title: Optimal approaches to data collection and analysis of potential immune mediated disorders in clinical trials of new vaccines.
abstract: BACKGROUND
  The potential for development of autoimmune diseases after vaccination with new vaccines containing novel adjuvants is a theoretical concern. Randomised, placebo-controlled trials are the best method for assessing a potential causal relationship between an adverse event and vaccination, but usually have a sample size too small to detect adverse events occurring in <1% of subjects. Incomplete case documentation may hamper definitive diagnoses, preventing accurate causality assessment. To date there are no guidelines for collection, documentation and monitoring of potential immune mediated disorders (pIMD) reported in the course of clinical trials with adjuvanted vaccines.
  
  
  OBJECTIVE
  This paper proposes a methodology for collection of pIMDs in clinical vaccine trials, with the objective of obtaining complete and reliable data using standardised methodology for its collection and analysis.
  
  
  CONCLUSIONS
  The role of the study investigator in prospective, standardised safety data collection is key and can be facilitated by providing a pIMD list in study documents and disease-specific standard questionnaires to assist timely and thorough documentation. External expert review of histopathology samples or other specialised diagnostic data would increase diagnostic accuracy. Centralised case ascertainment using standard case definitions would identify true cases of interest. We propose collection of safety data for at least 6 months and up to one year after the last vaccine dose. Bio-banking as a platform for collecting samples from enrolled patients for future use (e.g., to measure biomarkers of diagnostic, prognostic or predictive utility) could eventually provide valuable information in cases where a pIMD is diagnosed during the study period.
  
  
  CONCLUSIONS
  Standardised collection of safety data to allow appropriate analyses are optimal approaches for detecting rare events in clinical trials. Appropriate data analysis will then more reliably define potential causal relationships with vaccination.
authors: GlaxoSmithKline Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. fernanda.tavares@gsk.com
authors: Fernanda
authors: F
authors: Tavares Da Silva
authors: Filip
authors: F
authors: De Keyser
authors: Paul-Henri
authors: PH
authors: Lambert
authors: William H
authors: WH
authors: Robinson
authors: René
authors: R
authors: Westhovens
authors: Christian
authors: C
authors: Sindic
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D016907:Adverse Drug Reaction Reporting Systems; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology*; D002986:Clinical Trials as Topic; D003625:Data Collection / Q000379:methods* / Q000592:standards; D006801:Humans; D017410:Practice Guidelines as Topic; D014611:Vaccination; D014612:Vaccines / Q000009:adverse effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D014612:Vaccines