title: Testing the usefulness of the number needed to treat to be harmed (NNTH) in benefit-risk evaluations: case study with medicines withdrawn from the European market due to safety reasons.
abstract: OBJECTIVE
  To explore the usefulness of number needed to treat to be harmed (NNTH), in benefit-risk assessments, by studying the agreement between NNTH values and withdrawals of medicines from European market due to safety reasons.
  
  
  METHODS
  Medicines with data from longitudinal studies were included. Studies were identified from European Medicines Agency's Reports. Meta-analyses were performed to pool odds ratios (OR) with 95% confidence-intervals (CI). Published control event rates were applied to ORs to calculate NNTHs (95%CI) for selected adverse events.
  
  
  RESULTS
  NNTH (95%CI) decreased from pre- to post-marketing for the eight medicines included: peripheral neuropathy (∞ vs. 12[non-significant; NS] with almitrine; heart valve disease with benfluorex (∞ vs. NNTH ranging from 7[4-13] to 7[5-9]); myopathy (-4096[NS] vs. 797[421-1690]), new-onset diabetes (113[NS] vs. 390[425-778]), bleeding (∞ vs. 517[317-1153]), and infection (∞ vs. 253[164-463]) with niacin-laropiprant; psychiatric disorders (12[7-34] vs. 9[5-24]) with rimonabant; myocardial infarction (MI) [-1305 vs. 270[89-4362]) with rofecoxib; MI (-510 vs. NNTH ranging from 152[55-4003] to 568[344-1350]) with rosiglitazone; cardiovascular events (∞ vs. 245[129-1318]) with sibutramine; and liver injury (∞ vs. 5957[NS]) with ximelagatran.
  
  
  CONCLUSIONS
  NNTH have potential of use as a supportive tool in benefit-risk re-evaluations of medicines and may help regulators to making decisions on drug safety.
authors.affiliation: a AIBILI - Association for Innovation and Biomedical Research on Light and Image , CHAD - Centre for Health Technology Assessment and Drug Research , Coimbra , Portugal.|b School of Pharmacy , University of Coimbra , Coimbra , Portugal.
authors.forename: Diogo
authors.initials: D
authors.lastname: Mendes
authors.affiliation: a AIBILI - Association for Innovation and Biomedical Research on Light and Image , CHAD - Centre for Health Technology Assessment and Drug Research , Coimbra , Portugal.|b School of Pharmacy , University of Coimbra , Coimbra , Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Alves
authors.affiliation: a AIBILI - Association for Innovation and Biomedical Research on Light and Image , CHAD - Centre for Health Technology Assessment and Drug Research , Coimbra , Portugal.|b School of Pharmacy , University of Coimbra , Coimbra , Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Batel Marques
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D005060:Europe / Q000453:epidemiology; D006801:Humans; D061366:Numbers Needed To Treat; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data; D018570:Risk Assessment / Q000379:methods*; D056737:Safety-Based Drug Withdrawals / Q000706:statistics & numerical data*
keywords: Benefit-risk assessment; NNTH; pharmacoepidemiology; pharmacovigilance; safety-based drug withdrawals