Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya Aids Vaccine Initiative (KAVI), Kenya

Abstract

BackgroundWith the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001.MethodologyParticipants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West.Principal findingsTwo hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment.ConclusionsParticipant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants.Trial registrationProtocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted.

Clinical laboratory reference values amongst children aged 4 weeks to 17 months in Kilifi, Kenya: A cross sectional observational study

“…‘Normal’ may not be ‘optimal’, thus the target population who may ultimately receive an intervention that is being tested may have characteristics that fall outside international reference values when in their usual state of health [15, 16]. Moreover, available reference data may not adequately cover the youngest age groups, be gender-specific, or may have been determined using older instruments or when characteristics of the population and interventions such as bed net distribution or micronutrient supplementation may have been different [17–20].…”

Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site MHgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa

“…Anemia is common in sub-Saharan Africa [ 1 ], and a frequent reason for exclusion from clinical studies [ 2 ]. During screening procedures for enrollment in clinical studies, hemoglobin levels are usually assessed using portable point-of-care hemoglobin meters with blood obtained by finger prick.…”

Evaluation of Locally Established Reference Intervals for Hematology and Biochemistry Parameters in Western Kenya

“…Despite these recorded differences, the Division of AIDS (DAIDS) National Institute of Health toxicity tables [ 17 ], are still used for grading the severity of adult and pediatric adverse events, whether or not they are considered to be related to the study intervention. This leads to unnecessary exclusion of would be participants misclassified as having abnormal hematologic parameters thereby escalating operational costs especially in phase I safety trials where there may not be a control group [ 18 – 20 ]. This may also lead to improper patient management through misclassification of adverse events.…”