Development and Initial Validation of a Patient-Reported Adverse Drug Event Questionnaire.

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).

Conclusion: 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.