The aim of this feasibility study is to estimate the parameters to inform a future randomised controlled trial that will evaluate whether the intervention plus standard care is more effective than standard care for enhancing the language and early communication skills and family health outcomes for children with Down Syndrome. We want to assess whether our early intervention can be delivered and rolled out through NHS Speech and Language Therapy Services.
The objectives are to:
- Determine whether parents of children with Down Syndrome are willing to be randomized
- Determine the acceptability of the intervention to speech and language therapists and effectiveness of recruitment of children with Down syndrome by speech and language therapists
- Identify different routes to identifying eligible children with Down Syndrome (pediatricians, health visitors, speech and language therapists, charities)
- Estimate follow up rate and adherence to intervention.
- Inform the measurement of health economic outcomes and resource implications of a parent-led intervention
- Determine the standard deviation of the primary outcome measure to inform a sample size calculation for a full trial
The effectiveness of the intervention will not be determined in this feasibility study but will be the aim of a subsequent full trial. The feasibility study’s outcomes will determine whether it would be viable to progress to a full-trial and whether adjustments need to made to the procedures, data collection methods, intervention delivery, and the intensity of support needed. We anticipate that NHS services will need to make ongoing changes due to the COVID19 pandemic, so it is likely we will need to make adjustments for the definitive trial.
Trial Design
This study is a two-arm randomised feasibility trial that will compare the intervention (in addition to standard NHS speech and language therapy) with no intervention (standard NHS speech and language therapy only) across three NHS sites. The intervention will be delivered by parents with the support of brief training and ongoing advice provided by NHS speech and language therapists over 10 weeks. The protocol has been developed in line with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist. See Figure 1 for a flow chart of the study.
Setting
The study will be conducted in 3 NHS sites in England, providing Speech and Language services across three geographical regions: Berkshire Health NHS Foundation Trust (BHFT), Oxford Health NHS Trust (OHFT) and North East London Foundation Trust (NELFT) (http://www.isrctn.com/ISRCTN13902755). All assessments will be conducted remotely using either online or paper questionnaires, with support by telephone. The study is being led by the University of Reading and the lead R&D organisation is BHFT.
Participants
Sample size
Between 25 and 30 children with Down syndrome aged between 11 and 36 months old will be enrolled in this feasibility study over a period of between 6 and 10 months. Given the feasibility nature of the study, no formal sample size calculations were performed, however the literature recommends a minimum of 24 participants [37,38,39] in order to derive a standard deviation.
Eligibility criteria
Inclusion Criteria
- Parent or guardian willing and able to provide informed consent on behalf of participant.
- Confirmed diagnosis of trisomy 21 (Down Syndrome).
- Male or female child, 11 to 36 months old at study entry.
- Parent/guardian has the literary and language skills needed to use intervention manual.
- The participant has not previously been entered into this study.
- The child is not currently taking part or planning to take part in a language based interventional study.
Exclusion Criteria
- Children with co-morbid conditions (for example Down syndrome and Autism Spectrum Disorder) as determined by the Principle Investigator.
- Any reason in the opinion of the Principal Investigator that the child is not suitable for study participation.
Intervention
The intervention focuses on promoting the development of early social communication skills and in particular, the child’s ability to respond to shared attention. The parent/guardian will be provided with an intervention manual (paper based), a bag of age-appropriate toys and links to short video demonstrations of the intervention, with explanation from either the PI or the child’s speech and language therapist. The intervention will be administered in the child’s home by the parent/guardian. The parent/guardian will be advised to progress through the stages of the intervention step by step and practise 3-6 times a week, totaling an hour a week, for 10 weeks. Support to deliver the intervention from the child’s speech and language therapist (SLT) (all of whom have had training on how the intervention works) will be available at the request of parents by telephone/email. Parents also have access to the PI of each site. The SLT will record all contacts from parents in the child’s case notes including duration and content of each contact. There will be two telephone calls from the PI, one at week 4 and the second at week 8 to offer support and check and ensure adherence to the intervention manual. They will ask a standard set of questions including how closely parents are following the manual, how often they do the intervention and for how long.
The participants in the intervention group will continue to also receive their usual care.
Comparator
The comparator is standard NHS speech and language therapy for this patient group.
Procedure
Speech and language therapists from participating NHS Trusts will identify potential participants (children with Down Syndrome) and their parents by reviewing their caseloads against the inclusion criteria. We will also publicise the study via other health care professionals and charities to give other potential participants the opportunity to self-refer to take part in the study.
The Speech and Language therapists (standard care team) will introduce the study to the parents of all potentially eligible children at a routine appointment, or will contact parents specifically to introduce the study, and ask them if they may be interested in taking part. The parent will be provided with a participant information sheet giving details of what study participation will involve and asked to contact the research team if they may be interested in taking part or if they have questions.
Parents will have as long as they need to consider participation and the opportunity to ask the speech and language therapist, the research team or other health professionals as many questions as they like in order to make their decision. Parents may choose to delay study entry to fit in with other family commitments. Where possible, reasons will be gathered if a family chooses not to participate by the child’s speech and language therapist.
Self-referring participants will receive the same information and have the same opportunities to discuss the study with members of the research team and ask any questions before they decide whether they would like to take part. If they do not currently have an NHS speech and language therapist, they will be advised to make a self-referral to their local service.
If they wish to take part, parents/guardians will contact the research team who will provide an electronic copy of the consent form. The consent form must be completed prior to commencement of any study activities. Given the age of the study population, 11-36 months old, the children will not be provided with information about the research nor will their assent be sought.
Randomisation
Once informed consent has been given and baseline assessments have been completed, participants will be randomised by the clinical trial manager or other designated team member via Sortition® (a secure web-based clinical trial randomisation software developed by the University of Oxford) using block randomisation to receive standard care (Control) or standard care plus the intervention (Intervention) in a 1:1 ratio, stratified by site, to account for regional differences in standard care. Following randomisation, the parents/guardians will be contacted by the study team, who will explain their child’s study allocation and what will happen next.
Intervention Group
Parents will be provided with a copy of the intervention manual (paper), a standard set of age-appropriate toys and books, a blank parent treatment diary and guidance on how to complete it, and a study schedule of planned conversations with members or the study team and when to complete the assessments. The study team will remind parents of the importance to the study findings of not sharing the manual with other parents.
Parents will be asked to use the manual to support their child in developing their skills in responding to bids for shared attention. The parents will be asked to follow the manual stages and undertake 1 hour of the intervention every week, split into several short sessions (3-6 per week), in whichever way the parent chooses. Parents will be asked to record the date and duration of each session, how many toys they used, and which stage they are working at, in the diary provided. Parents are asked to return electronically the diary weekly to the clinical trial manager.
Parents who do not complete the diary will be contacted by telephone or email at the end of the intervention period to remind them to return the diary, or to investigate the reasons for non-adherence. Two attempts will be made to contact parents, in order to respect their privacy and right to discontinue participation.
Control Group
The children allocated to the control group will receive the standard care for this patient group. SLTs will record all contacts with the family for the duration of the study in terms of duration and activity (assessment, advice, intervention)
At the end of the 6-month follow up period they will be provided with the intervention manual, accompanying materials and corresponding SLT or member of the study team support.
Adherence to the Intervention and Contamination
Adherence to the intervention will be monitored by using a weekly diary. The Principal Investigators/Site Leads will phone the parents twice during the intervention period: in weeks 4 and 8 to check adherence, with a window of +/- 5 days. They will ask a standard set of questions including how closely parents are following the manual, how often they do the intervention and for how long. Having this information will allow us to we have a log that can provide qualitative data as well as act as a metric of whether the intervention was acceptable to the parents and SLTs.
Any contamination that occurs between the intervention group and the control group will be measured at study entry. Parents will be asked whether they are familiar with the intervention materials, whether they have discussed the intervention with other parents or seen the manual, and whether they may have carried out any activities as described in the manual. This will be part of a questionnaire that asks about previous interventions the children may have had. During the post-randomisation process, when parents are contacted by a member of the study team who will explain to them what the allocation means, they will be reminded that the materials are for their own use only and with their own child only and are not to be shared with other parents. In addition, the fact that the control group will be given access to the manual and accompanying materials at the end of the study should minimise contamination risks as parents will be less likely to want to get hold of the manual via other parents.
Data collection
All children in the intervention and in the control group will be assessed by an assessor blind to group allocation before randomisation/pre-intervention, immediately post intervention (3 months after) and at a 6 month follow up, using the following instruments:
- Reading Communication Development Inventory [29], a parental checklist which assesses receptive and expressive language. This is also the primary outcome measure.
- Communication and Symbolic Behaviour Scale [30] which is a norm referenced instrument available as an online or paper questionnaire completed by parents/caregivers and assesses communicative functions, gestural communicative means, vocal communicative means, verbal communicative means, reciprocity, social-affective signalling, and symbolic behaviour. This is the secondary outcome measure
- Vineland Adaptive Behaviour Scale [31] assesses general cognitive and adaptive abilities and is completed by parents;
- Infant Toddler Quality of Life (ITQOL-SF47) [32] is a measure of infant quality of life
- Adult Quality of Life Questionnaire [33]
- Hospital Anxiety and Depression Scale [34]
Participants will also complete a demographic questionnaire at baseline. All questionnaires will be completed by parents online or using paper copies posted to the participant (if that is what the parent wishes), with support from a member of the research team, if required.
Outcomes
The effectiveness of the intervention will not be determined in this feasibility study. This will be assessed in a subsequent pilot/full trial. The feasibility study’s outcomes will determine whether it would be viable to progress to a full-trial and whether adjustments need to made to the procedures, data collection methods, intervention delivery, intensity, support needed. We will also calculate descriptive statistics which will we use for any future sample size calculation.
Objective 1: Are parents of children with Down Syndrome willing to be allocated to ‘standard care’ versus ‘standard care plus parent-led intervention’
During their meeting/telephone conversation or through email contact with their speech and language therapist (SLT), parents will be invited to take part in the study. The SLT will explain that if the parents agreed to participate, they would be randomly assigned to either ‘standard care’ (i.e. will get our intervention at a later time point), or standard care plus parent-led intervention group). If parents decline to participate, the SLT will invite them to state a reason (it will be important to know for a future full trial what the reasons for not accepting the intervention may be so these could be addressed), while assuring the parents that their decision will not affect their child’s future health provision. Parents’ responses will be coded using thematic analysis.
Objective 2: Acceptability of the intervention to speech and language therapists and their willingness/effectiveness to assist with participant recruitment
It is important to understand the speech and language therapists’ willingness to recruit to a future randomised control trial and support parents in the delivery of a parent-led intervention. To address this objective, all SLTs who had facilitated recruitment and/or the delivery of the intervention during the feasibility study, as well as other SLTs from Oxfordshire, Berkshire and other counties with paediatric caseloads will be invited to participate in an interview with a member of the research team. From this pool of participants, we will purposively sample so that all SLTs who had supported the delivery of our intervention during the feasibility study (10-12) take part, and SLTs who were not involved in the feasibility study with a range of specialisms are also represented. Potential participants will be invited to take part in a one-to-one interview (face-to-face or by telephone) with a member of the research team, who will use a topic guide developed in collaboration with the Public and Patient Involvement group. They will be audio-recorded and transcribed verbatim. Data will be collected until theoretical saturation is reached [35] (around 20-25 interviews). Data will be coded using NVivo (v11) and analysed using Framework Analysis [36].
Objective 3: Explore different methods to identify eligible children with Down Syndrome and other potential sites
Although speech and language therapists are the obvious professionals to help recruit children with Down Syndrome, not all children will be receiving support from SLT services and may still benefit from the intervention, hence we will also explore other routes, including paediatricians and charities which focus on supporting children with Down Syndrome. The chief investigator has collaborated with DownsEd International and Breakthrough Learning, and both charities support individuals with Down Syndrome. We will also make links with other potential NHS sites (so we have a bigger pool of sites for a future pilot/full randomised control trial).
Objective 4: Estimate retention and completion rates, adherence and acceptability of intervention to parents
The trial manager will keep a recruitment log to determine participation, adherence, drop-out and completion rates. These data will also be used to determine how long it would take to recruit participants into a full trial and the number of SLTs and sites needed. A parent weekly diary given to the parents will measure treatment intensity, completion rates and adherence to intervention. After completing the intervention, parents will be sent a questionnaire relating to their experience of the intervention, for example “how easy was it to follow the manual”.
Objective 5: To inform the measurement of health economic outcomes and resource implications of a parent-led intervention
We will identify how best to collect information about health outcomes for the children with Down Syndrome and their parents/carers as well as resource implications for the health service. Before the feasibility study commenced, we recruited 6 parents of children with Down Syndrome to take part in a focus group. The aim was to help us identify the most appropriate health outcome measures they thought would be useful to include in the feasibility study. These parents had older children with Down Syndrome and hence their children were not eligible to participate in the current feasibility study. The measures selected by the focus group (Adult Quality of Life Questionnaire the Hospital Anxiety and Depression Scale and the Infant Toddler Quality of Life Questionnaire will be administered pre-intervention, immediately post-intervention and 6 months post-intervention.
Objective 6: To determine the standard deviation of the outcome measure, which is needed to estimate sample size for a pilot/full trial. To estimate the standard deviation of the outcome measure, the literature recommends a minimum of 24 participants [37,38,39]. Descriptive statistics of the language measure (the Reading Communicative Development Inventory) will be derived.
Data analysis and presentation
Given the feasibility objectives of this study, the focus of data analysis will be descriptive. Recruitment and retention rates will be summarised and presented as a consort diagram. The number of participants enrolled, the number and percentage completing and withdrawing along with reasons for withdrawal will be summarised by intervention arm. Adherence to the intervention will also be summarised.
The language outcome measure (the Reading Communicative Development Inventory) will be summarised using descriptive statistics by visit and intervention arm. The Reading Communicative Development Inventory will also be analysed using mixed effect model for repeated measures with terms for baseline, site, age, intervention group, visit, baseline by visit and visit by intervention group. Repeated measures on a participant will be accounted for. Adjusted means, treatment differences and associated 95% confidence intervals will be presented.
The amount and percentage of missing data will be presented. Further exploratory analyses may be performed.
Health Economics/Health outcomes
The health economics component will explore the feasibility to identify and gather the relevant data required to evaluate the cost-effectiveness of the parent led intervention compared to usual care within a future full RCT. We will identify the intervention and trial costs (cost for manual, SLT costs, cost for material used in the intervention, cost of phone calls) from an NHS and personal social services perspective. We will also identify potential cost offsets and health care benefits. A descriptive analysis will be performed to assess the cost of the intervention and changes in health outcomes. During the feasibility study we will explore if there are more specific instruments that might be used to capture changes in health care status of children and their development using the IQToL and their parents/guardians using the AQoL and HADs. We will also investigate the possibility of capturing costs for families (private costs related to time and productivity losses). If the results are good, we could potentially run a within study economic evaluation to compare the changes in costs of the new intervention compared to the old one and the changes in outcomes.
Data management and security
Access to Identifiable and Sensitive Information
Direct access to the study data will only be given to authorised representatives from the Sponsor and host institution for monitoring and/or audit purposes to ensure compliance with regulations. Study staff will only have access to identifiable participant data if it is 1) in line with the informed consent given and 2) is essential for them to carry out their study role. Data will be de-identified as soon as it is practical to do so. The processing of the personal data of study participants will be minimised by use of a unique participant study ID on all study documents.
Research data will be kept secure and confidential, and access to personally identifiable data will only be granted to appropriate researchers and clinicians within the study research team. All questionnaire data will be labelled with numeric identifiers and data linking the identifier to patient information will be kept in a restricted access file separate to any other patient data.
Data Transfer, Storage and Archiving
All data transfer will be in line with the Sponsors standard operating procedures and the informed consent provided. Electronic Case Report Forms (CRF) s will be stored securely and password protected on University of Reading computers. The Chief Investigator will act as custodian of the data and ensure all regulatory and legal requirements are adhered to with support from the study sponsor. Personal data will be stored for 5 years after the study has ended.
Study governance
Project management will be organised at a number of levels, with a part-time trial manager working alongside the chief investigator (CI) and all the principal investigators. The CI has overall responsibility for the trial.
A Trial Steering Committee (TSC) will be established to provide oversight of the study. The TSC will meet 3 times in the first year and twice in the second year of the project. This committee includes an independent chair, independent statistician, a speech and language therapist not involved in the trial, the CI, all PIs, and at least one public and patient involvement representative and a person responsible for governance from the host organisation. The Steering Committee is chaired by an independent person (somebody who is an experienced Chief Investigator but not involved in the project). These meetings cover recruitment, adherence to protocol, monitor the rights and wellbeing of participants, finance and all NHS related issues. The Study Steering Committee will monitor the acceptability of the treatment and any potential adverse effects.
The Sponsor will be provided with direct access to source data and other documents if required for trial review.
Dissemination
The results of this study will be reported in peer reviewed scientific journals, conference presentations, publication on a website. The participants will be provided with a lay summary. Access to raw data and right to publish freely by all investigators in study or by independent steering committee on behalf of all investigators.