Prioritize Paxlovid for Unvaccinated Patients at High Risk of Severe COVID-19: Cost-effectiveness Analysis

A new analysis has determined the cost-effectiveness of nirmatrelvir/ritonavir (Paxlovid), granted emergency use authorization by the FDA, across various scenarios of vaccination status and risk for severe disease.

Use of nirmatrelvir/ritonavir (Paxlovid) should be prioritized for unvaccinated patients at high risk for severe infection with COVID-19, say researchers of a new cost-effectiveness analysis published in Open Forum Infectious Diseases.

The analysis, using a decision-analytic model, determined the cost-effectiveness of the treatment, which has received emergency use authorization (EUA) from the FDA, across various scenarios of vaccination status and risk for severe disease. Nirmatrelvir/ritonavir is currently recommended for elderly and other high-risk patients regardless of vaccination status, although the treatment has only been evaluated in unvaccinated patients in clinical trials.

“Given both the speed with which new therapeutic agents are being developed and the continuing urgency of the COVID-19 pandemic, decision makers will inevitably and repeatedly be asked to make approval and coverage decisions, long before the clinical and economic impacts of these treatment options are fully understood,” wrote the researchers.

In clinical trials, the 5-day oral antiviral treatment reduced hospitalizations by 89% and resulted in no deaths among unvaccinated patients older than 60 years, with at least 1 comorbidity associated with severe COVID-19. Interim results from one clinical trial showed a 70% reduction in hospitalizations among patients with no comorbidities and or/vaccination. However, the EUA designation for the treatment—for high-risk adults regardless of vaccination status—has been questioned by some stakeholders, citing other studies showing lower efficacy in high-risk unvaccinated patients (22%-67%) and close to no efficacy in low-risk vaccinated patients.

With a goal of promoting optimal use of the treatment, the researchers tested various strategies for nirmatrelvir/ritonavir use, including among unvaccinated patients at high risk of severe disease, finding that the treatment was cost saving in nearly every scenario and remained as such if efficacy exceeded 44%.

Throughout their study, the researchers also explored the cost-effectiveness of using the treatment among all patients at high risk for severe disease regardless of vaccination status, among all unvaccinated patients and vaccinated patients at high risk, and among all patients. The group noted that their analysis did not consider drug supply or budgetary constraints.

“Our analysis aims to establish a priori standards for priority setting in anticipation of future developments in COVID-19 treatment. We use nirmatrelvir/ritonavir as an illustrative ex- ample, but in the spirit of exploration, we allowed its effectiveness to range widely, from the clinical trial estimate of 89% to a low of 21%,” explained the researchers. “This reflects evidence that individual risk level, vaccination status, and time of treatment initiation will likely influence treatment effectiveness. It also acknowledges real-world studies suggesting reduced effectiveness with the newer Omicron variant and potentially reduced effectiveness in low-risk individuals.”

Outside of unvaccinated patients at high-risk for severe disease, the researchers recommended decision makers tailor their allocation of treatment to their particular settings, as there was no clear subsequent priority for nirmatrelvir/ritonavir use across strategies. The group found that cost-effectiveness varied based on willingness-to-pay thresholds, treatment cost and effectiveness, and the likelihood of severe disease. As part of their study, the group created an online tool that decision makers can leverage to make such decisions. The tool provides visualizations of optimal treatment allocation strategies based on user inputs for willingness-to-pay thresholds for hospitalizations and death.


Savinkina A, Paltiel A, Ross J, Gonsalves G. Population-level strategies for nirmatrelvir/ritonavir prescribing—a cost-effectiveness analysis. Open Forum Infect Dis. 2022;9(12):ofac637. doi:10.1093/ofid/ofac637

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