Quality of life, gross motor function, and actual everyday physical activity level in children with spastic Cerebral Palsy: (cost)effectiveness of combined treatment with multilevel botulinum-toxin injections and intensive functional physiotherapy.

Spastic Cerebral Palsy (CP) is a non-progressive syndrome of persistent movement or posture disorders, based on brain damage occurring within the first year of life. Symptoms mostly include motor impairments such as spasticity and/or dyskinesia in extremities, cognitive impairments usually are mild. CP often leads to serious disability in functioning; walking, transferring and moving are impossible or severely disturbed which, in turn, results in children being dependent from others and preventing them from doing activities that are regarded as important and “normal” for them. Although the incidence of CP is relatively small (2 per 1000 births, about 400 new cases each year in the Netherlands), it forms a large group in pediatric rehabilitation, especially because of the serious and long-term motor consequences. Young CP children are increasingly treated with an expensive and burdening treatment combination of multiple botulinum toxin type A injections followed by a period of functional intensive physiotherapy (BtA+iPT). Previous effect studies for BtA (with or without iPT) or iPT alone versus low frequency physiotherapy exercises as control intervention showed positive (short-term) effects in favor of BtA and/or iPT. These studies mainly focused on impairments of body structure and function, on gait-lab-measured functional capacity, on GMFM-measured gross motor function, or on perceived limitations of functioning. However, treatment effect has hardly been expressed as changes in quality of life and has not been expressed as changes in actually performed activities during daily functioning, whereas the latter is increasingly considered as topmost treatment goal for CP. Additionally, BtA+iPT has never been compared to iPT, cost-effectiveness has not been studied for treatments including BtA (with or without iPT), and high-quality randomized trials focusing on quality of life in the context of economic evaluation lack. Since a recent high-quality RCT showed that functional intensive physiotherapy alone significantly improved capacity, perceived participation, and quality of life in CP, there is all the more reason to analyze cost-effectiveness of BtA+iPT and to determine the added value of the costly BtA component. The aim of this 3-year study is to determine the long-term (cost-)effectiveness for combined BtA+iPT treatment compared to iPT treatment alone. This study is a multicenter RCT in which 2 groups of each 30 children (aged 4-12 yrs) with spastic Cerebral Palsy (GMFCS levels I-III) are studied during a follow-up period of maximally 8 months. One intervention group will receive combined multilevel BtA+iPT treatment (multiple botulinum toxin injections followed by a 12-week period of intensive physiotherapy exercises according to a standardized protocol of on average 4 hours per week) and the other intervention group will only receive the iPT component as treatment. At baseline and after 3 and 6 months follow-up both intervention groups will be compared for all primary and secondary outcome measures. Primary measures are 1) functional health status as measured by the Child Health Questionnaire (CHQ) Child and Parent Forms; 2) a condition-specific DISABKIDS health related quality of life questionnaire for CP; 3) the level of actually performed everyday physical activities (‘actual performance’) as measured with valid and reliable several-day ambulatory monitoring techniques; and 4) gross motor functioning as measured using the Gross Motor Function Measure (GMFM66). Assuming an average (±SD) health related quality of life of 55.9 (20.1) for the parent reported DISABKIDS ´physical well-being´ subscale (range 0-100) in CP children without intervention, a sample size of 60 children (30 per group) would have 80% power to detect a minimum difference of 14.5 points between the two groups (alpha=0.05). We will perform a full ex-post economic evaluation of BtA+iPT treatment compared to iPT treatment alone of children with spastic CP. The economic evaluation will be performed in accordance with the Dutch guidelines. We will take a societal perspective, and include health care costs and patient costs (time and travel). Cost-effectiveness will be assessed by calculating the incremental cost-effectiveness ratio. Cost-utility analyses will be done using costs per quality adjusted life year (QALY) as primary outcome measure. The Health Utilities Index (HUI) will be the primary outcome measure for the economic evaluation. The total duration of the project is 36 months. The first 6 months will include preparation and organization. During month 7 to 18 the patients will be included into the study, whereas during month 15-26 follow-up measurements will take place. From month 27 to the end of the study data analysis, economic evaluation, implementation and writing of scientific papers will take place.