title: Risk evaluation and monitoring in multiple sclerosis therapeutics.
abstract: BACKGROUND
  Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks.
  
  
  OBJECTIVE
  The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring.
  
  
  RESULTS
  Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making.
  
  
  CONCLUSIONS
  It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions.
authors.affiliation: Department of Neurosciences University Hospital Toulouse, France michel.clanet@inserm.fr.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Clanet
authors.affiliation: Department of Neurology, The University of Texas Health Science Center at Houston, USA.
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Wolinsky
authors.affiliation: AshtonMediCom, UK.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Ashton
authors.affiliation: Department of Neurology and Center for Neuropsychiatry, Medical Faculty, Heinrich-Heine-Universität im UKD, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Scientific and Clinical Review Associates LLC, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Reingold
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000465:Algorithms; D001291:Attitude of Health Personnel; D003142:Communication; D003661:Decision Support Techniques; D016903:Drug Monitoring / Q000379:methods*; D019317:Evidence-Based Medicine; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D010342:Patient Acceptance of Health Care; D018579:Patient Selection; D010361:Patients / Q000523:psychology; D010465:Perception; D010817:Physician-Patient Relations; D011159:Population Surveillance; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents
keywords: Risk; benefit; disease-modifying therapy; multiple sclerosis; safety; surveillance