Themed Section: COVID-19| Volume 25, ISSUE 5, P697-698, May 2022

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# Cost-Effectiveness of Remdesivir for COVID-19 Treatment: What Are We Missing?

Published:March 18, 2022
Since the beginning of the COVID-19 pandemic, at least 5.6 million people have died of COVID-19 globally as of January 2022.
Coronavirus map: tracking the global outbreak by.
In the early stages of the pandemic, nonpharmaceutical interventions (eg, closure of business, social distancing) were the primary mode of controlling the spread of the novel coronavirus, severe acute respiratory syndrome coronavirus 2, thereby reducing COVID-19–associated hospitalizations and deaths. One study estimated the total cost of the COVID-19 pandemic in the United States to be at least $16 trillion. • Cutler D.M. • Summers L.H. The COVID-19 pandemic and the$16 trillion virus.
Therefore, interventions that reduce the spread or mortality of COVID-19 would have immense social value.
Several effective treatments and vaccines are now available that can potentially change—and have changed—the landscape of COVID-19. Remdesivir was the first treatment for COVID-19 that received emergency use authorization in the United States in May 2020 and conditional approval in Europe in July 2020. Remdesivir was immediately in high demand because of the high COVID-19 burden. Although the clinical evidence was still emerging, Gilead Sciences, the manufacturer of remdesivir, had to set a price of the treatment for a disease that had caused a global pandemic and affected every sector of human life. Priced at $520 per vial ($3120 for the 5-day treatment course) in the United States and £340 per vial (£2040 for the 5-day treatment course) in the United Kingdom, remdesivir has been at the center of a debate regarding how to assess its value for treating COVID-19.
Two studies published in the current issue of Value in Health attempted to evaluate the cost-effectiveness of remdesivir for COVID-19 treatment. Whittington et al

Whittington M, Pearson S, Rind D, Campbell J. The cost-effectiveness of remdesivir for hospitalized patients with COVID-19 [published online February 18, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.11.1378.

conducted their analysis in the United States and Rafia et al

Rafia R, Martyn-St James M, Harnan S, Metry A, Hamilton J, Wailoo A. A cost-effectiveness analysis of remdesivir for the treatment of hospitalized patients with COVID-19 in England and Wales [published online February 20, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.12.015.

in England and Wales. Interestingly, both studies reached a similar conclusion—remdesivir is cost-effective if it reduces mortality in patients with COVID-19 and not cost-effective otherwise. Whittington et al

Whittington M, Pearson S, Rind D, Campbell J. The cost-effectiveness of remdesivir for hospitalized patients with COVID-19 [published online February 18, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.11.1378.

estimated the incremental cost-effectiveness of ratio (ICER) of remdesivir equal to $298 200 per quality-adjusted life-year (QALY) without mortality benefit and$50 100 per QALY with mortality benefit. Rafia et al

Rafia R, Martyn-St James M, Harnan S, Metry A, Hamilton J, Wailoo A. A cost-effectiveness analysis of remdesivir for the treatment of hospitalized patients with COVID-19 in England and Wales [published online February 20, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.12.015.

found the corresponding ICERs to be > £1 million per QALY without mortality benefit and £12 400 per QALY with mortality benefit.
These studies are important and aim to shed light on the marginal value of medical interventions, a much-needed exercise as healthcare costs continue to climb in the United States and other countries. Although both studies shed light on factors influencing cost-effectiveness, unfortunately, we could not conclude whether remdesivir is cost-effective or not. The critical piece of the puzzle is the survival benefit of remdesivir versus the standard of care—although the hazard ratio of survival was < 1, statistical significance was not achieved in a recent meta-analysis conducted by the Solidarity trial consortium.
• Pan H.
• Peto R.
• et al.
WHO Solidarity Trial Consortium
Repurposed antiviral drugs for COVID-19—interim WHO solidarity trial results.
Rafia et al

Rafia R, Martyn-St James M, Harnan S, Metry A, Hamilton J, Wailoo A. A cost-effectiveness analysis of remdesivir for the treatment of hospitalized patients with COVID-19 in England and Wales [published online February 20, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.12.015.

found that remdesivir would be deemed cost-effective in England and Wales if the hazard ratio was ≤ 0.915. Whittington et al

Whittington M, Pearson S, Rind D, Campbell J. The cost-effectiveness of remdesivir for hospitalized patients with COVID-19 [published online February 18, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.11.1378.

also found that remdesivir was cost-effective in the United States when the hazard ratio was 0.91.
It is worth noting that both studies considered different scenarios and assumptions that could have affected the ICER in either direction. First, Whittington et al

Whittington M, Pearson S, Rind D, Campbell J. The cost-effectiveness of remdesivir for hospitalized patients with COVID-19 [published online February 18, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.11.1378.

did not consider long COVID-19 in their analysis, which could have overestimated the benefits of remdesivir. When remdesivir reduces hospital or intensive care unit (ICU) stay, it could also reduce the risk of kidney injury and the associated long-term sequala.
• Ghosn M.
• Attallah N.
• et al.
Severe acute kidney injury in critically ill patients with COVID-19 admitted to ICU: incidence, risk factors, and outcomes.
Even without survival benefits, the authors found the ICER of remdesivir is highly dependent on how COVID-19 hospitalizations are reimbursed—the cost-effectiveness of remdesivir becomes more favorable when more costly hospitalization-bundled payments are prevented, whereas, under a per diem hospitalization reimbursement structure, remdesivir becomes more cost-effective if there is a length of stay improvement associated with the treatment.
Second, both studies did not consider the positive effect of remdesivir on reducing hospital crowding, which would be a direct effect arising from a reduced length of stay. During the peaks of COVID-19 waves, hospital overcrowding occurred in several states that affected the care of patients with COVID-19 and without COVID-19. By reducing the length of hospitalization of patients with COVID-19, remdesivir could have influenced the availability of hospital beds and ICUs to patients with COVID-19 and without COVID-19. For example, one study estimated the additional COVID-19 mortality because of a 1% change in the average capacity of ICU and non-ICU beds.

Karaca-Mandic P, Sen S, Georgiou A, Zhu Y, Basu A. Association of COVID-19-related hospital use and overall COVID-19 mortality in the USA [published online August 19, 2020]. J Gen Intern Med. https://doi.org/10.1007/s11606-020-06084-7

Future studies should consider such dynamics in assessing the total value of remdesivir, not so much in deriving differential pricing during peak and nonpeak times but instead taking a long-term view of the pandemic. These effects and potential cost-offsets could be included in the healthcare sector perspective itself.
Third, both studies only determined the cost-effectiveness of remdesivir from the healthcare sector perspective and did not consider the societal perspective. Although the use of the healthcare sector perspective is common and recommended as one of the reference case analyses,
• Sanders G.D.
• Neumann P.J.
• Basu A.
• et al.
Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine [published correction appears in JAMA. 2016;316(18):1924].
is it sufficient in the case of the COVID-19 pandemic? The adverse impact COVID-19 pandemic on human life has been more than anything we have seen—or will very likely see—in our lifetimes. In addition to 5.6 million deaths in the past 2 years, COVID-19 has been associated with a mental health crisis, increased opioid overdose deaths, increased alcohol consumption, delayed diagnosis of several cancers, adverse effects on children’s education, and reduced workforce availability. Health and healthcare-related losses only account for half of the total economic costs of COVID-19.
• Cutler D.M.
• Summers L.H.
The COVID-19 pandemic and the $16 trillion virus. We may need to reassess our methods for conducting cost-effectiveness of interventions (pharmaceutical and nonpharmaceutical) for COVID-19. Imagine a drug that does not affect mortality or hospitalization but helps a patient with symptomatic COVID-19 to recover and come out of quarantine in half the time. The value for such a drug would be negligible under the current methods used, and when such results translate to pricing, it would certainly disincentivize such innovations. Finally, COVID-19 highlights the case where the value of insurance is of central importance in determining the value of a treatment. The availability of effective treatment is valued based on the benefits it provides to patients and all nonpatients who are at risk of contracting the infection. Recent works discuss a way to incorporate these values, which should be part of both the healthcare sector and societal perspective. • Lakdawalla D.N. • Phelps C.E. Health technology assessment with risk aversion in health [published correction appears in J Health Econ. 2021;78:102474]. , • Lakdawalla D.N. • Phelps C.E. Health technology assessment with diminishing returns to health: the Generalized Risk-Adjusted Cost-Effectiveness (GRACE) Approach. Especially in the United States, where the ultimate goal of these analyses is to derive value-based prices, it is not hard to envision why a societal perspective or an expanded healthcare perspective should be considered as the base case for medical interventions, especially those directed to COVID-19. Indeed, capturing all aspects of COVID-19 into analysis from a full societal perspective would be a daunting task, but that hardly rationalizes ignoring many aspects of nontraditional value items inside and outside the healthcare sector that are easy to incorporate in this analysis. We hope that the cost-effectiveness analyses of using remdesivir presented in Whittington et al Whittington M, Pearson S, Rind D, Campbell J. The cost-effectiveness of remdesivir for hospitalized patients with COVID-19 [published online February 18, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.11.1378. and Rafia et al Rafia R, Martyn-St James M, Harnan S, Metry A, Hamilton J, Wailoo A. A cost-effectiveness analysis of remdesivir for the treatment of hospitalized patients with COVID-19 in England and Wales [published online February 20, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.12.015. when viewed in the context of the population impact of the COVID-19 pandemic catalyze the discussions around conducting a full assessment of the value of remdesivir. We also hope that future clinical studies would provide much-needed data on the benefit—or no benefit—of remdesivir on reducing COVID-19 mortality, which is the most influential factor affecting the cost-effectiveness results. ## Article and Author Information Author Contributions: Concept and design: Chhatwal, Basu Acquisition of data: Chhatwal Analysis and interpretation of data: Chhatwal Drafting of the manuscript: Chhatwal, Basu Critical revision of the paper for important intellectual content: Chhatwal, Basu Obtaining funding: Chhatwal Supervision: Chhatwal Conflict of Interest Disclosures: Dr Chhatwal reported receiving consulting fees from Bayer and Novo Nordisk and reported serving as a member of the board of Value Analytics Labs. Dr Basu reported receiving consulting fees from Salutis Consulting LLC and reported serving as a member of the board of Salutis Consulting LLC. Drs Chhatwal and Basu are editors for Value in Health and had no role in the peer-review process of this article. No other disclosures were reported. Funding/Support: The authors received no financial support for this research. ## References 1. Coronavirus map: tracking the global outbreak by. New York Times. February 26, 2022; • Cutler D.M. • Summers L.H. The COVID-19 pandemic and the$16 trillion virus.
JAMA. 2020; 324: 1495-1496
2. Whittington M, Pearson S, Rind D, Campbell J. The cost-effectiveness of remdesivir for hospitalized patients with COVID-19 [published online February 18, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.11.1378.

3. Rafia R, Martyn-St James M, Harnan S, Metry A, Hamilton J, Wailoo A. A cost-effectiveness analysis of remdesivir for the treatment of hospitalized patients with COVID-19 in England and Wales [published online February 20, 2022]. Value Health. https://doi.org/10.1016/j.jval.2021.12.015.

• Pan H.
• Peto R.
• et al.
• WHO Solidarity Trial Consortium
Repurposed antiviral drugs for COVID-19—interim WHO solidarity trial results.
N Engl J Med. 2020; 384: 497-511
• Ghosn M.
• Attallah N.
• et al.
Severe acute kidney injury in critically ill patients with COVID-19 admitted to ICU: incidence, risk factors, and outcomes.
J Clin Med. 2021; 10: 1217
4. Karaca-Mandic P, Sen S, Georgiou A, Zhu Y, Basu A. Association of COVID-19-related hospital use and overall COVID-19 mortality in the USA [published online August 19, 2020]. J Gen Intern Med. https://doi.org/10.1007/s11606-020-06084-7

• Sanders G.D.
• Neumann P.J.
• Basu A.
• et al.
Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost-effectiveness in health and medicine [published correction appears in JAMA. 2016;316(18):1924].
JAMA. 2016; 316: 1093-1103
• Lakdawalla D.N.
• Phelps C.E.
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J Health Econ. 2020; 72: 102346
• Lakdawalla D.N.
• Phelps C.E.
Health technology assessment with diminishing returns to health: the Generalized Risk-Adjusted Cost-Effectiveness (GRACE) Approach.
Value Health. 2021; 24: 244-249