Drug Safety

, Volume 28, Issue 8, pp 731–740 | Cite as

Trends in Spontaneous Adverse Drug Reaction Reports to the French Pharmacovigilance System (1986—2001)

  • Frantz Thiessard
  • Emmanuel Roux
  • Ghada Miremont-Salamé
  • Annie Fourrier-Réglat
  • Françoise Haramburu
  • Pascale Tubert-Bitter
  • Bernard Bégaud
Original Research Article


Background: The French pharmacovigilance system is based on a network of 31 regional centres located in teaching hospitals and coordinated by the French Medicines Agency (‘Agence Francaise de Securite Sanitaire des Produits de Santé’ [Afssaps]). Since 1984, they have shared a common database of adverse drug reactions (ADRs) that are spontaneously reported by healthcare professionals. The objective of this study is to describe the characteristics of the reports and the reporting trends in the French pharmacovigilance spontaneous reporting database from 1986 to 2001.

Methods: All the reports from January 1986 to December 2001 were included. Drugs and ADRs were translated to anatomical therapeutic chemical (ATC) codes and MedDRA classifications, respectively.

Results: The total number of reports was 197 580 over the 16-year period, with linearly increase over time. The median (interquartile range [IQR]) age of the patients was 53 (34–70) and the male/female ratio was 0.82. The median (IQR) time between the date of occurrence of the ADR and the date of report was 73 days (34–166). The reporter was a specialist in 74% of the reports and a general practitioner in 17%. The annual rate of reporting according to medical demography strongly increased for the specialists, especially since 1994. At least one ADR was considered as serious in 44.8% of the reports. The ADRs were most frequently related to nervous system drugs (23%), followed by cardiovascular drugs (19%) and systemic anti-infectives (17%). The latter class had the fastest progression mostly due to antiretroviral therapy since 1996. According to the Medical Dictionary for Regulatory Activities (MedDRA) coding, the system organ most often reported was skin and subcutaneous tissue disorders (29%), followed by nervous system disorders (19%), gastrointestinal disorders (12%), blood and lymphatic system disorders (12%), vascular disorders (12%) and general disorders and administration site conditions (12%).

Discussion: All spontaneous reporting systems are affected by under-reporting. One of their goals is to generate early signals, which might be more affected by reporting bias than by under-reporting. Some improvements should be made in the design of the French database, but data collected since 1986 constitute an essential tool for the routine work of the 31 pharmacovigilance centres.

Conclusion: This first description of the data of the French pharmacovigilance database involving all drugs and ADRs shows an increasing tendency to reporting over time, especially in specialists and for systemic anti-infective drugs. The database that uses hierarchical international classifications for drugs and adverse reactions may be used for further studies and could be the basis for an automatic signal generation system.


Anatomical Therapeutic Chemical Spontaneous Reporting Causality Assessment Spontaneous Reporting System Pharmacovigilance Centre 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to acknowledge the assistance of Nicholas Moore of EA3676, Université Victor Segalen, Bordeaux, France, and Pascal Auriche and Carmen Kreft-Jais of Agence Française de Sécurité Sanitaire des Produits de Santé (Afssaps), Paris, France. No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.


  1. 1.
    Moore N, Kreft-Jais C, Dahnani A. Spontaneous reporting - France. In: Mann RD, Andrews EB, editors. Pharmacovigilance. Chichester: Wiley, 2002: 209–17CrossRefGoogle Scholar
  2. 2.
    Articles R. 5144-9. et R. 5144-9. du decret n° 84-402 du 24 mai 1984 portant application de l’article L. 605 du code de la santé publique et relatif à la pharmacovigilance. JORF 1984; 116: 1687Google Scholar
  3. 3.
    Moore N, Biour M, Paux G, et al. Adverse drug reaction monitoring: doing it the French way. Lancet 1985; II: 1056–8CrossRefGoogle Scholar
  4. 4.
    Begaud B, Evreux JC, Jouglard J, et al. Imputation of the unexpected or toxic effects of drugs: actualization of the method used in France. Therapie 1985; 40: 111–8PubMedGoogle Scholar
  5. 5.
    International Conference on Harmonisation. Guidance on addendum to E2C clinical sfety data management: periodic safety update reports for marketed drugs. Fed Regist 2004; 69: 5551–2Google Scholar
  6. 6.
    USA Food and Drug Administration. International Conference on Harmonisation. Clinical safety data management: definitions and standards for expedited reporting [ICH-E2A ]. Rockville (MD): U.S. Dept. of Health and Human Services, 1995Google Scholar
  7. 7.
    Agence du médicament. Déclaration d’effet indésirable susceptible d’être dûà un médicament ou produit mentionnéà l’article R.5144-1[online]. Available from URL: [Accessed 2004 Oct 19]Google Scholar
  8. 8.
    Miller GC, Britt H. A new drug classification for computer systems: the ATC extension code. Int J Biomed Comput 1995; 40: 121–4PubMedCrossRefGoogle Scholar
  9. 9.
    Wertheimer AI. The defined daily dose system (DDD) for drug utilization review. Hosp Pharm 1986; 21: 233–4, 239–41, 258PubMedGoogle Scholar
  10. 10.
    Ronning M, Blix HS, Harbo BT, et al. Different versions of the anatomical therapeutic chemical classification system and the defined daily dose: are drug utilisation data comparable? Eur J Clin Pharmacol 2000; 56: 723–7PubMedCrossRefGoogle Scholar
  11. 11.
    Brown EG, Wood L, Wood S. The medical dictionary for regulatory activities (MedDRA). Drug Saf 1999; 20: 109–17PubMedCrossRefGoogle Scholar
  12. 12.
    Brown EG. Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART. Drug Saf 2002; 25: 445–52PubMedCrossRefGoogle Scholar
  13. 13.
    Stata Corporation. Intercooled Stata 6.0. College Station: Stata Corporation; 2000Google Scholar
  14. 14.
    Meyboom RH, Egberts AC, Edwards IR, et al. Principles of signal detection in pharmacovigilance. Drug Saf 1997; 16: 355–65PubMedCrossRefGoogle Scholar
  15. 15.
    Rossi AC, Knapp DE, Anello C, et al. Discovery of adverse drug reactions: a comparison of selected phase IV studies with spontaneous reporting methods. JAMA 1983; 249: 2226–8PubMedCrossRefGoogle Scholar
  16. 16.
    Lacoste-Roussillon C, Pouyanne P, Haramburu F, et al. Incidence of serious adverse drug reactions in general practice: a prospective study. Clin Pharmacol Ther 2001; 69: 458–62PubMedCrossRefGoogle Scholar
  17. 17.
    Pouyanne P, Haramburu F, Imbs JL, et al. Admissions to hospital caused by adverse drug reactions: cross sectional incidence study. French pharmacovigilance centres. BMJ 2000; 320: 1036PubMedCrossRefGoogle Scholar
  18. 18.
    Begaud B, Martin K, Haramburu F, et al. Rates of spontaneous reporting of adverse drug reactions in France [letter]. JAMA 2002; 288: 1588PubMedCrossRefGoogle Scholar
  19. 19.
    Moride Y, Haramburu F, Requejo AA, et al. Under-reporting of adverse drug reactions in general practice. Br J Clin Pharmacol 1997; 43: 177–81PubMedCrossRefGoogle Scholar
  20. 20.
    Alvarez-Requejo A, Carvajal A, Begaud B, et al. Under-reporting of adverse drug reactions: estimate based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharmacol 1998; 54: 483–8PubMedCrossRefGoogle Scholar
  21. 21.
    Smith CC, Bennett PM, Pearce HM, et al. Adverse drug reactions in a hospital general medical unit meriting notification to the Committee on Safety of Medicines. Br J Clin Pharmacol 1996; 42: 423–9PubMedCrossRefGoogle Scholar
  22. 22.
    Sweis D, Wong IC. A survey on factors that could affect adverse drug reaction reporting according to hospital pharmacists in Great Britain. Drug Saf 2000; 23: 165–72PubMedCrossRefGoogle Scholar
  23. 23.
    Agence du médicament. Bonnes pratiques de pharmacovigilance. Saint-Denis: Agence du médicament, 1994 [online]. Available from: URL: [Accessed 2004 Oct 19]Google Scholar
  24. 24.
    Davis S, Raine JM. Spontaneous reporting - UK. In: Mann RD, Andrews EB, editors. Pharmacovigilance. Chichester: Wiley, 2002: 195–207CrossRefGoogle Scholar
  25. 25.
    Begaud B, Martin K, Fourrier A, et al. Does age increase the risk of adverse drug reactions? Br J Clin Pharmacol 2002; 54: 550–2PubMedCrossRefGoogle Scholar
  26. 26.
    Carbonin P, Pahor M, Bernabei R, et al. Is age an independent risk factor of adverse drug reactions in hospitalized medical patients? J Am Geriatr Soc 1991; 39: 1093–9PubMedGoogle Scholar
  27. 27.
    Moore TJ, Weiss SR, Kaplan S, et al. Reported adverse drug events in infants and children under 2 years of age. Pediatrics 2002; 110: e53PubMedCrossRefGoogle Scholar
  28. 28.
    Kaushal R, Bates DW, Landrigan C, et al. Medication errors and adverse drug events in pediatric inpatients. JAMA 2001; 285: 2114–20PubMedCrossRefGoogle Scholar
  29. 29.
    Martin RM, Biswas PN, Freemantle SN, et al. Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. Br J Clin Pharmacol 1998; 46: 505–11PubMedCrossRefGoogle Scholar
  30. 30.
    Simpson JM, Bateman DN, Rawlins MD. Using the Adverse Reactions Register to study the effects of age and sex on adverse drug reactions. Stat Med 1987; 6: 863–7PubMedCrossRefGoogle Scholar
  31. 31.
    van Grootheest K, Olsson S, Couper M, et al. Pharmacists’ role in reporting adverse drug reactions in an international perspective. Pharmacoepidemiol Drug Saf 2004; 13: 457–64PubMedCrossRefGoogle Scholar
  32. 32.
    Eland IA, Belton KJ, van Grootheest AC, et al. Attitudinal survey of voluntary reporting of adverse drug reactions. Br J Clin Pharmacol 1999; 48: 623–7PubMedCrossRefGoogle Scholar
  33. 33.
    Hughes ML, Whittlesea CM, Luscombe DK. Review of national spontaneous reporting schemes: strengths and weaknesses. Adverse Drug React Toxicol Rev 2002; 21: 231–41PubMedGoogle Scholar
  34. 34.
    Jankovic S. Stimulating spontaneous reporting of adverse drug reactions by a patient: directed incentive. Drug Saf 2003; 26: 741–2PubMedCrossRefGoogle Scholar
  35. 35.
    Auvray L, Dumesnil S, Le Fur P, et al. Données synthétiques sur la consommation pharmaceutique en un mois, France 2000. In: Santé, soins et protection sociale en 2000 - Annexes. Paris: CREDES, 2001: 110Google Scholar
  36. 36.
    Meyboom RH, Hekster YA, Egberts AC, et al. Causal or casual? The role of causality assessment in pharmacovigilance. Drug Saf 1997; 17: 374–89PubMedCrossRefGoogle Scholar
  37. 37.
    Miremont G, Haramburu F, Begaud B, et al. Adverse drug reactions: physicians’ opinions versus a causality assessment method. Eur J Clin Pharmacol 1994; 46: 285–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Frantz Thiessard
    • 1
  • Emmanuel Roux
    • 2
  • Ghada Miremont-Salamé
    • 1
  • Annie Fourrier-Réglat
    • 1
  • Françoise Haramburu
    • 1
  • Pascale Tubert-Bitter
    • 2
  • Bernard Bégaud
    • 1
  1. 1.EA3676, IFR99, Case 11, ISPEDUniversité Victor Segalen Bordeaux 2SaignatFrance
  2. 2.INSERM U472ParisFrance

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