Department of Medicine, Department of Veterans Affairs Puget Sound Healthcare System, Seattle, Washington2Department of Medicine, University of Washington, Seattle3Group Health Research Institute, Seattle, Washington.
Veterans Engineering Resource Center, Department of Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennyslvania5Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
JAMA Intern Med. 2014 Mar;174(3):391-7. doi: 10.1001/jamainternmed.2013.13328.
Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention.
To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease.
DESIGN, SETTING, AND PARTICIPANTS: Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease.
Level of estimated glomerular filtration rate (eGFR) and proteinuria.
Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25.
The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses.
Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.
老年人通常被排除在临床试验之外。如果在临床试验中，接受年轻试验人群中测试的预防干预措施的老年人不太可能存活足够长的时间来经历干预措施针对的那些结果，那么在临床环境中应用这些干预措施可能会降低预防效果。
将血管紧张素转换酶抑制剂和血管紧张素 II 受体阻滞剂预防终末期肾病 (ESRD) 的主要随机临床试验报告的治疗效果外推到患有慢性肾脏病的老年患者的真实世界人群中。
设计、地点和参与者：在退伍军人事务部医疗中心进行的回顾性队列研究中的模拟研究。我们纳入了 371470 名 70 岁或以上的慢性肾脏病患者。
估计肾小球滤过率（eGFR）和蛋白尿水平。
在该队列成员中，我们评估了 30%的相对风险降低对每治疗 3 例患者（NNT）以预防 1 例 ESRD 的预期效果。这些限制是为了模拟血管紧张素转换酶抑制剂和血管紧张素 II 受体阻滞剂预防 ESRD 的主要试验中所达到的治疗效果。这些试验报告了在 2.6 至 3.4 年的观察期内相对风险降低 23%至 56%，从而 NNT 预防 1 例 ESRD 为 9 至 25。
该队列成员中预防 1 例 ESRD 的 NNT 范围从基线风险最高（eGFR 为 15-29 mL/min/1.73 m2 ，尿蛋白试纸检测为≥2+）的患者的 16 例到基线风险最低（eGFR 为 45-59 mL/min/1.73 m2 ，尿蛋白试纸检测为阴性或 trace ，eGFR 为≥60 mL/min/1.73 m2 ，尿蛋白试纸检测为 1+）的患者的 2500 例。即使暴露时间延长至 10 年以上，并且在所有敏感性分析中，大多数患者都属于 NNT 超过 100 的组。
试验对象与患有 CKD 的老年患者真实世界人群之间的基线风险和预期寿命的差异可能会降低预防 ESRD 干预措施对个体患者的边际收益。
