Mental Health Award: Integrating sleep and circadian science into our understanding and treatment of anxiety, depression and psychosis

International
Posted 1 year ago

As part of our new strategic focus, Wellcome aims to develop new and improved early interventions for anxiety, depression and psychosis, in ways that reflect the priorities and needs of people experiencing these conditions. This work involves advancing scientific understanding of how brain, body and environment interact in the trajectory of these problems; and finding new and useable ways to predict, identify and intervene as early as possible.

Disturbances in sleep and circadian rhythms can predict the onset and relapse of mental disorder, are common in cases of depression, anxiety, bipolar disorder and schizophrenia, and have a major bearing on quality of life. Greater severity of insomnia and/or circadian disruption is associated with higher levels of psychopathology and suicidality, increased risk of relapse, and poorer treatment outcomes.

However, as highlighted in our recent report on the current research landscape relating sleep and circadian rhythms to mental health, significant knowledge gaps remain. This award aims to advance understanding of the roles played by sleep and circadian rhythm disturbance in the development and resolution of anxiety, depression and psychosis – with a view to enabling effective early detection and intervention. Harnessing recent neuroscientific, technological and analytic advances will allow deeper characterisation of the changes occurring in sleep and circadian function, the underlying mechanisms driving these changes and their contributions to the development and maintenance of anxiety, depression and psychosis in diverse populations.

About your proposal

What are we looking for? 

We are interested in applications that advance understanding of the dynamic changes that occur in sleep and circadian rhythm across trajectories and phases of anxiety, depression and psychosis, in different developmental, geographical, societal and cultural contexts.

This should involve research projects that will advance knowledge in relation to at least one of the following:

  • The biological and/or psychological mechanisms through which sleep and circadian disruption influence and are influenced by anxiety, depression and psychosis.
  • Identification and/or validation of sleep and circadian markers that enable early stratification of people with anxiety, depression and/or psychosis.
  • Development of novel or improved early interventions for anxiety, depression and psychosis, which target sleep and/or circadian processes.

We take anxiety, depression, and psychotic disorders as broadly defined categories to include all types of anxiety and depressive disorder (including obsessive compulsive disorder and post-traumatic stress disorder) and all forms of psychotic disorder (including schizophrenia, postpartum psychosis, and bipolar disorder).

We recognise that the current diagnostic categories are imperfect but removing all categories or creating new ones also presents difficulties. We therefore use the terms anxiety, depression, and psychosis to refer to overlapping constellations of thoughts, feelings, and behaviours that have historically been classified as discrete conditions.

Applications should: 
  • Have sufficient scope and ambition, such that the findings have the potential to transform early intervention options for people with anxiety, depression and/or psychosis (either directly or in time).
  • Be hypothesis driven, and include an underpinning mechanism or, where that is lacking, investigation of the underpinning mechanism should be included as part of the application.
  • Integrate both sleep and circadian measures, rather than focusing solely on one or the other.
  • Combine measurement of sleep-circadian function with investigation of symptoms, behaviours, environment and treatment variables during wakefulness (for example: mood, energy, activity, light exposure and medication), where possible in the home environment.
  • Sample dimensional sleep and circadian measures, and/or examine a range of sleep disorders additional to insomnia (for example: hypersomnia, sleep disordered breathing, circadian-rhythm sleep wake disorders, nightmare disorder). Please also see the section on Recommended common measures for sleep and circadian function.
  • Use the most appropriate methodologies to address the research question. These may include, but are not limited to, subjective measures, polysomnography, EEG, circadian biomarkers and actigraphy, as well as novel but appropriately performance-evaluated methods such as digital phenotyping.
  • Include validated measures for anxiety, depression and psychosis (see Recommended common measures for anxiety, depression and psychosis).
  • Include functional outcome measures or measures of quality of life, with a clear rationale for the measures chosen.
  • Draw on relevant preclinical findings to advance the field.
Applications may: 
  • Adopt a transdiagnostic approach to examining sleep-circadian disturbance across target disorders.
  • Sample longitudinal and dynamic changes in sleep, circadian function and psychopathology over phases of illness and developmental timepoints.
  • Use interventional study designs to identify and test underlying causal mechanisms.
  • Include work packages involving secondary analysis of data.
  • Include work packages involving animal models and healthy volunteers to elucidate mechanisms, but these should not be the sole focus of the application.
  • Examine mechanisms underlying inter-individual vulnerability and resilience to the effects of sleep-circadian disruption.
  • Involve the development of novel circadian biomarkers, sleep sensing-technologies and analytic approaches.
  • Consider the potential for the research to have applicability, acceptability, and scalability in settings beyond its specific context, including in low- and middle-income settings.

Recommended common measures for sleep and circadian function

To support our common measures approach, we plan to define a standardised set of core measures for sleep and circadian science, in conjunction with the external community. This will occur in parallel with the funding call. We ask you to include and justify your preferred measures in your application. Following the final funding decisions, we will request successful award holders to input into the process of defining common measures, through attendance at a workshop, and to implement the recommendations as part of their research. Wellcome will work with award holders to make any necessary amendments to project plans and budgets.

In addition to using the recommended measures, applicants can supplement these measures with other data collection tools, as appropriate.

We also want to encourage harmonisation across studies and will support data sharing, pooling and analysis across the portfolio. We will convene successful award holders, ahead of the award start date, in order to explore potential opportunities for collaboration and harmonisation across projects to maximise linkages and impact. 

As a member of the Common Measures Board for Mental Health Science, Wellcome is committed to identify and adopt common measures so that, in time, data can be combined and compared across studies to answer crucial research questions. Teams planning to conduct research projects with human participants and to collect data on anxiety and/or depression must use (as a minimum) one or more of the following recommended measures:

  • PHQ-9 (adults)
  • GAD-7 (adults)
  • RCADS-25 (children and adolescents)

In exceptional circumstances when these measures are not feasible (for example, due to length), we may agree to the use of shorter versions (for example, PHQ-2, GAD-2, RCADS-10), however, the reasoning for this must be clearly justified.

Please note that we do not currently have an agreed measure for psychosis, therefore, applicants should use the measure(s) that is most appropriate to address their research question.

 

Applications must demonstrate the involvement of lived experience expertise in the planning, design, and delivery of the research. We recognise that there are a range of ways that research teams can involve and collaborate with people with lived experience. For example, this may include, but not be limited to, expert advisors, coapplicants, collaborators, or advisory group members. We are open to any methods of involvement that teams choose but expect lived experience experts to be involved in the most appropriate ways to inform multiple aspects and stages of the research project. It is key for us is that this is not tokenistic or a tick box exercise.

For further information on what we mean by ‘people with lived experience’, including guidance for meaningful involvement, see the guidance provided.

 

For translational research, we expect the following to be considered, as is relevant to the proposal:

  • the subsequent development steps required leading to regulatory approval
  • the key desired attributes of your healthcare innovation
  • any clinical, manufacturing, regulatory or marketing issues known that may affect the ability to deliver the product to market
  • a downstream partner
  • the future implementation strategy, including delivery and market penetration.

Research must consider potential uptake from the outset. For example:

  • applicants may engage with potential end users of research, including people experiencing anxiety, depression or psychosis, caregivers/families, clinicians and service managers for future implementation and impact for policy
  • applicants may engage with stakeholders, such as policymakers, health care professionals, regulatory bodies and downstream partners, as appropriate, during the research process to ensure results are implementable, scalable, suitable for commercialisation and in line with policy and end users’ needs
  • applicants may employ a mixed methods approach and include social science and health economics expertise (as appropriate) to ensure that the interventions are appropriate, acceptable and feasible and that any potential social, cultural or economic barriers to implementation are examined
  • proposed research may consider and include measures such as (but not limited to) acceptability, adoption, appropriateness, affordability, costs, feasibility, fidelity, penetrance and sustainability, as relevant.

 

What are we not looking for?  

The following are out of scope for this Mental Health Award:

  • Studies exploring neurodevelopmental conditions, neurodegenerative diseases, or mental health problems outside of the broad categories of anxiety, depression, and/or psychosis as detailed above (for example eating disorders, substance abuse are out of scope). However, for mental health applications out of scope for this call please consider our Discovery Research schemes.
  • Universal (population-level) preventative interventions and/or interventions focused on managing chronic mental health problems unless relevant to advance early intervention.
  • ‘Blue skies’ or curiosity-driven research.
  • Applications with epidemiology or implementation science research as the sole focus of the proposal.
  • Applications with research involving animal models or healthy volunteers as the sole focus of the proposal.
  • Phase III trials of pharmacological interventions, although please contact us to discuss repurposing opportunities.
  • Health systems research around the distribution and uptake of interventions.
  • Direct service provision or support for access to current services.
  • Healthcare reorganisation.
  • Applications that do not include the involvement of lived experience experts in the proposed project.
  • Applications that do not comply with Wellcome’s research environment principles of open science and relevant diverse inputs.

 

Below we provide additional guidance to completing various sections in the full application. Please follow these as appropriate for your individual project.

The proposal 

Provide your answer to this question as a PDF attachment. The uploaded document must be no longer than 4000 words* in length, in 11-point Arial font and portrait format.

This document should include:

1. Aims and key deliverables

  •  Please include a vision statement that specifies what you are looking to achieve with the funding requested and what you want to achieve in the longer term.
  • The specific aims and objectives of the proposed project.

2. Background and justification 

The unmet need and strength of the research question.

  • The scientific background to the project.
  • The justification for the proposed research, which may include (but is not limited to): your focus on anxiety depression and/or psychosis, the specific population involved and how the research meets the needs of end users.
  • Description of how the proposed research will advance knowledge in relation to at least one of the following:
    • Mechanistic underpinning of the bi-directional role of sleep and circadian disruptions in the development and resolution of anxiety, depression and/or psychosis.
    • Identification and/or validation of sleep and circadian markers that enable early stratification of people with anxiety, depression and/or psychosis.
    •  Development of early interventions for anxiety, depression and/or psychosis that target sleep and/or circadian processes and the competitive advantage of such interventions.
  • The supporting hypothesis and underpinning mechanism or plan to investigate it.
  • Support from existing evidence (for example, existing literature, systematic reviews/meta-analyses, proof of concept data or pilot data as relevant).

The potential for impact. 

  • The potential for the research to have a significant and measurable impact on early intervention in anxiety, depression and/or psychosis.
  • The potential for different geographical, societal and cultural contexts to impact on the research.
  • Please also address:
    • How you will consider the potential uptake of the research from the outset.
    • The potential for the research to have applicability and acceptability in settings beyond the specific context of the research.

3. Details of the planned activities

  • An overview of the proposed workplan, clarifying how it will address the research question(s).
  • The proposed methodology under each work package.
  • Where relevant, please include details on interventions, research design (including trial design), target populations, sample size and power, community and patient group involvement (this can also be included under ‘Additional Information’).
  • The outcomes to be measured and the specific sleep, circadian rhythm, mental health, functional and/or quality of life measures and analyses to be used, plus justification. Please indicate if these measures have been validated in the proposed settings or how you propose to validate these.
  • The key risk-reducing steps to be addressed and overcome.
  • For intervention development, please include a description of the pathway to impact beyond this funding, considering:
    • What subsequent development steps are required?
    • Who the downstream partner could be (which may include further development by the applicant)?
    • Are there any clinical, manufacturing, regulatory or marketing issues known that may affect the ability to deliver the product to market?
    • What would the implementation strategy be, including delivery and market penetration?
    • If you have outlined any regulatory considerations or risks above, show evidence that you are accounting for regulatory requirements in the product development pathway.
    • For projects that do not include a clinical trial you should still outline the likely clinical pathway.
    • Include the target product profile or key desired attributes of your healthcare innovation.
    • How you will consider equitable access to the assets developed through this research.

4. Details of how you will involve people with lived experience

Please include information on how people with lived experience of anxiety, depression and/or psychosis (ideally with the sleep and circadian issues relevant to the research topic) will be involved in multiple stages of the design, delivery, and dissemination of the project. As part of this please explain:

  • Your approaches to involvement at each stage of the project in detail.
  • How you plan to identify and recruit people with lived experience with the relevant skills to work on the project. As part of this please also clearly state the relevant skills and expertise you are looking for from the people with lived experience you plan to work with.
  • How the proposed research is feasible from the perspective of lived experience expertise (for example, recruitment plans are feasible and appropriate, intervention protocol is appropriate, plans for participant retention are suitable, protocol or methodology proposed is inclusive towards under-served groups).

People with lived experience should be appropriately compensated or paid for their time. This information should be included under the “Costs requested and Justification” section, along with any additional costs needed to ensure your lived experience involvement plans are appropriately budgeted for. Please see our guidance on involving people with lived experience for further information on how to involve people with lived experience in your research.

5. Research location and environment

  • Describe how the research location(s) can provide the necessary research infrastructure and resources to support the research goal.
  • Describe how the research environment will support and develop your research capabilities and management/leadership skills.

6. Timetable and milestones (as appropriate)

*This PDF upload will not count as part of your three pages of optional additional information (see below). You should embed figures, graphs, and tables, if essential to the proposal, in the text. You may upload other essential information separately, for example: references, unpublished data, letters of support. The additional information should not be an extension of the proposal. You must provide all information pertinent to your proposal within the application form (it is not acceptable to refer to additional unpublished information on personal websites). If more than one organisation will be involved in the project, indicate what work will be undertaken at each organisation. You must cite any references in full, including all authors, the full title of each publication, journal title, year, volume, and pages. Citations to preprints should state ‘Preprint’, the repository name, and the article persistent identifier (for example, DOI). You may shorten references with more than 10 authors to et al, but please ensure that your position as author (if applicable) remains clear.

Additional information

You may provide up to three A4 pages of additional information, such as Gantt charts, figures, graphs, or additional unpublished data. Please embed it within the text of your upload for your proposal or upload it separately under ‘Additional information’. If the additional information exceeds the equivalent of three pages of A4 we will return your application to you to reduce the amount of information.

Team composition and management

Describe the roles of all applicants and how the project will be managed and led. (500 words max.)

Please indicate how the team is uniquely positioned to deliver this project and realise your long-term vision.

  • Comment on whether the proposed team has worked together in the past and, if so, describe any key outcomes or achievements from these collaborations.
  • If you are collaborating for the first time, comment on how and why you have chosen to work with the people and/or organisations listed.

 

For completeness and for applicants’ planning purposes we provide below the full assessment criteria and weightings that will be used at the full application stage. At the shortlisting stage, a simplified rubric will be used.

Assessment criteria for full applications 

There are four weighted criteria:

  1. The research question, the proposed methodology and the potential for impact (40%)
  2. Suitability and expertise of the team (20%)
  3. Lived experience involvement (20%)
  4. Suitability of research location, research environment, and research culture (20%)
1. The research question, the proposed methodology and the potential for impact (40%) 

Rationale and potential for impact:

  • The research has sufficient scope and ambition, such that the findings  have the potential to have a significant and measurable impact on early intervention (for example, early symptom presentation, including early relapses, or the earliest point of contact with a healthcare system) for people with anxiety, depression and/or psychosis.
  • The proposed research project will lead to insights into the interdependent roles of sleep and circadian rhythm disruption in the development and resolution of anxiety, depression and/or psychosis or vice versa.
  • The proposed research is hypothesis driven and includes an underpinning mechanism or the project includes plans to investigate this mechanism.
  • The proposed research is well justified, involves characterisation of changes in sleep and circadian rhythms in relation to anxiety, depression and/or psychosis and will advance knowledge in relation to at least one of the following:
    • Mechanistic underpinning of the bi-directional role of sleep and circadian disruptions in development and resolution of anxiety, depression and/or psychosis.
    • Identification and/or validation of sleep and circadian markers that enable early stratification in anxiety, depression and/or psychosis.
    • Development of early interventions for anxiety, depression and/or psychosis that target sleep and/or circadian processes, with demonstrated competitive advantage.
  • The proposed research project includes a clearly defined population and has considered how it meets the needs of end users.
  • Where appropriate:
    • The proposed research has considered how the research may be impacted by different contexts and whether there is potential for the research to have applicability and acceptability in settings beyond the specific context of the research.
    • Uptake of research has been considered from the outset.

Strength of evidence: 

  • The proposal includes evidence that supports its feasibility and potential for impact.
  • The proposal includes information on the competitive advantage of the intervention under development relative to anything that’s already available or being developed.

Strength of methodology: 

  • There is a clear project plan that addresses the hypothesis/research question.
  • The proposed methodological approach is appropriate, well-designed, feasible, and supported by relevant evidence or expertise (for example, the choice of model system is justified, the sample is adequately powered, for human studies a recruitment plan is in place, participant heterogeneity is being harnessed and/or considered in the study design).
  • The study incorporates both sleep and circadian measures and considers measurement during wakefulness as well as sleep.The use of measures is justified.
  • The study incorporates measures of anxiety, depression and/or psychosis and functional outcomes or measures of quality of life, which are justified.
  • The project is achievable in the timelines proposed.​
  • The resources requested are appropriate and well justified.​
2. Suitability and expertise of the team (20%)  

Lead applicant:

  • Has research experience relevant to the project, as evidenced through research outputs and/or preliminary data (as appropriate for their career stage).
  • Has the experience needed to drive and lead a collaborative research programme.
  • Has experience of people and research management and training, as appropriate for their career stage.
  • Can contribute at least 20% of their research time to this project.

Coapplicants:

  • The expertise of the coapplicants is essential for the delivery of the project and their contribution to the project is justified.
  • The coapplicants have the appropriate time (can contribute a minimum of 10% of their research time) and necessary resources available to deliver the project.

Team:

  • The team has the necessary expertise and technical skills to deliver the proposed research project.
  • There is a justified team approach whereby all applicants are necessary to deliver the proposed research and there is evidence that the proposed collaboration would be feasible and fruitful (for example, the team has appropriate management plans in place, describing how the collaboration will be organised and run day-to-day).
  • The team has the necessary expertise to effectively involve and collaborate with people with lived experience of anxiety, depression and/or psychosis in the proposed project.
  • Where research occurs in more than one location, applications include coapplicants based in each country where the research will take place.
  • Applicants have contributed and are committed to fostering a positive and inclusive research culture.
3. Lived experience involvement (20%) 
  • People with lived experience of anxiety, depression and/or psychosis (ideally with the sleep and circadian issues relevant to the research topic) are involved in multiple stages of the design, delivery, and dissemination of the project.
  • Approaches to involvement (or lack of involvement) at each stage of the project should be explained in detail.
  • The proposed research is feasible from the perspective of lived experience expertise.
  • People with lived experience are appropriately compensated or paid for their time.
  • An appropriate number of people with lived experience are involved in the application.
  • Plans to involve people with lived experience in the project are appropriately costed and budgeted.
4. Suitability of research location, research environment, and research culture (20%) 

Assessment of this criteria should take into consideration the context for example, geographical location and local context or commercial environment.

Research location and environment:

  • The research environment is suitable to support and develop the applicants and their proposed research.
  • The research environment(s) is supportive of the research project, has plans to promote a diverse and inclusive environment and will help the applicant to develop their research capabilities, and leadership and management skills.
  • The applicants have access to the necessary research infrastructure.

Research culture:

  • Detailed description of how the applicants will contribute to and develop a positive and inclusive research culture. This may (but is not limited to) include:
    • Project management plans, including how project priorities and decisions will be determined.
    • Equitable plans for collaborating with researchers in low resource settings.
    • Plans for how contributions to research outputs will be credited as appropriate.
    • Plans for leadership and people management or development, supporting collaborations, research integrity and contributions to the wider research community.

Outputs management plans:

  • Detailed description of a suitable outputs management plan (for example, depositing, sharing, and storing data, open access publishing).
  • Applicants manage their research outputs in a way that will achieve the greatest health benefit.

 

  • Duration of award: projects of any duration up to 5 years.
  • Level of funding: projects of any budget up to £3 million.

You should ask for a level and duration of funding that is justifiable for your proposed research. You must justify all costs within the costs section of your application.

If your proposal is likely to exceed the proposed level or duration of funding, please get in touch with us.

Eligibility and suitability

What we offer

How to apply

1. Before you apply

  • Make sure you read everything on this page, including the material linked in the Useful documents section.
  • Consider submitting questions relating to the call by 5th September 2022 through the Mental Health inbox – mentalhealth@wellcome.org – and include the title of the call in the subject line.
  • Watch our webinar with the Mental Health team for more information on this funding call and answers to the pre-submitted questions.
  • Questions submitted after the 5th September will be answered through a Frequently Asked Questions page to be uploaded after the webinar.
  • Get some tips to help you write your grant application.
  • You do not need to contact us before you write and submit your application.

2. Submit your full application to your host organisation for approval

  • Complete your application on Grant Tracker.
  • Get some guidance on using Grant Tracker.
  • View the Sample Application Form
  • Submit it to the ‘authorised organisational approver’ at your host organisation for approval. Make sure you leave enough time for the approver to review and submit your application before the deadline. The approver may ask you to make changes to your application.

3. Host organisation reviews your application and submits it to us 

  • Your application must be submitted by 17:00 (GMT/BST) on the deadline day.

4. Shortlisting 

  • A committee will review your application. Committee membership will be comprised of a diverse range of international and UK experts and lived experience advisors and will take into account Wellcome’s diversity and inclusion priorities. View the Sleep, Circadian Rhythms and Mental Health Advisory Committee.
  • If shortlisted, we will invite you for interview.

5. Interviews 

  • A committee will interview shortlisted candidates online, and make funding recommendations to Wellcome. Committee membership will be the same as the Shortlisting Committee.
  • Accessibility requirements will be accommodated.
  • We will provide information on the structure of the interview, and interview committee membership.
  • The focus of the interview will be on questions and answers. The committee will assess across the full set of criteria rather than one specific aspect of the proposal. They will consider your proposal and interview responses and will make funding recommendations to Wellcome.

6. Funding decision 

  • Final funding decisions will be made by Wellcome’s Mental Health Team.
  • You will receive an email notification of the funding decision soon after the decision has been made.

7. Feedback 

  • Written feedback will be provided to those applicants unsuccessful at interview, including the reasons for a decision.

Details of how we will handle any personal or confidential information contained in your application are available in our Grants Privacy and Confidentiality Statement.

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