Search

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.

CITATION: Kredo, T., et al. 2018. How good are our guidelines? four years of experience with the SAMJ’s AGREE II review of submitted clinical practice guideline. South African Medical Journal, 108(11):883-885, doi:10.7196/SAMJ.2018.v108i11.13646.

The COVID-19 pandemic requires urgent decisions regarding treatment policy in the face of rapidly evolving evidence. In response, the South African Essential Medicines List Committee established a subcommittee to systematically review and appraise emerging evidence, within very short timelines, in order to inform the National Department of Health COVID-19 treatment guidelines. To date, the subcommittee has reviewed 14 potential treatments, and made recommendations based on local context, feasibility, resource requirements and equity. Here we describe the rapid review and evidence-to-decision process, using remdesivir and dexamethasone as examples. Our experience is that conducting rapid reviews is a practical and efficient way to address medicine policy questions under pandemic conditions.

Trastuzumab was added to the South African Essential Medicines List (EML) in 2017 for the adjuvant management of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. However, access has remained inconsistent, as some provinces continue to regard trastuzumab as unaffordable within the contexts of their respective oncology budgets. The intention of providing access to trastuzumab through its inclusion on the EML, therefore, has not been met. The National EML Committee (NEMLC) recently reviewed newly published peer-reviewed information investigating the impact of a shorter trastuzumab treatment period on both clinical efficacy and safety. On account of this review, and with a view to improving access while reducing cost and toxicity, the NEMLC has revised the duration of trastuzumab therapy, i.e. from 12 months to 6 months in the adjuvant management of early HER2-positive breast cancer. This article explores and reports on the data used to make this policy amendment.

Summary Sedation is often required to improve patient comfort during the placement of local blocks in eye surgery. The ideal sedative should have a rapid onset of action and be able to ensure immobility while allowing for patients to respond to verbal commands. Furthermore, ideal sedatives should provide amnesia, have a sufficiently short duration of action to facilitate patient cooperation during surgery, have minimal side effects and allow for a rapid return to home-readiness. Combined analgesic and sedative regimes are widely used in tandem with local/regional blocks; however, potential problems with sedative/narcotic agents are considerable. These complications include ventilatory depression and loss of airway control with hypoxia and hypercapnia, and may cause the patient to become confused intra-operatively. The role of sedation in a wide variety of ophthalmic procedures as well as the variation in sedative agents used with regards to dosage regimes and drug combinations as applied in clinical practice can only be illustrated by referring to the published data. As a result, the goal of this paper is to examine the spectrum of sedative drugs that have been used in the process of eye surgery as published in the literature since 1990 with special attention being given to the pharmacodynamics and clinical applications of relevant drugs in current use. In conclusion there does not seem to be one drug or one regimen indicative of standardization of sedation practice in eye surgery. It rather seems as if there could be a competition between drugs and regimens for the position of the best and most favourable place in the armamentarium of sedationists and anaesthesiologists. There could be strong indications from the literature that drugs like midazolam, propofol,and remifentanil are the favourites for sedation in eye surgery. It might be necessary to take another look at the group of alpha-2 adrenergic agonists and also perhaps at low-dose ketamine.

Treatment guidelines are important in influencing public policy, promoting distributive justice and advocating better healthcare delivery for those in need. With an increased frequency in publication of clinical guidelines in South Africa, there is a heightened responsibility to ensure the application of due process throughout their development and publication. The need for consensus opinion is critical in the application of evidence-based medicine principles, and clinical guidelines contribute fundamentally towards the process of decision making and prioritisation. The SAMJ has recognised these imperatives as well as the important role that guidelines play in setting standards for clinical practice. In fulfilling this obligation, this editorial introduces the journal’s readership to the AGREE II instrument as an objective appraisal mechanism against which prospective clinical guidelines will be assessed prior to their publication.

Rhesus macaques (Macaca mulatta) are an important primate model species in several areas of biomedical research. The wide geographic distribution of this species has led to significant genetic differentiation among local and regional populations. These regional differences can be important factors in the selection of the most appropriate subjects for particular research studies, as animals from different populations can respond differently to the same experimental treatment. Consequently, it is valuable to confirm the ancestry of individual rhesus monkeys from geographically distinct populations. Using DNA samples obtained from rhesus macaques from six National Primate Research Centers, we tested a set of 384 potential ancestry informative single nucleotide polymorphisms (SNPs) and identified a final panel of 91 SNPs that can reliably distinguish Indian-origin from Chinese-origin rhesus monkeys. This genetic test can be used to determine the ancestral origin of animals and to detect individuals that are hybrids between these two regional populations. To demonstrate use of the SNP panel, we investigated the ancestry of 480 animals from the Yerkes NPRC (YNPRC) for which the colony records were insufficient to clearly establish ancestry. Three of the YNPRC animals tested were determined to be hybrids. This SNP ancestry tool will be useful to researchers, colony managers, and others who wish to evaluate the ancestral origin of individual rhesus macaques, and therefore will facilitate more effective and efficient use of these animals in biomedical research.

Animal models to study the process of TB pathogenesis and vaccine development are of importance. NHP models, especially Rhesus macaques, are attractive because of available resources to evaluate their immunogenetic backgrounds and the aerosol model closely mimics the human infection route. In this study, we characterized the MHC immunogenetic background of a cohort of animals that have been vaccinated and/or infected with Mtb, defining 54 new immunodominant CD4 T cell epitopes using IFNγ ELISPOTs with antigens utilized in human clinical trials. Antigens which are immunodominant in humans are also immunodominant in rhesus macaques, including Rv3875 (ESAT-6) and Rv3874 (CFP10). Interestingly, the shared responses were not due to common ancestry or inbreeding upon identifying MHC alleles. Instead, the results indicate promiscuous binding, which is the first account of this phenomenon in the rhesus macaque TB model of infection. These results suggest that while the CD4 response of NHPs to TB is broad and heterogeneous, epitope sets can be defined to broadly follow and characterize these responses in genetically heterogeneous NHP animal cohorts. To our knowledge, this is the first comprehensive epitope identification effort for non-human primates. We reveal a profound repertoire overlap between epitopes recognized in NHPs and in humans. These findings have important implications for the evaluation of new vaccines and diagnostics in the setting of non-human primate model of TB.

Women who inherit a BRCA1 or BRCA2 mutation have an 80-90% chance of developing breast cancer. Gene targeting techniques were used to create a Brca2-deficient mouse. A portion of exon 10 was replaced with the Neo gene resulting in premature truncation of the protein product. Examination of normal mammary ductal development in 129(+/+) and 129(+/Brca2-) mice revealed phenotypic differences between the two genotypic classes. 129(+/+) and 129(+/Brca2-) mice and several inbred mouse strains were used to study the effect of genetic background on radiation induced mammary tumor induction. BALB/c and SWR mice are susceptible to radiation induced mammary tumorigenesis and C57BL/6, FVB/N and C3H mice are relatively resistant. While FVB/N mice do not develop tumors, radiation treatment has a dramatic effect on ductal morphogenesis. To date, no mammary tumors have been observed in the 129(+/+) and 129(+/Brca2-) mice. Brca2-deficient mice were crossed to p53 mutant mice to generate four genotypic classes of offspring. A study is in progress to assess the consequences of harboring mutation in the two tumor suppressor genes with and without radiation exposure. The mammary tumor susceptible BALB/c and resistant C57BL/6 mouse strains being used to make mice congenic for the Brca2 mutation.

Epstein-Barr virus (EBV) is a gamma-Herpesvirus associated with lymphoma or nasopharyngeal carcinoma in immunocompromised patients. Lymphocryptovirus (LCV) infection of rhesus macaques replicates several characteristics of the human EBV infection. EBNA-1 is a nuclear virus protein expressed in all phases of EBV/LCV infections, essential for survival, malignant transformation, tumor progression and escape from host immune response. In spite of its importance for viral replication and survival, EBNA-1 is poorly immunogenic during lytic or latent infection. However, since protection against select experimental infections was achieved after enhancement of antigen immunogenicity through immunization, we hypothesized that eliciting EBNA-1-specific responses during chronic latent infection could increase control of EBV/LCV in vivo. We therefore attempted to enhance and broaden LCV EBNA-1 responses via immunization with an AdC68-LCV-EBNA-1 vector in groups of rhesus macaques that were latently infected with LCV but exhibiting low baseline responses. Following immunization, several CD4+ and CD8+ T cell epitopes were identified through IFN-g ELISPOT assays either as novel or markedly expanded responses. One such novel expanded CD8+ T cell epitope was mapped to a 9-mer peptide restricted by Mamu B*029, and a tetramer was developed for staining of specific CD8+ T cells. The study provides proof of concept that EBNA-1 may be a suitable vaccine target.

A survey1 of writing about ethnic prejudice and the media in Australia reveals concerns, reactions and assertions but little systematic or sustained study. Understandable emotion and predictable politics, including the politics of image, have been more influential in claims than have more careful or detached attempts to gather information, analyse and report. Much more could be studied and known and will need to be if practice is to be better informed and effective.