Introduction Increasing clinical use of Intrathecal baclofen (ITB) in Australian tertiary paediatric hospitals, along with the need for standardised assessment and reporting of adverse events, saw the formation of the Australian Paediatric ITB Research Group (APIRG). APIRG developed a National ITB Audit tool designed to capture clinical outcomes and adverse events data for all Australian children and adolescents receiving ITB therapy.
Methods and analysis The Australian ITB Audit is a 10 year, longitudinal, prospective, clinical audit collecting all adverse events and assessment data across body functions and structure, participation and activity level domains of the ICF. Data will be collected at baseline, 6 and 12 months with ongoing capture of all adverse event data. This is the first Australian study that aims to capture clinical and adverse event data from a complete population of children with neurological impairment receiving a specific intervention between 2011 and 2021. This multi-centre study will inform ITB clinical practice in children and adolescents, direct patient selection, record and aid decision making regarding adverse events and investigate the impact of ITB therapy on family and patient quality of life.
Ethics and dissemination This project was approved by the individual Human Research Ethics committees at the six Australian tertiary hospitals involved in the study. Results will be published in various peer reviewed journals and presented at national and international conferences.
Trial registration number ACTRN 12610000323022; Pre-results.
- intrathecal baclofen therapy
- neurological impairment
- adverse event reporting
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Strengths and limitations of this study
A whole population-based study on the short-term and long-term effects of intrathecal baclofen therapy in paediatrics.
Data collection of outcomes across all domains of the International Classification of Functioning, Disability and Health.
National registry of intrathecal baclofen therapy adverse events for the ongoing evaluation of safety and efficacy.
The study cohort was limited to age 16 years and younger as this enabled adequate data collection prior to transition to adult services in Australian hospitals.
Disabling spasticity and secondary dystonia are common problems in chronic neurological conditions such as cerebral palsy (CP). Spasticity is the most common form of hypertonia seen in children with CP1 and can be a significant problem for many paediatric patients with spinal cord injury and traumatic brain injury. Spasticity is a velocity-dependent resistance to muscle stretch that occurs when ‘resistance (to external movement) increases with increasing speed of stretch and/or resistance (to externally imposed movement) rises rapidly above a threshold speed or joint angle’.2 This differs from dystonia, which is characterised by involuntary muscle contractions that cause repetitive movements and twisted postures.3 In the clinical setting, severe spasticity and dystonia are often associated with pain, sleep disorders, feeding issues and difficulties with positioning, transfers, dressing and personal cares and reduced quality of life.4–6
Development of intrathecal baclofen
Baclofen is a gamma-amino butyric acid (GABA) agonist. It acts on the GABA-B receptors in the spinal cord to reduce abnormal muscle tone. Oral baclofen is a widely used oral medication to manage spasticity of cerebral or spinal origin. The effectiveness of oral baclofen is limited by its side effects such as sedation, confusion and lethargy. Intrathecal baclofen (ITB) delivered by an implanted pump and catheter can work directly at the spinal cord level to reduce spastic tone through presynaptic inhibition. Because of direct delivery to the central nervous system (CNS), the required dose is less than 1% of that delivered orally.
ITB was first used in adult patients with spasticity of spinal origin.7 Albright et al 8 demonstrated its efficacy for the management of spasticity of cerebral origin. In 2000, the American Academy for Cerebral Palsy and Developmental Medicine published a systematic review of the literature on the treatment of spasticity in CP with ITB.9 ITB is effective in the reduction of spasticity as well as dystonia and is frequently used to treat hypertonicity associated with CP. A recent Cochrane review concluded that the effectiveness of ITB for treating spasticity in children with CP is limited by small sample sizes and methodological issues.10
The European consensus statement on the use of ITB therapy in paediatric spasticity recommends its use in children with CP, Gross Motor Function Classification System (GMFCS) levels IV and V where spasticity interferes with patient’s activities and/or quality of life.11 The authors cited levels 3 and 4 evidence in this population.9 12–15 In addition to the long-term reduction of hypertonicity, the authors have reported improvement in comfort, positioning, ease of care provision and motor function in select groups of individuals and a reduction in the anticipated need for orthopaedic surgery.14 16–18 Progression of hip dislocation may be reduced with ITB, although the effect of ITB on the progression of scoliosis is controversial.19 20
Complications of ITB therapy
It is well recorded in the literature that ITB therapy has adverse events (AEs).21–30 In a review of 430 consecutive patients implanted with an ITB pump at a single centre, Motta and Antonello24 analysed the rates of major complications of ITB therapy requiring surgical intervention: cerebrospinal fluid leakage, infection and catheter malfunction. Their results were consistent with others reported in the literature with 25% of patients experiencing major complications. The European consensus on the appropriate use of ITB therapy in paediatric spasticity recommended procedures to reduce complications, including omission of the ITB test and, particularly in young and small patients, subfascial rather than subcutaneous pump placement.11 In addition, a key factor in improving outcomes for patients is treatment in a centre dedicated to providing ITB, by specialist physicians who have experience in this procedure.
Assessment of ITB in paediatric cohorts
Historically, assessment of interventions, such as ITB in paediatric cohorts, have largely occurred at the Body Functions and Structures level of the International Classification of Functioning, Disability and Health (ICF)31 and fail to address the main concerns of children and their carers.32 A literature review of paediatric ITB studies in CP (n=19) revealed 15 studies used assessments at the Body Functions and Structures level of the ICF, the majority reporting Modified Ashworth scores13 22 23 25 28–30 33–37 or Dystonia Scale scores.25 27 30 38–40 Seven studies reported motor outcomes using the Gross Motor Function Measure41 (GMFM)13 25 33 35 42 or Melbourne 240 43 assessments, and six studies reported goal outcomes using a variety of validated (n=2)30 38 or internally designed (n=4)13 14 22 23 goal setting instruments. Health-related quality of life was addressed as an outcome measure in 13 studies, but few used paediatric validated instruments, and the majority reported on internally designed, non-validated questionnaires or parental interviews (n=13).13 14 22 23 25 27 29 30 33 35 36 40 44
ITB in Australia
Paediatric ITB therapy commenced in Australia in 1999 and is now an established intervention in comprehensive CP clinical management programmes at six tertiary paediatric hospitals in Australia.
In 2009, the Australian Paediatric ITB Research Group (APIRG) was convened with medical, nursing and allied health representatives from all the tertiary paediatric hospitals providing ITB therapy in Australia. The main purpose of APIRG was to establish an agreed national ITB assessment protocol and AEs recording system. The comprehensive assessment protocol was based on the best available evidence regarding assessment tools across all domains of the ICF.31 A national study was proposed as each centre implanted small numbers of ITB systems each year, allowing a larger pool of information. This information would be available to guide future ITB intervention. Prospective collection of data would allow the following:
The use of a standardised assessment protocol, centres could collect more information if desired.
Evaluation of the safety and efficacy of ITB therapy via a centralised AEs data collection system.
Collection of patient and carer satisfaction with ITB therapy.
Support benchmarking for individual centres against national data.
Methods and analysis
A 10-year prospective multicentre clinical audit of all new patients commencing ITB therapy in Australia under the age of 16 years, between 2011 and 2021.
Study population and recruitment
All new patients commencing ITB therapy in Australia under the age of 16 years are eligible for inclusion in the study. An upper age limit of 16 years was determined in order to allow sufficient data collection post pump implant prior to transition to adult services, which usually occurs at around age 18 years in most Australian paediatric tertiary hospitals. The decision regarding the suitability of ITB therapy for individual patients is made by their families and the patient’s rehabilitation and movement disorder’s team following a multidisciplinary assessment process, including a test dose of intrathecal baclofen. There are no specific exclusion criteria.
Participation in the study is voluntary, and participants can withdraw consent without fear of their withdrawal affecting their normal care. If a patient requires ITB therapy to be ceased, no ongoing data will be collected following pump removal.
The hospitals currently participating in the Australian ITB Audit include Princess Margaret Hospital for Children, Perth, Western Australia; The Children’s Hospital at Westmead, Sydney, New South Wales; Lady Cilento Children’s Hospital, Brisbane, Queensland; The Royal Children’s Hospital, Melbourne, Victoria; Monash Children’s Southern Health, Melbourne, Victoria; and The Women’s and Children’s Hospital, Adelaide, South Australia.
It is anticipated that 12 to 15 ITB pumps are implanted each year in Australian children and adolescents. Data will be collected for 10 years in order to be clinically relevant.
Classification and outcome measures
All participants will be classified at baseline and comprehensive data collected at baseline prior to pump implant, then at 6 and 12 months post pump implant, then annually (see table 1 for assessments and protocols). The selection of assessment tools and the outcome measures were guided by the ICF31 and, where possible, are validated measures developed for CP and/or paediatric use.
Background and demographic data
Patient background and demographic data including gender, date of birth, diagnosis and comorbidities are collected. Current medications are recorded prior to implant then at each time point. Health status, as defined by the number of hospital admissions and length of stay, is also collected at each time point. Table 2 describes the demographic data collected at the time of enrolment into the audit.
Diagnoses and comorbidities: Diagnoses are categorised below, and comorbidities are defined in table 3.
Acquired brain injury—CNS tumour; hypoxic, including near drowning and status epilepticus, infection/inflammatory, stroke; traumatic, including non-accidental injury
CP—either bilateral or unilateral involvement, with spastic, dystonic, spastic/dystonic or dyskinetic tone presentation
Genetic—metabolic, primary dystonia, progressive/degenerative conditions (eg, hereditary spastic paraplegia), other
Spinal cord conditions—from any cause (eg, multiple sclerosis, trauma, infection)
Additional information recorded
Data regarding the ITB test dose are recorded, including test dose and sedation method, dose required for response and test dose AEs
Baclofen concentration and total daily dose
Changes in nutrition, speech, swallow and use of augmentative communication
Salivary control is measured using the Drooling Impact Scale45
Musculoskeletal interventions, such as botulinum toxin A injections and any orthopaedic surgery are also recorded for the 2 years prior to entry to the study and at each successive time point.
After pump implant, the following is recorded: implant date, age of patient at implant, pump and catheter model and serial number, catheter tip height, implant technique and antibiotic use.
Classification of the sample
Classification using the GMFCS Expanded and Revised,46 the Manual Ability Classification System (MACS),47 the Communication Function Classification System (CFCS)48 and the Functional Mobility Scale (FMS)49 are documented for children with CP. Equivalent classifications are allocated to non-CP participants, where relevant. These classification systems contribute to a functional performance view of daily life for individuals with CP, in accordance with the WHO ICF.31
GMFCS: Functional status can be categorised with respect to gross motor function by using the five levels of the gross motor classification system for CP.50 The levels assigned describe a child’s ability in self-initiated movements, with a focus on sitting and walking. The GMFCS is clinically relevant51 and both reliable and valid, with high inter-rater reliability52 and good construct validity with the GMFM (r=0.91).53
MACS is a 5-point scale corresponding to the structure of the GMFCS. This scale classifies how a child uses their hands to perform day-to-day activities that are appropriate for their age.47 The inter-rater reliability of the MACS is reported as excellent (intraclass correlation coefficient (ICC) 0.97, 0.96–0.98).47
CFCS is a tool used to classify the everyday communication of an individual with CP into one of five levels according to effectiveness of communication.48 The CFCS demonstrates content validity and shows very good test–retest reliability (ICC 0.82), good professional inter-rater reliability (ICC 0.77 for classification of children older than 4 years) and moderate parent–professional inter-rater reliability.48
The FMS allows the classification of functional mobility in children 4 to 18 years, taking into account the range of assistive devices the child might use.49 The FMS rates walking ability at three specific distances, 5, 50 and 500 m, representing the child’s mobility in the home, school and community. The distances are a guide—it is the environment that is most relevant. The FMS requires rating of what the child actually does at a point in time, not what they can do or used to be able to do, to record mobility status.
Assessment of body structures and function
Passive range of motion of the limbs will be measured with goniometry.
Hypertonia is defined by abnormally increased resistance to passive stretch while the patient is attempting to maintain a relaxed state of muscle activity.2 This is assessed clinically using passive movements about a joint to determine muscular resistance. Hence, the increased tone or hypertonia is perceived by the examiner. Hypertonia may be as result of spasticity, dystonia or rigidity. The level of passive resistance of muscles will be recorded using the Modified Ashworth Scale.54
Spasticity will be measured and quantified using the Modified Tardieu Scale (MTS), which is a valid, reliable and sensitive abridged version of the Tardieu Scale.55 56 The MTS is consistent with current definitions of spasticity assessing muscle response to passive movement at varying velocities, including rapid passive movement.
The Barry Albright Dystonia Scale38 will be used to record dystonia severity in patients with dystonia. It is a 5-point ordinal scale that rates dystonia severity across eight body regions. The scale has some evidence of reliability,38 57 validity38 57–60 and excellent responsiveness to change for patients with secondary dystonia in ITB25 27 30 34 38 61–63 and for other dystonia-related interventions.64–67
Hip migration percentage is a radiographic measure of the amount of ossified femoral head that is not covered by the ossified acetabular roof68 when measured from a frontal view of an anteroposterior pelvic radiograph.68
Spinal scolioisis will be measured from anteroposterior radiographs and will be quantified as the Cobb angle.69 70
Drooling: The Drooling Impact Scale45 is a measure to evaluate the impact of drooling in children with neurological disorders. The tool has established reliability and validity as a subjective measure of the impact of drooling on caregivers and families, and it is sensitive to changes in drooling.45 Changes in saliva control had been anecdotally noted following ITB therapy.
Assessment for ambulant participants
In ambulant patients, GMFCS levels I, II or III or equivalent, additional information is assessed and recorded, including the following:
The 1 minute walk test is a measure of functional ability and walking endurance. Children are tested at their maximal walking speed with the distance covered in 1 minute recorded. Validity71 and reliability72 have been established for this measure.
The Gillette Functional Assessment Questionnaire (FAQ) (short version) is taken from the Skill Mastery of Typically Developing Children. The FAQ is a 10-level parent-report walking scale encompassing a range of walking abilities from non-ambulatory to ambulatory in all community settings. The FAQ is a reliable and valid scale for documenting functional change in children with chronic neuromuscular conditions. Parents or carers are asked to choose the level that best describes their child’s usual or typical walking abilities.73
Sagittal gait patterns: The Winters, Gauge and Hicks74 classification of hemiplegic gait describes four types of gait patterns based on the sagittal plane kinematics of the ankle, knee, hip and pelvis. Similarly, the classification of common gait patterns in children with spastic diplegia has also been developed by Rodda and Graham.75 Their work draws heavily on patterns of knee involvement in spastic diplegia by Sutherland and Davids.76
Paediatric Evaluation of Disability Inventory (PEDI) is a standardised assessment of how a child functions with an impairment in the context of their daily life. It has established reliability and validity to detect the presence, extent and area of a functional delay in children with physical impairment or combined physical and cognitive impairment.77 The PEDI is designed to measure a child’s ability across three measurement scales: functional skills, caregiver assistance and modifications measure. Each scale is divided into three domains, including self-care, mobility and social function.
Goals and quality of life, ease of care assessment
The collection of patient and carer satisfaction with ITB therapy is one of the primary outcomes from this study. Change in parents ratings on individualised goal performance and satisfaction with goal attainment will be obtained with the Canadian Occupational Performance Measure (COPM).78 In addition, changes in quality of life, ease of caregiving and health status will be monitored.
Goal setting: ITB therapy is goal directed, either for increased function or improved comfort and ease of care. Individualised goal setting, in collaboration with families, is generally acknowledged as an integral aspect of intervention.79 Goals are determined with the child and family using the COPM,78 an established reliable and valid measure.80 The COPM is an individualised goal setting measure, providing a structure for the identification of goals in the occupational performance areas of self-care, productivity and leisure. It measures outcome based on individual performance and satisfaction with performance.78 Goals are identified with the client and family, then rated on a 10-point scale for performance, how well they feel they can complete the activity, and satisfaction with performance, how satisfied they are with their current ability to complete the activity. For the purposes of the study, up to a maximum of five goals are prioritised and goal performance and satisfaction are set at baseline and reassessed at 6 then 12 months.
Quality of life, health status and ease of care assessment: quality of life can be defined as ‘an individuals’ perception of their position in life, in the context of culture and value systems in which they live and in relation to their goals, expectations, standards and concerns’.81 Quality of life is an important construct to consider for all children with CP as there is likely to be some impact not only on the physical but also the social and emotional well-being of the child and their family. In this study, the quality of life and the health status of the participants as well as the caregiver burden on families will be measured. A variety of questionnaires will be used due to the differing domains they cover, comparison to previous ITB studies and emerging psychometric data to support their use. Quality of life will be measured at baseline, 6 months and 12 months post pump implant. The study uses the Cerebral Palsy—Quality of Life Questionnaire,82 the Care and Comfort Hypertonicity Questionnaire (CCHQ)83 and the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD).84
The CP-QoL is a CP-specific questionnaire designed to be used for children between the ages of 4 and 12 years. This study will use the parent-proxy version. The CP-QoL measures seven areas of a child’s life: social well-being and acceptance, participation and physical health, emotional well-being, pain and impact of disability, and access to services and family health.
The CCHQ questionnaire was developed to evaluate functional care needs and, to a lesser extent, quality of life in children with increased tone of cerebral origin, particularly those with ‘severe’ CP.83 Early work on the CCHQ has been undertaken to establish content validity, and the CCHQ has also been shown to be sensitive enough to detect changes when ITB was offered or dose levels were changed.83 Formal evaluation of reliability and validity has not been finalised. It is a self-report questionnaire and requires parents or caregivers to rate how easy or difficult it is for them or their child in the last 2 weeks to perform a range of tasks relative to a cooperative person without a disability. The areas covered include personal care, positioning/transferring and comfort and interaction/communication.
The CPCHILD evaluates function and health status, caregiver burden and health-related quality of life in children with severe CP. It has been validated for use for caregivers of children with severe developmental disabilities such as those with non-ambulatory CP and traumatic brain injury, who would be categorised in level IV or V of the GMFCS.84 Responsiveness to change has been demonstrated following hip surgery in children with CP, GMFCS levels IV and V.85 The domains of the CPCHILD include personal care; positioning, transferring and mobility; comfort and emotions; communication and social interactions; and health. It also comments on pain and the importance of QOL items to the child.
The Australian Therapeutic Goods Administration (TGA) defines an AE as unintended and sometimes harmful occurrences associated with the use of a medicine, vaccine or medical device.86 The TGA has adopted the Good Clinical Practice guidelines for the conduct of clinical trials from the International Conference on Harmonisation.87 This national audit is a centralised, systematic AE reporting system for all children and adolescents receiving ITB therapy in Australia.
A paediatric rehabilitation specialist experienced in the use of ITB therapy at each site grades each AE according to the type, severity and causality. The date the AE occurred is recorded; for events that last several days, the first date of the event is recorded. AEs are divided into SynchroMed system related, drug related and patient related (see table 4). The severity of the AE is rated as mild, moderate or severe (see table 5). For causality, events are graded as unrelated or unlikely, possibly related or probably/definitely related to ITB therapy (defined in table 6). These are attributed on the basis of patient history, onset or duration of symptoms and consistency with previous literature of AE reported to be related to ITB therapy. The classification of AE in this manner is based on the Office of Human Research Protections guidance on unanticipated problems and AEs.88 The intervention required and the outcome for ITB therapy are also recorded (see figure 1).
Data collected at each hospital site is deidentified and entered into the Australian ITB Audit Tool Access database. Data are collected and entered at baseline, 6 months and 12 months and annually after ITB pump insertion. AE data are collected from date of pump implant to date of termination from the study. Data collection ceases if ITB therapy ceases, the patient dies or once patients transition to adult services.
It is anticipated that an annual report will be generated from the national study by APIRG and distributed to the participating hospitals.
This protocol paper presents the background and study design of a 10-year longitudinal, prospective, clinical audit. It is the first Australian study aiming to capture ongoing clinical and AE data from a complete population of children with neurological impairment receiving ITB therapy. The study ensures standardisation of ITB assessment across all Australian ITB centres and collection of a minimum data set for every child receiving ITB therapy.
Assessment of outcomes across the domains of the ICF, using psychometrically robust outcome measures where possible, will ensure comparison to studies in the literature and contribute further to the accumulating literature around ITB therapy for children. Collection of individualised goal performance and satisfaction with performance as well as quality-of-life data enables assessment of the impact of ITB on personal cares, patient satisfaction and burden of care. Standardisation of AE classification and reporting provides the opportunity to further our understanding and management. Combing data across sites allows the association between certain AE and hypertonia types (spastic vs dystonic) and different diagnoses to be further explored. Data collected will also help identify the timing of certain complications, their management and outcomes and enable cross-centre collaboration regarding expected and unexpected complications. This information is important to inform future recommendations of this intervention in paediatric populations.
Combining data from the small numbers from each participating site will provide insight into the specific diagnostic groups most likely to have the greatest benefit and carer satisfaction from ITB and ensures data can be used to guide ongoing clinical decision making and AE problem solving around ITB therapy for Australian children and adolescents.
Ethical considerations and dissemination
All participating Australian sites obtained individual ethics approval from their Human Research Ethics committees: The Children’s Hospital at Westmead, NSW HREC 10/CHW/59; Princess Margaret Hospital for Children, Perth, WA HREC Ref 1797EP; Lady Cilento Children’s Hospital, QLD HREC/10/QRCH/2; The Royal Children’s Hospital, VIC HREC 32052; Monash Children’s Southern Health, VIC HREC 11103B; and The Women’s and Children’s Hospital, SA, WCH HREC 388A.
All eligible participants and their families/caregivers are provided with a Child and a Parent Information Sheet regarding the study, and signed consent is obtained from the participant’s parents and/or caregivers, and the participant if they are able. When patients are from culturally and linguistically diverse backgrounds, health interpreter services available at each study site are used to explain the study and to gain signed consent.
Results of this study will be published in relevant peer-reviewed journals. Results will also be presented at relevant national and international conferences.
The authors acknowledge the Australian Intrathecal Baclofen Therapy Research Group Australia, of which they are all members. The authors thank Adam Scheinberg and Lisa Copeland for reviewing the manuscript and Brian Hoare, Melinda Randall, Natasha Bear, Kirstie Morgan and Caroline Vardy for their involvement in the initial study design.
Contributors KS, GH and MK all contributed equally to the written content of this article.
Funding The initial Australian ITB User groups, from where APIRG originated, were sponsored by Medtronic as was the development of the Access Data base used in this study. No ongoing funding has been provided by Medtronic, and Medtronic has no access to data or manuscripts.
Competing interests All authors were members of the original research group responsible for the project design and have contributed to the national meetings regarding this project since it commenced in 2011. None of the authors received any additional external funding to develop this protocol. Medtronic did sponsor Australia-wide educational activities where the authors and members of the research group met to discuss the ongoing nature of this study as part of a larger educational activity. Medtronic also sponsored the development of the database used in this study with an unrestricted educational grant but has provided no further ongoing funding and does not have access to any data or manuscripts.
Ethics approval All participating Australian sites obtained individual ethics approval from their Human Research Ethics Committees(HREC): The Children’s Hospital at Westmead, NSW HREC 10/CHW/59; Princess Margaret Hospital for Children, Perth, WA HREC Ref 1797EP; Lady Cilento Children’s Hospital, QLD HREC/10/QRCH/2; The Royal Children’s Hospital, VIC HREC 32052; Monash Children’s Southern Health, VIC HREC 11103B and The Women’s and Children’s Hospital, SA, WCH HREC 388A.
Provenance and peer review Not commissioned; externally peer reviewed.
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