Systematic assessment of decision-analytic models for chronic myeloid leukemia

Several tyrosine kinase inhibitors (TKIs) are approved for the treatment of chronic myeloid leukemia (CML). Decision-analytic modeling can help to extrapolate data from short-term clinical trials and also consider quality of life when evaluating different treatment strategies.

Our goal was to describe and analyze the structural and methodological approaches of published decision-analytic models for various treatment strategies in CML and to derive recommendations for the development of future CML models.

We performed a systematic literature search in electronic databases (MEDLINE/PreMEDLINE, EconLit, EMBASE, NHS EED, and Tuft's CEA Registry) to identify published studies evaluating CML treatment strategies using mathematical models. The search was updated in August 2013.

The models were required to compare different treatment strategies in relation to relevant clinical and patient-relevant health outcomes [e.g., life-years gained, quality-adjusted life-years] over a defined time horizon and population.

We used standardized forms for data extraction, description of study design, methodological framework, and data sources for each model.

We identified 18 different decision-analytic modeling studies. Of these, 17 included economic evaluations. Modeling approaches included decision trees, Markov cohort models, state-transition models with individual (Monte Carlo) simulations, and mathematical equations. Analytic time horizons ranged from 2 years to a lifetime. Treatment strategies compared included bone marrow or stem cell transplantation, conventional chemotherapy, interferon-α, and TKIs. Only one model evaluated a second-generation TKI. Most models did not report a model validation. All models conducted deterministic sensitivity analyses and four reported a probabilistic sensitivity analysis.

Articles that were not published in English or German were not included in this review. Our literature search was restricted to published full-text articles in certain databases. Therefore, publications that met our inclusion criteria but were published in different databases, different languages, or as abstracts only may have been missed.

While several well-designed models of CML treatment strategies exist, there remains a need for the assessment of the long-term efficacy and cost effectiveness of novel treatment options such as second-generation TKIs. Additionally, these models should be validated using independent data.