title: Development and Initial Validation of a Patient-Reported Adverse Drug Event Questionnaire.
abstract: BACKGROUND
  Direct patient reporting of adverse drug events (ADEs) is relevant for the evaluation of drug safety. To collect such data in clinical trials and postmarketing studies, a valid questionnaire is needed that can measure all possible ADEs experienced by patients.
  
  
  OBJECTIVE
  Our aim was to develop and test a generic questionnaire to identify ADEs and quantify their nature and causality as reported by patients.
  
  
  METHODS
  We created a draft list of common ADEs in lay-terms, which were classified in body categories and mapped to the Medical Dictionary for Regulatory Activities (MedDRA(®)) terminology. Questions about the nature and causality were derived from existing questionnaires and causality scales. Content validity was tested through cognitive debriefing, revising the questionnaire in an iterative process. Feasibility and reliability were assessed using a Web-based version of the questionnaire. Patients received the questionnaire twice. Feasibility was assessed by the reported time needed for completion and ease of use. Reliability was calculated using Cohen's kappa and proportion of positive agreement (PPA) on: (1) any ADE at patient level; (2) similar ADEs at MedDRA(®) System Organ Class level; and (3) the same ADE at ADE-specific level.
  
  
  RESULTS
  In the development phase, 28 patients with type 2 diabetes or asthma/chronic obstructive pulmonary disease (COPD) participated. Questions and answer options were rephrased, layout was improved, and changes were made in the classification of ADEs. The final questionnaire consisted of 252 ADEs organized in 16 body categories, and included 14 questions per reported ADE. A total of 135 patients using a median of five different drugs completed the Web-based questionnaire twice. The median completion time was 15 min for patients not reporting any ADE, and 30 min for patients reporting at least one ADE. Three quarters of the patients found the questionnaire easy to use. Test-retest reliability was acceptable at patient level (κ = 0.50, PPA 0.64) and at MedDRA(®) System Organ Class level (κ = 0.52, PPA 0.54), but was low at ADE-specific level (κ = 0.38, PPA 0.38).
  
  
  CONCLUSIONS
  We developed a generic patient-reported ADE questionnaire and confirmed its content validity. The questionnaire was feasible and reliable for reporting any ADE and similar ADEs at MedDRA(®) System Organ Class level. Additional work is, however, needed to reliably quantify specific ADEs reported by patients.
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD Groningen, The Netherlands.
authors.forename: Sieta T
authors.initials: ST
authors.lastname: de Vries
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD, Groningen, The Netherlands.
authors.forename: Peter G M
authors.initials: PG
authors.lastname: Mol
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD, Groningen, The Netherlands.
authors.forename: Flora M
authors.initials: FM
authors.lastname: Haaijer-Ruskamp
authors.affiliation: Department of Clinical Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 196, 9700 AD, Groningen, The Netherlands. p.denig@umcg.nl.
authors.forename: Petra
authors.initials: P
authors.lastname: Denig
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D057566:Self Report / Q000592:standards*; D012737:Sex Factors; D011795:Surveys and Questionnaires / Q000592:standards*; D055815:Young Adult
references.citation: J Natl Cancer Inst. 2009 Dec 2;101(23):1624-32
references.pmid: 19920223
references.citation: Qual Life Res. 2000 Feb;9(1):13-27
references.pmid: 10981203
references.citation: J Clin Epidemiol. 2000 May;53(5):499-503
references.pmid: 10812322
references.citation: Aliment Pharmacol Ther. 2001 Jan;15(1):137-42
references.pmid: 11136287
references.citation: J Clin Oncol. 2007 Dec 1;25(34):5374-80
references.pmid: 18048818
references.citation: Pharmacoepidemiol Drug Saf. 2011 Jun;20(6):591-7
references.pmid: 21538671
references.citation: Curr Med Res Opin. 2009 Apr;25(4):929-42
references.pmid: 19257798
references.citation: Qual Life Res. 2009 Nov;18(9):1263-78
references.pmid: 19784865
references.citation: Ann Pharmacother. 1992 Jul-Aug;26(7-8):890-6
references.pmid: 1504394
references.citation: J Clin Epidemiol. 1990;43(6):551-8
references.pmid: 2189948
references.citation: Br J Psychiatry. 1995 May;166(5):650-3
references.pmid: 7620752
references.citation: J Adv Nurs. 1997 May;25(5):999-1007
references.pmid: 9147205
references.citation: Arch Intern Med. 2005 Jan 24;165(2):234-40
references.pmid: 15668373
references.citation: BMC Fam Pract. 2008 Jun 15;9:35
references.pmid: 18554418
references.citation: Br J Clin Pharmacol. 2007 Feb;63(2):148-56
references.pmid: 17274788
references.citation: Value Health. 2008 Sep-Oct;11(5):913-26
references.pmid: 18494753
references.citation: Clin Pharmacol Ther. 1981 Aug;30(2):239-45
references.pmid: 7249508
references.citation: Int J Nurs Stud. 2001 Oct;38(5):497-510
references.pmid: 11524097
references.citation: Urology. 2006 Aug;68(2 Suppl):9-16
references.pmid: 16908336
references.citation: Br J Clin Pharmacol. 2002 Mar;53(3):318-25
references.pmid: 11874396
references.citation: Diabet Med. 1994 Apr;11(3):253-61
references.pmid: 8033523
references.citation: Med Care. 2011 Oct;49(10):948-55
references.pmid: 21642876
references.citation: Respir Res. 2006 Oct 24;7:131
references.pmid: 17062139
references.citation: J Rheumatol. 2001 May;28(5):1188-91
references.pmid: 11361211
references.citation: Qual Life Res. 2003 May;12(3):229-38
references.pmid: 12769135
references.citation: Mayo Clin Proc. 2005 Feb;80(2):203-10
references.pmid: 15704775
references.citation: Phys Ther. 2005 Mar;85(3):257-68
references.pmid: 15733050
references.citation: J Sleep Res. 2007 Dec;16(4):439-47
references.pmid: 18036091
references.citation: Drug Saf. 2011 May 1;34(5):429-36
references.pmid: 21513365
references.citation: Expert Opin Drug Saf. 2012 Jan;11(1):45-51
references.pmid: 22007719
references.citation: Ann Intern Med. 2006 Feb 21;144(4):257-61
references.pmid: 16490911
references.citation: Value Health. 2007 Nov-Dec;10 Suppl 2:S94-S105
references.pmid: 17995479
references.citation: Med Care. 1992 Jun;30(6):473-83
references.pmid: 1593914
references.citation: Int J Clin Pract. 2009 Feb;63(2):233-42
references.pmid: 19196362
references.citation: Health Qual Life Outcomes. 2011 Sep 29;9:83
references.pmid: 21958008
references.citation: Psychol Health. 2012;27(5):570-87
references.pmid: 21827288
references.citation: Drug Saf. 2011 Mar 1;34(3):221-31
references.pmid: 21332246
references.citation: J Am Med Inform Assoc. 2000 Jul-Aug;7(4):416-25
references.pmid: 10887169
references.citation: Qual Life Res. 2010 May;19(4):483-7
references.pmid: 20151208
references.citation: J Clin Epidemiol. 1993 May;46(5):423-9
references.pmid: 8501467
references.citation: Health Qual Life Outcomes. 2006 Oct 11;4:79
references.pmid: 17034633
references.citation: Biometrics. 1977 Mar;33(1):159-74
references.pmid: 843571
references.citation: Headache. 2004 Nov-Dec;44(10):978-82
references.pmid: 15546260
references.citation: J Clin Epidemiol. 2011 Jan;64(1):96-106
references.pmid: 21130355
references.citation: Value Health. 2009 Nov-Dec;12(8):1075-83
references.pmid: 19804437
references.citation: Br J Psychiatry. 2009 Sep;195(3):202-10
references.pmid: 19721108
references.citation: Br J Community Nurs. 2011 Mar;16(3):146-51
references.pmid: 21378658