When Clinical Trials Disagree.
When Clinical Trials Disagree.
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当临床试验不一致时。
DOI：
10.1016/j.juro.2018.02.3084
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Gulati,Roman
中科院分区：
文献类型：
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作者：
Etzioni,Ruth;Gulati,Roman
在临床和公共卫生研究中，随机试验对于了解什么有效是必不可少的。试验可以避免观察性研究的许多已知偏差，并提供一个看似简单的推理方法，即如果各组之间的结果存在显著差异，则干预有效。然而，试验具有众所周知的局限性。结果可能无法推广到其他人群或其他时间范围。同样，令人困惑的是，类似干预措施的试验可能会产生相互矛盾的结果。不幸的是，在这些情况下，没有普遍接受的方法来理解证据。几项前列腺癌干预试验发表了相互矛盾的结果。在治疗局部疾病的情况下，SPCG-4（斯堪的纳维亚前列腺癌组研究编号4）显示，与观察等待相比，前列腺切除术显著降低了前列腺癌死亡率1，但美国的PIVOT（前列腺癌干预与观察试验）并未发现死亡率显著降低。2然而，SPCG-4是在最低限度筛查的男性中进行的，而PIVOT中的大多数癌症是通过筛查检测出来的。ProtecT（前列腺癌症检测和治疗）试验最近显示，在筛查发现癌症的男性中，前列腺切除术或放疗与主动监测相比，没有显着的死亡率优势，尽管数量很少（每组少于10例前列腺癌死亡）。3对于前列腺特异性抗原（PSA）筛查，ERSPC（欧洲前列腺癌筛查随机研究）显示死亡率显著降低20% 4，但美国PLCO（前列腺癌、肺癌、结直肠癌和卵巢癌）筛查试验显示，筛查并未显著降低死亡率。5除了不同的人群外，试验还规定了不同的筛查和随访方案。PLCO每年对男性进行6年筛查，由患者和医生决定是否因PSA ≥ 4.0 ng/mL而转介活检，而ERSPC每2 - 4年对男性进行一次筛查，所有男性的标准为PSA ≥ 3.0 ng/mL。PLCO的活检频率较低，对照组的筛查水平高于ERSPC。在英国进行的CAP（PSA检测前列腺癌的随机分组试验）试验与两项已发表的试验明显不同，只有一项筛查试验，随机实践中的参与率仅为60%，只有大约35%的合格男性接受测试。6
IN clinical and public health research randomized trials are indispensable for learning about what works. Trials can avoid many known biases of observational studies and provide a seemingly simple recipe for inference, ie if outcomes differ significantly between groups, the intervention works. However, trials have well-known limitations. Results may not generalize to other populations or other time horizons. Also, perplexingly, trials of similar interventions may yield conflicting results. Unfortunately, in these situations there is no universally accepted recipe for making sense of the evidence. Several trials of prostate cancer interventions have published contradictory findings. In the case of treatment for localized disease SPCG-4 (Scandinavian Prostate Cancer Group study number 4) revealed that prostatectomy significantly reduced prostate cancer mortality compared to watchful waiting 1 but the US based PIVOT (Prostate Cancer Intervention Versus Observation Trial) did not find a significant mortality reduction. 2 However, SPCG-4 was conducted in men with minimal screening while the majority of cancers in PIVOT were detected by screening. The ProtecT (Prostate testing for cancer and Treatment) trial recently showed no significant mortality benefit of prostatectomy or radiotherapy over active monitoring in men with screen detected cancers, although numbers were small (less than 10 prostate cancer deaths in each group). 3 For prostate specific antigen (PSA) screening, the ERSPC (European Randomized Study of Screening for Prostate Cancer) revealed a significant 20% mortality reduction 4 but the US based PLCO (Prostate, Lung, Colorectal, and Ovarian) cancer screening trial indicated no significant mortality reduction due to screening. 5 Beyond different populations the trials specified different screening and followup protocols. The PLCO screened men every year for 6 years and referral to biopsy for PSA 4.0 ng/mL or greater was decided by the patient and physician, whereas the ERSPC screened men every 2 to 4 years and referral to biopsy for PSA 3.0 ng/mL or greater was standard for all men. The PLCO experienced a lower frequency of biopsy and a higher level of screening on the control arm than the ERSPC. TheCAP (Cluster randomised triAl of PSA testing for Prostate cancer) trial, ongoing in the United Kingdom, differs markedly from either published trial with only a single screening test, a participation rate of barely 60% among randomized practices and only approximately 35% of eligible men receiving the test. 6