Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies.
Validity, significance, strengths, limitations, and evidentiary value of real-world clinical data for combination therapy in Alzheimer's disease: comparison of efficacy and effectiveness studies.
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DOI：
10.1159/000335156
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Doody RS
中科院分区：
文献类型：
--
作者：
Atri A;Rountree SD;Lopez OL;Doody RS
随机对照疗效试验 (RCT) 是阿尔茨海默病 (AD) 干预措施的监管批准所必需的科学黄金标准，但提供的有关实际治疗效果的信息有限。目的：比较随机对照试验与长期观察对照研究 (LTOC) 中批准的 AD 治疗组合的证据性质。 RCT 与 LTOC 中单一疗法 [胆碱酯酶抑制剂 (ChEI) 或美金刚] 和联合疗法 (ChEI + 美金刚) 的优势、局限性和证据水平的比较。随机对照试验在数月内对精心挑选的人群进行了检查。 LTOC 多年来收集了大量人群的多个 AD 阶段的数据。 RCT 和 LTOC 显示出相似的模式，倾向于联合治疗而不是单一治疗，而不是安慰剂/不治疗。与单一疗法相比，长期联合疗法减少了认知和功能下降，并延迟了入住疗养院的时间。持续治疗与减慢衰退有关。虽然 LTOC 使用对照组，并针对多个协变量进行调整，具有较高的外部效度以及有利的伦理、实用和成本考虑，但其局限性包括由于缺乏安慰剂比较和随机化而导致的潜在选择偏差。自然 LTOC 提供了补充性长期 II 级证据，以补充短期 RCT 中有关 AD 治疗有效性的 I 级证据，否则这些证据可能无法获得。需要一个协调的策略/联盟来汇集来自多个中心的 LTOC 数据，以估计 AD 治疗的长期比较有效性、风险/收益和成本。
Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. Objective: To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization. Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed.
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影响因子：
9.9
作者：
Rogers, SL;Farlow, MR;Walshe, TM
通讯作者：
Walshe, TM
影响因子：
--
作者：
Raskind, MA;Peskind, ER;Damaraju, CV
通讯作者：
Damaraju, CV
DOI：
10.1186/alzrt7
发表时间：
2009-10-21
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Rountree SD;Chan W;Pavlik VN;Darby EJ;Siddiqui S;Doody RS
通讯作者：
Doody RS
影响因子：
120.7
作者：
Tariot, PN;Farlow, MR;Gergel, I
通讯作者：
Gergel, I
影响因子：
2.8
作者：
Hansen, Richard A.;Gartlehner, Gerald;Kaufer, Daniel I.
通讯作者：
Kaufer, Daniel I.