Category: Papers

[Commentary] Recruitment of pregnant and breastfeeding women in pharmacokinetic studies: strategies, opportunities, barriers, and recommendations

Pregnant and breastfeeding women are often under-represented in clinical research, including pharmacokinetic studies, due to ethical and logistical challenges. This paper examines strategies to improve the recruitment and retention of this demographic in pharmacokinetic research, drawing on experiences from five studies conducted at the Infectious Diseases Institute, Makerere University, Uganda.

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[Review Article] Cross-disciplinary mathematical modelling to benefit healthcare – could clinical pharmacology play an enabling role?

In December 2023, Stellenbosch University, Fundisa African Academy of Medicines Development and Pharmacometrics Africa convened a virtual cross-disciplinary symposium to discuss concepts of mathematical modelling applied in various interrelated scientific fields, including the science of pharmacometrics. Experts from different fields were invited to share their insights for a deeper understanding of the application, experiences, challenges and foresight of mathematical modelling in their fields. The goal was to provide an opportunity to highlight the current interlinks amongst the disciplines and possible avenues/collaborations for future research and applications. To highlight and share what we learned, a review article was just published in the British Journal of Clinical Pharmacology – you can read a copy at this link. Abstract: Clinical pharmacology is often the nexus in any cross-disciplinary team that is seeking solutions for human healthcare issues. The use and application of real-world data and artificial intelligence to better understand our ecosystem has influenced our view at the world and how we do things. This has resulted in remarkable advancements in the healthcare space and development of personalized medicines with great attributes from the application of models and simulations, contributing to a more efficient healthcare development process. A cross-disciplinary symposium was held in December 2023, whereby experts from different scientific disciplines engaged in a high-level discussion on the opportunities and challenges of mathematical models in different fields, possible future developments and decision making. A strong interlink amongst the disciplines represented was apparent, with clinical pharmacology identified as the one which integrates various scientific

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[Perspective Paper] Addressing health equity for breastfeeding women: primaquine for Plasmodium vivax radical cure

Read the paper here This article summarizes the clinical and modelling evidence for a favourable benefit:risk evaluation of P. vivax radical cure with primaquine for breastfeeding women without the need for infant G6PD testing, supporting a change in policy. This adjustment to current treatment guidelines would support health equity in regard to effective interventions to protect women and their children, enhance malaria control strategies, and advance P. vivax elimination. Abstract Plasmodium vivax malaria remains a global health challenge, with approximately 6.9 million estimated cases in 2022. The parasite has a dormant liver stage, the hypnozoite, which reactivates to cause repeated relapses over weeks, months, or years. These relapses erode patient health, contribute to the burden of malaria, and promote transmission. Radical cure to prevent relapses requires administration of an 8-aminoquinoline, either primaquine or tafenoquine. However, malaria treatment guidelines updated by the World Health Organization (WHO) in October 2023 restrict primaquine use for women breastfeeding children < 6 months of age, or women breastfeeding older children if their child is G6PD deficient or if the child’s G6PD status is unknown. Primaquine restrictions assume that 8-aminoquinoline exposures in breast milk would be sufficient to cause haemolysis in the nursing infant should they be G6PD deficient. WHO recommendations for tafenoquine are awaited. Notably, the WHO recommends that infants are breastfed for the first 2 years of life, and exclusively until 6 months old. Repeated pregnancies, followed by extended breastfeeding leaves women in P. vivax endemic regions potentially vulnerable to relapses for many years. This puts women’s health at risk, increases the malaria burden,

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[Research Paper] Clinical pharmacology considerations and drug–drug interactions with long-acting cabotegravir and rilpivirine relevant to sub-Saharan Africa

Abstract: This review aims to consider pharmacokinetic characteristics of cabotegravir and rilpivirine and describe anticipated drug–drug interactions (DDIs) with frequent concomitant medications in African settings. Relevant co-medications were identified from the WHO 2021 List of Essential Medicines. All original human and physiologically based pharmacokinetic studies published in English on PubMed, discussing DDIs with LAI cabotegravir and rilpivirine prior to April 2023, were reviewed. Read the entire paper here This featured research paper was written in part by members of our Uganda chapter. For more information on this local chapter, visit this page.

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[Research Paper] Attaining Equity of Access to Research: Perspective on Research in Pregnancy and Breastfeeding Following Dolores Shockley Lecture at ASCPT2024

Abstract Everybody deserves access to evidence-based information to make decisions about their health. However, in many situations, clinical trial eligibility criteria mean that specific data do not exist for certain groups of individuals. These include pregnant and breastfeeding women, children, older people, those with hepatic and renal dysfunction, those with acute severe illness, and those with multiple co-morbidities and interacting medications. Resultantly, there may not be specific drug-dosing information for many patients who are treated in a clinical setting. The ASCPT2024 Dolores Shockley Lecture focused on the equitable access to research with a specific focus on clinical pharmacology studies in pregnancy and breastfeeding. To ensure the safe, effective use of medication in pregnancy and breastfeeding, women should be included in clinical trials and pharmacokinetic studies when a medication is anticipated to be used in women of childbearing potential. Community groups should be involved at all stages of research to maintain transparency and trust. This ensures that local priorities are investigated, that communities understand the findings and are empowered to make evidence-based decisions about their own medication use. Principles informing the design of such studies in pregnancy and lactation are in existence. Mathematical techniques such as physiologically-based pharmacokinetic modeling and stochastic simulation and estimation can enhance study design, and population pharmacokinetic modeling be used to understand variability within and between individuals. Data should be made findable, accessible, interoperable, and reusable (FAIR). Information (and where necessary, training) regarding the use of these approaches should be provided to decision-making stakeholders such as ethics

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[Research Paper] Pharmacokinetics and safety of twice-daily ritonavir-boosted atazanavir with rifampicin

Critical drug-drug interactions (DDI) and hepatotoxicity complicate concurrent use of rifampicin and protease inhibitors. We investigated whether dose escalation of atazanavir/ritonavir could safely overcome the DDI with rifampicin. Read the full paper here This featured research paper was written in part by members of our Uganda chapter. For more information on this local chapter, visit this page.

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Bridging the Skills Gap: Empowering African Regulators through Innovative Training [Report]

Many regulatory agencies across the African continent have been grappling with a critical shortage of skilled professionals due to resource constraints and a paucity of training opportunities. It is this gap that the South African Health Products Regulatory Authority (SAHPRA) and other African agencies highlighted in a paper published in the British Journal of Clinical Pharmacology, and intended to fill when they invited Pharmacometrics Africa to develop Africa-centric training opportunities in the regulatory sciences. Read on to discover what these efforts entailed, or download the report now. Pharmacometrics Africa and its partner network collaborated with a network of dedicated subject matter experts to proudly conclude the second iteration of their course, “A Primer for Clinical Assessors within African Regulatory Agencies.” This innovative initiative spans over 12 weeks and delivers a comprehensive curriculum aimed at building and refining the essential competencies required by clinical assessors working within regulatory bodies across Africa. The course takes participants on an intensive journey into assessing the clinical sections of regulatory dossiers with regards to efficacy and safety of new medicines that will be used in Africa. Through a combination of live tutorials and online coursework, participants dive deep into the intricacies of the field. What sets this initiative apart is its holistic approach, focusing on three distinct yet interconnected phases: Construction, Deconstruction, and Reconstruction of the Regulatory Dossier. These stages encompass the entire spectrum of regulatory work, from building robust dossiers to assessing their contents and supporting marketing authorizations. Recognizing the importance of varied perspectives,

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Perspective Paper: What are current barriers to a true global pharmacometric community?

Barriers to global pharmacometrics: educational challenges and opportunities across the globe Robin Michelet, along with several members of the global Pharmacometrics communiity, recently published a perspective paper based on a symposium held at the World Conference on Pharmacometrics (WCOP). This talk and panel discussion, titled “Training of the Next Generation of Pharmacometric Talent Around the World” explored the issues around good pharmacometrics education and provided an overview of different aspects that aid or hamper this goal. This paper focuses on the challenges and opportunities related to the movement of human capital (so-titled “Brain Drain”), the multidisciplinary nature of the field and the unbalanced spread of pharmacometrics across regions and regulatory agencies. You can read the article free of charge here. To learn more about how you can help support our efforts to strengthen the pharmacometric community in Africa, please visit our Get Involved page.

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Paper: Needs-driven talent and competency development for the next generation of regulatory scientists in Africa

“Capacity building programmes for African regulators should link education, training and research with career development in an approach that combines an academic base and experiential learning aligned within a competency framework.” A regulatory ecosystem that engages with a broad range of stakeholders will mean that expertise in the ever-expanding field of regulatory science filters into teaching and research in a symbiotic way. In this way capacity development interventions will be a collaborative approach between the learning context (academic and training institutions) and the performance context (regulatory agencies and industry), which will ultimately best serve the patients. Monitoring and evaluation of capacity development interventions will be essential to show value of investments and ultimately guide continued funding and sustainability. This paper reviews the skills and human capacity gaps, reports on regulatory assessment pathways used in Ghana, South Africa and Zimbabwe and outlines a staged tactical approach for Africa that builds on previous efforts to strengthen African regulatory ecosystems.

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