Health Care Utilization and Cost of Diagnostic Testing for Respiratory Infections

ABSTRACT

Objectives: This study compared all-cause health care resource use (HCRU) and costs between patients with acute oropharyngeal infections and respiratory tract infections (RTIs) receiving targeted syndromic real-time polymerase chain reaction (RT-PCR) tests with next-day results vs matched patients receiving other/no diagnostic tests.

Study Design: Propensity-matched, retrospective study.

Methods: Two cohorts with International Classification of Diseases, Tenth Revision, Clinical Modification codes for diagnosis or symptom(s) of oropharyngeal infection or RTI (first diagnosis = index) on an outpatient claim were identified in the IQVIA PharMetrics Plus database (July 2020-October 2023). HCRU and costs were examined over 6 months post index across 5 subcohorts: patients receiving syndromic RT-PCR and 4 matched subcohorts (other PCR, point-of-care [POC] only, culture, or no test).

Results: The mean (SD) costs for postindex total outpatient services ($2598 [$7564] vs $2970 [$8417]; P < .0001), physician office visit ($624 [$1150] vs $689 [$1082]; P = .0002), emergency department (ED) ($290 [$1145] vs $397 [$1630]; P = .0192), and other medical services ($1684 [$6799] vs $1883 [$7568]; P < .0001) were significantly lower for the oropharyngeal RT-PCR subcohort than the matched culture subcohort. The mean (SD) postindex costs for any outpatient medical services ($2796 [$11,453] vs $3221 [$7873]; P < .0001), physician office visits ($525 [$974] vs $703 [$2635]; P = .0057), ED visits ($253 [$1036] vs $355 [$1300]; P = .0011), and other medical services ($2018 [$10,986] vs $2163 [$6458]; P < .0001) were significantly lower for the RTI RT-PCR subcohort than the matched culture subcohort. Patients in both RT-PCR subcohorts had lower utilization of other medical services and any outpatient services compared with all matched comparator subcohorts.

Conclusions: This propensity-matched study provides evidence on the economic impact of syndromic RT-PCR tests for respiratory infections, highlighting their advantages over traditional diagnostic methods.

Am J Manag Care. 2025;31(9):In Press

Takeaway Points

• This propensity-matched study evaluated the impact of syndromic real-time reverse transcriptase–polymerase chain reaction (RT-PCR) tests for oropharyngeal infections and respiratory tract infections on subsequent health care resource use (HCRU) and costs in a large US population.
• Past research shows that the use of PCR tests to diagnose respiratory infections in clinical practice in the US is low despite high sensitivity and specificity in identifying causative pathogens.
• This study demonstrates that using syndrome-driven RT-PCR tests for patients with oropharyngeal infections and respiratory tract infections is associated with lower HCRU and costs through lower utilization of outpatient services.
• Lower HCRU and costs may be reflective of improved patient care.

Respiratory tract infections (RTIs) including acute oropharyngeal/respiratory infections are a serious health care concern in the US, with an age-standardized incidence of 339,703 per 100,000 people and accounting for 13.6 per 100,000 deaths (~2% of all deaths) in 2019.¹ Oropharyngeal infections and RTIs also result in substantial health care resource utilization (HCRU): almost one-fifth of all outpatient visits (193 visits per 1000 people)² and more than $1 billion in health care expenditures in the US.^3,4

Oropharyngeal infections, such as pharyngitis, characterized by sore throat, sneezing, cough, and/or fever,^2,5 can be caused by both viral and bacterial etiologies. Streptococcal infections alone account for more than 5.2 million outpatient visits among people younger than 65 years.^6,7 Common causes of other RTIs include respiratory viral pathogens, known bacterial pathogens such as Mycoplasma pneumoniae, and frequent colonizers of the respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae.

Accurate and timely diagnosis of oropharyngeal infections and RTIs is challenging because the clinical signs and symptoms are not pathogen specific, thereby delaying the initiation of targeted treatment when indicated.⁸ Traditional in-office diagnostic testing, including serological tests and rapid antigen detection point-of-care (POC) tests, lacks specificity and/or sensitivity, detects only a limited number of pathogens, and requires dedicated resources during the respiratory season. Culture-based techniques are time-consuming and often require technical expertise to interpret results, increasing the risk of misdiagnosis and adverse health outcomes.^3,9 Polymerase chain reaction (PCR)–based testing has emerged over the past decade as more accurate and sensitive at identifying complex and mixed bacterial compositions. Rapid molecular testing for viral conditions offers considerable advantages. It may reduce unnecessary antibiotic use, enhance antiviral prescribing, and minimize the need for additional ancillary testing.^8,10,11 Newer syndromic PCR tests provide fast results and a broader array of causative organisms/viruses based on patient presentation.^11,12 Despite the advantages over other tests, utilization of PCR tests in clinical practice remains low. Yet observational research has shown that, despite low overall utilization, antibiotic use is significantly lower in patients who received PCR testing (34.6%) compared with those with no testing (57.1%), indicating that identifying the causative pathogen can help guide appropriate treatment.¹³

Improved accuracy of diagnostic tests could have a considerable benefit for the patient population by enabling quicker and more accurate diagnosis, which may result in more timely treatment effectiveness and reduced symptom duration and severity. The COVID-19 pandemic drove wide adoption of molecular-based techniques, and with it, the expectation that results be delivered more quickly for common infections, leading to innovation for other respiratory applications. As several other studies have already demonstrated the benefit of PCR diagnostics on antibiotic prescribing for respiratory infections, this study aimed to investigate the potential impact of syndromic real-time PCR (RT-PCR) tests on patient outcomes by assessing HCRU and costs in real-world data from patients with oropharyngeal infections and other RTIs.

METHODS

Study Design, Data Source, and Funding

This retrospective, propensity-matched study aimed to compare the HCRU and costs among patients with oropharyngeal infections and RTIs during the 6 months after receiving a syndromic RT-PCR test (with next-day test results) with those among matched patients receiving other diagnostic tests or no laboratory tests for their respective infections.

The IQVIA PharMetrics Plus adjudicated claims database, representing a US commercially insured population younger than 65 years, was evaluated. This study was funded by HealthTrackRx.

Patient Population

Patients with an initial claim with an International Classification of Diseases, Tenth Revision, Clinical Modification code for diagnosis or relevant symptom(s) of oropharyngeal infections (oropharyngeal cohort) or RTIs (RTI cohort) in the outpatient setting between January 1, 2021, and April 30, 2023 (selection window), were identified (eAppendix Table 1 [eAppendix available at ajmc.com]). Patients with diagnosis codes for both oropharyngeal infections and RTIs were retained in the oropharyngeal cohort and excluded from the RTI cohort, resulting in mutually exclusive cohorts. The date of service for the first observed diagnosis was termed as the index date. The patients in each cohort were required to have continuous health plan enrollment during the 6 months prior to their index date (baseline period) and the 6 months after the index date (follow-up period). Patients with missing or invalid birth year, sex, region, or health plan enrollment dates were excluded.

Among adult patients in the oropharyngeal (Figure 1) and RTI (Figure 2) cohorts, 5 subcohorts were identified based on the diagnostic tests received on the index date. Four subcohorts who received the following on the index date—syndromic RT-PCR (HealthTrackRx), only or with POC provided by a reference laboratory; other PCR; POC only; and/or culture—were identified (Figure 1). Patients who received none of the relevant tests on the index date or within 2 days after were classified in the no test subcohort.

Baseline Patient Characteristics

Patient demographic characteristics were assessed pre- and post match for all subcohorts (Table 1). Comorbidities, including the Charlson Comorbidity Index (CCI) score¹⁴ and select non-CCI comorbidities, presence of similar previous infection, and total health care costs, as well as pharmacy, outpatient medical/emergency department (ED), and inpatient costs, were assessed during the 6-month baseline period.

Outcomes

The mean total (medical and outpatient pharmacy), outpatient services cost measures (eg, physician office visits, ED visits, or other medical services), and overall all-cause outpatient medical services were computed using the allowed amount recorded on the respective claims over the 6-month follow-up period beginning the day after the index date (index visit + 1 day to index visit + 180 days). The proportion of patients utilizing these services and the number of visits for each service per patient were reported. Pairwise postmatch comparisons were conducted for each of these HCRU and cost measures for the RT-PCR subcohorts with their respective comparators.

Statistical Analysis

Descriptive statistics were reported for patient demographic and baseline clinical characteristics for all subcohorts before matching. Standardized mean differences (SMDs) for each variable were computed as the difference in means or proportions of a variable divided by the pooled SD. Baseline imbalances in each demographic and clinical characteristic between the syndromic RT-PCR subcohort from the oropharyngeal cohort and the syndromic RT-PCR subcohort from the RTI cohort and the respective 4 comparative subcohorts were assessed using an SMD cutoff of at least 0.10. Patient demographic and clinical characteristics between each pair of cohorts were considered for inclusion in the respective propensity score model based on baseline imbalances and clinical relevance.

Direct matching was performed by age group, and propensity score matching (PSM) was used to adjust for other measured confounders and create 4 matched pairs of subcohorts for the oropharyngeal cohort (syndromic RT-PCR vs comparator [other PCR/POC only/culture/no test]) and the RTI cohort (syndromic RT-PCR vs comparator [other PCR/POC only/culture/no test]). A greedy nearest neighbor matching technique was used without replacement at a ratio of 1:1, using caliper widths of 0.01 of the SD of the logit of the propensity score.

Following PSM, weighted χ² tests were used to compare categorical and weighted t tests (mean). For comparisons between infrequent independent samples (eg, among patients with ≥ 1 hospitalization), parametric t test (mean) and nonparametric Wilcoxon rank sum test (median) were used because matching no longer applied.

RESULTS

Patient Demographics and Baseline Clinical Characteristics

After direct matching, 2149 patients remained in each matched pair of subcohorts (eAppendix Table 3). After pairwise PSM, the 4 pairs of subcohorts in the oropharyngeal cohort were well balanced (SMD < 0.1), with consistent age distribution, 66% women, 65% of patients residing in the South, 25% of patients with any antibiotic use, and 25% of patients with previous infection (Table 1). Antibiotic use and prior infection during the baseline period were included in the propensity matching characteristics to ensure that history of prior infection had no confounding impact on the health care utilization rates and costs during the follow-up period in this analysis.

Similarly, after direct matching by age and PSM by the other imbalanced factors, 1611 patients remained in each matched pair of RTI subcohorts (eAppendix Table 4). Post matching, the 4 pairs of subcohorts in the RTI cohort were also well balanced (SMD < 0.1), with consistent age distribution, 58% to 59% women, 75% of patients residing in the South, 21% of patients with any antibiotic use, and 4% to 5% of patients with previous infection (Table 1).

HCRU Outcomes

HCRU outcomes for oropharyngeal cohort. Overall, the syndromic RT-PCR subcohort (86.8%) had a significantly lower proportion with at least 1 outpatient visit compared with the other PCR (88.9%; P = .0302), POC only (89.0%; P = .0249), culture (89.9%; P = .0009), and no test (88.8%; P = .0366) subcohorts (Figure 3). The mean (SD) number of outpatient visits was also significantly lower among the syndromic RT-PCR subcohort (11.7 [16.1]) compared with the other PCR (12.7 [17.0]; P = .0003), POC only (12.2 [15.4]; P = .0242), culture (14.2 [19.9]; P < .0001), and no test (12.5 [17.7]; P = .0223) subcohorts (eAppendix Table 6).

The syndromic RT-PCR subcohort, only or in combination with POC, had a lower proportion with at least 1 outpatient physician office visit (84.3%) during follow-up compared with the matched subcohorts, but the differences were not statistically significant (Figure 3). The mean (SD) number of outpatient physician office visits was significantly lower among the syndromic RT-PCR subcohort compared with the culture subcohort (5.0 [7.0] vs 5.8 [7.7]; P = .0003) (eAppendix Table 6).

The syndromic RT-PCR subcohort had a significantly lower proportion of patients with at least 1 ED visit compared with the culture subcohort (14.4% vs 16.9%; P = .0232), and this proportion was similar to other subcohorts (Figure 3 [A]). The mean (SD) number of ED visits among the syndromic RT-PCR subcohort was significantly lower than in the matched culture subcohort (0.2 [0.7] vs 0.3 [0.8]; P = .0073) (eAppendix Table 6).

The syndromic RT-PCR subcohort had a significantly lower proportion with at least 1 other medical service visit (69.8%) (Figure 3 [A]) and number of other medical service visits compared with other subcohorts (P < .05 for both) (eAppendix Table 6).

HCRU outcomes for RTI cohort. The syndromic RT-PCR subcohort had a significantly lower proportion with at least 1 outpatient physician office visit (80.9%) (Figure 3 [B]) and mean (SD) number of outpatient physician office visits (4.5 [6.6]) compared with the culture subcohort (eAppendix Table 6).

The syndromic RT-PCR subcohort had a significantly lower proportion with at least 1 ED visit (12.2%) (Figure 3 [B]) and number of ED visits compared with the other PCR and culture subcohorts (P < .001 for both) (eAppendix Table 6).

The syndromic RT-PCR subcohort (69.6%) had a significantly lower proportion with at least 1 outpatient service (83.7%), lower utilization of at least 1 other medical service (Figure 3 [B]), and mean (SD) number of any outpatient visits (12.1 [25.2]) and use of other medical services (7.4 [21.8]) compared with other subcohorts in the 6-month follow-up period (except POC only) (P < .05 for all) (eAppendix Table 6).

Health Care Cost Outcomes

Health care cost outcomes for oropharyngeal cohort. The syndromic RT-PCR subcohort had significantly lower mean (SD) total (medical + pharmacy) costs per patient compared with the culture subcohort ($4892 [$14,418] vs $5568 [$14,915]; P = .0009) but significantly higher mean total costs compared with the matched POC only subcohort ($4747 [$17,745]; P = .0083). The mean (SD) total cost of any other medical services per patient over the 6-month follow-up period was $2598 ($7564) for syndromic RT-PCR, $2676 ($8678) for other PCR, $2483 ($8417) for POC only, $2970 ($8483) for culture, and $2707 ($8598) for no test. The difference in mean other medical services costs was statistically significant for syndromic RT-PCR vs culture (P < .0001). Additionally, the mean (SD) outpatient physician office visit ($624 [$1150] vs $689 [$1082]; P = .0002), ED ($290 [$1145] vs $397 [$1630]; P = .0192), and other medical services ($1684 [$6799] vs $1883 [$7568]; P < .0001) costs were also significantly lower in the syndromic RT-PCR subcohort compared with the culture subcohort (Table 2).

Health care cost outcomes for RTI cohort. The mean (SD) total (medical + pharmacy) health care costs per patient were significantly lower in the syndromic RT-PCR subcohort compared with the culture subcohort ($6321 [$24,502] vs $7404 [$23,306]; P < .0001) but not significantly different vs the other subcohorts. The mean (SD) cost of any other medical services over the 6-month follow-up period was significantly lower in the syndromic RT-PCR subcohort compared with the culture subcohort ($2796 [$11,453] vs $3221 [$7873]; P < .0001), but these mean costs were similar to those for all other subcohorts. The syndromic RT-PCR subcohort also had significantly lower mean (SD) costs for outpatient physician office visit ($525 [$974] vs $703 [$2635]; P = .0057), ED visit ($253 [$1036] vs $355 [$1300]; P = .0011) and other medical service costs ($2018 [$10,986] vs $2163 [$6458]; P < .0001) compared with the culture subcohort. However, the mean ED visit cost in the syndromic RT-PCR subcohort was significantly higher than in the POC only subcohort ($253 [$1036] vs $233 [$1521]; P = .0413). The mean cost of other medical services was also significantly lower in the syndromic RT-PCR subcohort compared with the no test subcohort ($2018 [$10,986] vs $2402 [$10,495]; P = .0312) (Table 2).

DISCUSSION

To our knowledge, this is the first US analysis to compare the HCRU and costs of using syndromic RT-PCR for oropharyngeal infections and RTIs vs matched comparator tests or no test. The overall findings suggest that the use of syndromic RT-PCR, either alone or with POC tests, is associated with lower HCRU in the 6-month follow-up period. In both the oropharyngeal and RTI cohorts, the syndromic RT-PCR subcohort consistently showed a significantly lower proportion with at least 1 other medical service and at least 1 overall outpatient service than other matched subcohorts, except for the overall outpatient services in the POC only subcohort for RTI, where differences were not significant. Furthermore, the syndromic RT-PCR subcohort had a significantly lower proportion with at least 1 ED visit than the culture subcohort in both cohorts. Specifically, the syndromic RT-PCR subcohort for RTI also demonstrated significantly lower HCRU for outpatient physician office visits than the culture and no test subcohorts and lower ED visits compared with the other PCR and culture subcohorts. Lower HCRU in the 6-month follow-up period is suggestive of lower need due to better care when the syndromic RT-PCR test was received. Although the impact of the magnitude of the observed reduction in HCRU may raise questions, the statistically significant findings in a large, diverse dataset with high variability indicate meaningfulness. Moreover, this reduction may have a more substantial impact when scaled across a large population. Further studies may consider focusing on refining the investigated population to determine whether a more pronounced reduction is associated with specific demographic and health considerations.

The syndromic RT-PCR subcohort demonstrated a lower mean number of other medical services visits per patient and overall outpatient services per patient compared with the matched comparator subcohorts in both cohorts. Additionally, the syndromic RT-PCR subcohort showed lower mean numbers of physician office and ED visits per patient compared with the matched culture subcohort within both cohorts. Of note, the syndromic RT-PCR subcohort had a significantly higher mean (SD) number of other medical services per patient vs the POC-only subcohort (7.4 [21.8] vs 7.3 [11.5]; P = .0329), despite the numerical differences being relatively small. This may be because, although cohorts were matched on several criteria, symptom severity and test availability were unknown. It is expected that those who received only a POC test had relatively low symptom severity and thus lower need for follow-up care.

Results from this study also demonstrate that syndromic RT-PCR testing with next-day results is associated with significantly lower total mean all-cause health care costs compared with the culture subcohort. The cost difference is particularly evident in total outpatient services, physician office visits, ED visits, and other medical services. In the oropharyngeal cohort, the postindex mean costs for outpatient services, outpatient physician office visits, ED visits, and other medical services were significantly lower in the syndromic RT-PCR vs culture subcohorts. Similarly, costs in the RTI cohort for any other medical services, outpatient physician office visits, ED visits, and other medical service costs were substantially lower in the syndromic RT-PCR subcohort compared with the matched culture subcohort. Lower overall health care costs may imply better health care management in the population who received the syndromic RT-PCR test. Thus, stakeholders who manage the care, costs, and outcomes of large populations may consider such findings in developing policies and procedures.

Overall, these results indicate substantial cost savings following syndromic RT-PCR testing compared with a culture test. Findings are particularly notable given that culture remains the standard of care when diagnosing oropharyngeal infections caused by Streptococcus pyogenes. Despite lower costs, use of culture for nonoropharyngeal RTIs may signify more severe or worsening symptoms compared with those who received only POC or PCR; additional non–claims-based studies are needed to investigate the impact of symptom severity on test selection and follow-up utilization. However, these results highlight the potential of next-day, syndromic RT-PCR to improve cost outcomes, and they extend prior research showing reductions in hospital length of stay,¹¹ reduced time to results,¹⁵ and higher sensitivity and specificity with PCR.¹⁵ In addition, previous work has demonstrated that use of multiplex PCR testing can contribute to reduced hospital stays and a reduction in unnecessary antibiotic prescriptions.^11,16,17 Taken together, this study provides additional evidence of the value of multitarget syndromic PCR testing in the outpatient setting and the potential overall outpatient cost savings. Several questions remain related to the impact of these tests on health care provider decision-making and patient outcomes, and additional prospective studies are needed to control for symptom severity, test selection, and how the time to result influences physician prescribing behavior.^10,14 Further, as a population-based study, relevant respiratory illnesses were included together based on overlapping symptomology and to ensure accurate identification of relevant claims. Future research should stratify data by specific diagnoses and/or payer to increase comparability between groups.

Strengths and Limitations

The study had several strengths. First, the large patient population enhances the generalizability and robustness of the findings. The use of a comprehensive, adjudicated US medical and pharmacy claims database allowed for capture of HCRU and costs across both outpatient and inpatient services. Additionally, the study’s propensity-matched design effectively balanced differences between subcohorts, reducing potential biases. Finally, the study is novel in its assessment of next-day syndromic multiplex RT-PCR.

However, findings should be interpreted considering limitations in retrospective claims analysis. Secondary claims data, collected for billing purposes and not research, may lead to miscoding and misclassification due to undercoding of conditions that are irrelevant to the reimbursement. The PharMetrics Plus database primarily includes claims from employer-sponsored commercial and self-insured plans. As a result, these findings may underrepresent patients older than 65 years and may not be generalizable to uninsured, Medicaid, or traditional Medicare populations. Lastly, although the subcohorts of interest were matched, confounding might remain due to factors not examined.

CONCLUSIONS

This propensity-matched study provides valuable insights into the economic impact of syndromic RT-PCR testing for oropharyngeal infections and RTIs, highlighting potential advantages over traditional diagnostic methods or no testing. Patients with syndromic real-time RT-PCR tests with or without POC tests on their first visit to an outpatient health care provider for oropharyngeal infections or other RTIs had reduced utilization of outpatient services compared with patients receiving another PCR test, a POC test only, culture, or no test. Furthermore, use of next-day syndromic RT-PCR tests resulted in substantial outpatient cost savings compared with culture tests. Lower costs and health care utilization observed with novel molecular testing may contribute to improved quality and value in patient care. Although these findings are significant, there are limitations to leveraging historical claims data that must be acknowledged. As such, these findings may not have broad generalizability. Future comparative studies are needed to examine how additional factors, including symptom severity and the speed to result delivery, impact targeted treatment decisions, drive lower downstream health care utilization, and lead to better patient outcomes to fully understand their role in reducing HCRU and costs. In addition, future research should aim to assess the timing of postindex health care utilization to delineate short-term repeat office visits associated with the same patient episode from long-term health care use differences. 

Author Affiliations: HealthTrackRx, Inc (AE, SEG, MSF, JR), Denton, TX; IQVIA, Inc (RD, JY, KC, EJW), Durham, NC.

Source of Funding: This study was funded by HealthTrackRx.

Author Disclosures: Dr Evans, Dr Goldberg, Dr Fragala, and Dr Reddy are employed by HealthTrackRx, one of the diagnostic solutions assessed in this article; Dr Goldberg also holds equity in HealthTrackRx. Dr Doshi, Ms Coyle, and Ms Wang are employed by IQVIA, which received funding from HealthTrackRx to conduct this analysis. Mr Yeaw was employed by IQVIA at the time of the study.

Authorship Information: Concept and design (AE, RD, JY, JR); acquisition of data (JY); analysis and interpretation of data (AE, RD, JY, KC, SEG, EJW, MSF, JR); drafting of the manuscript (RD, JY, KC); critical revision of the manuscript for important intellectual content (AE, RD, JY, SEG, EJW, MSF, JR); statistical analysis (KC, EJW);obtaining funding (AE, JR); administrative, technical, or logistic support (AE, RD, JR); project management (RD); and supervision (RD, JY, SEG, MSF).

Address Correspondence to: Azia Evans, PhD, HealthTrackRx, Inc, 1500 Interstate 35 W, Denton, TX 76207. Email: Azia.Evans@healthtrackrx.com.

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