Cameron Daniel J
Division of Medicine, First Medical Associates, 175 Main Street, Mt Kisco, NY 10549, USA.
Epidemiol Perspect Innov. 2006 Oct 17;3:12. doi: 10.1186/1742-5573-3-12.
To examine the generalizability of two National Institutes of Health (NIH)-funded double-blind randomized placebo-controlled clinical trials in patients with chronic Lyme disease and to determine whether selection factors resulted in the unfavorable outcomes.
Epidemiologic review of the generalizability of two trials conducted by Klempner et al. This paper considers whether the study group was representative of the general chronic Lyme disease population.
In their article in The New England Journal of Medicine, Klempner et al. failed to discuss the limitations of their clinical trials. This epidemiologic review argues that their results are not generalizable to the overall Lyme disease population. The treatment failure reported by the authors may be the result of enrolling patients who remained ill after an average of 4.7 years and an average of 3 previous courses of treatment. The poor outcome cited in these trials may be explained by having selected patients who had undergone delayed treatment or multiple treatments unsuccessfully. These selection factors were not addressed by the studies' authors, nor have they been discussed by reviewers. The trials have been over-interpreted by the NIH and widely publicized in a press release. The results have been extrapolated to other groups of Lyme disease patients by commentators, by a case discussant in an influential medical journal, and by health insurance companies to deny antibiotic treatment.
The Klempner et al. trials are assumed to be internally valid based on a Randomized Control Trial (RCT) design. However, this review argues that the trials have limited generalizability beyond the select group of patients with characteristics like those in the trial. Applying the findings to target populations with characteristics that differ from those included in these trials is inappropriate and may limit options for chronic Lyme disease patients who might benefit from antibiotic treatment.
检验两项由美国国立卫生研究院（NIH）资助的针对慢性莱姆病患者的双盲随机安慰剂对照临床试验的可推广性，并确定选择因素是否导致了不良结果。
对Klempner等人进行的两项试验的可推广性进行流行病学回顾。本文考虑研究组是否代表了一般慢性莱姆病患者群体。
在发表于《新英格兰医学杂志》的文章中，Klempner等人未讨论其临床试验的局限性。这项流行病学回顾认为，他们的结果无法推广至整个莱姆病患者群体。作者报告的治疗失败可能是由于纳入了平均患病4.7年且此前平均接受过3个疗程治疗后仍未康复的患者。这些试验中所引用的不良结果可能是由于选择了接受过延迟治疗或多次治疗均未成功的患者。这些选择因素未得到研究作者的讨论，评论者也未进行探讨。NIH对这些试验过度解读，并在一份新闻稿中广泛宣传。评论者、一份有影响力的医学杂志中的病例讨论者以及健康保险公司已将结果外推至其他莱姆病患者群体，以拒绝给予抗生素治疗。
基于随机对照试验（RCT）设计，Klempner等人的试验被认为在内部是有效的。然而，本回顾认为，这些试验的可推广性仅限于具有与试验中患者类似特征的特定患者群体之外。将研究结果应用于具有与这些试验中患者不同特征的目标人群是不合适的，这可能会限制那些可能从抗生素治疗中获益的慢性莱姆病患者的选择。
