Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Mayo Clinic School of Medicine, Rochester, MN, USA.
Cancer Invest. 2021 Jul-Aug;39(6-7):449-456. doi: 10.1080/07357907.2021.1942127. Epub 2021 Jul 5.
Large randomized controlled trials (RCTs) remain the gold standard for evaluating treatment efficacy. However, observational studies, including non-randomized cohort studies, as well as small RCTs have gained increasing attention especially during the SARS-CoV-2 pandemic where critical evaluation of limited therapeutic options are sought to improve patient care while awaiting results for subsequent RCTs. As the authors have previously discussed, RCTs and observational studies are complementary approaches which often appear synergistic with one another. While not all real-world studies are the same, the results of observational studies are notoriously subject to both known and unknown confounding factors. The utilization of COVID-19 Convalescent Plasma is a timely illustration of evaluating the efficacy and safety of a COVID-19 therapy given the dangerous and often lethal effects of the virus and the limited approved therapeutic options for the disease. While awaiting the results of large RCTS of convalescent plasma, serval observational cohorts and small RCTs have attempted to assess the efficacy and safety of this approach with very mixed results. Among the likely reasons for this failure to provide a definitive answer concerning the value of convalescent plasma are the many limitations inherent to addressing treatment efficacy in non-randomized studies. While such studies are often able to capture information on large numbers of individuals rapidly, it is important to understand that although larger numbers may enhance the precision of estimates provided, larger numbers, in and of themselves, do not increase the accuracy of estimates due to patient selection and other biases. At the same time, both observational studies and small RCTS are at risk for publication bias due to investigator, reviewer and editorial bias toward positive studies. In this commentary we discuss the advantages and limitations of these methodologic approaches when addressing urgently needed evidence on the effectiveness and safety of therapies in a crisis such as the COVID-19 pandemic.
大型随机对照试验（RCT）仍然是评估治疗效果的金标准。然而，观察性研究，包括非随机队列研究，以及小型 RCT，越来越受到关注，尤其是在 SARS-CoV-2 大流行期间，人们迫切需要评估有限的治疗选择，以改善患者护理，同时等待后续 RCT 的结果。正如作者之前讨论的那样，RCT 和观察性研究是互补的方法，它们经常相互协同。虽然并非所有真实世界的研究都是相同的，但观察性研究的结果众所周知受到已知和未知混杂因素的影响。COVID-19 恢复期血浆的使用是一个及时的例子，说明了评估 COVID-19 治疗方法的疗效和安全性，因为病毒的危险和致命影响以及该疾病有限的批准治疗选择。在等待大型 RCT 结果的同时，几个观察队列和小型 RCT 试图评估这种方法的疗效和安全性，结果非常不一致。导致未能提供关于恢复期血浆价值的明确答案的原因之一可能是在非随机研究中解决治疗效果时存在许多固有局限性。虽然此类研究通常能够快速收集大量个体的信息，但重要的是要理解，尽管更大的数量可能会提高提供的估计值的精度，但由于患者选择和其他偏差，更大的数量本身并不能提高估计值的准确性。同时，观察性研究和小型 RCT 都有发表偏倚的风险，因为研究人员、评论员和编辑对阳性研究存在偏见。在这篇评论中，我们讨论了在 COVID-19 大流行等危机中，当急需评估治疗效果和安全性的证据时，这些方法学方法的优点和局限性。
