A comparison of partitioned survival analysis and state transition multi-state modelling approaches using a case...

To construct and compare a partitioned-survival analysis (PartSA) and a semi-Markov multi-state model (MSM) to investigate differences in estimated cost effectiveness of a novel cancer treatment from a UK perspective.

Data from a cohort of late-stage cancer patients (N > 700) enrolled within a randomized, controlled trial were used to populate both modelling approaches. The statistical software R was used to fit parametric survival models to overall survival (OS) and progression-free survival (PFS) data to inform the PartSA (package "flexsurv"). The package "mstate" was used to estimate the MSM transitions (permitted transitions: (T1) "progression-free" to "dead", (T2) "post-progression" to "death", and (T3) "pre-progression" to "post-progression"). Key costs included were treatment-related (initial, subsequent, and concomitant), adverse events, hospitalizations and monitoring. Utilities were stratified by progression. Outcomes were discounted at 3.5% per annum over a 15-year time horizon.

The PartSA and MSM approaches estimated incremental cost-effectiveness ratios (ICERs) of £342,474 and £411,574, respectively. Scenario analyses exploring alternative parametric forms provided incremental discounted life-year estimates that ranged from +0.15 to +0.33 for the PartSA approach, compared with -0.13 to +0.23 for the MSM approach. This variation was reflected in the range of ICERs. The PartSA produced ICERs between £234,829 and £522,963, whereas MSM results were more variable and included instances where the intervention was dominated and ICERs above £7 million (caused by very small incremental QALYs).

Structural uncertainty in economic modelling is rarely explored due to time and resource limitations. This comparison of structural approaches indicates that the choice of structure may have a profound impact on cost-effectiveness results. This highlights the importance of carefully considered model conceptualization, and the need for further research to ascertain when it may be most appropriate to use each approach.