Table 2.
Results of included studies.
| Study | Cost and health outcome results (USD, 2020) | ICER/net benefit of interventions vs comparators | Cost-effectiveness threshold (if relevant) | Sensitivity and scenario analyses | Authors’ conclusions regarding cost effectiveness | Authors’ reported limitations and challenges |
|---|---|---|---|---|---|---|
| Águas et al (2021)24 | Dex vs SoC Incremental cost: $117m (90% CI $8.3-$455m). LYG: 102K (90% CI 37K-240K). Results assume 5-15% COVID-19 exposure. |
$1300/LYG (90% CI $90/LYG-$2800/LYG) | $0 to $3000/LYG | PSA: 95% of ICERs < $2000/LYG. Scenarios exploring Dex efficacy in people who need but cannot access oxygen (base case = 100%): 25%, 50% and 75%. ICER remains $700-800/LYG. |
Dex can be highly cost effective if given to hospitalized patients with COVID-19 requiring oxygen therapy. | NR |
| I.C.E.R. (2020)25 | Moderate to severe LYs: SoC = Rem = 15.164. QALYs: SoC 12.182; Rem 12.189 (+0.006). Costs: SoC $311 620; Rem $313 450 (+1830). Rem course: $3990. Mild LYs: SoC = Rem = 16.997. QALYs: SoC 13.703; Rem 13.704 (+0.001). Costs: SoC $315 630; Rem $318 380 (+2750). Rem course: $2750. |
Moderate to severe: £298 160/QALY Mild: $1.85m/QALY |
$50K/QALY: Rem price $2470 (moderate to severe), $70 (mild). $100K/QALY: Rem price $2770 (moderate to severe), $150 (mild). $150K/QALY: Rem price $3080 (moderate to severe), $220 (mild). |
Scenario with Rem survival benefit (HR = 0.84): $50K/QALY: Rem course $3980-4140 (moderate to severe), $690-760 (mild). $100K/QALY: Rem course $8750-9080 (moderate to severe), $2620-2740 (mild). $150K/QALY: Rem course $13 520-$14 020 (moderate to severe), $4540-4720 (mild). No PSA reported. |
The pricing estimate related to the threshold of $50K/QALY is the most policy-relevant consideration. This suggests a price of $2470 per Rem course for moderate to severe (vs actual $3990) and $70 for mild (vs actual $2750). | Important uncertainty remains regarding relative clinical effects and composition of hospitalizations by COVID-19 severity; hospitalization costs; long-term cost and health outcomes; evidence for other interventions. |
| Jo et al (2021)26 | SoC: $83 937. Dex (V) and Rem (NV): $69.3m; 408 deaths averted (vs SoC). Dex (N and NV): $84.1m; 689 DA (vs SoC). Rem (NV): $69.3m; 26 DA (vs SoC). Dex (V): $84.0m; 382 DA (vs SoC). |
All vs SoC Dex (V) and Rem (NV): dominant Dex (V and NV): $231/DA Rem (NV): dominant. Dex (V): $174/DA Fully incremental analysis: Dex (V) and Rem (NV): $175/DA; Dex (V) and Rem (NV): £52 491/DA Rem averts deaths by reducing LoS (15 d to 10 d), thereby reducing duration of ICU capacity breach |
$36K/death averted (from £3K/DALY averted, assuming average discounted life expectancy = 17 years (12 DALYs per death)). | Dex (V) and Rem (NV) no longer cost saving if ICU capacity is breached for 6 months. Rem not cost saving if ICU always at full capacity. Otherwise, cost saving even if LoS reduction is 1 day. PSA, Dex (V and NV): ∼100% ICERs < $1000/death averted. Rem strategies: ∼75% ICERs dominant. If Rem mortality efficacy is 30% (instead of 0%), fully incremental analysis: Dex (V) and Rem (NV) ICER: $78/DA. |
Dex (V) and Rem (NV) could avert 408 deaths and save $15 million vs SoC. Dex (V and NV) would maximize deaths averted (689) at an incremental cost of $159K. |
Confounding factors not captured can influence ICU capacity breaches: epidemic conditions, system capacity, policy. Did not consider changes in disease progression or severity, eg, time since symptom onset, age, comorbidities, adverse events, other medications. Cost associated with adverse events were not included. Time horizon was limited to projections from the NCEM. |
| Padula et al (2020)27 | Hypothetical antiviral treatment: $1299, 0.877 QALYs. Do nothing: $2115, 0.874 QALYs. |
Dominant (lower cost, higher QALYs) | $50K/QALY | PSA: treatment almost certainly cost effective vs no treatment. Results most sensitive to treatment efficacy. |
A treatment for COVID-19 presents excellent value to the US healthcare system and economy, if it is priced between $750 and $1250. | Probabilities are not time dependent, because of limited understanding of the disease. Risks and effects assumed equal for all groups and ages. Static population, with no death from other causes. Utilities obtained from non-COVID-19 population (SARS). Not all cost items relevant to healthcare system are captured. |
| Sheinson et al (2021)28 | LYs: SoC 12.423; tmt 12.961 (+0.538). QALYs: SoC 9.790; tmt 10.228 (+0.438). Costs Payer: SoC $277 978; tmt $288 005 (+10 027). Payer and societal: SoC $301 259; tmt $306 284 (+5025). FFS: SoC $281 684; tmt $290 196 (+8512). FFS and societal: SoC $304 965; tmt $308 475 (+3510). |
Payer: $22 933/QALY Payer and societal: $11 492/QALY FFS: $19 469/QALY FFS and societal: $8028/QALY |
$100K/QALY → FFS VBP = £37 710 $150K/QALY → FFS VBP = $59 572 |
All OWSA < £50K/QALY. Most sensitive parameter varies by perspective, eg, societal, age at death: 95 y → £18 632; 64 y → dominant. If no LoS benefit: FFS ICER ↑50%: $29 108. PSA (n = 5000), > 99% ICERs < $100K/QALY, max 95% upper bound: payer → $30 937. Almost all results in NEQ. |
Potential treatments reducing LoS, mortality, and mechanical ventilation use are likely to be cost effective, at a cost of $2500 per course. | The COVID-19 evidence base is immature, so the model may need to evolve in complexity as data emerge. Examines a hypothetical treatment with a proxy drug cost, rather than an actual potential treatment. Uncertainty exists for mechanical ventilation and long-term outcomes (used ARDS data instead). |
| Stevenson et al (2021)29 Emergency department |
(From 22 500 patients entering the model in 90 days:) Laboratory test with 6-h results: $214K, 11.5 QALYs lost. Rapid test with desirable TPP: $275K, 10.5 QALYs lost. Rapid test with acceptable TPP: $272K, 14.2 QALYs lost. Laboratory test (6 h) with weekly testing of asymptomatic staff: $307K, 9.4 QALYs lost. |
Highest NMB strategies: At $69K/QALY: laboratory test (6 h) with weekly testing of asymptomatic staff ∼$320K. At $42K/QALY: laboratory test (6 h), ∼$260K. At $28K/QALY: “no testing” strategy, ∼$80K (laboratory test [6 h] provides highest NMB among strategies with testing) |
$69K/QALY, $42K/QALY and $28K/QALY (used in NICE appraisals). | Results highly sensitive to test costs (if equal, rapid test with desirable TPP has highest NMB at $42K/QALY; including weekly testing of asymptomatic staff at $69K/QALY). Results sensitive to risk of a hospitalized patient needing ICU care (90% risk reduction → testing has much lower NMB). Various scenario analyses comparing “plausible” strategies (1 lab, 2 POC). In general, laboratory test (24 h) highest NMB at $42K/QALY, POCs (including weekly for asymptomatic staff) highest NMB at $69K/QALY. If laboratory test results take 6 h or less, POC tests unlikely to have ICER < $42K. If laboratory test results take ≥ 16 h and POC test results take 6 h or less, POC tests likely to have ICER < $42K. |
Given the heterogeneity of hospitals, no blanket solution can be provided. A POC test with a desirable TPP would appear to have a relatively high NMB, but this may be lower than a laboratory test with 6-h results. A POC test with an acceptable TPP would appear to have a lower NMB than a laboratory test with 24 h results. Testing asymptomatic staff and removing them from duty appears to have higher NMBs at higher cost/QALY thresholds. |
The model did not consider hospitalization via a different route than ED; implications for people with existing respiratory diseases; testing at discharge; cost of shutting clinics because of an outbreak. Simplifying assumptions for rapid tests (eg, no dedicated staffing). Considerable uncertainty in input parameters. Some sampling error. |
| Stevenson et al (2021)30 Residential care home |
(From 16 residents and 9 staff, using observed, real-world accuracy data, assuming facility is penetrated by 1 SARS-CoV-2 infection:) En suite care facility Rapid POC test: $7365, 2.37 QALYs lost. Laboratory test: $7786, 3.37 QALYs lost. Shared care facility Rapid POC test: $8090, 3.31 QALYs lost. Laboratory test: $7557, 2.97 QALYs lost. (Note: these results are erroneously transposed in primary study.) |
At all thresholds, POC test with desirable TPP characteristics provides highest NMB. All testing strategies cause a gain in NMB if the facility has been penetrated by an infection. All testing strategies cause a reduction in NMB if the facility has not been penetrated by an infection, because of unnecessary test costs and isolation |
$69K/QALY, $42K/QALY and $28K/QALY (used in NICE appraisals). | Results highly sensitive to diagnostic accuracy values and cost differential between the 2 types of test. Tests with desirable and observed accuracy may still have positive NMB if vaccination reduces the risk of critical care by up to 90% or reduces immunity by up to 90%. Regular lateral flow testing, with accuracy data from Public Health England and assuming $14 cheaper, may be cost effective (but this is exploratory, eg, assumes perfect adherence). |
It is only possible to draw broad conclusions from this analysis. POC tests have considerable potential for benefit for use in residential care facilities, providing they are sufficiently accurate. | Unclear whether the MHRA criteria for a “desirable” test can or will be met; may be unrealistic. Limitations include residents not stratified by risk for COVID-19; facilities only penetrated by 1 case initially; model progression time of 6 h may be too long to capture very small time effects; cost of hospitalization not included (this will favor less accurate tests); societal and wider capacity effects not captured. |
ARDS indicates acute respiratory distress syndrome; CI, confidence interval; DA, deaths averted; DALY, disability-adjusted life-year; Dex, dexamethasone; ED, emergency department; FFS, fee for service; ICER, incremental cost-effectiveness ratio; I.C.E.R., Institute for Clinical and Economic Review; ICU, intensive care unit; K, thousand; LoS, length of stay; LY, life-year; LYG, life-years gained; m, million; MHRA, Medicines and Healthcare Products Regulatory Agency; NEQ, north-east quadrant of the cost-effectiveness plane; NMB, net monetary benefit; NR, not reported; NV, nonventilated population; OWSA, one-way sensitivity analysis; POC, point of care; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life-year; Rem, remdesivir; SARS, severe acute respiratory syndrome; SoC, standard of care; TPP, target product profile for a diagnostic test; US, United States; USD, US dollars; V, ventilated population.