Behind the paper: “Potential health and economic impacts of dexamethasone treatment for patients with COVID-19”

Paper authors: Ricardo Águas, Adam Mahdi, Rima Shretta Peter Horby, Martin Landray, Lisa White & the CoMo Consortium

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On June 16, 2020, the RECOVERY trial, a large, multicenter, randomized, open-label trial performed in the United Kingdom, reported that dexamethasone administered for 10 days reduced mortality in hospitalised COVID-19 patients needing oxygen and ventilation by 18% and 36%, respectively1. At the time. there were just over 8 million cases and 437,000 deaths reported globally with 298,136 cases and 42,153 deaths in the United Kingdom alone2. The early release of trial results allowed clinicians to consider the use of this medicine prior to the peer-reviewed publication with guidelines in the UK and the USA rapidly updated to recommend its use. Estimates of worldwide lives saved by implementing the guidelines just 31 days before the official publication of the results were 15 000–30 000 deaths, based on a 25%–50% uptake of dexamethasone3. Since then, other studies and a WHO led meta-analysis have supported the value of corticosteroids in the management severe COVID-19 disease4.

In our paper recently published in Nature Communications5, we estimated that 12,000 (4,250 - 27,000) lives would be saved in the following epidemic months if this treatment were to be rolled out in the UK and 650,000 (240,000 - 1,400,000) globally over the same time period. This would translate to GBP 8,200 (650 - 17,500 at 90% confidence interval) per life saved and GBP 940 (65 - 2020 90% confidence interval) per life year gained. The National Institute for Health and Care Excellence (NICE) directives suggest that interventions with an incremental cost-effectiveness ratio (ICER) of less than £20,000 per quality-adjusted life-year (QALY) or life-year gained can be considered to be cost effective6 making dexamethasone treatment a clearly cost-effective option.

Although other treatments and particularly vaccines have taken over the headlines around the world, the significance of this cost-effective option for the management of severe COVID-10 patients and its potential to save lives is worth highlighting. During the seven-month period between July 2020 and January 2021, during which we estimate 8-15% of the UK population has been exposed to the virus7, there were 68,824 officially reported deaths in the UK8 and 1.7 million deaths globally. Given the estimated reduction in mortality when dexamethasone is provided to patients with severe respiratory illness1 we can easily calculate how many lives implementation of dexamethasone as a recommended COVID-19 therapy has saved. Assuming all severe COVID-19 patients requiring oxygen (invasive and non-invasive) received dexamethasone, we can infer that without dexamethasone the expected number of deaths would have been between 76,471 and 91,765 translating to 7,647- 22,406 lives saved. This estimate fits squarely within the confidence intervals generated in our analysis. We can then infer in retrospect that dexamethasone continues to be a cost-effective intervention as outlined in our paper.

Dexamethasone is an existing globally affordable and accessible treatment that can be highly cost effective if given to hospitalised COVID-19 patients requiring oxygen therapy. This drug can serve both to reduce mortality and mitigate the burden on health systems. Our findings illustrate that the rapid release of evidence prior to peer review could allow for a rapid roll-out of potentially cost-effective and life-saving interventions for people infected with COVID-19. The findings provide a foundation for the prospective adoption of dexamethasone treatment by low- and middle-income countries (LMICs), where access to oxygen therapy might be limited. However, to estimate the full potential of dexamethasone in the global fight against COVID-19, it is essential to extend the clinical research and analyse its cost-effectiveness in LMICs.

References

  1. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med 2020.
  2. Johns Hopkins University. COVID-19 Dashboard. 2020. https://coronavirus.jhu.edu/map.html (accessed June 2020.
  3. McMahon JH, Lydeamore MJ, Stewardson AJ. Bringing evidence from press release to the clinic in the era of COVID-19. Journal of Antimicrobial Chemotherapy 2020.
  4. The WHO Rapid Evidence Appraisal for COVID-19 Therapies Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA 2020; 324(13): 1330-41.
  5. Águas R, Mahdi A, Shretta R, et al. Potential health and economic impacts of dexamethasone treatment for patients with COVID-19. Nature Communications 2021; 12(1): 915.
  6. National Institute for Health and Care Excellence. The guidelines manual: process and methods. Assessing cost effectiveness; 2012.
  7. Chen X, Chen Z, Azman AS, et al. Serological evidence of human infection with SARS-CoV-2: a systematic review and meta-analysis. medRxiv 2020: 2020.09.11.20192773.
  8. Public Health England. Coronavirus (COVID-19) in the UK. 2021. https://coronavirus.data.gov.uk/.

rima.shretta@ndm.ox.ac.uk

Honorary Visiting Research Fellow, University of Oxford