Daifuku R, Movahhed H, Fotheringham N, Bear M B, Nelson S
Amgen, Thousand Oaks, California, USA.
Respir Med. 1996 Nov;90(10):587-92. doi: 10.1016/s0954-6111(96)90016-5.
Clinical trials of new therapeutics for community-acquired pneumonia (CAP) have typically used a subjective endpoint of clinical response. However, as this endpoint is not quantitative, it is subject to observer bias and renders the conduct of multicenter trials difficult. For the purposes of conducting a clinical trial of filgrastim, as an adjunct to antibiotics for the treatment of CAP, a set of clinical criteria were developed prospectively to determine the time when a clinical cure was achieved, based on respiratory rate, temperature, oxygenation and roentgenographic findings, which was termed the time to resolution of morbidity (TRM). The TRM was evaluated on the first 100 patients entered in this clinical trial. As no clear reference standard exists, the predictive value for the duration of parenteral antibiotics (AB) and the length of hospital stay (LOS) was compared with that provided by a widely used classification system for severity of disease, APACHE II. The TRM was found to correlate significantly better with AB or LOS than APACHE II (P < 0.001). Furthermore, TRM offers the benefit over the endpoints of LOS and AB of being specifically designed to measure the patient's response to therapy, and, in fact, may aid physicians in determining the duration of parenteral antibiotic therapy. Hence, TRM is relevant to the clinician and is a useful tool to ensure uniformity in the assessment of the response to a new therapeutic in a multicenter clinical trial.
社区获得性肺炎（CAP）新疗法的临床试验通常采用临床反应这一主观终点。然而，由于该终点不是定量的，易受观察者偏差影响，且使多中心试验的开展变得困难。为了开展一项关于非格司亭作为抗生素辅助治疗CAP的临床试验，前瞻性地制定了一套临床标准，以根据呼吸频率、体温、氧合和影像学检查结果确定达到临床治愈的时间，这被称为发病缓解时间（TRM）。在该临床试验纳入的首批100例患者中对TRM进行了评估。由于不存在明确的参考标准，将肠外抗生素（AB）使用时长和住院时间（LOS）的预测价值与一种广泛使用的疾病严重程度分类系统APACHE II所提供的预测价值进行了比较。结果发现，TRM与AB或LOS的相关性显著优于APACHE II（P < 0.001）。此外，与LOS和AB终点相比，TRM具有专门设计用于衡量患者对治疗反应的优势，实际上可能有助于医生确定肠外抗生素治疗的时长。因此，TRM对临床医生具有相关性，是确保多中心临床试验中对新疗法反应评估一致性的有用工具。
