Horwitz R I, Viscoli C M, Clemens J D, Sadock R T
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Am J Med. 1990 Nov;89(5):630-8. doi: 10.1016/0002-9343(90)90182-d.
Therapeutic efficacy is often studied with observational surveys of patients whose treatments were selected nonexperimentally. The results of these surveys are distrusted because of the fear that biased results occur in the absence of experimental principles, particularly randomization. The purpose of the current study was to develop and validate improved observational study designs by incorporating many of the design principles and patient assembly procedures of the randomized trial. The specific topic investigated was the prophylactic effectiveness of beta-blocker therapy after an acute myocardial infarction. To accomplish the research objective, three sets of data were compared. First, we developed a restricted cohort based on the eligibility criteria of the randomized clinical trial; second, we assembled an expanded cohort using the same design principles except for not restricting patient eligibility; and third, we used the data from the Beta Blocker Heart Attack Trial (BHAT), whose results served as the gold standard for comparison. In this research, the treatment difference in death rates for the restricted cohort and the BHAT trial was nearly identical. In contrast, the expanded cohort had a larger treatment difference than was observed in the BHAT trial. We also noted the important and largely neglected role that eligibility criteria may play in ensuring the validity of treatment comparisons and study outcomes. The new methodologic strategies we developed may improve the quality of observational studies and may be useful in assessing the efficacy of the many medical/surgical therapies that cannot be tested with randomized clinical trials.
治疗效果通常通过对非实验性选择治疗方法的患者进行观察性调查来研究。由于担心在缺乏实验原则，尤其是随机化的情况下会出现有偏差的结果，这些调查结果受到怀疑。本研究的目的是通过纳入随机试验的许多设计原则和患者招募程序，开发并验证改进的观察性研究设计。所研究的具体主题是急性心肌梗死后β受体阻滞剂治疗的预防效果。为了实现研究目标，对三组数据进行了比较。首先，我们根据随机临床试验的纳入标准建立了一个受限队列；其次，我们采用相同的设计原则，但不限制患者纳入标准，组建了一个扩展队列；第三，我们使用了β受体阻滞剂心肌梗死试验（BHAT）的数据，其结果作为比较的金标准。在这项研究中，受限队列和BHAT试验的死亡率治疗差异几乎相同。相比之下，扩展队列的治疗差异比BHAT试验中观察到的更大。我们还注意到纳入标准在确保治疗比较和研究结果有效性方面可能发挥的重要且在很大程度上被忽视的作用。我们开发的新方法策略可能会提高观察性研究的质量，并可能有助于评估许多无法通过随机临床试验进行测试的内科/外科治疗的疗效。
