Stevens Wendy, Kamali Anatoli, Karita Etienne, Anzala Omu, Sanders Eduard J, Jaoko Walter, Kaleebu Pontiano, Mulenga Joseph, Dally Len, Fast Pat, Gilmour Jill, Farah Bashir, Birungi Josephine, Hughes Peter, Manigart Olivier, Stevens Gwynn, Yates Sarah, Thomson Helen, von Lieven Andrea, Krebs Marietta, Price Matt A, Stoll-Johnson Lisa, Ketter Nzeera
University of Witwatersrand and Contract Laboratory Services, Johannesburg, South Africa.
PLoS One. 2008 Apr 30;3(4):e2043. doi: 10.1371/journal.pone.0002043.
An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study.
Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP).
Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.
了解非洲潜在志愿者的健康状况对于安全、高效地开展临床试验至关重要，尤其是对于招募健康个体的预防性技术（如疫苗）试验而言。用于非洲临床试验志愿者筛查、入组和随访的临床安全实验室值，很大程度上基于欧洲和北美的工业化国家得出的值。本报告描述了一项多中心非洲实验室参考区间研究招募期间的基线发病率。
邀请年龄在18至60岁之间的无症状者参与在七个地点（卢旺达基加利；乌干达马萨卡和恩德培；肯尼亚康格米、肯雅塔国家医院和基利菲；赞比亚卢萨卡）开展的横断面研究。设计上保证了性别均等。急性病患者、孕妇、经期女性或有显著临床发现的个体未被纳入。每位志愿者提供血液用于血液学、免疫学和生物化学参数检测，提供尿液用于尿液分析。若发现登记的志愿者感染艾滋病毒、梅毒或乙肝和丙肝呈阳性，则将其排除。实验室检测按照良好临床实验室规范（GCLP）进行。
在筛查的2990名志愿者中，2387名（80%）被纳入，2107名（71%）被纳入分析（男性占52%，女性占48%）。筛查出志愿者的主要原因包括体格检查异常（228/603，38%）、重大病史（76例，13%）以及无法完成知情同意程序（73例，13%）。一旦入组，被排除在分析之外的主要原因包括检测出乙肝表面抗原（106/280，38%）和丙肝抗体（95例，34%）。这是首次按照GCLP标准开展的大规模多地点研究，旨在描述适用于临床试验潜在志愿者的非洲实验室参考区间。所有筛查的潜在志愿者中约三分之一不符合分析条件；大多数因医学原因被排除。
