The Biomarkers Study, short for “Characterisation of Novel Microbicide Safety Biomarkers in East and South Africa”, was initiated with the overall aim of establishing baseline ranges of biomarkers related to the vaginal environment in African target populations for microbicide trials. Funded by European and Developing Countries Clinical Trials Partnership (EDCTP), this was a multi-centre trial with sites in Kenya (ICRH), Tanzania (MITU/NIMR), Rwanda (Projet Ubuzima) and South Africa (RHRU). The study was initi- ated at Mombasa, the Kenyan site and the subject of this report, in November 2010 with the mandate to enroll 170 HIV-negative female participants i.e.: 30 adolescents, 30 pregnant and 110 non-pregnant adults.
Upon enrollment [visit 1 (v1)], participants were required to attend to six other follow-up visits within eight months: first four visits each a fortnight apart, and every three months for the last two visits. With the last participant having been recruited in August 2011, study completion was anticipated for April 2012.
In the year 2012, a total of 60 participants were seen – seven for v6 and v7, and 53 for v7. The last participant was seen on 20 April 2012 bringing the overall number of participants who attended to all follow-up visits to 142 (83.5%), with 28 participants having discontinued due to relocation from catchment area (26/28) or declining speculum examination (2/28). Of the 28 discontinued participants 10 were in the adolescents group, two pregnant and 16 non-pregnant adults. Overall, a total of 151 participants (22/30 adolescents, 28/30 pregnant and 101/110 non-pregnant adults) attended to v7 follow-up; 19 participants missed some visits but attended to the last visit.
During the follow up visits, STI and HIV tests were performed for all participants while antenatal care was provided to pregnant participants. No HIV sero-conversions were noted in all groups. All 11 deliveries during the year were safe with live births out- comes.
Subject to the follow up visit, laboratory tests were performed for: a range of STIs, HIV, helminthes, urinalysis and pregnancy.
Additionally, the ICRH clinical research laboratory undertook to processing and storage of samples in preparation for immunolog- ical biomarker tests that would be performed at Antwerp Institute of Tropical Medicine (ITM). In total 129 samples were handled in 2012, with the last sample being cleared in May 2012. The labora- tory then coordinated three sample shipments in 2012 to ITM for further testing as pre-planned.
Two pass verification (double entry) was employed to ensure quality of data entered for Biomarker study. The last data entry was done in August 2012. Data cleaning was done on an ongoing basis upon completing of a visit’s entry. Query resolution was done both internally (with the laboratory and clinic) and externally in which the study statistician addresses queries to the site for clarifications. The clean data set was commu- nicated in December 2012 to the central data manager in Antwerp pending database locking.
Regulatory & Quality
The study was conducted in keeping with good clinical practice (GCP) standards complying with regulatory authorities [ethics review commission (ERC), national council for science & technology (NCST) & ministry of health (MoH)] require- ments. All severe adverse events (SAEs) occurring during the study period were reported and acknowl- edged by ERC in Feb 2012. For the year 2012, two SAEs (1 gastro- enteritis in pregnancy & 1 emergen- cy caesarian section) were reported bringing to 11 the total SAEs noted in study. It is noteworthy that none of the SAEs was perceptibly related to the study procedures.
Permit renewal for the study was sought and granted in September 2012 for the study to last till 15th August 2013, a year’s extension. Approval for shipment of samples to Antwerp for testing was also sought and obtained in May 2012.
Internal quality monitoring showed good compliance with GCP standards with a minimal error rate of 2 – 5% noted. ICRHK’s internal monitor was also charged with the external auditing of the South Africa and Rwanda sites. One audit was conducted in February 2012, for Wits Reproductive and HIV Institute (WrHI), the South Africa site.
EDCTP (European and Developing Countries Clinical Trials Partnership)
Dr. Kishor Mandaliya (ICRH, Kenya)
WRHI, South Africa; Projet Ubuzima, Rwanda; MITU/NIMR, Tanzania; Ghent University and Institute for Tropical Medicine, Belgium; AIGHD/AMC, The Netherlands; London School and Medical Research Council, UK