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Research Article
2 December 2025

Evaluating the feasibility of a network meta-analysis comparing treatment options in polycythemia vera

Authors: Paul Walden, Noemi Hummel https://orcid.org/0009-0000-5656-5025 [email protected], Agnieszka Kopiec, Zuzanna Maliszewska, and Emi NaslaziAuthor Info & Affiliations
Volume 15, Number 1
https://doi.org/10.57264/cer-2025-0142
PDFFormats

Abstract

Aim: Polycythemia vera (PV), a rare, chronic myeloproliferative neoplasm, that negatively impacts patient outcomes, and optimal therapy remains unclear due to a lack of head-to-head trials. A targeted literature review and feasibility assessment for an indirect comparison of ropeginterferon alfa-2b-njft versus peginterferon alfa-2a or ruxolitinib, using standard of care comprising hydroxyurea (HU) as a common comparator was conducted. Materials & methods: A targeted literature review evaluated clinical comparative evidence for PV treatments published between January 2014 and May 2024 in PubMed and relevant conference abstracts. End points of interest included complete hematologic response, molecular response, allele burden, event-free survival and safety. The feasibility of a network meta-analysis (NMA) was evaluated based on homogeneity of patient populations, treatment regimens and end point definitions. Results: Of 193 PubMed records and 460 conference abstracts screened, 40 records were included, representing evidence from 11 randomized controlled trials and 10 observational studies. Among these, 20 studies formed connected evidence networks for the end points of interest. Substantial heterogeneity across studies precluded a robust NMA: patient populations varied (newly diagnosed, high-risk, low-risk, HU-refractory or -intolerant), complete hematologic response definitions differed (e.g., requirement for absence of disease-related symptoms), molecular response thresholds were inconsistent, follow-up durations varied and definitions of standard of care ranged from almost exclusive use of HU to mixed regimens. Conclusion: An NMA for PV treatments was not feasible due to significant clinical and methodological heterogeneity across studies, including differences in patient characteristics, treatments, outcome definitions and follow-up times. These findings highlight the importance of standardized clinical trial designs and outcome definitions to enable robust comparative evidence generation for rare conditions like PV.

Plain language summary

What is this article about?

This article explores is the possibility of comparing different treatments for polycythemia vera (PV), a rare blood cancer, using a method called network meta-analysis (NMA). NMA allows researchers to compare treatments even when direct clinical trials are missing. The study reviewed existing research to assess if this method can be reliably used, given the differences across PV studies.

What were the results?

The review included 40 records that were assessed for feasibility and found significant variability between studies, in how treatments and patient outcomes were defined, which patients were included, what treatments were used as ‘best available therapy’, and when outcomes were measured. Due to this variability, the requirements for a valid NMA were not met, making it unsuitable for comparing PV treatments based on the current evidence.

What do the results mean?

These findings mean that using NMA to compare PV treatments is currently not reliable given the inconsistencies across studies. Alternative methods, like patient level analyses (e.g., matching adjusted indirect comparison or simulated treatment comparison), might be more appropriate but require detailed patient data that are often unavailable. This highlights the challenges of assessing treatments for rare conditions like PV and underscores the importance of more standardized study designs and data to enable better informed treatment decisions.

Supplementary Material

File (supplementary table 1.docx)
File (supplementary table 2.docx)
File (supplementary table 3.docx)

References

Papers of special note have been highlighted as: • of interest
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