title: About the necessity to manage events coded with MedDRA prior to statistical analysis: proposal of a strategy with application to a randomized clinical trial, ANRS 099 ALIZE.
abstract: BACKGROUND
  Since 2003, the Medical Dictionary for Regulatory Activities (MedDRA) is the regulatory standard for safety report in clinical trials in the European Community. Yet, we found no published example of a practical experience for a scientifically oriented statistical analysis of events coded with MedDRA. We took advantage of a randomized trial in HIV-infected patients with MedDRA-coded events to explain the difficulties encountered during the events analysis and the strategy developed to report events consistently with trial-specific objectives.
  
  
  METHODS
  MedDRA has a rich hierarchical structure, which allows the grouping of coded terms into 5 levels, the highest being "System Organ Class" (SOC). Each coded term may be related to several SOCs, among which one primary SOC is defined. We developed a new general 5-step strategy to select a SOC as trial primary SOC, consistently with trial-specific objectives for this analysis. We applied it to the ANRS 099 ALIZE trial, where all events were coded with MedDRA version 3.0. We compared the MedDRA and the ALIZE primary SOCs.
  
  
  RESULTS
  In the ANRS 099 ALIZE trial, 355 patients were recruited, and 3,722 events were reported and documented, among which 35% had multiple SOCs (2 to 4). We applied the proposed 5-step strategy. Altogether, 23% of MedDRA primary SOCs were modified, mainly from MedDRA primary SOCs "Investigations" (69%) and "Ear and labyrinth disorders" (6%), for the ALIZE primary SOCs "Hepatobiliary disorders" (35%), "Musculoskeletal and connective tissue disorders" (21%), and "Gastrointestinal disorders" (15%).
  
  
  CONCLUSIONS
  MedDRA largely enhanced in size and complexity with versioning and the development of Standardized MedDRA Queries. Yet, statisticians should not systematically rely on primary SOCs proposed by MedDRA to report events. A simple general 5-step strategy to re-classify events consistently with the trial-specific objectives might be useful in HIV trials as well as in other fields.
authors.affiliation: INSERM, U593, F-33076 Bordeaux, France. valerie.journot@bordeaux.inserm.fr
authors.forename: Valérie
authors.initials: V
authors.lastname: Journot
authors.forename: Sophie
authors.initials: S
authors.lastname: Tabuteau
authors.forename: Fidéline
authors.initials: F
authors.lastname: Collin
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chene
authors.forename: Corinne
authors.initials: C
authors.lastname: Rancinan
mesh_terms: D003627:Data Interpretation, Statistical; D005568:Forms and Records Control; D015658:HIV Infections; D006801:Humans; D016032:Randomized Controlled Trials as Topic