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Next-Generation Sequencing vs Culture-Based Methods for Diagnosing Periprosthetic Joint Infection After Total Knee
Michael T Torchia1, Daniel C Austin1, Samuel T Kunkel1
1Department of Orthopaedics, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Background:
Periprosthetic joint infection (PJI) after total knee arthroplasty is challenging to diagnose. Compared with culture-based techniques, next-generation sequencing (NGS) is more sensitive for identifying organisms but is also less specific and more expensive. To date, there has been no study comparing the cost-effectiveness of these two methods to diagnose PJI after total knee arthroplasty.
Methods:
A Markov, state-transition model projecting lifetime costs and quality-adjusted life years (QALYs) was constructed to determine the cost-effectiveness from a societal perspective. The primary outcome was incremental cost-effectiveness ratio, with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses were performed to evaluate parameter assumptions.
Results:
At our base case values, culture was not determined to be cost-effective compared to NGS, with an incremental cost-effectiveness ratio of $422,784 per QALY. One-way sensitivity analyses found NGS to be the cost-effective choice above a pretest probability of 45.5% for PJI. In addition, NGS was cost-effective if its sensitivity was greater than 70.0% and its specificity greater than 94.1%. Two-way sensitivity analyses revealed that the pretest probability and test performance parameters (sensitivity and specificity) were the largest factors for identifying whether a particular strategy was cost-effective.
Conclusion:
The results of our model suggest that the cost-effectiveness of NGS to diagnose PJI depends primarily on the pretest probability of PJI and the performance characteristics of the NGS technology. Our results are consistent with the idea that NGS should be reserved for clinical contexts with a high pretest probability of PJI. Further study is required to determine the indications and subgroups for which NGS offers clinical benefit.
Insights
Next-generation sequencing (NGS) is more cost-effective for diagnosing periprosthetic joint infection (PJI) after knee replacement when the pretest probability of infection is high. This advanced molecular technique offers better value than traditional culture methods in specific clinical scenarios.
Area of Science:
- Orthopedic Surgery
- Infectious Diseases
- Health Economics
Background:
- Diagnosing periprosthetic joint infection (PJI) after total knee arthroplasty presents significant challenges.
- Next-generation sequencing (NGS) offers higher sensitivity than culture-based methods but at a greater cost and lower specificity.
- Comparative cost-effectiveness studies for PJI diagnosis using NGS versus culture are lacking.
Purpose of the Study:
- To evaluate the cost-effectiveness of NGS compared to traditional culture methods for diagnosing PJI after total knee arthroplasty.
- To determine the conditions under which NGS becomes a more economically viable diagnostic strategy.
Main Methods:
- A Markov state-transition model was developed to project lifetime costs and quality-adjusted life years (QALYs).
- The analysis adopted a societal perspective, calculating the incremental cost-effectiveness ratio (ICER).
- Sensitivity analyses were conducted to assess the impact of varying parameter assumptions on the model's outcomes.
Main Results:
- Culture-based methods were not cost-effective compared to NGS, with an ICER of $422,784 per QALY at base case values.
- NGS was identified as the cost-effective option when the pretest probability of PJI exceeded 45.5%.
- NGS demonstrated cost-effectiveness if its sensitivity was above 70.0% and specificity above 94.1%, with pretest probability being a major determinant.
Conclusions:
- The cost-effectiveness of NGS for PJI diagnosis is contingent upon the pretest probability of infection and the performance characteristics of the NGS technology.
- NGS is recommended for clinical settings with a high pretest probability of PJI.
- Further research is needed to define specific indications and patient subgroups that benefit most from NGS in PJI diagnosis.
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