title: A modified prescription-event monitoring study to assess the introduction of Seretide Evohaler in England: an example of studying risk monitoring in pharmacovigilance.
abstract: BACKGROUND
  Monitoring was required for the introduction of non-chlorofluorocarbon (CFC) propellants in metered dose inhalers (MDIs) to ensure that there were no unexpected adverse events due to the new products. A postmarketing surveillance study has been conducted to evaluate the introduction of the MDI Seretide Evohaler (hydrofluoroalkane-134a inhaler containing salmeterol and fluticasone propionate).
  
  
  OBJECTIVE
  To summarise the modified prescription-event monitoring (PEM) study conducted to evaluate the introduction of Seretide Evohaler and discuss the relevance of this type of study towards pharmacovigilance risk-management planning.
  
  
  METHODS
  Modified PEM methodology was used to examine the introduction of Seretide Evohaler into general practice in England. Patients were identified from the first National Health Service prescriptions dispensed in England for Seretide Evohaler. One postal questionnaire was sent to the prescribing doctor, requesting demographic information, severity of the indication, concomitant medication for this condition, smoking history, event data 3 months prior to and 3 months after the first prescription for Seretide Evohaler and also reason for stopping if it had been stopped. Pregnancies, deaths and selected events were followed up. Incidence density ratios were calculated to compare event rates 3 months prior to and 3 months after the introduction of Seretide Evohaler. A matched cohort analysis examined oral corticosteroid use and hospital admissions between the pre- and post-exposure periods.
  
  
  RESULTS
  The cohort comprised 13,464 patients prescribed Seretide Evohaler, with a response rate of 62%. There was no significant difference in the length of courses of oral corticosteroid use when the pre- and post-exposure periods were compared. A matched cohort analysis showed there was no increase in the use of oral corticosteroids (relative risk [RR] 0.95; 95% CI 0.90, 0.99) or hospital admissions in the post-exposure period (RR 0.87; 95% CI 0.73, 1.04). When the number of patients with events were compared for the periods 3 months before and 3 months after exposure, fewer events were reported in the post-exposure period. There were 64 patients who experienced adverse events within an hour of using Seretide Evohaler, including one report of paradoxical bronchospasm and one of myocardial infarction with fatal outcome that were both assessed as possibly related to treatment.
  
  
  CONCLUSIONS
  The results of the study suggest that the introduction of Seretide Evohaler was generally well tolerated. The modified methodology has allowed a comparison of the event rates before and after the introduction of this CFC-free inhaler into general practice.
authors: Drug Safety Research Unit, Southampton, UK. michael.perrio@dsru.org
authors: Michael J
authors: MJ
authors: Perrio
authors: Lynda V
authors: LV
authors: Wilton
authors: Saad A W
authors: SA
authors: Shakir
mesh_terms: D000328:Adult; D000335:Aerosol Propellants / Q000009:adverse effects*; D000368:Aged; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000009:adverse effects*; D004338:Drug Combinations; D004739:England; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000009:adverse effects*; D008297:Male; D036501:Metered Dose Inhalers / Q000009:adverse effects*; D008875:Middle Aged; D011247:Pregnancy; D011358:Product Surveillance, Postmarketing; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D000420:Albuterol; D000730:Androstadienes; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons
references: Respir Care. 2005 Sep;50(9):1201-8
references: 16122403
references: Respir Care. 2005 Oct;50(10):1304-12; discussion 1312
references: 16185366
references: Arch Dis Child. 2002 Dec;87(6):457-61
references: 12456538
references: Thorax. 2000 Aug;55(8):662-5
references: 10899242
references: Respir Med. 2001 Feb;95(2):136-46
references: 11217910
references: Treat Respir Med. 2004;3(1):35-44
references: 15174892
references: Chest. 2006 Jan;129(1):15-26
references: 16424409
references: Eur Respir J. 2004 Sep;24(3):420-5
references: 15358701
references: Drugs. 2005;65(12):1715-34
references: 16060707
references: Lancet. 2001 Dec 1;358(9296):1872-3
references: 11741629
references: Ann Allergy Asthma Immunol. 2003 Sep;91(3):263-9
references: 14533658
references: Int J Clin Pract. 2005 Jul;59(7):754-9
references: 15963199
references: Pharmacoepidemiol Drug Saf. 1999 Apr;8 Suppl 1:S37-45
references: 15073885
references: Pharmacoepidemiol Drug Saf. 2003 Jan-Feb;12(1):17-29
references: 12616844
references: BMC Public Health. 2004 Aug 07;4:35
references: 15298712
references: Med J Aust. 2003 Mar 3;178(5):214-6
references: 12603184
references: J Asthma. 2004;41(8):797-806
references: 15641629
references: J Paediatr Child Health. 2002 Feb;38(1):59-62
references: 11869402
references: Clin Ther. 2006 Jan;28(1):73-85
references: 16490581
references: J Pediatr (Rio J). 2004 Nov-Dec;80(6):441-6
references: 15622419
references: Drug Saf. 2004;27(8):509-17
references: 15154824
references: Eur Respir J. 2003 Apr;21(4):633-6
references: 12762348
references: Br J Gen Pract. 1997 Feb;47(415):91-4
references: 9101692
references: Pharmacoepidemiol Drug Saf. 2005 Jun;14(6):377-87
references: 15517542
references: BMJ. 1998 Jul 11;317(7151):119-20
references: 9657787