Publishing protocols for trials of complex interventions before trial completion – potential pitfalls, solutions and the need for public debate

Background - Open Science is ‘the movement to make scientific research, data and dissemination accessible to all levels of an inquiring society’. In the spirit of the Open Science movement, advance publication of protocols for clinical trials is now being advocated by BioMed Central, BMJ Open and others. Simultaneously, participants are becoming increasingly active in their pursuit and sharing of trial- and health- related information. Whilst access to protocols alongside published trial findings has clear benefits, advance publication of trial protocols is potentially problematic for trials of complex behavioural interventions. In this article we explain, with examples, how this could lead to unblinding, ‘contamination’ between intervention and control groups and deliberate biasing of assessment outcomes by participants. We discuss potential solutions and demonstrate the need for public debate about how this issue is best managed. Conclusion - Triallists may still be underestimating participants’ interest in information. This needs to change: joint and open discussions with the public are needed to inform how we should proceed

Publishing protocols for trials of complex interventions before trial completion – potential pitfalls, solutions and the need for public debate

Background - Open Science is ‘the movement to make scientific research, data and dissemination accessible to all levels of an inquiring society’. In the spirit of the Open Science movement, advance publication of protocols for clinical trials is now being advocated by BioMed Central, BMJ Open and others. Simultaneously, participants are becoming increasingly active in their pursuit and sharing of trial- and health- related information. Whilst access to protocols alongside published trial findings has clear benefits, advance publication of trial protocols is potentially problematic for trials of complex behavioural interventions. In this article we explain, with examples, how this could lead to unblinding, ‘contamination’ between intervention and control groups and deliberate biasing of assessment outcomes by participants. We discuss potential solutions and demonstrate the need for public debate about how this issue is best managed. Conclusion - Triallists may still be underestimating participants’ interest in information. This needs to change: joint and open discussions with the public are needed to inform how we should proceed

How do parents frame their engagement experience in early intervention? A grounded theory study

PURPOSE: Parent and therapist engagement and partnership are critical in early intervention physiotherapy and occupational therapy for infants with cerebral palsy to improve outcomes. The main aim of this study was to understand how parents perceive their engagement experience in early intervention over time. METHODS: Grounded theory methodology was used. Twenty parents of diverse backgrounds participated in 22 interviews (including some repeated longitudinally) to reflect on their engagement experience within the context of early intervention community services provided in the UK NHS. RESULTS: The findings highlight how parents' perspectives of their engagement in EI change according to critical circumstances, including their preceding neonatal trauma, the at-risk CP label, firmer diagnosis of CP and their child's response to intervention. We theorise that this disrupted transition experience to parenthood becomes part of parental framing (or sense-making) of their engagement in EI. Overlapping frames of uncertainty, pursuit and transformation capture and explain nuances in parents' engagement patterns within EI over time. CONCLUSION: This theorising has implications for early intervention therapists in how they engage in the lives of families and partner with parents to support healthier parental transition, wellbeing and subsequent improved infant outcomes

Wrist-Worn devices to encourage affected upper limb movement in unilateral cerebral palsy: Participatory design workshops

Background: Unilateral (Hemiplegic) cerebral palsy (UCP) causes weakness and stiffness affecting one sided of the body, often impacting activities of daily living. Upper limb therapy at effective intensity is not accessible to most. Aim: To determine stakeholder views on design of an approach using wrist-worn devices and a smartphone application to encourage use of the affected upper limb for children with hemiplegia. Method: Four participatory design workshops and one young people's advisory group workshop incorporating views of five young people with hemiplegia, 13 typically developing peers aged 8–18 years, four parents, three occupational therapists, one teacher and two paediatricians. Two special educational needs co-ordinators were consulted separately. Peers were included to explore a study design whereby each child with hemiplegia would have a participating “buddy”. Topics included views on an acceptable wrist-worn device and smartphone application, participant age range, involvement of a buddy, and barriers to using the technology in a school setting. Ethical/welfare considerations included data security, and potential risks around providing smartphones to young children. Results: Children wanted a comfortable, conventional-appearing wristband incorporating a watch face and a secure, well-fitting strap. They were prepared to wear a band on each wrist. They wanted support with explaining the study to schoolteachers. Most schools restricted smartphone use during the school day: the study design accommodated this. Children agreed with a game as reward but had different views on an acceptable game; direct access to feedback data was preferred by some. Parents commented on the lack of access to upper limb therapy for children with UCP; therapists concurred. The proposed participant age range was widened based on feedback. Typically developing children were prepared to be buddies to help a friend with CP. Stakeholders were reassured by data security explanations and plans to provide internet safety information to participants. Conclusion: The participatory design process informed plans for the proof-of-concept stage of the study, hopefully leading to an approach that will be fun, easy to integrate into everyday life, and have the capacity to increase use of the affected arm and hand

Feasibility trial of an early therapy in perinatal stroke (eTIPS)

Background: Perinatal stroke (PS) affects up to 1/2300 infants and frequently leads to unilateral cerebral palsy (UCP). Preterm-born infants affected by unilateral haemorrhagic parenchymal infarction (HPI) are also at risk of UCP. To date no standardised early therapy approach exists, yet early intervention could be highly effective, by positively influencing processes of activity-dependent plasticity within the developing nervous system including the corticospinal tract. Our aim was to test feasibility and acceptability of an "early Therapy In Perinatal Stroke" (eTIPS) intervention, aiming ultimately to improve motor outcome. Methods: Design: Feasibility trial, North-East England, August 2015-September 2017. Participants were infants with PS or HPI, their carers and therapists. The intervention consisted of a parent-delivered lateralised therapy approach starting from term equivalent age and continuing until 6 months corrected age. The outcome measures were feasibility (recruitment and retention rates) and acceptability of the intervention (parental questionnaires including the Warwick-Edinburgh Mental Wellbeing Scale (WEBWMS), qualitative observations and in-depth interviews with parents and therapists). We also reviewed clinical imaging data and undertook assessments of motor function, including the Hand Assessment for Infants (HAI). Assessments were also piloted in typically developing (TD) infants, to provide further information on their ease of use and acceptability. Results: Over a period of 18 months we screened 20 infants referred as PS/HPI: 14 met the inclusion criteria and 13 took part. At 6 months, 11 (85%) of those enrolled had completed the final assessment. Parents valued the intervention and found it acceptable and workable. There were no adverse events related to the intervention. We recruited 14 TD infants, one of whom died prior to undertaking any assessments and one of whom was subsequently found to have a condition affecting neurodevelopmental progress: thus, data for 12 TD infants was analysed to 6 months. The HAI was well tolerated by infants and highly valued by parents. Completion rates for the WEBWMS were high and did not suggest any adverse effect of engagement in eTIPS on parental mental wellbeing. Conclusion: The eTIPS intervention was feasible to deliver and acceptable to families. We plan to investigate efficacy in a multicentre randomised controlled trial

Can wrist-worn devices and a smartphone application influence arm activity in children with unilateral cerebral palsy? A proof-of-concept study

Aim: To determine whether a wrist-worn triaxial accelerometer-based device and software (including smartphone application), incorporating feedback, is feasible, acceptable, and can lead to increased affected upper limb use during everyday activities in children with unilateral cerebral palsy (UCP). Methods: Study design: Mixed methods proof of concept study. Participants: Children aged 8–18 years with UCP; age-matched typically developing controls (“Buddies”), therapists. Intervention: Baseline (2 weeks): devices recorded arm activity. Active feedback (6 weeks): devices also gave vibratory prompts if affected arm activity fell below pre-set personalised thresholds (UCP group only; control group continued as per Baseline). Final 2 weeks: as baseline. Both groups accessed a smartphone application providing feedback on relative arm motion throughout the study. Assessment and analysis: ABILHAND-Kids questionnaires and MACS classifications captured baseline participant characteristics (UCP group). Accelerometer data was used to calculate relative arm activity (signal vector magnitude) corrected for time worn/day, and trends in relative arm activity examined using single case experimental design (both groups). In-depth interviews with families, “Buddies” and therapists assessed feasibility and acceptability of implementation. A framework approach was used for qualitative data analysis. Results: We recruited 19 participants with UCP; 19 buddies; and 7 therapists. Five participants (two with UCP) did not complete the study. Baseline mean (stdev) ABILHAND-Kids score of children with UCP who completed the study was 65.7 (16.2); modal MACS score was II. Qualitative analysis demonstrated acceptability and feasibility of the approach. Active therapist input for this group was minimal. Therapists appreciated the potential for summary patient data to inform management. Arm activity in children with UCP increased in the hour following a prompt (mean effect size z = 0.261) for the non-dominant hand, and the dominant hand (z = 0.247). However, a significant increase in affected arm activity between baseline and intervention periods was not demonstrated. Discussion: Children with UCP were prepared to wear the wristband devices for prolonged periods. Whilst arm activity increased bilaterally in the hour following a prompt, increases were not sustained. Delivery of the study during the COVID-19 pandemic may have negatively influenced findings. Technological challenges occurred but could be overcome. Future testing should incorporate structured therapy input

Development of paradigms for future assessment of cortical plasticity during development and following early lesions

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Improving outcomes in cerebral palsy with early intervention: new translational approaches

The aim of this Research Topic was to collate articles describing prediction of outcomes of pre- and perinatal lesions leading to cerebral palsy, basic research in animal models and human subjects, and ideas for, and trials of, interventions in the first two years of life.CP arises from insults to the sensorimotor cortex, subcortical axon tracts and subplate. The aetiology is complex and often multifactorial. The outcome is not simply a loss of voluntary control due to disruption of descending pathways, but also involves abnormal development of reflex and corticospinal circuitry. CP may be viewed as aberrant plasticity in response to a lesion, indeed, abnormalities in movement are subtle at first but develop subsequently. It is misleading to suppose that developmental mechanisms are self-reparative. The challenge is to understand activitydependent fine tuning of neural circuitry during normal development and to find how to promote desirable plasticity whilst limiting undesirable effects following developmental lesions. However, before proposing interventions, we have to develop our ability to predict the severity of neonatal insults.We solicited a variety of articles, including long and short reviews, original research and opinion pieces, from both basic scientists and clinicians. Likewise we, as editors, have complementary knowledge and experience in this area. Anna Basu is an academic pediatric neurologist and Gavin Clowry is a developmental neuroscientist