Cost-effectiveness modeling for neuropathic pain treatments: investigating the relative importance of parameters using an open-source model

Aims: The study objective was to develop an open-source replicate of a cost-effectiveness model developed by National Institute for Health and Care (NICE), in order to explore uncertainties in health economic modeling of novel pharmacological neuropathic pain treatments.

Materials and methods: The NICE model, consisting of a decision tree with branches for discrete levels of pain relief and adverse event (AE) severities, was replicated using R, and used to compare a hypothetical neuropathic pain drug to pregabalin. Model parameters were sourced from NICE’s clinical guidelines and associated with probability distributions to account for underlying uncertainty. A simulation-based scenario analysis was conducted to assess how uncertainty in efficacy and AEs affected the net monetary benefit (NMB) for the hypothetical treatment at a cost-effectiveness threshold of £20,000 per QALY.

Results: Relative to pregabalin, an increase in efficacy was associated with greater NMB than an improvement in tolerability. A greater NMB was observed when efficacy was marginally higher than that of pregabalin, while maintaining the same level of AEs than when efficacy was equivalent to pregabalin, but with a more substantial reduction in AEs. In the latter scenario, the NMB was only positive at a low cost-effectiveness threshold.

Limitations: The replicate model shares the limitations described in the NICE guidelines. There is a lack of support in scientific literature for the assumption that increased efficacy is associated with a greater reduction in tolerability. The replicate model also included a single comparator, unlike the NICE model.

Conclusions: Pain relief is a stronger driver of NMB than tolerability, at a cost-effectiveness threshold of £20,000 per QALY. Health technology assessment decisions which are influenced by NICE’s model may reward efficacy gains, even if they are associated with more severe AEs. This contrasts with recommendations from clinical guidelines for neuropathic pain, which place more equal weighting on improvements in efficacy and tolerability as value drivers.     

A cost-utility study of the use of pregabalin added to usual care in refractory neuropathic pain patients in a Swedish setting

Abstract

Objectives:

Patients refractory to older therapies for neuropathic pain (NeP) have few remaining therapeutic options. This study evaluates the cost-utility of pregabalin in the treatment of patients with refractory neuropathic pain in Sweden, from a healthcare and a societal perspective.

Study limitations:

The use of non-randomized (observational) data to determine the effectiveness of treatments for NeP. The use of non-Swedish data for some input parameters in the model.

Methods:

A previously constructed discrete event simulation model was adapted to compare pregabalin combined with usual care to usual care alone in a Swedish setting. Pain profiles were generated using clinical data from five non-randomized pregabalin studies in refractory NeP patients. Utility data were generated from a UK survey of patients with NeP. Cost data were generated from the Swedish Dental and Pharmaceutical Benefits Board (TLV’s) product price database, a national NeP register, and a regional registry study. Indirect costs were estimated from published sources. One-way and probabilistic sensitivity analyses evaluated uncertainty in the model’s output.

Results:

The incremental cost-effectiveness ratio (ICER) for pregabalin plus usual care treatment compared to usual care was 51,616 SEK/€5364 and 123,993 SEK/€12,886 with and without indirect costs, respectively. One-way sensitivity analyses confirmed the clinical input data as the main driver of the model; even considerable changes to all other input parameters had only a modest effect on the ICER. The ICER remained well below a conservative threshold of 347,495 SEK /€36,113/£30,000 in all scenarios modelled.

Conclusions:

This study found pregabalin combined with usual care to be cost-effective compared to usual care in patients with refractory NeP from a Swedish Health Care perspective. Moreover, sensitivity analysis showed pregabalin’s cost-effectiveness to be robust in all scenarios modelled.