Prospective cohort studies

Retrospective comparative cohort studies

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Infections (e.g. rubella, toxoplasmosis, CMV, herpes simples) – maternal TORCH

Multiple pregnancy

Intrauterine growth retardation

Haemorrhagic events

Hypoxic ischemic events at term/post term

neonatal encephalopathy

Apgar score at 10 min (Low/very low below 4/3)

Neonatal sepsis

Extreme prematurity 24 - 27 (+6 days) weeks gestational age)

Premature 28 - 31 (+6 days) weeks gestational age

Late premature babies (32-37 weeks gestational age)

Infections: meningitis and encephalitis

Clotting disorders /hyper coagulation in mother

Trauma/non-accidental injury

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed according to the process described in the NICE guidelines manual (2012).

If comparative cohort studies are included, the minimum number of events per covariate to be recorded to ensure accurate multivariate analysis.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Observational studies:

Prospective cohort studies

Retrospective cohort studies

Cross sectional studies

Registry data

UK

Europe

North America

Australia

New Zealand

Congenital brain malformations (e.g. mal-development of brain folding [gyri and sulci] and non-genetic conditions such as congenital infections)

Periventricular leucomalacia/damage of the white matter/white matter injury

hypoxic ischaemic injury (including perinatal and antenatal injury and stroke)

Intraventricular haemorrhage

Acquired traumatic injury

Congenital and acquired infection

Kernicterus

Neonatal encephalopathy

Neonatal Hypoglycaemia

The quality of the evidence for an outcome (i.e. across studies) will be assessed using GRADE according to the NICE guidelines manual (2012).

The quality of the evidence of each study will be assessed using the tool developed and published by Munn et al. 2014 for studies reporting prevalence.

Systematic reviews of observational studies

Observational prospective and retrospective studies.

Observational studies (prospective and retrospective) with sample size > 50 participants.

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Age ranges (under 8 months and above 8 months)

Low risk infants and children

gestational age

multiple birth

socioeconomic status

hypoxic events

neonatal sepsis.

Abnormality of movement

Under 8 months

Excessive crying/irritability

Feeding difficulties

Asymmetry of movement (gross and fine)

Abnormal muscle tone

Over 8 months old

Asymmetry of movement

Feeding difficulties

Persistent toe walking (equinus)

Delayed motor milestones

Under 8 months

Delayed sitting

Above 8 months

Delayed walking

Tools to identify clinical and developmental manifestations:

General Movement Assessment

Bayley Scale of Infant Development

Amiel-Tison neurological assessment

Infant Motor Profile

Risk of cerebral palsy (RRs, ORs, aRRs, aORs)

Sensitivity: the proportion of true positives of all cases diagnosed with CP in the population

Specificity: the proportion of true negatives of all cases not-diagnosed with CP in the population.

Positive Predictive Value (PPV): the proportion of patients with positive test results who are correctly diagnosed.

Negative Predictive Value (NPV): the proportion of patients with negative test results who are correctly diagnosed.

Area under the Curve (AUC): are constructed by plotting the true positive rate as a function of the false positive rate for each threshold.

Likelihood ratios

Prevalence of true positives

Risk of cerebral palsy (RRs, ORs, aRRs, aORs)

Sensitivity: the proportion of true positives of all cases diagnosed with cerebral palsy in the population

Specificity: the proportion of true negatives of all cases not-diagnosed with cerebral palsy in the population.

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

For cohort studies which report associations between manifestation and diagnosis, the NICE checklist based on Hayden JA, Cote P, Bombardier C (2006) Evaluation of the quality of prognosis studies in systematic reviews. Annals of Internal Medicine 144: 427–37 will be used to assess bias.

For prognostic studies, multivariate analysis will be used.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Prospective observational studies

Retrospective observational studies reporting clinical and developmental manifestations at diagnosis in children with a progressive neurological disorder, or other neuromuscular disorder not due to cerebral palsy.

Age ranges (under 2 year old and above 2 year old)

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Regression of speech

deterioration of vision

Regression of acquired motor skills

Lack of obvious risk factors for cerebral palsy

Family history

Severe muscle wasting

Neurometabolic (leukodystrophy; mitochondrial disorder)

Neuromuscular (SMA, muscular dystrophy)

Tumours (benign and malignant)

Genetic disorders (hereditary spastic paraparesis, progressive dystonia, Rett Syndrome)

Spinal cord disorders

The methodological quality of each study will be assessed using NICE checklists according to the process described in the NICE guidelines manual (2012)

Data analysis

Meta-analysis will not be conducted

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Systematic reviews of observational studies

Observational studies:

retrospective or prospective cohorts

cross-sectional studies, e.g. based on registry data

timing of birth (preterm vs term)

children with clear history of full term HIE/neonatal encephalopathy

children with no clear history or unusual developmental progress.

Stratified analyses:

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Magnetic resonance imaging + clinical assessment

Magnetic resonance imaging + clinical assessment + neonatal cranial ultrasound

Magnetic resonance imaging + clinical assessment + neonatal cranial ultrasound + other blood, urine or Cerebro-spinal fluid (CSF) investigations

Clinical assessment alone

Clinical assessment + neonatal cranial ultrasound

Clinical assessment + neonatal cranial ultrasound + other blood, urine or Cerebro-spinal fluid (CSF) investigations

Considered aetiology changed after MRI performed

Recognition of the following patterns of abnormality for aetiology:

Periventricular leucomalacia / white matter injury

Deep grey matter / basal ganglia lesions (typical of Hypoxic ischemic injury)

Diffuse encephalopathy

Brain Malformations (e.g. mal-development of brain folding [gyri and sulci] and non-genetic conditions such as congenital infections)

Focal ischaemic infarct or haemorrhagic lesions

Confirmation/ruling out of genetic or progressive movement disorders (as per study)

Periventricular leucomalacia / white matter injury

Deep grey matter / basal ganglia lesions (typical of Hypoxic ischemic injury)

Diffuse encephalopathy

Brain Malformations (e.g. mal-development of brain folding [gyri and sulci] and non-genetic conditions such as congenital infections)

Focal ischaemic infarct or haemorrhagic lesions

before 1 month (corrected for gestation)

1 month to 2 years of age

2-4 years of age

age (1)

treatment received (2)

level of cognition (3)

type of cerebral palsy

type of dysarthria

severity of functional disability

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Severity of functional disability (GMFCS levels)

Hypoxic ischemic encephalopathy (most likely to have early MRI before hospital discharge)

High risk babies (prematurity, twins/triplets, HIE, IUGR)

Low risk babies (lack of identified risk factors, present with developmental delay)

Early scan: before the age of 1 month (corrected for gestation)

1 month to 2 years of age

2-4 years of age

No MRI

MRI at different ages

Proportion of children and young people with epilepsy

Proportion of children and young people with feeding problems

Severity of functional disability using -

Gross Motor System Classification

The Manual Ability Classification System

communication problems

cognitive problems

changes in health-related quality of life (e.g. Lifestyle Assessment Questionnaire – Cerebral Palsy [LAQ-CP])

Mortality

Severity of functional disability

the methodological quality of each study should be assessed and the quality of the evidence for an outcome (i.e. across studies) will be assessed using GRADE as per the methods outlined in The Manual (2012).

Synthesis of data:

studies using only univariate analysis will be excluded

meta-analysis will not be conducted

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

the ability to walk

the ability to talk

life expectancy?

Severity of functional disability

Type of motor disorder

Cognition

Age.

Severity of functional disability

Type of motor disorder

Cognition

Age

Enteral tube feeding

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Severity of functional disability (GMFCS levels)

Level of cognition (measure of severity of brain injury)

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Delayed sitting

Severity of functional disability (GMFCS levels)

Level of cognition (measure of severity of brain injury)

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Uncontrolled epilepsy

Swallowing difficulties/dysphagia including need for enteral tube feeding

Severity of functional disability (GMFCS – 5 levels)

Level of cognition (as a measure of severity of brain injury)

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Comorbidities (epilepsy, scoliosis and chest infections)

Swallowing difficulties/dysphagia including need for enteral tube feeding

Survival

Ability to walk (including independent community walking/functional walking)

Ability to talk

Survival

Ability to walk (including independent community walking/functional walking)

Ability to talk

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed according to the process described in the NICE guidelines manual (2012)

Studies using only univariate analysis will be excluded.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Qualitative studies (for example, interviews, focus groups, observations)

Surveys (which include qualitative data)

Infants – 18 months and below

Children – 18 months – 12 years

Adolescents– 12 – 18 years

Young people - 18 - 25 years

Level of cognitive function

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Information content and type with regards to cerebral palsy

Information regarding cerebral palsy

Information regarding identification, cause and prognosis of cerebral palsy

Information about intervention type

Information about feeding and swallowing

Information about pain recognition and management

Information about transition of care

Information about commonly used medications

Information about named individual for point of contact

Information about possible comorbidities and accessing appropriate services/resources for managing them

Information about patient pathway and points of access

Information about education and health care

Information about sexuality and relationships

Information about lifestyle, leisure and social issues

Information about independent living

Information about organisations (support groups and charities, and their contact details)

Verbal

Written

Online

Apps

Play

Use of jargon and terminology

The methodological quality of each study will be assessed using qualitative study quality checklists and the quality of the evidence will be assessed by a modified GRADE approach (CER-QUAL) for each theme.

Data synthesis

Thematic analysis of the data will be conducted and findings presented.

Prospective cohorts

Retrospective cohorts

Infants – 0-6 months and 6 to 18 months

Children (18 months to 11 years)

Adolescents and young people (11 to 25 years)

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

VF + clinical assessment

FEES + clinical assessment

Clinical assessment of eating, drinking and swallowing using:

VF

FEES

[oral] motor difficulties (tongue movement, chewing, transfer to posterior pharynx, initiation of swallow etc.)

Vocal cord function

aspiration or risk of aspiration

Post-swallow pooling/residue

Nasopharyngeal reflux/regurgitation

oesophageal obstruction/dysmotility

Sensitivity

Specificity

Positive Likelihood Ratios

Negative Likelihood Ratios

Identifying the mechanisms underlying difficulties with eating, drinking and swallowing

Identifying risk of aspiration (leading to respiratory pathology)

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Randomised controlled trials (RCTs).

If no RCTs are available we will look for abstracts of RCTs and observational studies.

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

Infants, children and young people with cerebral palsy up to 25 years of age.

If no direct evidence of cerebral palsy population is found, a mixed population of children and young people with neurodisabilities will be considered.

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Food and fluid thickeners/texture modification

Postural management/modifications

Feeding techniques including pacing

Sensory therapy

Oro-motor therapies

Pharmacological

Feeding equipment

intervention versus no intervention

intervention versus placebo

intervention A versus intervention B

physiological function of the oropharyngeal mechanism (determined by clinical evaluation, VF, or FEES)

change in diet consistency a child is able to consume (developmentally appropriate oral diet; texture/consistency of foods and fluids must be modified; supplementary feeding required)

Respiratory health - presence of a history of confirmed aspiration pneumonia or recurrent chest infection (with or without pneumonia with suspected prandial aspiration aetiology)

nutritional status/changes in growth (weight and height percentiles)

child’s level of participation in mealtime routine/length of meal times(time taken to feed).

psychological wellbeing of parents and carers

acceptability of programme

survival

Nutritional status/changes in growth (weight and height percentiles)

child’s level of participation in mealtime routine/length of meal times (time taken to feed).

Respiratory health - presence of a history of confirmed aspiration pneumonia or recurrent chest infection (with or without pneumonia with suspected prandial aspiration aetiology)

The methodological quality of each study will be assessed and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012).

Data analysis:

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies at high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the included evidence

Randomised controlled trials (RCTs).

If no RCTs are available we will look for abstracts of RCTs and cohort studies

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

Children and young people with cerebral palsy from birth to 25 years.

For enteral feeding interventions, only population from birth to 18 years of age will be examined, as 18 years and over enteral feeding interventions are covered in CG32.

If no direct evidence of cerebral palsy population is found, a mixed population of children and young people with neurodisabilities will be considered.

Treatment duration and dose within standard range.

Exclusions: terminally ill patients, patients in ICU, patients who have experienced stroke or are receiving emergency care.

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Gastrostomy or jejunostomy tube feeding

Naso-gastric tube feeding

Oral nutrition support:

• high calorie feeds

Lifestyle changes:

• physical activity
• dietary changes

Antiemetics:

• Domperidone (trade name: Motilium)
• Metoclopramide (Maxolon, Reglan, Octamide)
• Erythromycin (can be used as an antiemetic if low doses are given)

Intervention versus no intervention

Intervention versus placebo

Intervention versus other intervention

Oral feeding vs tube feeding

Gastrostomy vs oral feeding

Jejunostomy vs oral feeding

Oral feeding vs anti-reflux medication

Other

Anthropometric measures:

• Weight
• Growth percentile

Adverse events:

• complications of feeding tubes
• complications of antiemitics
• vomiting frequency

Dietary intake - food offered and consumed.

Health related quality of life: using Child Health Questionnaire

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

Data analysis

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

For continuous data final and change scores will be pooled and if any study reports both, the method used in the majority of studies will be analysed.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies with high risk of bias.

A list of excluded studies will be provided following weeding

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

Stratified analyses:

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Physiological and oro-motor

• Facial Oral Tract therapy
• Talk tool
• Beckman

Articulation, speech sound, phonology, minimal pairs, dyspraxia programme

Tactile-kinesthetic

• PROMPT

Sub-systems

• Speech sub-systems
• Lee Silverman

Intra-oral/orthodontic

• Castillo-Morales appliance
• Innsbruck Sensori Motor Activator and Regulator
• Palatal Training Aid
• electropalatography)

Medical therapies/tone management

• Muscle relaxants (baclofen, L-dopa, trihexyphenidyl)
• Botox
• Acupuncture
• Postural management
• DBS

SALT versus no treatment

Intervention A versus intervention B

Quality of life

Speech intelligibility (for example percentage intelligibility)

Participation (including communication)

Self-confidence

Family stress and coping

Satisfaction of patient and family with treatment

Critical outcomes:

Participation

Speech intelligibility

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies with high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Only tools that are externally validated will be assessed

Note all individual adverse event frequencies in case needed for health economic model

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Alternative and Augmentative Communication (AAC):

Pictures or Symbol systems

Signing and gesture systems (for example Makaton)

Tangible symbols/objects of reference (objects used to represent words)

Speech generating devices (SGDs) or voice output communication aids (VOCAs)

Text based (written or computer)

Therapies given to familiar communication partners with the aim of changing the conversation style

intervention versus no intervention

intervention A versus intervention B

Communication production

Change in communication production

Change in sign/symbol production

Impact on family: stress, coping

Parental satisfaction

Participation

Quality of life

Preliminary classification of the outcomes for decision making:

Participation

Change in communication production

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

Synthesis of data:

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

For continuous data final and change scores will be pooled and if any study reports both, the method used in the majority of studies will be analysed.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies with high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

No restrictions on RCT sample size

If limited evidence is found, observational studies with sample size > 30 participants will be considered.

Treatment duration and dose within standard range

Stratified analyses:

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Sensitivity analysis: including and excluding studies with a high risk of bias.

Surgery

Pharmacologic treatments

Botulinum toxin

Physical/postural, oro-motor and oro-sensory therapies

Behavioural interventions

Intra-oral appliances

Acupuncture

Intervention versus no intervention

Intervention versus placebo

Intervention versus other intervention

Reduction of frequency and severity of drooling (including specific rating scales and volume)

Health-related quality of life.

Psychological wellbeing (for example, depression or anxiety).

Adverse effects:

• Pharmacological treatment: visual disturbance and constipation.
• Botulinum: swallowing problems and breathing problems.
• Surgery: ranulae and chest infection.

1. Drooling severity and frequency

2. Quality of life

3. Adverse effects

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012).

Meta-analysis will be conducted wherever possible

To apply NGA process for defining MIDS for intervention evidence reviews.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies with high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

To assess clinical importance for this outcome, the following minimal important difference thresholds were agreed by the Committee:

Thomas-Stonell and Greenberg scale: 2-points reduction (1 point for each section of the scale)

Teacher Drooling scale: 3-points reduction difference

Drooling Impact score: 10-points reduction

Systematic reviews of observational studies

Prospective cohort studies

If insufficient prospective evidence is found:

Retrospective comparative cohort studies

Case-control studies will be reviewed if insufficient retrospective comparative cohort studies are found

Age

Gender

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

GMFCS group

Type of cerebral palsy (spasticity/dyskinetic)

Anticonvulsant therapy

Nutritional inadequacy

Low Vitamin D status

Low weight for age, low weight/height or low BMI SD scores

History of metabolic bone disease of pre-mature birth

Risk of low volume bone mineral density- adjusted for the key confounders

Risk of low impact fractures- adjusted for the key confounders

As adjusted HR/ORs

A BMC or BMD z-score of more than 2 SDs below expected (less than −2) should be labelled “low for age.” The diagnosis of osteoporosis in children be made only when both low bone mass (BMC or BMD z-scores of less than −2) and a clinically significant fracture history (defined previously) are present.

Risk of low volume bone mineral density- adjusted for the key confounders

Risk of low impact fractures- adjusted for the key confounders

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

If comparative cohort studies are included, the minimum number of events per covariate to be recorded to ensure accurate multivariate analysis.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Randomised controlled trials (RCTs).

If no RCTs are available we will look for abstracts of RCTs and observational studies.

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

Age

Gender

Weight

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Primary prevention (those who have, or are at risk of, low bone mineral density but with no prior fractures)

Secondary prevention (those who have had a low impact fracture)

Use of standing frame as postural management

Use of vibration therapy as passive exercise

Active exercise programmes:

• rebound therapy
• static bicycle
• treadmill training

Active physiotherapy programme

Calcium supplementation

Vitamin D supplementation/sunlight

Calcium supplementation with vitamin D

Nutrition support (oral nutrition support, tube feeding, food fortification advice, dietetic advice)

Bisphosphonates

Intervention vs no intervention

Intervention versus other intervention

Alteration on DEXA score (levels of bone mineral density)

Change in frequency of minimally traumatic fractures

Patients satisfaction/acceptability

QoL

Pain

Adverse effects (drugs) for example:

• Bone fragility
• Gastric/oesophageal irritation/ulceration

Alteration on DEXA score (levels of bone mineral density)

Change in frequency of minimally traumatic fractures

Patients satisfaction/acceptability

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

Data analysis:

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews. Relevant MIDs discussed and agreed with the committee: A BMC or BMD z-score of more than 2 SDs below expected (less than −2) should be labelled “low for age.” The diagnosis of osteoporosis in children be made only when both low bone mass (BMC or BMD z-scores of less than −2) and a clinically significant fracture history (defined previously) are present.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies with high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Prospective cohort studies

Retrospective cohort studies

Cross sectional studies

Registry data

age ranges: <5 years; 5-11 years; 11-18; 18-25

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Sensitivity analysis: including and excluding studies with a high risk of bias.

musculo-skeletal pain/discomfort (including: hip pain, back pain or scoliosis, and spasticity)

gastrointestinal pain/discomfort

surgical pain/discomfort

physical therapy causing pain/discomfort

dysmenorrhea

dental pain

headache

Sleep disordered breathing (including obstructive sleep apnoea and sleep apnoea)

Seizures

Behavioural difficulties (including ADHD)

Pain

Prevalence of pain, discomfort, distress and sleep disturbance

The quality of the evidence will be assessed according to the process described in the NICE guidelines manual (2012)

The quality of the evidence of each study will be assessed using the tool developed and published by Munn et al. 2014 for studies reporting prevalence.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

provide guidance on tools to identify pain in children and young people with cerebral palsy that are reliable and valid.

assist parents, carers and health care professionals in recognising the clinical manifestation of pain, discomfort, distress and sleep disturbance in children and young people with cerebral palsy

assist in the onward specialist referral and management for those children and young people with cerebral palsy

ability to communicate

level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

age ranges: <5 years; 5-11 years; 11-18; 18-25

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Paediatric pain profile (1)

Non-communicating child’s pain checklist – revised/post-operative version

Face, legs, activity, cry, consolability Scale

Wong-Baker FACESR Pain Rating Scale (2)

Individualised Numeric Rating scale (Likert) (3)

Disdat

reliability

validity

sensitivity

specificity

reliability

validity

The quality of the evidence will be assessed according to the process described in the NICE guidelines manual (2012)

The methodological quality of each study will be assessed using the following tool: Jerosch-Herold, C (2005) An evidence-based approach to choosing outcome measures an checklist for the critical appraisal of validity, reliability and responsiveness studies. British Journal of Occupational Therapy, 68 (8). pp. 347-353.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the included evidence

Randomised controlled trials (RCTs).

If no RCTs are available we will look for abstracts of RCTs and observational studies.

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

age ranges: <5 years; 5-11 years; 11-18; 18-25

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)severity of functional disability (GMFCS level)

Psychological therapy

Cognitive behavioural therapy (CBT)

Physical therapy

Postural management/equipment review/reassessment (seating, wheel chairs, splints)

hydrotherapy

Analgesics:

• Paracetamol
• ibruprofen

Anticonvulsants:

• Gabapentin
• pregabalin
• carbamazepine
• sodium valproate (in CYP with CP but no epilepsy)
• Benzodiazepines
• diazepam
• Opioids
• Fentanyl patches

Intervention A versus intervention B

placebo

no treatment

pain control

distress

physical function (Multidimensional Pain Inventory Interference Scale / Brief Pain Inventory interference items)

emotional function (for example, depression or anxiety using Beck’s depression inventory)

adverse events, including withdrawal

health-related quality of life (for example, Peds-QL, Pediatric QOL-CP module or EQ-5D)

Parent and carer outcomes (e.g. anxiety)

pain control

distress

health-related quality of life

The methodological quality of each study will be assessed and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012).

Data analysis:

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analyses

If heterogeneity is found, sensitivity analysis will be performed, removing studies at high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the included evidence.

Randomised controlled trials (RCTs).

If no RCTs are available we will look for abstracts of RCTs and observational studies.

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

age ranges: <5 years; 5-11 years; 11-18; 18-25

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)severity of functional disability (GMFCS level)

type of measurement for sleep disturbances (i.e. sleep diaries and actigraphy)

melatonin

sleep systems/ sleep positioning (postural devices, wedges and supports)

Age appropriate sleep routine (termed as sleep hygiene programmes)

alimemazine

vallergan

chloral hydrate

clonidine

any other pharmacological or non-pharmacological intervention that is used to reduce sleep disturbance

placebo

no treatment

sleep quality, measured for example, by polysomnography (gold standard) or by other methods such as wrist actigraphy, sleep diaries, Sleep Habits Questionnaire

adverse events, including withdrawal

day time emotional wellbeing/lability

health-related quality of life (for example, Peds-QL, Pediatric QOL-CP module or EQ-5D)

The methodological quality of each study will be assessed and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012).

Data analysis:

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat analysis (ITT), then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

For continuous data final and change scores will be pooled and if any study reports both, the method used in the majority of studies will be analysed.

If heterogeneity is found, sensitivity analysis will be performed, removing studies at high risk of bias.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the included evidence

Systematic reviews of observational studies

Observational studies:

Prospective cohorts

Cross-sectional studies

Observational studies (prospective and retrospective) with sample size > 50 participants.

Age ranges: <5 years; 5-11 years; 11-18 years; 18-25 years

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Communication difficulties (verbal/non verbal)

Self-report Mood and Feelings Questionnaire (MFQ)

Hospital anxiety and depression scale (HADs)

Beck youth inventories

CHQ 50 – child health questionnaire 50

CP Child - quality of life questionnaire

Strengths and difficulties questionnaire

Child behaviour checklist

GHQ – DoH

Sensitivity

Specificity

Positive predictive value

Negative predictive value

Area under the curve

Reliability/validity

Sensitivity/specificity

Positive and negative likelihood ratios

Odds ratios

The methodological quality of each study will be assessed using NICE checklists and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE guidelines manual (2012)

Randomised controlled trials (RCTs).

If no RCTs are available we will look for abstracts of RCTs and observational studies.

No restriction to RCT sample size

If limited RCT evidence is found, observational studies with sample size > 30 participants will be considered.

Children – 18 months to 12 years

Adolescents– 12 to 18 years

Young people - 18 to 25 years

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Ability to communicate

Individualised self-help – 16 years and above – will depend on cognitive ability

Behavioral technigues –eg relaxation techniques, mindfulness

Cognitive behavioural therapy

Psychoeducational groups

Psychotherapy (wide term – could cover CBT etc etc etc)

Family therapy

Antidepressants (including SSRIs)

• Amitryptylline
• Diazepam
• Fluoxetine
• Citalopram
• Sertraline

Anxiolytics

• Buspirone

Physical

• physical activity

Counselling and support:

• Group based peer support programme
• counselling

No intervention

Control

placebo group

other interventions

Health related quality of life of children and young people with CP as well as parents and carers (for example, KIDSCREEN-10, PedsQL, CHQ, European generic HRQOL, CPQOL-child, CPQOL-teen)

Social participation

Emotional health (for example, SDQ)

Improvement in behaviour (for example, Behaviour Problems Inventory/index) Child Behaviour Checklist

Psychological wellbeing (for example, Beck Youth Inventory)

Parent/carer impression of change (for example, Kiddle-SADs (at school starting age))

Adverse effects (side effects of meds – sedation, drowsiness, change in movement, worsening of siezures)

Suicide risk

Sleep quality

Health related quality of life

Emotional Health

Adverse effects

The methodological quality of each study will be assessed and the quality of the evidence will be assessed by GRADE for each outcome according to the process described in the NICE manual (2012)

Data analysis:

Meta-analysis will be conducted wherever possible

If studies use available care analysis (ACA) and intention to treat (ITT), then ACA will be preferred over ITT

To apply NGA process for defining MIDS for intervention evidence reviews.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analysesIf heterogeneity is found, sensitivity analysis will be performed, removing studies with high risk of bias

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Auditory

Gustatory

Olfactory

Tactile

Vestibular

Proprioception (somatosensory)

Visual

Age ranges: <5 years; 5-11 years; 11-18; 18-25.

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)

Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Sensory integration (traditional method) (sight, sound, taste, smell, touch, balance, body position, tactile, sensory diet, sensory lifestyle)

Goal-directed therapy /Activity focussed and goal directed therapy/Task-orientated therapy

Occupational therapy (Activity analysis, CO-OP approach (cognitive orientation to daily occupational performance)

Computer based programmes (for example, videogame therapy, computer enhanced therapy to improve balance)

Neuro-psychological and educational psychological support (behavioural training)

Regarding assessments of general sensory processing there are various versions of the Sensory Profile that are commonly used and there is also the Sensory Integration Praxis Test (SIPT) developed by Jane Ayres.

Control

No treatment

Other interventions

Combinations of interventions

Improvement in processing sensory and perceptual information (for example, improvement in learning, cognitive function, emotional well-being, physical function, socialising and making friends)

Health related quality of life (Child health questionnaire, CPQOL)

Improvement in psychological wellbeing (anxiety and depression) (for example, HADS, Becks Depression Inventory)

Wellbeing of parents and carers (for example, Becks Depression inventory)

Goal attainment scales

Regarding outcome measures for the sensory / perceptual question there are several visual perceptual assessments commonly used by occupational therapists. These include:

The Beery Visual Motor Assessment (VMI) (6 editions)

The Test of Visual Perception Sills (TVPS) (3 editions)

Motor Free Visual Perception Test (MVPT) (4 editions)

Improved sensory and perceptual function

Health related quality of life

Improved psychological wellbeing

The methodological quality of each study should be assessed and the quality of the evidence for an outcome (i.e. across studies) will be assessed using GRADE according to NICE guidelines manual (2012).

Synthesis of data:

Meta-analysis will be conducted wherever possible

If studies use available case analysis (ACA) and intention to treat (ITT) then ACA will be preferred over ITT.

To apply NGA process for defining MIDS for intervention evidence reviews.

Final and change scores will be pooled and if any study reports both, change scores will be used in preference over final scores.

If studies only report p-values from parametric analyses, and 95% CIs cannot be calculated from other data provided, this information will be plotted in GRADE tables, but evidence may be downgraded.

If studies only report p-values from non-parametric analyses, this information will be plotted in GRADE tables without downgrading the evidence, as imprecision cannot be assessed for non-parametric analysesIf heterogeneity is found, sensitivity analysis will be performed, removing studies at high risk of bias

Prospective cohort studies

Retrospective cohort studies

Cross sectional studies

Registry data

Infants – 18 months and below

Children – 18 months – 12 years

Adolescents– 12 – 18 years

Young people - 18 - 25 years

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic))

Severity of functional disability (GMFCS levels)

Level of cognition (treatments require sustained attention, ability to follow commands and ability to understand the impact of limited intelligibility)

Pre-natal and perinatal cerebral palsy

Behavioural difficulties

Cognitive and learning disabilities

Hearing difficulties

Visual difficulties

Vomiting, regurgitation and reflux

Constipation

Epilepsy (particularly in specific subgroups)

Communication difficulties

The quality of the evidence has been assessed by using the tool developed and published by Munn et al. 2014 that assesses critical issues of internal and external validity that must be considered when addressing validity of prevalence data.

Synthesis of data:

Data from Surveilance for Cerebral Palsy in Europe (SCPE) registry (which includes UK data); the Victorian cerebral palsy register and the CPUP (Scandinavian/ Norweigan database) will be used as key sources of prevalence of comorbidities where possible.

For comorbidities not reported in the key registries: average rates of comorbidities will be presented as ranges.

A list of excluded studies will be provided following weeding

Evidence tables and an evidence profile will be used to summarise the evidence

Qualitative studies (for example, interviews, focus groups, observations)

Surveys (which include qualitative data)

Purely quantitative studies (including surveys with only descriptive quantitative data)

Infants – 18 months and below

Pre-school children – 18 months - 60 months

Primary/ Junior school children – 5 – 11 years

Adolescents– 11 – 18 years

Young adults - 18 - 25 years

Severity of functional disability (GMFCS levels)

Children from ethnic minorities

Children with multiple comorbidities

Children who are undergoing/ recovering from a major intervention (e.g. hip and spine surgery and gastrostomy)

Parents whose specific demographic, geographic, religious or cultural beliefs may affect or restrict their ability to engage or to accept help.

Looked after children/ children who are subject to the safeguarding process

Independent living

access to transport/adaptable accessible vehicles

Training in independent travel (depending on level of severity of cerebral palsy)

Mentoring support

Access to services

Social care assessments at time of diagnosis to assess the needs of children and young people and family and signposting of available social care options

Access to age appropriate recreation/play/portage opportunities

Access to support groups/activity groups

Access to appropriate educational vocational /work opportunities >16 years of age

Specialist nurse involvement, OT

Attending clinics on the same day or joint clinics

Advice and information provided

Advice on respite care

Information and advice on personal care

Advice, guidance and access to aids, equipment, hoists with adaptations to home/school

Advice and guidance on benefits (DLA/ ESA /carers allowance) and disability allowances

The methodological quality of each study will be assessed using qualitative study quality checklists and the quality of the evidence will be assessed by a modified GRADE approach (CER-QUAL) for each theme.

Data synthesis

Thematic analysis of the data will be conducted and findings presented.

Qualitative studies (for example, interviews, focus groups, observations)

Surveys (which include qualitative data)

Purely quantitative studies (including surveys with only descriptive quantitative data)

Adolescents – 12 – 16 years

Young people - 16 – 18 years

Young people - 18 - 25 years

Type and motor distribution of cerebral palsy (spastic unilateral, spastic bilateral, ataxic, and dyskinetic)Severity of functional disability (GMFCS levels)

Severity of cognitive disability

Degree of independence

Level of comorbidities

Transition clinic: Transition lead (consultant/social worker) preparation of plan of transition for individual and family/carers, MDT structured approach

Health care professional training in transition to improve practice

Transition programme/preparation period and education programme (for young person to be able to function in the adult clinic, and able to manage illness mostly independently of parents and staff). Use of transition questionnaires.

Involvement of young people and family/carer in planning, implementing and reviewing transition

Communication point of contact information (written, verbal, and email format), and clarity about process (eg, nurse rehabilitation specialist, community paediatrician)

Key transition therapist as part of paediatric and adult service

Involvement of multiagency: health care, social care and education and passing information to adult services (e.g., admin support for records and appointments, transfer checklist, medical and MDT summaries before transfer)

Communication/co-ordination between paediatric and adult services

Timing of transition with education and other agencies (eg social services) to make it as seamless and as flexible as possible (e.g., a joint transition clinic that consists of both paediatric and adult team members)

Information for young people and carers/family about health needs of cerebral palsy as an adult, about treatment centres, available support services and resources and funding, may need to be in different format if they cannot read.

Delivering information to the adult services- for example, booklet or passport for young people carry with them when attending hospital and other appointments.

Timing (age of transition) to take account of individual circumstances and problems.