Patients Enrolled in Randomized Controlled Trials Do Not Represent the Inflammatory Bowel Disease Patient Population
Patients Enrolled in Randomized Controlled Trials Do Not Represent the Inflammatory Bowel Disease Patient Population
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DOI：
10.1016/j.cgh.2012.02.004
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发表时间：
2012-09-01
影响因子：
12.6
通讯作者：
Kornbluth, Asher
中科院分区：
文献类型：
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作者：
Ha, Christina;Ullman, Thomas A.;Kornbluth, Asher
背景与目的：已进行多项随机对照试验（RCT）以确定生物制剂对炎症性肠病（IBD）的治疗效果。然而，随机对照试验结果的外部效度可能会受到严格的选择标准的影响。我们调查了在常规临床实践中遇到的有资格入组IBD生物制剂关键RCT的患者比例。方法：我们对三级转诊中心的中重度IBD成人患者进行了回顾性队列研究。从美国食品药品监督管理局批准的已发表的生物制剂RCT中提取入选和排除标准，并应用于研究人群。研究结果：206例IBD患者中只有31.1%（34%为克罗恩病[CD]，26%为溃疡性结肠炎）有资格参加任何选定的RCT。患者将被排除，因为他们患有狭窄或穿透性CD，服用高剂量类固醇，患有合并症或既往暴露于生物制剂，或接受局部治疗。在不符合试验条件的溃疡性结肠炎患者中，23.3%接受结肠切除术，31.7%接受英夫利西单抗治疗，有效率为63.2%。在82例不符合试验条件的CD患者中，约有一半（49.4%）接受了生物治疗，缓解率（60%）低于符合试验条件的患者（89%; P = 0.03）。结论：在门诊实践中评价的大多数中重度IBD患者没有资格入组生物试剂的关键RCT;这一发现提出了关于其临床试验人群以外的治疗疗效的重要问题。需要对随机对照试验设计和选择标准的透明度进行额外评价，以确定试验结果是否可以推广到人群。
BACKGROUND & AIMS: Multiple randomized controlled trials (RCTs) have been conducted to determine therapeutic efficacy of the biological agents for the inflammatory bowel diseases (IBD). However, the external validity of findings from RCTs might be compromised by their stringent selection criteria. We investigated the proportion of patients encountered during routine clinical practice who would qualify for enrollment into a pivotal RCT of biological agents for IBD. METHODS: We performed a retrospective cohort study of adult patients with moderate-severe IBD who presented to a tertiary referral center. Inclusion and exclusion criteria were extracted from published RCTs of biologics approved by the Food and Drug Administration and applied to the study population. RESULTS: Only 31.1% of 206 patients with IBD (34% with Crohn's disease [CD], 26% with ulcerative colitis) would have been eligible to participate in any of the selected RCTs. Patients would have been excluded because they had stricturing or penetrating CD, took high doses of steroids, had comorbidities or prior exposure to biologics, or received topical therapies. Of the trial-ineligible patients with ulcerative colitis, 23.3% had colectomies, and 31.7% received infliximab, with a 63.2% response rate. Approximately half (49.4%) of the 82 trial-ineligible patients with CD received biological therapies, with lower response rates (60%) than trial-eligible patients (89%; P = .03). CONCLUSIONS: Most patients with moderate-severe IBD evaluated in an outpatient practice would not qualify for enrollment in a pivotal RCT of biological reagents; this finding raises important questions about their therapeutic efficacy beyond the clinical trial populations. Additional evaluation of the transparency of RCT design and selection criteria is needed to determine whether trial results can be generalized to the population.