Division of Rheumatology, UMDNJ Scleroderma Program, New Brunswick, NJ 08903, USA.
Clin Trials. 2010 Feb;7(1):85-9. doi: 10.1177/1740774509355838. Epub 2009 Dec 23.
Scleroderma Lung Study (SLS) was designed to evaluate the efficacy and safety of oral cyclophosphamide (CYC) versus placebo taken for 1 year for scleroderma-associated interstitial lung disease. An independent medication control officer (MCO), usually a physician, at each center was assigned to monitor laboratory and clinical toxicity of study medication and regulate its dosing based on these results. By having an MCO who watched and managed toxicity, the study investigators were free to care for study patients and to assess study outcomes without the potential bias of knowing toxicity data (toxicity from cyclophosphamide is distinctive - cytopenias and hematuria in particular).
To assess the usefulness of an MCO, whose chief role was to maintain safety while retaining the blinding in the clinical trial.
Patients had safety laboratory testing every 2-4 weeks and results were sent directly to the MCO within 2 days of the test. Other clinical adverse events (AEs) were reported by the patient to a nurse coordinator who reported them to the MCO who then managed the AEs to preserve the blinding of investigators caring for the patients. The MCO was provided pre-determined algorithms for dose adjustments of test medication based on the presence and severity of laboratory abnormalities.
Safety monitoring by the MCO was effective in the early detection of drug toxicity with provision of appropriate medical intervention on a timely basis. At the same time, investigator blinding appeared to be maintained.
The testing of MCO effectiveness in maintaining blinding and consistency was not defined as an a priori hypothesis and thus complete data relating to the efficacy of the MCO were not collected in a prospective fashion.
An MCO and pre-specified monitoring and dosing guidelines, coupled with uniform pre-specified responses to AEs, may be used effectively to preserve investigator blinding and provide consistency in response to AEs in a clinical trial setting, even when AEs of the test medication are distinctive.
硬皮病肺研究（SLS）旨在评估口服环磷酰胺（CYC）与安慰剂治疗硬皮病相关间质性肺病 1 年的疗效和安全性。每个中心都指定了一名独立的药物控制官（MCO），通常是一名医生，负责监测研究药物的实验室和临床毒性，并根据这些结果调整其剂量。通过让 MCO 观察和管理毒性，研究人员可以自由照顾研究患者并评估研究结果，而不会因了解毒性数据而产生潜在偏见（环磷酰胺的毒性是独特的 - 特别是血细胞减少症和血尿）。
评估 MCO 的有用性，其主要作用是在临床试验中保持安全性的同时保持盲法。
患者每 2-4 周进行一次安全性实验室检查，结果在检查后 2 天内直接发送给 MCO。其他临床不良事件（AE）由患者报告给护士协调员，协调员报告给 MCO，然后由 MCO 管理 AE，以保持照顾患者的研究人员的盲法。MCO 根据实验室异常的存在和严重程度，提供了预先确定的测试药物剂量调整算法。
MCO 的安全性监测有效地早期发现药物毒性，并及时提供适当的医疗干预。与此同时，研究人员的盲法似乎得到了维持。
未将 MCO 维持盲法和一致性的有效性测试定义为预先假设，因此未以前瞻性方式收集与 MCO 疗效相关的完整数据。
MCO 和预先指定的监测和剂量指南，加上对 AE 的统一预先指定的反应，可有效地用于在临床试验环境中维持研究人员的盲法，并对 AE 做出一致的反应，即使测试药物的 AE 是独特的。
