The Cost-Effectiveness of the JAKPOT Prediction Rule for Erythrocytosis
Key Takeaways:
- The JAKPOT prediction rule was developed to identify patients with erythrocytosis who are unlikely to have JAK2 mutations and may not require further JAK2 testing.
- Upfront JAK2 testing was more cost-effective than the JAKPOT prediction rule in study cohorts, resulting in higher quality-adjusted life years (QALYs) gained.
- Upfront JAK2 testing yielded incremental cost-effectiveness ratios (ICERs) well below the $100 000 willingness-to-pay (WTP) threshold compared to the JAKPOT rule.
Although fewer than 5% of erythrocytosis cases are caused by JAK2 mutations, identifying these mutations is important because they are strongly associated with polycythemia vera, a myeloproliferative neoplasm that can lead to an increased risk of thrombotic complications. Accurate identification of patients with JAK2 mutations can therefore help guide diagnosis and disease management.
The JAKPOT rule exempts JAK2 testing for patients who do not meet any of the following criteria: red blood cell count greater than 6.45 × 1012/L, platelet count greater than 350 × 109/L, and neutrophil count greater than 6.2 × 109/L.
Study Methods and Outcomes
Researchers compared the cost-effectiveness of the JAKPOT rule against upfront JAK2 testing for all patients with erythrocytosis. The study included patients treated at the Beth Israel Deaconess Medical Center (BIDMC), the University of Illinois College of Medicine Peoria (UIC), and the Veterans Affairs (VA) health system.
The primary outcomes included the ICER and the incremental net monetary benefit (iNMB) at a WTP threshold of $100 000 per QALY gained.
JAKPOT Rule vs Upfront JAK2 Testing
Researchers identified 2308 patients at BIDMC, 1819 patients at UIC, and 50 827 patients at the VA who underwent JAK2 testing. After exclusions, each cohort had 476, 681, and 8288 patients remaining for JAKPOT confirmation, respectively.
JAKPOT sensitivity across cohorts was 0.94, 0.73, and 0.81, respectively; specificity was 0.52, 0.69, and 0.69, respectively; and negative predictive value was 0.98, 0.95, and 0.98, respectively.
In the BIDMC and VA cohorts, upfront JAK2 testing yielded 360 and 510 QALYs gained at $6.9 and $30.3 million more than the JAKPOT rule, respectively. At a $100 000 WTP, this resulted in ICERs of $19 000 and $60 000 per QALY gained, respectively. BIDMC patients had an iNMB of $29.4 million, and VA patients had an iNMB of $20.5 million. These findings suggest upfront JAK2 testing to be the more cost-effective strategy.
Implications for Managed Care
Although the JAKPOT rule can rule out erythrocytosis patients unlikely to have a JAK2 mutation, insufficient test sensitivity indicates upfront JAK2 testing as a more cost-effective strategy.
According to the study’s authors, “Health systems can assess and tailor the cost-effectiveness of JAKPOT by considering practical factors such as local follow-up capacity and JAK2 mutation prevalence. This versatility allows for a dynamic, locally adaptable approach to diagnostic stewardship, making our findings relevant across a range of care settings.”
Reference
Lam DB, Ito S, Ryu J, et al. JAKPOT prediction rule for erythrocytosis: external validation and cost‐effectiveness analysis. Am J Hematol. 2026;101(9):2412–2416. doi:10.1002/ajh.70390
