Evolution of the Randomized Controlled Trial in Oncology Over Three Decades
Evolution of the Randomized Controlled Trial in Oncology Over Three Decades
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DOI：
10.1200/jco.2008.16.5456
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发表时间：
2008-11-20
影响因子：
45.3
通讯作者：
Krzyzanowska, Monika K.
中科院分区：
文献类型：
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作者：
Booth, Christopher M.;Cescon, David W.;Krzyzanowska, Monika K.
目的随机对照试验（RCT）是建立临床肿瘤新疗法的金标准。在这里，我们记录了肿瘤随机对照试验的设计、赞助和结果随时间的变化。方法回顾1975 ~ 2004年发表在6种主要期刊上的评价乳腺癌、结直肠癌（CRC）和非小细胞肺癌（NSCLC）全身治疗的随机对照试验报告。两位作者摘录了有关试验设计、结果和结论的数据。作者的结论采用7分李克特量表进行评分。对于每项研究，主要终点的效应量被转换为汇总测量值。结果共纳入321项符合条件的随机对照试验（乳腺48%，结直肠癌24%，非小细胞肺癌28%）。随着时间的推移，随机对照试验的数量和规模显著增加。在研究期间，营利性/混合性赞助大幅增加（4%至57%；P < .001）。越来越多地使用事件发生时间测量（从39%到78%），越来越少地使用反应率（从54%到14%）作为主要终点（P < 0.001）。在研究期间，效应量保持稳定。作者更有可能强烈支持实验组（P = 0.017）。主要终点和行业赞助的显著P值分别与实验药物的认可独立相关（比值比[OR] = 19.6, 95% CI， 8.9至43.1,OR = 3.5, 95% CI， 1.6至7.5）。结论肿瘤领域的随机对照试验规模越来越大，且越来越有可能得到行业的赞助。现代随机对照试验的作者更有可能强烈支持新疗法。以营利为目的的赞助和统计上显著的结果与实验臂的认可独立相关。
PurposeThe randomized controlled trial (RCT) is the gold standard for establishing new therapies in clinical oncology. Here we document changes with time in design, sponsorship, and outcomes of oncology RCTs.MethodsReports of RCTs evaluating systemic therapy for breast, colorectal (CRC), and non-small-cell lung cancer (NSCLC) published 1975 to 2004 in six major journals were reviewed. Two authors abstracted data regarding trial design, results, and conclusions. Conclusions of authors were graded using a 7-point Likert scale. For each study the effect size for the primary end point was converted to a summary measure.ResultsA total of 321 eligible RCTs were included (48% breast, 24% CRC, 28% NSCLC). Over time, the number and size of RCTs increased considerably. For-profit/mixed sponsorship increased substantially during the study period (4% to 57%; P < .001). There was increasing use of time-to-event measures (39% to 78%) and decreasing use of response rate (54% to 14%) as primary end point (P < .001). Effect size remained stable over the study period. Authors have become more likely to strongly endorse the experimental arm (P = .017). A significant P value for the primary end point and industry sponsorship were each independently associated with endorsement of the experimental agent (odds ratio [OR] = 19.6, 95% CI, 8.9 to 43.1, and OR = 3.5, 95% CI, 1.6 to 7.5, respectively).ConclusionRCTs in oncology have become larger and are more likely to be sponsored by industry. Authors of modern RCTs are more likely to strongly endorse novel therapies. For-profit sponsorship and statistically significant results are independently associated with endorsement of the experimental arm.