title: Relating spontaneous adverse experience reports to scores on a questionnaire querying tolerability.
abstract: In this study, we examined the relation between spontaneously reported adverse experiences and responses given on the comparison of ophthalmic medications for tolerability (COMTOL) checklist questionnaire which queries the frequency and bother of specific side-effects known to be associated with topical ophthalmic agents used to treat ocular hypertension or open-angle glaucoma, and the impact that the side-effects have on health-related quality of life. The study was a 4-week, randomized, open-label, two-period cross-over clinical trial comparing dorzolamide and pilocarpine in 92 patients who were also receiving timolol for the treatment of ocular hypertension or open-angle glaucoma. Patients completed the COMTOL questionnaire at baseline and at the end of each period and spontaneous reports of adverse experiences (AEs) were collected throughout the study by the investigator. Since there were only 3 spontaneously reported AEs related to drug treatment while patients received dorzolamide and since COMTOL scores indicated a low level of side-effects, the analyses were limited to pilocarpine treatment periods. We discovered that during the pilocarpine treatment periods, a large percentage (94%) of the 47 patients, who failed to spontaneously report any adverse experiences, indicated on the COMTOL that they had experienced side-effects. These discrepancies between the methods of spontaneous reports and a checklist questionnaire are similar to those previously reported in the literature for other drugs. Unlike previous literature, we went beyond identifying discrepancies with the two reporting methods and we looked for possible explanations for why the discrepancies existed. We discovered that patients who spontaneously reported AEs expressed more bother from these specific side-effects on the questionnaire than patients who did not spontaneously report AEs. As well, patients who spontaneously reported AEs and discontinued drug as a result of the AEs expressed on the COMTOL the greatest bother from side-effects. This trend of increasing negative impact (as patients reported AEs and discontinued) was also observed with COMTOL global question scores on the impact of side-effects on health-related quality of life, the impact of activity limitations on quality of life, satisfaction with medication and compliance with medication. Therefore, spontaneous reporting of side-effects appears to be detecting the most clinically meaningful side-effects.
authors.affiliation: Department of Health Economic Statistics, Merck Research Laboratories, West Point, PA, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Barber
authors.forename: N C
authors.initials: NC
authors.lastname: Santanello
mesh_terms: D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects; D018592:Cross-Over Studies; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects; D011795:Surveys and Questionnaires; D013876:Thiophenes / Q000009:adverse effects; D013999:Timolol / Q000009:adverse effects
chemical_list: D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D013999:Timolol; C062765:dorzolamide