Introduction
The aim of the Health Technology Assessment (HTA) Programme is to ensure that high quality research information on the clinical effectiveness, cost-effectiveness and broader impact of healthcare treatments and tests are produced in the most efficient way for those who plan, provide or receive care from NHS and social care services. The commissioned workstream invites applications in response to calls for research on specific questions which have been identified and prioritised for their importance to the NHS, patients and social care.
Research question
- Is it feasible to conduct a study to examine the effectiveness of repetitive Transcranial Magnetic Stimulation for adolescents with depression, which has not responded to at least one antidepressant and psychological therapy?
- If feasibility is established, what is the clinical and cost-effectiveness of repetitive Transcranial Magnetic Stimulation in the treatment of adolescents with depression which has not responded to at least one antidepressant and psychological therapy?
- Intervention: Repetitive Transcranial Magnetic Stimulation (rTMS) in addition to usual care. Applicants to define the type of rTMS and treatment regimen.
- Patient group: Adolescents with a diagnosis of moderate to severe depression, which has not responded to at least one antidepressant and psychological therapy. Applicants to define and justify exact criteria including age range.
Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field. - Setting: Mental health services.
- Control: Applicants to define and justify a suitable control, e.g., sham rTMS procedure, in addition to usual care.
- Study design: A two stage study starting with a feasibility study leading into the main clinical evaluation. Applicants should identify and fully define appropriate stop/go criteria for a full trial.
Stage one: A feasibility study to determine whether future effectiveness research is possible and to establish key parameters of a potential future study. (See Rationale for further information.)
(The decision to go ahead with Stage two will be based on the agreed outcomes of the feasibility study.)
Stage two: A randomised controlled trial to evaluate the clinical and cost effectiveness of rTMS. - Important outcomes: Change in symptoms of depression. Health-related quality of life.
Other outcomes: Anxiety, self-harm, suicidal acts, social functioning, impact on relationships, medication use, further psychological therapy, occupational/educational outcomes, patient acceptability, side effects, cost-effectiveness.
Existing Core Outcomes should be included amongst the list of outcomes unless a good rationale is provided to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex (and other demographic factors where relevant). - Minimum duration of follow-up: 1 year.
Longer-term follow up: If appropriate, researchers should consider obtaining consent to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study.
If there is a full trial, the mechanism of action of the intervention is also of interest. Applicants who are successful in applying to this call are encouraged to consider applying to the MRC-NIHR Efficacy and Mechanism Evaluation (EME) Programme to investigate the mechanism of action. The EME Researcher-Led funding opportunity can be found here.
Rationale
The World Health Organisation (WHO) states that depression is the fourth leading cause of illness and disability in the adolescent age group. There are a range of symptoms that an adolescent with depression may experience, but the condition is characterised by a depressed mood and a diminished interest or pleasure in activities. Depression can have a huge detrimental impact on a young person’s home, educational and social life. It is suggested that 75% of mental illness in adults begins during adolescence.
For moderate to severe adolescent depression, NICE recommends offering a psychological therapy and if there is no response, then consideration can be given to adding an antidepressant. Combined treatment of medication and psychological therapy can also be considered as an initial treatment for moderate to severe depression in 12–18-year-olds. However, it is estimated that 40% of adolescent depression does not respond to treatment with an antidepressant or evidence-based psychotherapy. In these circumstances, the NICE guidance recommends that there should be a multidisciplinary review when an alternative psychological therapy can be considered but beyond that further treatment options are limited.
Currently for adults with depression, which hasn’t responded sufficiently to standard treatments, there is an additional NICE-recommended treatment option of repetitive Transcranial Magnetic Stimulation (rTMS), which uses pulsing magnetic fields to activate or suppress the brain centres associated with depression. The evidence for the use of rTMS in adolescents is not as advanced as it is in adults, but two recent systematic reviews have found that there is a signal of effect for the treatment and that it is safe to use in the age group.
The rate of mental illness in adolescents has increased significantly in the last decade. The need for additional effective and safe treatments is of high importance to both patients and clinicians. rTMS has the potential to be an additional treatment option for adolescents with moderate to severe depression who have not found standard treatments helpful or for whom they are not suitable. Therefore, the HTA programme is interested in commissioning research to (a) evaluate the feasibility of delivering a trial of rTMS to this patient group in the NHS and, if feasibility is successfully demonstrated, to (b) evaluate the clinical and cost effectiveness of rTMS.
As well as establishing the key parameters of a potential future trial, it is anticipated that the feasibility study will also identify the acceptability of rTMS to patients (and their parents/carers where appropriate) across different ethnic and socioeconomic groups, whether there is capacity in the NHS rTMS services to deliver a full trial, and both the views and knowledge of healthcare professionals working in Child and Adolescent Mental Health Services about the intervention.
Additional commissioning brief background information
A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email htaresearchers@nihr.ac.uk.
Making an application
If you wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page. To select this call, use the filters on the right of the screen or search using the call name and/or number.
Your application must be submitted on-line no later than 1pm on the 30 November 2022. Applications will be considered by the HTA Funding Committee at its meeting in January 2023.
Guidance notes and supporting information for HTA Programme applications are available.
Important: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in May 2023.
Applications received electronically after 1300 hours on the due date will not be considered.
For commissioned topics, the Programme strongly discourages the practice of the same co-applicant joining more than one competing team. There may be unusual circumstances where the same person could be included on more than on application eg a lead from a named charity or a unique national expert in a condition.
For such exceptions (i) each application needs to state the case as to why the same person is included (ii) the shared co-applicant should not divulge application details between teams and (iii) both teams should acknowledge in their application that they are aware that one of their co-applicants is part of a competing application and that study details have not been shared.
Should you have any queries please contact us by email at htacommissioning@nihr.ac.uk.