A cost-consequence analysis of the Xpert Xpress CoV-2/Flu/RSV plus test strategy for the diagnosis of influenza-like illnesses

Figures & data

Figure 1. Model structure.

Table 1. Essential model inputs.

Parameter	Model input		Source
Incidence rate (per 100,000)
Patients with ILI symptoms	81.42%		Assumption; sum of influenza, SARS-CoV-2, RSV, and unknown ailment incidence rates
Patients with influenza	2.7%		CDC 2023 estimate^25
Patients with SARS-CoV-2	5.98%		Johns Hopkins SARS-CoV-2 dashboard 2023^26
Patients with RSV	Adults	1.37%	Tong 2010^12
	Children	3.37%
Patients with influenza & SARS-CoV-2	0.05%		Dadashi 2021^5
Patients with influenza & RSV	0.09%		Reina 2018^7
Patients with SARS-CoV-2 & RSV	0.31%		Kim 2020^6
Patients with influenza, SARS-CoV-2, & RSV	0.002%		Steponavicene 2023^27
Test specifications	Sensitivity	Specificity
Influenza
Xpert Xpress	0.97	0.97	Liu 2022*^28
Multiplex PCR	0.90	0.99	Genilotti 2022^29
Influenza PCR + SARS-CoV-2 PCR	0.94	0.99	Genilotti 2022^29
Duplex antigen	0.69	0.97	Genilotti 2022^29
Influenza antigen + SARS-CoV-2 antigen	0.69	0.97	Genilotti 2022^29
SARS-CoV-2
Xpert Xpress	0.99	0.97	Lee 2021^30
Multiplex PCR	0.88	0.98	Jarrom 2022^┼^26
Influenza PCR + SARS-CoV-2 PCR	0.88	0.98	Jarrom 2022^26
Duplex antigen	0.76	0.99	Brummer 2022^31
Influenza antigen + SARS-CoV-2 antigen	0.76	0.99	Brummer 2022^31
RSV
Xpert Xpress	0.96	1.00	Liu 2022^28
Multiplex PCR	0.91	0.99	Genilotti 2022^29
Costs
Diagnostic tests
Xpert Xpress (MultiPlex)	$142.63		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 0241 U
Multiplex PCR	$142.63		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 87636/87637
Singleplex PCR Influenza	$95.80		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 87502
Singleplex PCR SARS-CoV-2	$51.31		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 87501/87635
Duplex antigen test	$30.94		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 87428
Influenza A/B antigen test	$14.13		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 87400
SARS-CoV-2 antigen test	$35.33		Clinical Laboratory Fee Schedule (23CLABQ1) and (22CLABQ4); CPT 87426

* Weighted mean of influenza A and B.

^┼ In absence of real-world data for the duplex antigen test, it was assumed to have the same sensitivity and specificity as the single antigen tests.

^{^} The Influenza PCR + SARS-CoV-2 PCR, Duplex antigen, and Influenza antigen + SARS-CoV-2 antigen test strategies do not test for RSV.

Table 2. Cost-consequence model results.

Description	Xpert Xpress	Multiplex PCR	Influenza PCR + SARS-CoV-2 PCR	Duplex antigen	Influenza antigen + SARS-CoV-2 antigen
Testing
Tests (n)	203,548	203,548	407,095	680,872	884,420
Tests averted with Xpert Xpress	N/A	0	203,548	477,325	680,872
Costs
Testing	$29,031,980	$29,031,980	$29,943,873	$39,814,731	$43,584,431
Treatment	$53,099,369	$88,652,191	$92,142,464	$90,266,420	$90,266,420
Hospitalizations	$55,702,933	$58,524,394	$58,971,026	$57,773,297	$57,773,297
ICU	$6,610,537	$7,588,243	$7,611,701	$7,218,748	$7,218,748
MV	$6,478,020	$7,054,077	$7,101,656	$6,856,193	$6,856,193
Total costs	$150,922,839	$190,850,884	$195,770,720	$201,929,389	$205,699,089
Budget impact estimates
Testing cost (PMPM)	$2.42	$2.42	$2.50	$3.32	$3.63
Incremental testing PMPM	N/A	$0.00	$0.08	$0.90	$1.21
Total cost PMPM	$12.58	$15.90	$16.31	$16.83	$17.14
Incremental total cost PMPM	N/A	$3.33	$3.74	$4.25	$4.56
Percent of treatments correctly prescribed*
Oseltamivir	74%	28%	27%	22%	22%
Nirmatrelvir/ritonavir	87%	46%	44%	48%	48%
RSV management	100%	32%	9%	29%	29%
Azithromycin	79%	78%	76%	79%	79%
Healthcare resource utilization
Hospitalizations (n)	4,942	5,130	5,173	5,089	5,089
ICU (n)	936	996	1,004	977	977
MV (n)	601	623	629	619	619
Deaths (n)	207	227	228	216	216
Pneumonia (n)	2,235	2,453	2,870	2,335	2,335
Number needed to test (to prevent an…)
… additional correct treatment	N/A	25	12	30	30
… additional inappropriate treatment	N/A	2.8	2.5	2.5	2.5
… additional hospitalization	N/A	1,083	879	1,384	1,384
… additional ICU admission	N/A	3,375	3,003	4,876	4,876
… additional MV	N/A	9,495	7,473	11,785	11,785
… additional death	N/A	10,178	10,094	22,618	22,618
… additional case of pneumonia	N/A	932	320	2,028	2,028
Cost-consequence outcomes
Net correct treatment courses	133,419	53,610	35,930	44,156	44,156
Total cost per correct treatment course	$1,131	$3,560	$5,449	$4,573	$4,658
Test cost per correct treatment course	$218	$542	$833	$902	$987
Avoided hospitalizations**	N/A	188	232	147	147
Avoided ICU**	N/A	60	68	42	42
Avoided MV**	N/A	21	27	17	17
Deaths averted**	N/A	20	20	9	9

* Proportion of correct treatments was defined as the number of correctly prescribed treatments divided by the number of total treatments prescribed (e.g. the number of oseltamivir treatment courses prescribed to patients with influenza divided by total number of oseltamivir prescriptions).

**Relative to Xpert Xpress.

Figure 2. Deterministic sensitivity analysis.

Table 3. Cost-consequence model scenario analyses.

Scenario	Description	Updated model inputs	Model outputs
1	Test specifications (sensitivity and specificity) are replaced with estimates from package insert estimates for each modeled strategy.	Influenza (sensitivity, specificity) Xpert Xpress (100%, 100%) Multiplex PCR (100%, 100%) Singleplex PCR (100%, 100%) Duplex antigen (100%, 99.75%) Influenza A/B antigen (92.20%, 100%) SARS-CoV-2 Xpert Xpress (100%, 100%) Multiplex PCR (100%, 100%) Singleplex PCR (100%, 100%) Duplex antigen (95.24%, 99.35%) SARS-CoV-2 A/B antigen (95.50%, 99.20%) RSV Xpert Xpress (100%, 100%) Multiplex PCR (100%, 100%)	Total cost per correct treatment course Xpert Xpress = $1,033 Multiplex PCR = $3,104 Influenza PCR + SARS-CoV-2 PCR = $5,469 Duplex antigen = $3,892 Influenza antigen + SARS-CoV-2 antigen = $4,050
2	Empiric treatment assumptions are removed for PCR testing strategies and modified for antigen testing strategies.	Percentage of patients receiving empiric treatment of influenza with oseltamivir within antigen testing strategies: 35.0% Percentage of patients receiving empiric treatment of SARS-CoV-2 with nirmatrelvir/ritonavir within antigen testing strategies: 17.5%	Total cost per correct treatment course Xpert Xpress = $1,131 Multiplex PCR = $1,164 Influenza PCR + SARS-CoV-2 PCR = $1,353 Duplex antigen = $3,602 Influenza antigen + SARS-CoV-2 antigen = $3,670
3	Incidence estimates of influenza, SARS-CoV-2, and RSV are replaced with higher estimates, corresponding to 10-year historical maximums.	Medical visits among patients with ILI: 50% (assumption) Influenza incidence: 12,611 per 100,000^45 SARS-CoV-2 incidence: 37,764 per 100,000^9	Total cost per correct treatment course Xpert Xpress = $1,272 Multiplex PCR = $2,240 Influenza PCR + SARS-CoV-2 PCR = $2,461 Duplex antigen = $2,040 Influenza antigen + SARS-CoV-2 antigen = $2,074

Alshaikh FS, Godman B, Sindi ON, et al. Prevalence of bacterial coinfection and patterns of antibiotics prescribing in patients with COVID-19: a systematic review and meta-analysis. PLoS One. 2022;17(8):e0272375. doi: 10.1371/journal.pone.0272375.

 PubMed Web of Science ®Google Scholar

Jarrom D, Elston L, Washington J, et al. Effectiveness of tests to detect the presence of SARS-CoV-2 virus, and antibodies to SARS-CoV-2, to inform COVID-19 diagnosis: a rapid systematic review. BMJ Evid Based Med. 2022;27(1):33–45. doi: 10.1136/bmjebm-2020-111511.

 PubMedGoogle Scholar

Tong S, Amand C, Kieffer A, et al. Incidence of respiratory syncytial virus related health care utilization in the United States. J Glob Health. 2020;10(2):020422. doi: 10.7189/jogh.10.020422.

 PubMed Web of Science ®Google Scholar

Dadashi M, Khaleghnejad S, Abedi Elkhichi P, et al. COVID-19 and influenza co-infection: a systematic review and meta-analysis. Front Med (Lausanne). 2021;8:681469. doi: 10.3389/fmed.2021.681469.

 PubMed Web of Science ®Google Scholar

Reina J, Dueñas J. Respiratory co-infections between influenza viruses and respiratory syncytial virus (2014-2017). Coinfecciones respiratorias entre los virus gripales y el virus respiratorio sincitial (2014-2017). An Pediatr (Engl Ed). 2019;90(2):118–119. doi: 10.1016/j.anpedi.2018.02.011.

 PubMedGoogle Scholar

Kim D, Quinn J, Pinsky B, et al. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA. 2020;323(20):2085–2086. doi: 10.1001/jama.2020.6266.

 PubMed Web of Science ®Google Scholar

Steponavičienė A, Burokienė S, Ivaškevičienė I, Stacevičienė I, Vaičiūnienė D, Jankauskienė A. Influenza and Respiratory Syncytial Virus Infections in Pediatric Patients during the COVID-19 Pandemic: A Single-Center Experience. Children (Basel). 2023;10(1).

 PubMed Web of Science ®Google Scholar

Liu YL, Xie TA, Lin GL, et al. Diagnostic accuracy of xpert xpress flu/RSV for the detection of influenza and respiratory syncytial viruses. Jpn J Infect Dis. 2022;75(2):183–191. doi: 10.7883/yoken.JJID.2020.987.

 PubMed Web of Science ®Google Scholar

Gentilotti E, De Nardo P, Cremonini E, et al. Diagnostic accuracy of point-of-care tests in acute community-acquired lower respiratory tract infections. A systematic review and meta-analysis. Clin Microbiol Infect. 2022;28(1):13–22. doi: 10.1016/j.cmi.2021.09.025.

 PubMed Web of Science ®Google Scholar

Lee J, Song J-U. Diagnostic accuracy of the cepheid xpert xpress and the abbott ID NOW assay for rapid detection of SARS-CoV-2: a systematic review and meta-analysis. J Med Virol. 2021;93(7):4523–4531. doi: 10.1002/jmv.26994.

 PubMed Web of Science ®Google Scholar

Brümmer LE, Katzenschlager S, McGrath S, et al. Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: an updated systematic review and meta-analysis with meta-regression analyzing influencing factors. PLoS Med. 2022;19(5):e1004011-e1004011. doi: 10.1371/journal.pmed.1004011.

 Web of Science ®Google Scholar