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21/580 Maintenance treatment for bipolar disorder commissioning brief

Contents

Introduction

The aim of the 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

In the maintenance treatment of bipolar disorder, what is the effectiveness of lithium, an antipsychotic or a combination of lithium and an antipsychotic?

  1. Intervention: Lithium vs antipsychotic vs a combination of lithium and antipsychotic.  Applicants to define and justify drugs and regimens.
  2. Patient group: Adults with bipolar disorder suitable for maintenance treatment. Exact inclusion criteria to be defined and justified by applicants. 
    Applications are encouraged which include recruitment from geographic populations with high disease burden which have been historically underserved by research activity in this field and should include all people eligible for recruitment.
  3. Setting: Secondary care.
  4. Comparator: The interventions will act as each other’s comparator.
  5. Study design: A randomised controlled trial with an internal pilot phase to test key trial processes such as recruitment and adherence. Clear stop/go criteria should be provided to inform progression from pilot to full trial. All three comparisons are valued equally.
  6. Important outcomes: Health-related quality of life. Symptom control. Relapse. Time to stopping allocated treatment.
  7. Other outcomes: Function, side effects, patient acceptability, hospitalisation, service utilisation, treatment adherence, discontinuation, occupational/educational outcomes, comorbid mental health conditions, physical health, suicidal ideation, use of emergency medication, cost effectiveness.
    Where established Core Outcomes exist, they should be included amongst the list of outcomes unless there is good reason to do otherwise. Applicants are encouraged to report recruitment and findings disaggregated by sex (and other demographic factors where relevant).
  8. Minimum duration of follow-up: 2 years.
  9. Longer-term follow up: If appropriate, researchers should consider obtaining consent from participants to allow potential future follow up through efficient means (such as routine data) as part of a separately funded study.

Rationale

Bipolar disorder is a lifelong condition that affects approximately 1-2% of the UK population.  Symptoms include recurrent manic and depressive episodes and, on average, people with bipolar disorder are symptomatically ill almost half the time. The disorder is associated with considerable impairment to personal, social and occupational functioning.

Bipolar disorder can be categorised as bipolar disorder type I or type II.  The former is made when someone has had at least one episode of mania which has lasted longer than a week. A diagnosis of bipolar disorder type II is made when there has been at least one major depressive episode and at least one hypomanic episode. Currently medication is the most helpful treatment for patients with bipolar disorder for both the acute episodes and, because of the high rate of recurrence, for maintenance treatment to prevent further recurrences.

NICE states that lithium should be offered as first-line, long-term pharmacological treatment for bipolar disorder. However, in practice both lithium and antipsychotics e.g. olanzapine and quetiapine, are prescribed individually and in combination. Both medications can have significant side effects and whilst helpful for many, relapses still occur.  There is little evidence about which is best in the long-term.

The decision about the type of maintenance treatment made between clinician and patient is an important one and the benefits and harms of each medication either on its own or in combination, must be weighed carefully because of the impact of side effects and recurrence on a patient’s quality of life. 

These decisions are currently being taken based on an inadequate evidence base and NICE highlight that the relative effects of both types of medication as monotherapy and in combination are not known, especially with regards to quality of life.

Therefore, the HTA programme is interested in commissioning research in this area to resolve this uncertainty.

Co-production, which ensures that the research demonstrates an equal partnership with service commissioners, providers and service users (or their advocates), should be embedded throughout the life cycle of the project from application to completion. Applicants may wish to consult the NIHR INVOLVE guidance on co-producing research.

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 March 2022. Applications will be considered by the HTA Funding Committee at its meeting in May 2022.

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 September 2022.

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: htacommissioning@nihr.ac.uk