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Background: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. Methods: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. Results: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. Conclusions: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic represents an unprecedented challenge for clinical research. The Pneumococcal Vaccine Schedules (PVS) study is a non-inferiority, interventional trial in which infants resident in 68 geographic clusters are randomised to two different schedules for pneumococcal vaccination. From September 2019 onwards, all infants resident in the study area became eligible for trial enrolment at all Expanded Programme on Immunisation (EPI) clinics in the study area. Surveillance for clinical endpoints is conducted at all 11 health facilities in the study area. PVS is conducted as a collaboration between the Medical Research Council Unit The Gambia (MRCG) at LSHTM and the Gambian Ministry of Health (MoH). The COVID-19 pandemic caused many disruptions to PVS. MRCG instructed interventional studies that participant enrolment be suspended on 26 March 2020, and a public health emergency was declared in The Gambia on 28 March 2020. Enrolment in PVS restarted on 1 July 2020 and was suspended again on 5 August 2020 after The Gambia experienced a sharp increase in COVID-19 cases in late July 2020 and restarted again on 1 September 2020. During periods of suspended enrolment of infants at EPI clinics, PVS continued safety surveillance at health facilities, albeit with disruptions. During the periods of suspended enrolment, infants who had been enrolled before 26 March 2020 continued to receive the PCV schedule to which they had been randomly allocated based on their village of residence, whereas all other infants received the standard PCV schedule. Throughout 2020 and 2021, the trial faced numerous technical and operational challenges: disruption to MoH delivery of EPI services and clinical care at health facilities; episodes of staff illness and isolation; disruption of MRCG transport, procurement, communications and human resource management; and also a range of ethical, regulatory, sponsorship, trial monitoring and financial challenges. In April 2021, a formal review concluded that the pandemic had not compromised the scientific validity of PVS and that the trial should continue as per protocol. The continuing challenges that COVID-19 poses to PVS, and other clinical trials will persist for some time. [ABSTRACT FROM AUTHOR]