Pharmacometrics, the mathematical approaches to describe the transfer of drug through different biological compartments, are essential tools in clinical pharmacology research. The ethical necessity to study drugs accurately in the populations where they are to be used is increasingly recognized. To maximise the value of clinical data, study design and analysis must be appropriate. Historically, many datasets have been sent from African countries to better-resourced settings for analysis, but in recent years it has been demonstrated that capacity can be built and sustained within low and middle-income countries (LMIC)3. We report the establishment of the Uganda Chapter of Pharmacometrics Africa, to share learning with other countries seeking to build similar capabilities.

Pharmacometrics Africa is a not-for-profit company registered in South Africa as an established platform for interested groups to establish and run open-access quantitative clinical pharmacology educational programs in partnership with local research organizations and academic groups. Pharmacometric research and clinical application is pivotal in characterising and optimising treatments, especially for complex or understudied populations. The application of pharmacometrics in drug development during recent years has led to an increase in the adoption of this technique in many drug companies and increased the demand for skilled pharmacometricians globally. Stringent regulatory authorities such as the US-FDA and EMA have increasingly populated their review groups with these scientists, further increasing the demand for the expertise and, more importantly, evidencing the impact and importance of pharmacometrics within the drug development cycle. Creative solutions are required to provide adequate training resources for the future. Pharmacometrics is nascent in Africa. Here, we report on establishing the Ugandan Chapter of Pharmacometrics Africa. This aims to transfer primary training responsibility to local institutions and faculty for sustainability and to build upon regional strengths in pharmacometrics. Creating a local centre of excellence will help attract both regional and international collaborations on quantitative clinical pharmacology. We summarize our experience, key lessons learnt and future perspectives.

Warfarin has existed for more than seven decades and has been the anticoagulant of choice for many thromboembolic disorders. The recent introduction of direct acting oral anticoagulants (DOACs) has however caused a shift in preference by healthcare professionals all over the world. DOACs have been found to be at least as effective as warfarin in prevention of stroke in patients with atrial fibrillation and in treatment of venous thromboembolism. In sub-Saharan Africa, however, the widespread use of DOACs has been hampered mainly by their higher acquisition costs. As the drugs come off patent, their use in sub-Saharan Africa is likely to increase. However, very few trials have been conducted in African settings, and safety concerns will need to be addressed with further study before widespread adoption into clinical practice.

Patients in sub-Saharan Africa generally have poor anticoagulation control. We review the potential reasons for this poor control, as well as the potential solutions. Challenges include the affordability and centralisation of anticoagulation care, problems with access to medicines and INR monitoring, the lack of locally-validated standardized dosing protocols, and low levels of anticoagulation knowledge among health care workers and patients. Increasing numbers of patients will need anticoagulation in the future because of the epidemiological transition in the region. We propose that locally-developed “warfarin care bundles” which address multiple anticoagulation challenges in combination may be the most appropriate solution in this setting currently.

Aim Patients on anti-tuberculosis (anti-TB) therapy are at risk of drug-induced liver injury (DILI). MicroRNA-122 (miR-122) and cytokeratin-18 (K18) are exploratory DILI biomarkers. To explore their utility in this global context, circulating miR-122 and K18 concentrations were measured in UK and Ugandan populations on anti-TB therapy for mycobacterial infection. Methods European patients receiving anti-TB therapy were recruited at the Royal Infirmary of Edinburgh, UK (ALISTER-ClinicalTrials.gov Identifier: NCT03211208). African patients with HIV-TB coinfection, receiving anti-TB and anti-retroviral therapy (ART), were recruited at the Infectious Diseases Institute, Kampala, Uganda (SAEFRIF-NCT03982277). Serial blood samples, demographic and clinical data were collected. MiR-122 was quantified using PCR. K18 was quantified using the M65 ELISA. Results The study had 235 participants (healthy volunteers (n=28); ALISTER: active TB (n=30), latent TB (n=88), non-tuberculous mycobacterial infection (n=25); SAEFRIF: HIV-TB coinfection (n=64)). In the absence of DILI, there was no difference in miR-122 and K18 across the groups. Both miR-122 and K18 correlated with alanine transaminase activity (ALT) (miR-122: r=0.52, 95%CI=0.42-0.61, P<0.0001. K18: r=0.42, 95%CI=0.34-0.49, P<0.0001). There were two DILI cases: baseline ALT was 18 and 28 IU/L, peak ALT 431 and 194 IU/L; baseline K18 58 and 219 U/L, peak K18 1247 and 3490 U/L; baseline miR-122 4 and 17 fM, peak miR-122 60 and 336 fM, respectively. Conclusion In European and African patients treated with anti-TB therapy miR-122 and K18 correlated with ALT and increased with DILI. Further work should determine the diagnostic and prognostic utility of miR-122 and K18 in this global context-of-use.