The average Adjusted Symptom Score, a new primary efficacy end-point for specific allergen immunotherapy trials
The average Adjusted Symptom Score, a new primary efficacy end-point for specific allergen immunotherapy trials
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DOI：
10.1111/j.1365-2222.2011.03700.x
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发表时间：
2011-09-01
影响因子：
6.1
通讯作者：
Devillier, P.
中科院分区：
文献类型：
--
作者：
Grouin, J-M.;Vicaut, E.;Devillier, P.
背景 在临床试验中，免疫治疗对过敏性鼻结膜炎症状的疗效通常用平均鼻结膜炎总症状评分（ARTSS）来评估。与安慰剂相比，有效治疗与较低的 ARTSS 相关，但使用救援药物缓解症状会降低 RTSS，并降低积极治疗组和安慰剂组之间的平均差异。目的 开发和描述平均调整症状评分 (AdSS)，这是反映过敏性鼻结膜炎试验中症状严重程度和救援药物使用情况的新终点。方法 为了计算 AdSS，RTSS 调整如下：如果患者在第 d 天服用救援药物，则该天的 AdSS (AdSS(d)) 定义为 RTSS(d) 或 AdSS(d-1) 的值，以较高者为准。第二天的 AdSS (AdSS(d+1)) 定义为 RTSS(d+1) 或 AdSS(d) 的值，以较高者为准。每日 AdSS 的平均值（季节期间）是根据两项研究五草花粉舌下免疫治疗片对成人和儿童患者的疗效进行事后计算的，并与 ARTSS 和其他三个结果指标（平均救援药物评分 (ARMS)、ARTSS 和平均综合评分）进行比较。 结果 平均 AdSS 清楚地区分了活性治疗和安慰剂治疗，并证实了原始 ARTSS 结果。调整救援药物的使用降低了观察到的安慰剂效应。 结论和临床相关性 在草花粉过敏性鼻结膜炎试验中，平均 AdSS 可以作为 ARTSS 的主要疗效终点，作为一个有价值的替代方案。通过调整救援药物使用的 RTSS，AdSS 可以更准确地估计症状严重程度和治疗效果。 AdSS 目前正在大型临床试验中进行前瞻性测试。
Background In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups.Objective To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials.Methods To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSS(d)) is defined as the value of RTSS(d) or AdSS(d-1), whichever is higher. The AdSS on the following day (AdSS(d+1)) is defined as the value of RTSS(d+1) or AdSS(d), whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score).Results The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect.Conclusion and Clinical Relevance The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials.