What makes Down syndrome different?
It is hardly surprising, but perhaps worthy of comment, that bringing up a child with Down syndrome is, without exception, presented as a complex and challenging experience.81,82 The perceived ‘vulnerability’ and ‘dependence’ of the child heightens the parenting role and increases the sense of responsibility felt by the parent for the care and development of their child. A range of other, varied, emotions and feelings are also present in relation to specific personal experiences that are associated with bringing up a child who has Down syndrome. These include anger, resentment, denial, stigma, ‘fight’, ‘being part of a wider community’ and ‘responsibility to others’. The challenge of ‘working things out’, i.e. practical everyday things, was evident throughout the data, alongside some of these more emotional/social features. For example:
Interview 6:
You go through something with your child, don’t you and that is the way it always works with a child like J. You learn, pick up hints, tips, whatever has gone on and then you hope to pass that onto somebody else. I mean, [being] ‘mum’, it is so much more with a child like J, it is all about finding out what works, what’s the best thing, doing the best thing for them and if you can then pass that onto future children so they don’t have to, you know, find a way through themselves, absolutely. That is a good thing.
Strengths and weaknesses
The study was informed by a multidisciplinary research team supported by an engaged advisory group contributing the parent, patient and lay perspective, as well as independent clinical advice. As such, we feel that the questions asked in all elements of the research were appropriate and covered relevant issues to inform the feasibility and, if appropriate, design of future research.
This study achieved a lower than expected response rate from both parents and professionals, but arguably provides representative sample sizes for the qualitative elements of the study. It is likely that neither group is truly representative of the population that they were selected to represent. As in all similar research, it is likely that respondents were those who were more interested in the topic expressing more coherently thought-through opinions. The issue here is whether that means future research in a wider population would be more or less feasible?
Responses to the Delphi review were received from 28 professionals, with 24 completing all three rounds. Although a small number, this group encompasses the range of professionals involved in the care of children with Down syndrome and glue ear and the responses in terms of consensus or lack of it, and the pathways to achieving it were similar to previously reported Delphi reviews. A Health Technology Assessment publication on consensus methods68 indicates that as few as 12 participants may be required to ensure reliability and that as numbers increase response rates may diminish, possibly making the process counterproductive, in that bigger numbers might broaden ownership of the consensus and may lead to diminishing response rates that undermine the value of initially including more people.
From the 24 respondents who completed all three rounds of the review it has been possible to draw conclusions in consistent themes. The range of responses and the fact that consensus was not achieved immediately, or in some instances, at all, indicates that differences of attitude do exist between the various professions. Any negative attitudes would need to be controlled for in a future study.
A key element of representativeness for parents was their knowledge and experience of glue ear. From clinical experience we expected the majority of children to have had glue ear and expected the parents responding to be those whose children had experienced the condition but only just > 50% said that a doctor had diagnosed glue ear. This may be because we used the term ‘doctor’ or it may be because professionals do not actually say ‘glue ear’. More parents reported that their child had medical problems with their ears than those who said the child had been diagnosed with glue ear. It is likely that the parents responding are generally representative of those who might be asked to consider participation in a RCT.
Design of future research
For any future study to be successful it must achieve a high level of recruitment, both of parents to agree to their children taking part and of professionals to agree to recruit participants. The key issue in design is to encourage and not discourage participation.
Choice of interventions
There is currently clinical equipoise concerning the ‘best’ treatment for glue ear for children with Down syndrome. Clinicians identified conventional HAs, softband BAHA and grommets to be the most effective treatment options in this population, and these interventions, along with WW, and grommets and adenoidectomy, are possible interventions that might productively be investigated in a future research study. In restricting the scope of a future study to two treatment options, clinicians here prioritised softband BAHA and grommets. BAHAs are not routinely offered in all clinical services in the UK but a research study, appropriately funded could facilitate their provision. However, if found to be the intervention of choice, standard clinical provision would have to be implemented. A study including surgery, i.e. grommet insertion, may not be attractive to all parents, although some would welcome the chance for their child to receive this intervention. The inclusion of WW for this population of children would probably not be appropriate owing to the inferred element of ‘wasting time’. Data generated here also confirm that research should not incorporate alternative therapies or decongestants as treatment options.
There may be an argument for smaller in-depth studies in particular subgroups, for example a study of the role of antibiotics in children with Down syndrome who suffer recurrent infections, as a number of parents in this study reported improvements after antibiotics.
Choice of design
Randomisation was seen as a barrier by both parents and professionals, and an observational study of outcomes from clinically determined interventions might be more successful in recruiting participants.
Barriers and facilitators: parents’ perspective
Any proposed research study needs to respond to the broad similarities of parenting a child with Down syndrome (multiple symptoms, social–developmental issues, practical difficulties, etc.) and also needs to accommodate and negotiate the variety of highly personal perspectives and experiences that families have demonstrated. Individual willingness to participate in any future research is most likely to be influenced by familial experiences of medical professionals, exposure to life-threatening/life-saving medical procedures, and the nature and severity of their child’s symptoms and/or behavioural issues, more so than any general perspective on glue ear, Down syndrome or medical research.
Willingness to participate in a research study will not only vary between families, but also would vary over time. Times when symptoms are not well controlled, when treatment is not working, when the study treatment options are new, might all be times when a family might be more likely to participate in a study, whereas some degree of stability and control in the condition, and treatment options to which the child has already been exposed, might discourage participation. Research would certainly be unattractive at those times when the condition is being managed well. At this time research might be perceived as risking previously gained improvement.
There might exist a similarly complex and possibly contradictory relationship between a child’s age and a family’s willingness to take part in research. Research involving younger children might be perceived to have the greatest impact (most years of benefit, unlikely to have a stable treatment regime to disturb) but is also likely to be perceived as most risky and potentially traumatic to both child and parents, particularly for parents of very young children who are adjusting to parenting a disabled child. Times of transition are known to be times when parents become more concerned about communication, i.e. starting school and transfer from infant to junior to secondary education, particularly if separate schools. Concern often peaks when plans are being considered for the secondary phase of education. The timing of an invitation to participate in research perhaps requires further investigation.
That parents in this study described children with lesser or greater behavioural issues, who are more or less confident in new situations, who are more or less comfortable with treatments and more or less happy with strangers, once again reinforcing the range of circumstances that typify this population. Although clinic visits in a future research study might work for one family, home visits would be essential for another; frequent data collection might be acceptable to one but impossible for another; the involvement of unknown researchers might be unproblematic to some but a source of stress for others, etc. Some general principles might be postulated: recognise and limit disruption to family routines; generate child-friendly environments for appointments; be flexible about appointment times, accommodating school and work; recognise that families often have other children to care for; and be geographically accessible, ensuring that involvement does not require lots of travel (children’s centres were suggested as a possible venue). These are simple principles of good practice in undertaking research but are particularly relevant for this population.
It is hard to find concrete recommendations with respect to recruitment strategies and who is best placed and most likely to succeed in recruiting families to a study. Families would need to feel confident in the person who approached them to become involved; for some this meant someone already involved in the care of their child, whereas for others this meant a member of the team doing the research. Support and recommendation from other families were mentioned on a number of occasions. Overall, it might be summarised that the person who approaches families needs to be ‘credible’, he/she needs to appear knowledgeable about the challenges that families face, and also what the research will involve.
Detail about research processes was indicated to be important. Without detail about what is being asked of them, and what the outcomes might be, families cannot make a fully informed decision. A clear explanation of the chosen research design is essential as evidenced by a lack of understanding of randomisation expressed by some parents. A high level of recruitment could be compromised by parents withdrawing when their child is allocated to an intervention that they definitely do not want.
Barriers and facilitators: professionals’ perspective
Data generated here confirm that clinicians consider glue ear to be an important and challenging condition that can have significant impacts upon the health, behaviour and development of children with Down syndrome. That glue ear can affect hearing and communication – with direct consequences for social and emotional development, behavioural development and educational success – in a population that is already challenged by developmental delay reinforces the importance of effective management in this population. That Down syndrome is typified by a variety of symptoms, by symptoms that come and go, and by different manifestations in different children emphasises the complexity of the syndrome in both manifestation and management. It is consequently not surprising that more than one-quarter of those surveyed here could not isolate a single/prime symptom that might inform their clinical decision-making, and that more than two-thirds (70 out of 99) indicated that knowledge of multiple and varied factors are required to inform the management of glue ear in a child with Down syndrome.
This is a condition that clinicians find difficult to be entirely confident about treating, and a condition for which new evidence-based guidelines would be welcomed and would probably have a positive impact upon clinical management. Clinicians would support future research into the management of glue ear in children with Down syndrome, and the Delphi review demonstrated that significant numbers of clinicians would be willing to recruit to an appropriate study. That the variety of symptoms associated with glue ear, the complexity of management and the clinical and developmental difficulties associated with Down syndrome might act as barriers to the success of any future research study were rejected by the clinical population consulted here.
A consensus that research should seek improvements in a child’s hearing and in a child’s speech, language and communication was easily reached, and this reflects a professional assessment that these symptoms are frequent, difficult for the child and their family, and challenging to manage. A more detailed assessment of these data shows that hearing difficulties are identified as the most frequent problem associated with glue ear and also the most important challenge to address in Down syndrome (ranked first by most clinicians here). However, when all responses are considered (i.e. not just ranking first), listening, understanding communication and using communication all overtake hearing in this professional assessment of the most common and challenging symptoms of glue ear in children with Down syndrome. From a professional point of view, although future research might appropriately take improvements in hearing as its primary outcome, it should also definitely incorporate improvements in communication as a secondary objective. This assessment also reflects the opinion that improvements in hearing might be objectively measured more easily than improvements in communication.
There was some recognition that involvement in research might offer benefits for professional and career development but, in the main, professionals viewed an enhanced evidence base and better management of glue ear in Down syndrome as its key benefits. It should be noted, however, that this positive assessment did not extend to feeling confident that participation in a study would bring immediate clinical or non-clinical improvements for those children included. Most professionals surveyed here indicated that both observational and RCT research design might bring positive results, and most felt confident in describing both the benefits and processes associated with research. It is important to note that more professionals indicated that they would be happier to recruit families to an observational study rather than to a RCT, and that more than one-third of those who said that they would be happy recruiting to an observational study were not sure that they would do so for a RCT.
Differences in the views expressed by professionals might be attributed to a difference between those responsible for provision of interventions for glue ear, i.e. ENT surgeons and audiologists, and those who work with the outcomes of a hearing loss, i.e. SLTs and paediatricians, who support parents and children in daily life. Perhaps these data indicate a desirability for closer collaboration.
Throughout our data it is clear that professionals view this as an important and challenging topic; every child is different and every case requires different clinical management. Cases are complicated, typified by a complex interplay of those symptoms associated with glue ear and those symptoms associated with Down syndrome. These are symptoms that are difficult to distinguish and difficult to isolate, and it is this complex characteristic that makes future study both worthwhile and challenging. Yet this is a challenge that professionals here consider important to tackle; a challenge that all support, in principle at least, and that many, importantly, indicate that they would practically support should any study be undertaken.
Outcomes in a future trial
We explored the relevant areas of outcome rated as important by parents and professionals in order to contribute to the design of any future study through closed questions assessing importance, open discussion in interviews and focus groups, and in comparison with a data set derived from the responses of parents of children with glue ear but not Down syndrome. The outcome domains identified as important included speech, language and communication development, social development, hearing, school progress and quality of life of the children and parents, including issues around behaviour, sleep and general well-being. Children with Down syndrome exhibit wide variation in these measures and, in order to accurately reflect that variation, it would be necessary to include a number of measures in any future study.
We attempted to address this complexity of appropriate domains of outcome needed in future trials and whether or not measurement of these outcomes would be practical and feasible. It is apparent that the complexity due to variation in presentation of children with Down syndrome (particularly in the area of communication) and the overlapping impact of various domains raises challenges in being clear about causality and attribution of any identified improvement in any given domain.
Although speech and language were considered to be most important by parents and professionals as outcomes from any intervention, formal assessment with validated standard tools might be challenging as some existing tools (e.g. those assessed here) are not seen as appropriate for children with Down syndrome. Pre- and post-descriptive data would be most useful and, in relation to speech, an objective intelligibility rating.
In addressing any recommendation of research outcome measures, we have to see treatment in its larger context as attempting to help Down syndrome families, rather than alleviating middle ear disease as such, even though it is the direct manifestation of middle ear disease that can be helped by the treatments available. Previous research in children with glue ear who do not have Down syndrome found some evidence for improvements in hearing, leading to improvements in speech/language (M Haggard, personal communication), but the clinical outcomes in language in children with Down syndrome make it totally unclear whether improvements should be larger (via a synergistic multiplication) or smaller (because of a ceiling that cannot be shifted by therapy at this level.) Not only the parental prioritisation, but also the need for high reliability and ecological validity demands inclusion of a multifaceted assessment of language in any trial with performance as well as rating measures. A single main outcome measure cannot be justified under any circumstances. Outcomes should be multiple, based on the identified domains of concern and others relevant to the treatability of the glue ear, but should not be exclusively oriented to assessment of hearing.
It will be important to incorporate outcome measures that not only address elements of importance to parents and children, but also consider the practicalities of measurement, including time. Impact on communication is central and parental report via questionnaires may contribute a time-efficient measure. At the heart of any measure of effectiveness should be the question ‘Does helping the condition and its consequence, i.e. glue ear and hearing, help the child not only in communication, but also in social and educational progress and in the impact on behaviour and the family?’.
Any measure would first need to be sensitive enough, within subjects, to detect a difference due to an intervention over what would be a relatively short period of time and, second, measure outcomes that are affected mostly by hearing problems rather than by other consequences of Down syndrome. Although standardised assessments are not usually used clinically with children who have Down syndrome, they are used in research, often necessarily with caveats about how performance was affected by other factors. For example, it is difficult to score a child’s expressive responses when they have highly unintelligible speech. Another important issue in this context is the range of cognitive ability in the children and the effect of that on obtaining traditional outcome measures of hearing thresholds, speech discrimination and speech production. Outcomes of any future research study assessing treatment options for glue ear in children with Down syndrome might include speech, language and communication development; social development; hearing; school progress and quality of life of the child and parents, including issues around behaviour, sleep and general well-being. Children with Down syndrome will exhibit wide variation in these measures and, in order to accurately reflect that variation, it would be necessary to include a number of measures in any future trial. Key issues in any assessment of communication are the widespread reliance on signing systems for children with Down syndrome in the preschool years, and the variation in attention control and interaction.
Economic modelling
The intention of the economic modelling was to demonstrate the EVPI for interventions to treat children with Down syndrome with chronic OME. The models we examined had several limitations.
First, they iterate for only two cycles, notionally 2 years of life for the child, up to the age of 5 years. This may be too long a period in the context of a RCT, and too short a period in terms of clinical management. If trials are for shorter periods then the time lapse between repeated rounds of surgery is shortened with possible implications on adverse consequences; the need to extract and/or reinsert grommets in particular may raise. On the other hand, in extending to additional years of clinical management, rates of recovery from surgery and rates of spontaneous recovery improve with the age of the child and this adjustment would need to be incorporated. Our assumption on fixed recovery rates is a conservative estimate of the benefits of interventions for chronic OME.
Second, the model includes softband BAHA, which has a 3-year maintenance contract, while including only the first year of possible benefit from the BAHA. This would suggest that the model underestimates the benefits from the BAHA device. However, it is worth noting that the clinical care pathways model chooses BAHA only to be part of the cost-effective pathway when its costs are considerably lowered and it is always tolerated.
Third, the majority of the parameters are based upon expert opinion. This demonstrates the limited evidence available in this field, making construction of an economic model in this topic difficult. There is also the consideration of the link between PTA hearing loss and QALYs. The mapping of hearing loss to QALYs was based upon unpublished work conducted by Simon Dixon, and correspondence with the author allowed access to the data. The ordinary least squares regression used to develop the mapping estimate was deemed acceptable up to a hearing loss of 40 dB; however, SAs showed that robustness to the mapping could not be assumed.
Another consideration was the possibility of a microcosting analysis of the HA intervention. This was the method used in the NICE guidance.17 The cost of HAs in the NICE guidance17 is slightly larger, and hence this model could potentially be underestimating the costs of the HA intervention; however, the costs used are the current NHS reference costs (see Table 32), which represent the current reimbursement of HAs, which could potentially be seen as more relevant.
Despite these limitations, to the authors’ knowledge this is the first economic evaluation that has been conducted on interventions for OME in children with Down syndrome. In comparison with the economic evaluation conducted for the NICE guidance17 on OME, the clinical pathways model is more flexible, allowing the child to be managed with different treatments over time, implying that the model is more representative of the clinical situation.
Finally, both models assume a greater degree of hearing loss in a child with Down syndrome than a child in the general population.
The VOI analysis in the clinical care pathways model identifies greatest value in improving surgery recovery rates, with a population EVPI of £357,000. There is no capacity for benefit in research directed towards reducing surgery complication rates. The surgery-focused trial model also identifies a capacity to derive value from research into improving surgical recovery rates, provided that research costs do not exceed approximately £650,000. Finally, symptom management with BAHA appears the least preferred option, with a very small EVPI derived.
