Newborn and child health national and provincial clinical practice guidelines in South Africa, Nigeria and Malawi: a scoping review.

BACKGROUND: Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017-2022). METHODS: We searched relevant websites (June-July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument. RESULTS: We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47-83), and clarity of presentation 81% (67-94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4-32) and editorial independence 6% (0-27). CONCLUSION: National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development.

GRADE Concept 7: Issues and Insights Linking Guideline Recommendations to Trustworthy Essential Medicine Lists.

OBJECTIVES: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well. STUDY DESIGN AND SETTING: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework. RESULTS: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods. CONCLUSION: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries.

Rehabilitation and primary care treatment guidelines, South Africa.

The World Health Organization recognizes rehabilitation as an essential component of universal health coverage (UHC). In many countries, UHC builds on a standard benefits package of services that is informed by the country's essential medicines list, standard treatment guidelines and primary health care essential laboratory list. In South Africa, primary health care is largely provided and managed by primary health-care nurses and medical officers in accordance with primary health care standard treatment guidelines. However, rehabilitation is mostly excluded from these guidelines. This paper describes the 10-year process that led to rehabilitation referral recommendations being considered for inclusion in South Africa's primary health care standard treatment guidelines. There were five key events: (i) a breakthrough moment; (ii) producing a scientific evidence synthesis and formulating recommendations; (iii) presenting recommendations to the national essential medicines list committee; (iv) mapping rehabilitation recommendations onto relevant treatment guideline sections; and (v) submitting revised recommendations to the committee for final consideration. The main lesson learnt is that, by working together, rehabilitation professionals can be of sufficient number to make a difference, improve service delivery and increase referrals to rehabilitation from primary health care. A remaining challenge is the lack of a rehabilitation representative on the national essential medicines list committee, which could hamper understanding of rehabilitation and of the complexities of the supporting evidence.

L'Organisation mondiale de la Santé considère la réadaptation comme un élément indispensable de la couverture sanitaire universelle (CSU). Dans de nombreux pays, la CSU repose sur un modèle de prestations de services qui tient compte de la liste nationale de médicaments essentiels, des directives thérapeutiques normalisées et d'une liste des analyses en laboratoire essentielles dans le cadre des soins primaires. En Afrique du Sud, les soins primaires sont majoritairement assurés et gérés par du personnel infirmier et médical, conformément aux directives thérapeutiques normalisées en la matière. En revanche, la réadaptation n'y figure généralement pas. Le présent document décrit les dix années de processus qui ont permis d'émettre des recommandations de référence relatives à la réadaptation, que l'Afrique du Sud envisage d'inscrire dans ses directives thérapeutiques normalisées de soins primaires. Cinq événements clés ont été retenus: (i) un moment charnière; (ii) la réalisation d'une synthèse des preuves scientifiques et la formulation de recommandations; (iii) la présentation de ces recommandations au comité responsable de la liste nationale de médicaments essentiels; (iv) l'intégration des recommandations en matière de réadaptation dans les rubriques correspondantes des directives thérapeutiques; et enfin, (v) la soumission des recommandations révisées au comité pour examen final. Le principal enseignement tiré est qu'en collaborant, les professionnels de la réadaptation peuvent être suffisamment nombreux pour faire la différence, améliorer la qualité des services et augmenter les transferts depuis les soins primaires vers les structures de réadaptation. Un défi subsiste: l'absence de représentants du secteur au sein du comité responsable de la liste nationale de médicaments essentiels, ce qui pourrait nuire à la compréhension de la réadaptation et du degré de complexité des faits qui l'étayent.

La Organización Mundial de la Salud reconoce que la rehabilitación es un componente esencial de la cobertura sanitaria universal (CSU). En muchos países, la cobertura sanitaria universal depende de un paquete estándar de servicios que se basa en la lista de medicamentos esenciales del país, las directrices de tratamiento estándar y la lista de laboratorios esenciales de atención primaria. En Sudáfrica, la atención primaria la prestan y gestionan en gran medida el personal de enfermería y los médicos de atención primaria, de conformidad con las directrices de tratamiento estándar de la atención primaria. Sin embargo, la rehabilitación queda excluida en su mayor parte de estas directrices. Este artículo describe el proceso de 10 años que llevó a que se contemplara la posibilidad de incluir las recomendaciones de derivación a rehabilitación en las directrices de tratamiento estándar de la atención primaria en Sudáfrica. Hubo cinco acontecimientos clave: (i) un momento decisivo; (ii) la elaboración de una síntesis de datos científicos y la formulación de recomendaciones; (iii) la presentación de las recomendaciones al comité de la lista nacional de medicamentos esenciales; (iv) la adaptación de las recomendaciones de rehabilitación a las secciones pertinentes de las directrices de tratamiento; y (v) la presentación de las recomendaciones revisadas al comité para su estudio final. La principal lección aprendida es que, trabajando juntos, los profesionales de la rehabilitación pueden ser lo bastante numerosos como para marcar la diferencia, mejorar la prestación de servicios y aumentar las derivaciones a la rehabilitación desde la atención primaria. Un desafío que aún persiste es que no hay un representante de la rehabilitación en el comité de la lista nacional de medicamentos esenciales, lo que podría dificultar la comprensión de la rehabilitación y de las complejidades de las pruebas que la sustentan.

Health Technology Assessment in Support of National Health Insurance in South Africa.

South Africa has embarked on major health policy reform to deliver universal health coverage through the establishment of National Health Insurance (NHI). The aim is to improve access, remove financial barriers to care, and enhance care quality. Health technology assessment (HTA) is explicitly identified in the proposed NHI legislation and will have a prominent role in informing decisions about adoption and access to health interventions and technologies. The specific arrangements and approach to HTA in support of this legislation are yet to be determined. Although there is currently no formal national HTA institution in South Africa, there are several processes in both the public and private healthcare sectors that use elements of HTA to varying extents to inform access and resource allocation decisions. Institutions performing HTAs or related activities in South Africa include the National and Provincial Departments of Health, National Treasury, National Health Laboratory Service, Council for Medical Schemes, medical scheme administrators, managed care organizations, academic or research institutions, clinical societies and associations, pharmaceutical and devices companies, private consultancies, and private sector hospital groups. Existing fragmented HTA processes should coordinate and conform to a standardized, fit-for-purpose process and structure that can usefully inform priority setting under NHI and for other decision makers. This transformation will require comprehensive and inclusive planning with dedicated funding and regulation, and provision of strong oversight mechanisms and leadership.

Comment on Hosseini et al. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 2134.

Medicines have been re-purposed as therapeutics for COVID-19 and it is with great interest that we read the publication entitled, "Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis" [...].

The Current Situation Regarding Long-Acting Insulin Analogues Including Biosimilars Among African, Asian, European, and South American Countries; Findings and Implications for the Future.

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities.

Knowledge, attitudes, and perceptions of long-acting reversible contraceptive methods among healthcare workers in sub-Saharan Africa.

OBJECTIVE: To assess the knowledge, attitudes and perceptions (KAP) of long-acting reversible contraceptive (LARC) methods among healthcare workers (HCWs) in sub-Saharan Africa (SSA). METHODS: A systematic review and meta-analysis were conducted following the PRISMA method. Two authors independently searched three electronic databases for studies published between 2000 and January 2020 reporting on the KAP of LARC methods among HCWs in SSA. Titles and abstracts were screened against eligibility criteria, data were extracted and the included studies were assessed for risk of bias. A meta-analysis of proportions for 11 pre-determined questions relating to LARC KAP was performed. Heterogeneity was explored using the I2 -statistic and publication bias investigated using funnel plots and Egger's tests. RESULTS: Twenty-two studies comprising 11,272 HCWs from 11 SSA countries were included. 50% (95% CI: 34%, 67%) of HCWs had received intrauterine contraceptive device (IUCD) insertion training while 63% (95% CI: 44%, 81%) expressed a desire for training. Only 27% (95% CI: 18%, 36%) deemed IUCD appropriate for HIV-infected women. Restrictions for IUCD and injectables based on a minimum age were imposed by 56% (95% CI: 33%, 78%) and 60% (95% CI: 36%, 84%), respectively. Minimum parity restrictions were observed among 29% (95% CI: 9%, 50%) of HCWs for IUCDs and 36% (95% CI: 16%, 56%) for injectable contraceptives. Heterogeneity was high and publication bias was present in two of the 11 questions. CONCLUSION: The systematic review and meta-analysis indicate that unnecessary provider-imposed restrictions may hinder the uptake of LARC methods by women in SSA.

Cost-effectiveness analysis of flucytosine as induction therapy in the treatment of cryptococcal meningitis in HIV-infected adults in South Africa.

BACKGROUND: Cryptococcal meningitis in HIV-infected patients in sub-Saharan Africa accounts for three-quarters of the global cases and 135,000 deaths per annum. Current treatment includes the use of fluconazole and amphotericin B. Recent evidence has shown that the synergistic use of flucytosine improves efficacy and reduces toxicity, however affordability and availability has hampered access to flucytosine in many countries. This study investigated the evidence and cost implications of introducing flucytosine as induction therapy for cryptococcal meningitis in HIV-infected adults in South Africa. METHODS: A decision analytic cost-effectiveness and cost impact model was developed based on survival estimates from the ACTA trial and local costs for flucytosine as induction therapy in HIV-infected adults with cryptococcal meningitis in a public sector setting in South Africa. The model considered five treatment arms: (a) standard of care; 2-week course amphotericin B/fluconazole (2wk AmBd/Flu), (b) 2-week course amphotericin B/flucytosine (2wk AmBd/5FC), (c) short course; 1-week course amphotericin B/flucytosine (1wk AmBd/5FC) (d) oral course; 2-week oral fluconazole/flucytosine (oral) and e) 1-week course amphotericin B/fluconazole (1wk AmBd/Flu). A sensitivity analysis was conducted on key variables. RESULTS: The highest total treatment costs are in the 2-week AmBd/5FC arm followed by the 2-week oral regimen, the 1-week AmBd/5FC, then standard of care with the lowest cost in the 1-week AmBd/Flu arm. Compared to the lowest cost option the 1-week flucytosine course is most cost-effective at USD119/QALY. The cost impact analysis shows that the 1-week flucytosine course has an incremental cost of just over USD293 per patient per year compared to what is currently spent on standard of care. Sensitivity analyses suggest that the model is most sensitive to life expectancy and hospital costs, particularly infusion costs and length of stay. CONCLUSIONS: The addition of flucytosine as induction therapy for the treatment of cryptococcal meningitis in patients infected with HIV is cost-effective when it is used as a 1-week AmBd/5FC regimen. Savings could be achieved with early discharge of patients as well as a reduction in the price of flucytosine.

Fixed dose drug combinations - are they pharmacoeconomically sound? Findings and implications especially for lower- and middle-income countries.

Introduction: There are positive aspects regarding the prescribing of fixed dose combinations (FDCs) versus prescribing the medicines separately. However, these have to be balanced against concerns including increased costs and their irrationality in some cases. Consequently, there is a need to review their value among lower- and middle-income countries (LMICs) which have the greatest prevalence of both infectious and noninfectious diseases and issues of affordability.Areas covered: Review of potential advantages, disadvantages, cost-effectiveness, and availability of FDCs in high priority disease areas in LMICs and possible initiatives to enhance the prescribing of valued FDCs and limit their use where there are concerns with their value.Expert commentary: FDCs are valued across LMICs. Advantages include potentially improved response rates, reduced adverse reactions, increased adherence rates, and reduced costs. Concerns include increased chances of drug:drug interactions, reduced effectiveness, potential for imprecise diagnoses and higher unjustified prices. Overall certain FDCs including those for malaria, tuberculosis, and hypertension are valued and listed in the country's essential medicine lists, with initiatives needed to enhance their prescribing where currently low prescribing rates. Proposed initiatives include robust clinical and economic data to address the current paucity of pharmacoeconomic data. Irrational FDCs persists in some countries which are being addressed.