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Cost-Effectiveness of Plasma Microbial Cell-Free DNA Sequencing When Added to Usual Care Diagnostic Testing for
Andrew J Sutton1, Daniel S Lupu2, Stephen P Bergin3,4
1Cytel, Inc., Waltham, MA, USA.
Introduction:
Immunocompromised host pneumonia (ICHP) is an important cause of morbidity and mortality, yet usual care (UC) diagnostic tests often fail to identify an infectious etiology. A US-based, multicenter study (PICKUP) among ICHP patients with hematological malignancies, including hematological cell transplant recipients, showed that plasma microbial cell-free DNA (mcfDNA) sequencing provided significant additive diagnostic value.
Aim:
The objective of this study was to perform a cost-effectiveness analysis (CEA) of adding mcfDNA sequencing to UC diagnostic testing for hospitalized ICHP patients.
Methods:
A semi-Markov model was utilized from the US third-party payer's perspective such that only direct costs were included, using a lifetime time horizon with discount rates of 3% for costs and benefits. Three comparators were considered: (1) All UC, which included non-invasive (NI) and invasive testing and early bronchoscopy; (2) All UC & mcfDNA; and (3) NI UC & mcfDNA & conditional UC Bronch (later bronchoscopy if the initial tests are negative). The model considered whether a probable causative infectious etiology was identified and if the patient received appropriate antimicrobial treatment through expert adjudication, and if the patient died in-hospital. The primary endpoints were total costs, life-years (LYs), equal value life-years (evLYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio per QALY. Extensive scenario and probabilistic sensitivity analyses (PSA) were conducted.
Results:
At a price of $2000 (2023 USD) for the plasma mcfDNA, All UC & mcfDNA was more costly ($165,247 vs $153,642) but more effective (13.39 vs 12.47 LYs gained; 10.20 vs 9.42 evLYs gained; 10.11 vs 9.42 QALYs gained) compared to All UC alone, giving a cost/QALY of $16,761. NI UC & mcfDNA & conditional UC Bronch was also more costly ($162,655 vs $153,642) and more effective (13.19 vs 12.47 LYs gained; 9.96 vs 9.42 evLYs gained; 9.96 vs 9.42 QALYs gained) compared to All UC alone, with a cost/QALY of $16,729. The PSA showed that above a willingness-to-pay threshold of $50,000/QALY, All UC & mcfDNA was the preferred scenario on cost-effectiveness grounds (as it provides the most QALYs gained). Further scenario analyses found that All UC & mcfDNA always improved patient outcomes but was not cost saving, even when the price of mcfDNA was set to $0.
Conclusions:
Based on the evidence available at the time of this analysis, this CEA suggests that mcfDNA may be cost-effective when added to All UC, as well as in a scenario using conditional bronchoscopy when NI testing fails to identify a probable infectious etiology for ICHP. Adding mcfDNA testing to UC diagnostic testing should allow more patients to receive appropriate therapy earlier and improve patient outcomes.
Insights
Adding plasma microbial cell-free DNA (mcfDNA) sequencing to usual care (UC) diagnostics for immunocompromised host pneumonia (ICHP) improves patient outcomes. This cost-effectiveness analysis (CEA) indicates mcfDNA sequencing is a valuable diagnostic tool for ICHP.
Area of Science:
- Infectious Diseases
- Genomics
- Health Economics
Background:
- Immunocompromised host pneumonia (ICHP) presents diagnostic challenges, with standard tests often failing to identify the causative pathogen.
- Plasma microbial cell-free DNA (mcfDNA) sequencing has demonstrated additive diagnostic value in ICHP patients, particularly those with hematological malignancies.
Purpose of the Study:
- To conduct a cost-effectiveness analysis (CEA) of integrating mcfDNA sequencing into the diagnostic workup for hospitalized ICHP patients.
- To evaluate the economic value of mcfDNA sequencing compared to usual care (UC) diagnostic strategies.
Main Methods:
- A semi-Markov model was employed from a US third-party payer perspective, incorporating direct costs over a lifetime horizon with a 3% discount rate.
- Comparisons included: All UC, All UC plus mcfDNA, and Non-Invasive (NI) UC plus mcfDNA with conditional bronchoscopy.
- Primary endpoints were costs, life-years (LYs), equal value life-years (evLYs), and quality-adjusted life-years (QALYs), with extensive sensitivity analyses performed.
Main Results:
- Adding mcfDNA sequencing to All UC resulted in higher costs ($165,247 vs $153,642) but improved outcomes (10.11 QALYs gained vs 9.42 QALYs gained), yielding a cost/QALY of $16,761.
- The NI UC & mcfDNA & conditional UC Bronch strategy also increased costs ($162,655 vs $153,642) and effectiveness (9.96 QALYs gained vs 9.42 QALYs gained), with a cost/QALY of $16,729.
- Probabilistic sensitivity analysis indicated All UC & mcfDNA is preferred above a $50,000/QALY willingness-to-pay threshold, consistently improving outcomes regardless of mcfDNA cost.
Conclusions:
- The addition of mcfDNA sequencing to UC diagnostic testing for ICHP is likely cost-effective, especially when used with conditional bronchoscopy for non-invasive test failures.
- Implementing mcfDNA testing can facilitate earlier appropriate antimicrobial therapy, thereby enhancing patient outcomes in ICHP management.
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