risk assessment for clinical trials has been discussed before, but no comprehensive structured procedure leading to risk-adapted quality management has been published so far. Such a procedure is of particular interest for noncommercial trials in order to optimally use the sparse resources.
  
  
  OBJECTIVE
  To provide a structured procedure for risk analysis in clinical trials. To propose strategies for on-site monitoring adapted to the risks identified.
  
  
  RESULTS
  The risk analysis refers to the risk of noncompliance with the main objectives of Good Clinical Practice. It takes into account risks of the study intervention compared to the risks a patient would run if treated outside a protocol as well as further potential risks regarding patient safety, patient rights, or the credibility of results. The risk analysis is based on detailed questionnaires, which are used to draw up (a) an on-site monitoring strategy recommendation, (b) a list of trial-specific tasks to be covered by on-site monitoring, and (c) a specification of further quality management measures e.g., central monitoring measures. The resulting risk-adapted monitoring strategies focus on the trial's critical aspects, and differ in terms of the recommended extent of on-site activities.
  
  
  CONCLUSIONS
  The effectiveness of the proposed risk analysis and risk-adapted monitoring has not yet been confirmed. However, the ADAMON project (prospective cluster-randomised study of trial-specific adapted strategies for on-site monitoring in combination with additional quality management measures) has been started in Germany to investigate whether a trial-specific, risk-adapted, reduced on-site monitoring strategy is as effective as an intensive monitoring strategy with regard to the occurrence of serious or critical audit findings. Twelve clinical trials planning to recruit more than 3200 patients participate in this investigation.
  
  
  CONCLUSIONS
  Our proposal will provide sponsor-investigators and other noncommercial sponsors with an instrument that may facilitate risk analysis and the implementation of targeted quality management measures.
authors.affiliation: Clinical Trial Centre Leipzig, University of Leipzig, Leipzig, Germany. oana.brosteanu@kksl.uni-leipzig.de
authors.forename: Oana
authors.initials: O
authors.lastname: Brosteanu
authors.forename: Peggy
authors.initials: P
authors.lastname: Houben
authors.forename: Kristina
authors.initials: K
authors.lastname: Ihrig
authors.forename: Christian
authors.initials: C
authors.lastname: Ohmann
authors.forename: Ursula
authors.initials: U
authors.lastname: Paulus
authors.forename: Beate
authors.initials: B
authors.lastname: Pfistner
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schwarz
authors.forename: Anke
authors.initials: A
authors.lastname: Strenge-Hesse
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zettelmeyer
mesh_terms: D002985:Clinical Protocols; D026661:Clinical Trials Data Monitoring Committees / Q000458:organization & administration; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D003657:Decision Making; D006801:Humans; D011786:Quality Control; D017010:Reminder Systems; D012107:Research Design; D018570:Risk Assessment; D017751:Safety Management / Q000458:organization & administration