Rapid evidence reviews to inform COVID-19 treatment guidelines in South Africa

Introduction/ Background: In March 2020, the South African National Essential Medicines List Committee established a multidisciplinary expert panel to review emerging evidence for COVID-19 medicines quickly and systematically. Recommendations inform National Department of Health COVID-19 guidelines. We describe implementation of this rapid review mechanism and the impact of recommendations on medicines utilisation. Methods: A protocol was developed for conducting rapid reviews, including the formulation of pre-specified review question, search of at least 2 databases, data extraction and synthesis, evidence appraisal, and summarising key findings and recommendations (PROSPERO registration: CRD42021286710). The COVID-nma initiative was engaged, using global evidence syntheses, adapted to local context. National Surveillance Centre medicines procurement data were analysed, monitoring the impact of the guidelines on medicine use. Pre-pandemic medicine use (2019) was compared to pandemic use (2020), as a ratio of utilisation per 1000 uninsured population for corticosteroids, azithromycin, colchicine, and vitamin C. Results: To date the committee have reviewed 26 medicines (for treatment and prevention of COVID-19) by conducting 52 rapid reviews (including updates and evidence summaries). Review of aggregate procurement data showed that utilisation of corticosteroids (that is recommended for hospitalised COVID-19 patients on oxygen), increased 1.6-fold across all 9 South African provinces. Colchicine and azithromycin (not recommended to treat COVID-19) use did not change. However, use of vitamin C (not recommended) increased 2.2-fold. Impact: A generic rapid review protocol using GRADE principles and an explicit evidence-to-decision framework promoted adaptation of global evidence to develop robust and transparent guidelines. Medicines utilisation data, though, suggests that investment is needed to strengthen guideline implementation. Conclusion: Through extensive collaboration, the Department of Health managed therapeutic uncertainty by developing and implementing a rapid, robust, and transparent evidence-informed approach. However, the impact on clinical practice is uncertain, highlighting the need for more intensive investigation of patient-level prescribing data and engagement with healthcare providers.

Meta-analytic magic, ivermectin, and socially responsible reporting.

Some clinicians prescribe ivermectin for COVID-19 despite a lack of support from any credible South African professional body. They argue that when faced by clinical urgency, weak signals of efficacy should trigger action if harm is unlikely. Several recent reviews found an apparent mortality benefit by including studies at high risk of bias and with active rather than placebo controls. If these studies are discounted, the pooled mortality effect is no longer statistically significant, and evidence of benefit is very weak. Relying on this evidence could cause clinical harm if used to justify vaccine hesitancy. Clinicians remain responsible for ensuring that guidance they follow is both legitimate and reliable. In the ivermectin debate, evidence-based medicine (EBM) principles have largely been ignored under the guise thatin a pandemic the 'rules are different', probably to the detriment of vulnerable patients and certainly to the detriment of the profession's image. Medical schools and professional interest groups are responsible for transforming EBM from a taught but seldom-used tool into a process of lifelong learning, promoting a consistent call for evidence-based and unconflicted debate integral to clinical practice.

Essential medicine selection during the COVID-19 pandemic: Enabling access in uncharted territory

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.

Essential medicine selection during the COVID-19 pandemic: Enabling access in uncharted territory

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.