title: Comparing adverse event rates of oral blood glucose-lowering drugs reported by patients and healthcare providers: a post-hoc analysis of observational studies published between 1999 and 2011.
abstract: BACKGROUND
  Non-serious symptomatic adverse drug events (ADEs) affect the real benefit-risk ratio of a drug. Currently, such ADEs are quantified in different ways, often using reports from a healthcare provider or patients, resulting in large variations in estimated rates. Several studies showed that patients report bothersome or symptomatic ADEs more frequently than providers, but no comparisons to an external reference or gold standard have been made.
  
  
  OBJECTIVE
  We conducted a literature review to assess the agreement and concurrent validity of healthcare provider- and patient-oriented methods for quantifying symptomatic ADEs of oral blood glucose-lowering drugs in patients with type 2 diabetes mellitus.
  
  
  METHODS
  We systematically searched MEDLINE and EMBASE databases for observational studies reporting on rates of ADEs in patients treated for type 2 diabetes that were published between 1999 and 2011. We included nine observational studies reporting absolute rates of symptomatic ADEs in patients receiving monotherapy. We calculated 95% confidence intervals and assessed agreement between rates observed with different methods. We assessed concurrent validity using the range noted in the Summary of Product Characteristics (SPC) as the gold standard.
  
  
  RESULTS
  A comparison of rates reported by patients and providers was only possible using three studies of metformin that assessed mainly gastrointestinal (GI) ADEs. Provider-oriented methods by means of medical record review gave lower rates for abdominal pain (0.6-3.7%), dyspepsia (1.3-2.8%) and constipation (0.6-1.0%) than a patient questionnaire method (8.5%, 11.9% and 20.7%, respectively). For diarrhoea, the patient-reported rate (5.2%) was in agreement with the provider-based rates (1.6-7.6%). The majority of the rates reported by providers and patients were not corresponding with the ranges in the SPC. For GI ADEs the rates were all lower, whereas for lactic acidosis and hypoglycaemia the rates were higher.
  
  
  CONCLUSIONS
  Although it has repeatedly been proposed that patients' reports on safety should be incorporated with providers' reports, especially for symptomatic ADEs, the number of observational studies using patient-oriented methods for assessing ADEs other than hypoglycaemia are limited. Provider-based measurement tended to underestimate symptomatic ADEs. Patient-oriented methods seemed to give ADE rates that were closer to the rates reported in the SPC.
authors.affiliation: Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Liana
authors.initials: L
authors.lastname: Hakobyan
authors.forename: Flora M
authors.initials: FM
authors.lastname: Haaijer-Ruskamp
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.forename: Daniela
authors.initials: D
authors.lastname: Dobre
authors.forename: Petra
authors.initials: P
authors.lastname: Denig
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006282:Health Personnel; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D010361:Patients; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents
references.citation: Arch Intern Med. 2005 Jan 24;165(2):234-40
references.pmid: 15668373
references.citation: Br J Clin Pharmacol. 2007 Feb;63(2):148-56
references.pmid: 17274788
references.citation: Z Rheumatol. 2010 Nov;69(9):795-802
references.pmid: 21063828
references.citation: J Urol. 2010 Aug;184(2):525-31
references.pmid: 20620412
references.citation: Pharmacoepidemiol Drug Saf. 2009 Mar;18(3):240-5
references.pmid: 19148880
references.citation: Drugs Aging. 2008;25(7):611-22
references.pmid: 18582148
references.citation: Expert Opin Drug Saf. 2002 May;1(1):71-8
references.pmid: 12904162
references.citation: Am J Manag Care. 2008 Aug;14(8):530-9
references.pmid: 18690769
references.citation: Drug Saf. 2006;29(5):385-96
references.pmid: 16689555
references.citation: J Clin Oncol. 2004 Sep 1;22(17):3485-90
references.pmid: 15337796
references.citation: Ann Intern Med. 2006 Feb 21;144(4):257-61
references.pmid: 16490911
references.citation: Diabetes Res Clin Pract. 2010 Aug;89(2):e30-2
references.pmid: 20541826
references.citation: Ann Intern Med. 2004 May 18;140(10):795-801
references.pmid: 15148066
references.citation: N Engl J Med. 2010 Mar 11;362(10):865-9
references.pmid: 20220181
references.citation: Curr Med Res Opin. 2004 Apr;20(4):565-72
references.pmid: 15119994
references.citation: J Natl Cancer Inst. 2009 Dec 2;101(23):1624-32
references.pmid: 19920223
references.citation: Farm Hosp. 2005 Nov-Dec;29(6):364-6
references.pmid: 16433568
references.citation: Pharm World Sci. 2004 Jun;26(3):155-9
references.pmid: 15230363
references.citation: Aliment Pharmacol Ther. 2001 Jan;15(1):137-42
references.pmid: 11136287
references.citation: Drug Saf. 2007;30(8):669-75
references.pmid: 17696579
references.citation: J Headache Pain. 2009 Aug;10(4):235-9
references.pmid: 19495934
references.citation: J Urol. 1998 Jun;159(6):1988-92
references.pmid: 9598504
references.citation: Haemophilia. 2005 Jul;11(4):353-9
references.pmid: 16011587
references.citation: Pharmacotherapy. 1994 Mar-Apr;14(2):202-9
references.pmid: 8197040
references.citation: J Am Med Inform Assoc. 2004 Nov-Dec;11(6):492-8
references.pmid: 15299000
references.citation: EMBO Rep. 2008 Mar;9(3):221-4
references.pmid: 18311170
references.citation: Panminerva Med. 2000 Mar;42(1):23-6
references.pmid: 11019600
references.citation: Lancet Oncol. 2006 Nov;7(11):903-9
references.pmid: 17081915
references.citation: Clin Drug Investig. 2005;25(10):651-9
references.pmid: 17532710
references.citation: Ann Pharmacother. 2005 Oct;39(10):1640-6
references.pmid: 16159999
references.citation: Arch Intern Med. 2001 Jul 9;161(13):1653-9
references.pmid: 11434798
references.citation: Clin Ther. 2007 Jun;29(6 Pt 1):1284-92
references.pmid: 18036390
references.citation: J Clin Hypertens (Greenwich). 2008 Sep;10(9):716-22
references.pmid: 18844768
references.citation: Rheumatology (Oxford). 2011 Jan;50(1):152-60
references.pmid: 20871128