Barber B L, Santanello N C
Department of Health Economic Statistics, Merck Research Laboratories, West Point, PA, USA.
Int J Clin Pharmacol Ther. 1995 Nov;33(11):598-604.
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.
在本研究中，我们调查了自发报告的不良经历与在眼科药物耐受性比较（COMTOL）清单问卷上给出的回答之间的关系。该问卷询问了已知与用于治疗高眼压或开角型青光眼的局部眼科药物相关的特定副作用的频率和困扰程度，以及这些副作用对健康相关生活质量的影响。该研究是一项为期4周的随机、开放标签、两期交叉临床试验，在92名同时接受噻吗洛尔治疗高眼压或开角型青光眼的患者中比较了多佐胺和毛果芸香碱。患者在基线时以及每个阶段结束时完成COMTOL问卷，研究期间研究者收集自发报告的不良经历（AE）。由于患者接受多佐胺治疗时仅自发报告了3例与药物治疗相关的AE，且COMTOL评分显示副作用水平较低，因此分析仅限于毛果芸香碱治疗阶段。我们发现，在毛果芸香碱治疗阶段，47名未自发报告任何不良经历的患者中，有很大比例（94%）在COMTOL上表示他们经历过副作用。自发报告方法与清单问卷之间的这些差异与先前文献中报道的其他药物的差异相似。与先前文献不同的是，我们不仅识别了两种报告方法之间的差异，还寻找了差异存在的可能原因。我们发现，自发报告AE的患者在问卷上表示这些特定副作用带来的困扰比未自发报告AE的患者更多。此外，因AE而自发报告并停药的患者在COMTOL上表示副作用带来的困扰最大。随着患者报告AE并停药，这种负面影响增加的趋势在COMTOL关于副作用对健康相关生活质量的影响、活动受限对生活质量的影响、对药物的满意度以及药物依从性的总体问题评分中也有观察到。因此，副作用的自发报告似乎检测到了最具临床意义的副作用。
