Early value assessment consultation document for HTE10056 Digital therapy for chronic tic disorders and Tourette syndrome

Provision of services for chronic tic disorders and Tourette syndrome varies across the NHS. Barriers to access include a shortage of trained therapists and limited access to behavioural therapy, which is only available at a small number of specialist treatment centres. As a result, experts estimate that less than 20% of children and young people with chronic tic disorders and Tourette syndrome currently have access to behavioural therapies (Marino et al. 2023). Clinical experts noted that there is often a long waiting list for referral to specialist services.

Because of variations in expertise, access and availability of services across the UK, many people are not getting the diagnosis, treatment and support they need. Digital therapies may improve access as well as equity of access to treatment options for people with chronic tic disorders and Tourette syndrome.

Clinical experts highlighted that providing any available resources to manage tics will help and support people living with tics. Both clinical and patient experts highlighted the great unmet need in this population. So, the committee recommended using Online Remote Behavioural Intervention for Tics (ORBIT) and Neupulse in the NHS while more evidence is being generated.

The EAG prioritised 3 randomised controlled trials for assessment. Two studies compared ORBIT with psychoeducation; 1 was done in the UK and the other in Sweden. The third study was UK-based and compared Neupulse active stimulation with sham stimulation. The EAG noted that the overall risk of bias was low for the 3 trials. The EAG reported on evidence from the prioritised studies, which used the Yale Global Tic Severity Scale's (YGTSS) Total Tic Severity Score to assess tic severity. They showed that tic severity was lower in the intervention groups compared with the comparator groups at follow-up periods ranging from 4 weeks to 18 months. But, no significant improvements were observed between treatment groups in tic-related impairment and distress (measured using the impairment score of the YGTSS). Clinical experts noted that the YGTSS's impairment score is not used widely in the research framework. But they explained that it is helpful to understand how tics affect day-to-day participation and function by talking to people with chronic tic disorders and Tourette syndrome, and their parents or carers.

The committee considered that ORBIT collected follow-up data for up to 18 months. Neupulse is still at an early stage of development, so there is no data beyond 4 weeks. Both companies mentioned that the clinical benefit will be sustained after using their technologies. Clinical experts explained that 18 months follow up in the ORBIT trial is more than enough and that it is common to treat lifelong neurological conditions where the evidence is in the shorter term. In clinical practice, the variability of treatment response in chronic tic disorders and Tourette syndrome is difficult to measure in a trial. It is unknown whether treatments continue to provide clinical benefits for years afterwards.

The committee carefully considered the safety of using digital therapy to treat chronic tic disorders and Tourette syndrome while further evidence is generated. Two ORBIT studies reported adverse events. Common adverse events reported in the UK ORBIT study were low mood, an increase in tics, and anger or irritability. Two serious adverse events were recorded, but both were deemed to be unrelated to participation. The company for ORBIT mentioned that there was no difference in the occurrence of adverse events in people with comorbidities in its post-hoc analysis. There were no adverse events reported in the Neupulse study. The company for Neupulse said that it had monitored and recorded adverse events but had not published this information. It mentioned that most adverse events are related to gel pads not being used correctly, which causes skin irritation. The committee noted concerns about the patient support for Neupulse because it is a self-administered device.

ORBIT has a potential escalation process for people who need more intensive treatment or referral to other services. The company for Nepulse stated that it does not yet have an escalation process. The committee considered that services would need staff and resources to monitor and respond to unexpected events, and to escalate care when needed.

Clinical experts were concerned about the impact of using Neupulse in people with functional tics. The company for Neupulse indicated that it plans to provide the technology directly to people who have tics and that people can use Neupulse without a formal diagnosis. Clinical experts raised concerns about people using Neupulse outside of the healthcare professional's clinic. There is a possibility that it could have unintended effects for people with functional tics and comorbidities, such as suicidal thoughts, anxiety and attention deficit hyperactivity disorder. Clinical experts also suggested that people should continue working with healthcare professionals for their long-term care. The committee felt that more data is needed on the use of Neupulse in people with functional tics and comorbidities. The committee concluded that Neupulse should have a system in place that provides adequate and timely professional support in response to alerts and outputs from people using the technology.

Clinical experts mentioned that it is important to take people's preference into account when considering treatment because people tolerate tics differently. Some people are happy to be discharged after a psychoeducation session. Both companies said that their technologies are not intended to replace psychoeducation, and ORBIT includes psychoeducation as one of its modules.

ORBIT has 'e-coaches' (not therapists), who are usually assistant psychologists, to support and motivate engagement throughout the programme.

The company stated that Neupulse does not need to be worn all the time because intermittent stimulation is sufficient to provide clinical benefits. The app for Neupulse can be used as a tracker for tics and a control for the device. People with epilepsy are excluded from the Neupulse trial and are unlikely to be able to safely use the technology.

The EAG developed a Markov cohort model to assess the cost effectiveness of different therapies for chronic tic disorders and Tourette syndrome in children and young people 12 years and over, and in adults. The EAG did not include any subgroup analyses in the economic model because there was not enough evidence to inform subgroup-specific transition probabilities. The EAG suggested that it was not possible to determine a definitive base-case incremental cost-effectiveness ratio (ICER). They explained that this is due to a lack of long-term follow-up data and uncertainty about the intervention costs that might be needed to maintain effectiveness in the long term. There is substantial uncertainty surrounding the estimated ICERs. While there is uncertainty for both technologies, the magnitude of uncertainty for Neupulse is greater than it is for ORBIT, driven by Neupulse's shorter follow up. Probabilistic ICERs ranged from £642 per quality-adjusted life year (QALY) gained to ORBIT being not cost-effective. The probability of ORBIT being cost-effective at a threshold value of £20,000 per QALY ranged from 52% to 89% across a range of explored scenarios. The EAG explained that the uncertainty is because of the extrapolation of the trial results from a short time horizon to a lifetime horizon.

Cost-effectiveness results for Neupulse were highly uncertain due to a lack of published transition probability data, the short 4-week follow up and uncertainty surrounding the intervention cost. The EAG assumed that there were no intervention costs assigned to the waiting list control arm of the model and no additional training or therapist support costs would be incurred. The company for Neupulse explained that Neupulse is intended to be a self-administered technology, with the company-provided materials containing all the training needed. The company is currently doing a usability study to assess how people follow the provided information. The EAG noted that transition probabilities were based on small counts and longer follow up is needed to determine whether initially optimistic improvements can be sustained longer term.

The committee noted that the evidence informing the cost-effectiveness model was limited but there was plausibility of cost effectiveness. It concluded that it was appropriate to recommend both technologies for conditional use in the NHS while more evidence is being generated.

Patient experts explained that chronic tic disorders and Tourette syndrome are lifelong conditions that affect all aspects of life, and it is often difficult to get a diagnosis and treatment. In some areas of the country, it is impossible to get access to services. People are often referred to multiple services but are told that the services cannot help them and that tics are out of their remit. A patient expert said that treatment relies heavily on people getting a diagnosis, but 56% of people waited more than a year for one. Even when they get a diagnosis, treatment and support are minimal in most areas. Many people are diagnosed and discharged in the same appointment with no offers of treatment. This may mean that they have to pay for private treatment. NICE surveyed people with chronic tic disorders and Tourette syndrome, and their parents or carers, about their experiences. NICE received 1,508 responses to the patient survey. People who completed the survey said that for most people it can take a long time to get a diagnosis (most people need to wait at least 6 months to 2 years). The acceptance of using digital technologies varied between people who completed the survey. The patient survey highlighted that the treatment options for chronic tic disorders and Tourette syndrome are limited.

Patient experts advised that any recommended digital therapy should only be offered when needed. They also suggested that digital therapy should be offered as a supplementary treatment after psychoeducation. Psychoeducation should be offered to everyone with a diagnosis. The possibility of training education staff, social workers and support workers on the technology should be considered. A patient expert added that treatment will also have a wider therapeutic effect on carers, parents and families who are also negatively affected by the stigma surrounding tic disorders and Tourette syndrome. Patient experts expressed their concern that treatment may be shifting to digital therapy because it is cheaper and possibly easier to deliver than face-to-face care. They were concerned that this may be happening despite weak evidence of a clinical benefit compared with existing treatments.

The committee acknowledged that access to diagnosis and treatment for people with chronic tic disorders and Tourette syndrome is limited. One clinical expert stated that there is a long wait for specialist assessment. The availability of behavioural therapy is extremely limited, particularly for adults. Digital therapies could increase access to treatment by providing another option for people with chronic tic disorders and Tourette syndrome. A submission from a patient organisation noted that chronic tic disorders and Tourette syndrome can have significant lifelong impacts on a person's ability to lead a normal life. These conditions can cause pain, stigma, isolation and anxiety. They can also have significant detrimental effects on education and employment, as well as on a person's physical, emotional and mental health. Patient experts also noted that people with chronic tic disorders and Tourette syndrome may experience stigma and discrimination, especially in childhood. So, it is important to carefully consider how treatments are presented and administered, because they could draw unwanted attention or further exacerbate social challenges for these people.

The committee considered that most participants in at least one of the ORBIT studies (the UK study) were white. A clinical expert explained that it reflects the cohort of people with chronic tic disorders and Tourette syndrome in NHS practice.

A patient expert advised that digital therapy may not be accessible to all socio-economic groups. Additional support and resources may also be needed for people with visual or hearing impairments, cognitive impairment, problems with manual dexterity, learning disabilities or who have difficulty reading or understanding health-related information in English. People's ethnic, religious, and cultural backgrounds may affect their views of digital health technologies. Healthcare professionals should discuss the language and cultural content of the technologies with people before use.

Digital therapies may not be suitable for everyone. They are delivered using a smartphone, tablet or computer. People need regular access to a device with internet access to use the technologies. Additional support and resources may be needed for people who are unfamiliar with digital technologies or do not have access to smart devices or the internet. People with limited access to these technologies or who are less comfortable or skilled at using digital technologies may be less likely to benefit.

Neither of the technologies included in this assessment are currently used in the NHS. Both technologies function differently. The company for Neupulse stated that it is a self-administered device, but the committee suggested that both technologies should involve supervision from healthcare professionals.

There is limited evidence on the acceptance and adherence of using digital therapies in people with chronic tic disorders and Tourette syndrome. There were also uncertainties around whether people would need to use the ORBIT platform for the longer term after finishing the sessions and the effectiveness of repeated interventions after relapse.

For both technologies, there were evidence gaps related to population, intervention, comparators and outcomes. The committee concluded that there is potential benefit and some evidence to support recommending both digital therapies for people with chronic tic disorders and Tourette syndrome in the NHS with evidence generation, once appropriate regulatory approval is in place. The key evidence gaps were:

• Population: the relevant evidence for both technologies was around children and young people. There was limited evidence of the effects of using the technologies in adults. To get access to a diagnosis and treatment for adults with tic disorders is extremely difficult. The symptoms of tic disorders often fluctuate. Certain life events, such as periods of increased stress, can cause some adults with mild tics to experience severe symptoms if they cannot access treatment. So, more research is needed on the benefits and risks of using digital therapies in adults. The clinical experts also mentioned that people with attention deficit hyperactivity disorder, obsessive-compulsive disorder and autism spectrum disorder are under-represented in the trial compared with clinical practice. This difference might be due to the measures used to assess comorbidities in the trial, rather than the population itself. People with these conditions could be disadvantaged by using digital technologies. More evidence is needed on using the technologies in people with comorbidities.

• Intervention: there was limited evidence particularly for Neupulse. The clinical experts suggested that evidence for Neupulse is required for a minimum of 6 months, with 12 months being the ideal duration. For ORBIT, the EAG stated that having data from additional timepoints would support extrapolation of the effectiveness beyond 18 months. The clinical experts advised that a minimum of 3 months of data is collected, with 6 months being the ideal. This is in addition to the 18 months of ORBIT data. But, securing sufficient funding for a 2-year data collection period may present challenges.

• Outcomes: evidence is lacking on the effect of digital therapies on quality of life. The EAG would like evidence that captures how a reduction in severity impacts quality of life or activity in daily life. The clinical experts explained that the connection between the objective measure of tics and quality of life is difficult. The EAG stated that the CHU-9D (Child Health Utility 9D) reported in the ORBIT trial is the only available utility score for the modelled health states. The clinical experts suggested that considering outcome measures such as school and employment attendance, interviews with families and a qualitative survey may be beneficial. The process-evaluation study used during the ORBIT trial included both children and parents and carers. But, more children's reported response for their own health state is needed. It will be useful to have views from people with chronic tic disorders and Tourette syndrome and their parents and carers.

• Adverse events: more information related to the tolerability and comfort of using Neupulse is needed. The clinical experts also advised that more research is needed on the effects of stopping Neupulse.

• Cost and resource use: more evidence is needed on long-term costs needed to maintain long-term effectiveness. It would also be useful to know the training requirements, staff and resource use for Neupulse.