HIV/STI Reference Laboratory, Institute of Tropical Medicine, Antwerp, Belgium.
PLoS One. 2010 Oct 27;5(10):e13592. doi: 10.1371/journal.pone.0013592.
Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS) [1].
In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL), responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL.
Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented.
Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data. It is essential that sponsors provide adequate resources for implementation of such comprehensive technical assessment and monitoring systems.
ClinicalTrials.gov NCT00153777 and Current Controlled Trials ISRCTN95638385.
在过去的十年中，已经在发展中国家进行了几项三期微物杀菌剂试验。然而，资源有限的环境中的实验室并不总是具有提供符合临床试验高标准的实验室数据的经验、基础设施和能力。本文描述了在评估候选微物杀菌剂纤维素硫酸盐 6%（CS）[1]预防 HIV 和性传播感染（STI）效果的三期临床试验期间实施的实验室质量保证计划的设计和结果。
为了评估 CS 预防 HIV 和 STI 的效果，在 5 个地点进行了三期临床试验：非洲 3 个，印度 2 个。试验赞助商确定了一个国际中央参考实验室（ICRL），负责设计和管理质量保证计划，以保证实验室数据的可靠性。ICRL 提供有关测试的建议，评估当地实验室，组织培训，进行监督访问，进行重新测试，并准备控制板。当地实验室获得了 HIV 快速检测和沙眼衣原体/淋病奈瑟菌（CT/NG）扩增技术的控制板。各自的控制板样本由当地实验室进行检测，并与 ICRL 获得的结果进行比较。
总体而言，结果良好。然而，在 HIV 和 CT/NG 结果方面，ICRL 和现场实验室之间存在差异。一个特定的地点在研究开始后不久就遇到了 HIV 快速检测的困难。在所有地点，都发现 DNA 污染是 CT/NG 结果无效的原因。两个问题都及时发现并得到解决。通过对实验室工作人员的即时反馈、指导和重复培训，防止了更多的不准确。
应用于现场实验室的质量控制指南确保了最终研究数据的可靠性和有效性。赞助商必须为实施这种全面技术评估和监测系统提供足够的资源。
ClinicalTrials.gov NCT00153777 和当前控制试验 ISRCTN95638385。
