title: Disease-specific adverse events following nonlive vaccines: a paradoxical placebo effect or a nocebo phenomenon?
abstract: Vaccines can cause adverse reactions (AR), i.e. adverse events following immunization (AEFIs) due to the vaccine, such as local reactions or fever. In addition, live attenuated vaccines which replicate in vaccinees can cause disease-specific AR, e.g. measles-like rash following measles vaccination. However, nonlive vaccines because they are inactivated and they do not replicate in vaccinees, are not likely to cause disease-specific AR. The aim of the study was to assess whether safety signals could be generated by an undescribed bias in spontaneous reporting of disease-specific AEFIs with nonlive vaccines. All AEFIs of Sanofi Pasteur MSD vaccines spontaneously reported in France from January 2000 to June 2010, coded according to MedDRA terms and collected in the company's pharmacovigilance database were analyzed. Vaccine-event pairs of interest were selected a priori. The disproportionality reporting rate methodology was used, comparing the proportion of a given event reported following a given vaccine to its proportion reported following all other studied vaccines. The Reporting Odds Ratio (ROR) was used for signals detection for each vaccine-event pair selected. A total of 33,275 AEFIs were analyzed. The calculated ROR showed a statistically disproportionate reporting rate and generated false safety signals for almost all the pairs tested. Three nonlive vaccine pairs were striking: gynaecological symptoms and the quadrivalent human papillomavirus (qHPV) vaccine; trismus and tetanus vaccines; hepatobiliary disorders and hepatitis B vaccines. In conclusion we have identified a new vaccine AE spontaneous reporting bias: "disease-specific adverse events following nonlive vaccines", showing that vaccinees and healthcare professionals tend to report preferentially the symptoms of the disease against which the nonlive vaccine was administered. We suggest that bias is subordinate to a paradoxical placebo effect and/or a nocebo phenomenon.
authors.affiliation: Sanofi Pasteur MSD, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Okaïs
authors.forename: Constance
authors.initials: C
authors.lastname: Gay
authors.forename: Fabrice
authors.initials: F
authors.lastname: Seon
authors.forename: Lydie
authors.initials: L
authors.lastname: Buchaille
authors.forename: Emilie
authors.initials: E
authors.lastname: Chary
authors.forename: Benoît
authors.initials: B
authors.lastname: Soubeyrand
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D057286:Electronic Health Records; D006801:Humans; D015588:Observer Variation; D060735:Pharmacovigilance; D015990:Placebo Effect; D012107:Research Design; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000009:adverse effects*
chemical_list: D015164:Vaccines, Inactivated