People with spasticity following stroke have significantly higher care costs (particularly direct healthcare costs, and aged care costs) and lower quality of life than those survivors without spasticity [1,2,3]. Therefore, identifying effective therapies to reduce upper-limb spasticity and improve function are an important target for research.
International clinical guidelines support the use of botulinum toxin-A in conjunction with active rehabilitation as the preferred treatment . However, the optimum rehabilitation strategy remains undetermined. There are a lack of adequately powered randomised controlled trials evaluating the effect of botulinum toxin-A injections alone, compared to the injection plus active rehabilitation. However, consideration of the costs of providing care for these patients and ultimately consideration of the cost effectiveness of new therapies (namely, whether they are a worthwhile spend of the constrained resources of the healthcare budget as compared to other potential therapies) is another important factor .
There have been few studies of the economic impact of upper-limb spasticity following stroke. Lundström et al.  evaluated the healthcare costs for the year following stroke in those with and without spasticity in Sweden, and identified that direct health care costs were four times higher in those with spasticity compared to those without, predominantly due to increased costs of hospital care and post hospital community care (i.e. home help services, residential care etc). However, this study only included hospitalised patients and was based on only 25 participants with spasticity. More recently in the UK, Raluy-Callado  evaluated costs of care in over 2900 post-stroke spasticity patients and found that those with spasticity following stroke had double the healthcare costs of those without spasticity with increased hospital care contributing to increased costs in this group, but were not able to include information on home and community care in their estimate. In addition, the potential economic impacts of spasticity following stroke are broad ranging, with loss of workforce productivity among patients and their caregivers which persisit after the event . However, the potential cost-effectiveness of therapies is under-researched, with no economic evaluations to date evaluating the impact of evidence-based movement training combined with botulinum toxin-A injections [1, 7, 8]. Rychlik et al. 2016 evaluated the impact for the health care costs and quality of life of botulinum toxin-A treatment vs usual care without botulinum toxin-A. The study showed a significant improvement in the physical and mental health status of participants over the follow up period. Increased healthcare costs were evident for the participants who received the treatment, but despite higher incremental costs (driven by higher pharmaceutical and nursing home care costs) the study authors concluded the intervention was very likely to be considered cost effective due to the large gains in quality of life attributed to the intervention group compared to usual care. However a key limitation of this study was that it was not randomised and the results may have been influenced by confounding factors in the treatment and usual care groups . Conversely, the BoTULS trial evaluated the clinical and cost effectiveness of treating upper-limb spasticity with botulinum toxin-A plus physical therapy vs physical therapy alone over a 4 week intervention period. The study authors concluded that the intervention had a low probability of cost-effectiveness compared to usual care using the UK reference care willingness to pay threshold of £20,000 for an additional QALY gained .
In addition, there is an absence of studies from an Australian perspective. Makino et al. 2018  have published the only Australian based study which evaluated the cost-effectiveness of extending botulinum toxin-A therapy beyond the four treatments currently supported by the Pharmaceutical Benefits Scheme. This study was undertaken from the health-care payer perspective, and therefore included direct healthcare costs in the Markov-state transition model that was developed. It was found that extending the number of treatments beyond four was likely to be considered cost effective. However, the study authors didn’t include costs or benefits from rehabilitation or physical therapy in addition to the botulinum toxin-A in their analysis.
The cost of botulinum toxin-A injections is significant, calculated as $1673 Australian Dollars per treatment cycle and patients may receive multiple cycles of treatment [4, 8]. The InTENSE trial  aims to determine the clinical and cost effectiveness of including evidence-based movement training with botulinum toxin-A injections. Therefore, interventions to improve the long-term effect of botulinum toxin-A injections in this group could assist in improving quality of life of patients and reducing their healthcare and broader community care costs. Here we describe in detail the protocol for the economic evaluation to occur alongside the evaluation of clinical effect for the InTENSE trial.[…]