Introduction
Infertility is a disease of the male or female reproductive system defined by the failure to achieve pregnancy after 12 months or more of regular unprotected sexual intercourse. NICE estimate that infertility affects 1 in 7 heterosexual couples in the UK. Infertility may be caused by a number of different factors in either the male or female reproductive system and sometimes it is not possible to explain the causes of infertility.
Assisted conception is the use of a medical intervention to aid a person conceiving, also known as assisted reproductive technologies (ART). The type of treatment used depends on what is causing infertility. ARTs include: in vitro fertilisation (IVF), intrauterine insemination (IUI), intracytoplasmic sperm injection (ICSI) and fertility drugs. Treatments can be invasive and are expensive. They can cause side effects such as ovarian hyperstimulation syndrome, and can increase the risk of multiple pregnancies, which increases the risk of morbidity and mortality for the mother and baby. The success rate of these treatments is influenced by factors such as age, infertility diagnosis and BMI, but is around 4-32% for IVF.
Often during fertility treatments patients are offered optional additional or supplementary treatments known as treatment add-ons. These often claim to be effective at improving the live birth rate but evidence to support these claims is currently lacking. Treatment add-ons likely involve an additional cost and can cost hundreds or thousands of pounds each. The Human Fertilisation and Embryology Authority (HFEA), the UK fertility regulator, publish information including highlighting the available evidence for each treatment add on to help patients understand the scientific evidence available for each treatment ‘add-on’ and make an informed decision. Fertility treatment add-ons are also highlighted in the Governments Women’s Health Strategy as one of the ambitions for fertility, contraception and preconception.
It is the ambition of the MRC-NIHR Efficacy and Mechanism Evaluation Programme (EME) to fund trials that provide robust evidence as to the clinical performance (efficacy) of fertility treatment add- ons used during pre- and peri- conception and whether such treatments can be routinely, easily and effectively used to improve the outcome of assisted conception. We recognise that developing an application for such trials will likely involve collaborations between both NHS and private sectors which will require time and the navigation of specific challenges. There may also be opportunities to recognise methodological efficiencies by evaluating more than one intervention in parallel. The programme is therefore inviting applications for work which will accelerate the necessary learning and preparation to apply for the final call. This will take the form of an Application Development Award (ADA).
Call scope
Applications to this call must aim to accelerate the development of an application for a trial to evaluate interventions and/or technologies, individually or in combination to improve the effectiveness of fertility treatments. Applications for any trial must be positioned within remit of the MRC-NIHR EME Programme, as follows:
Patient group: Patients undergoing fertility treatment. Applicants should consider stratification by aetiology and the proposed mechanism of action of the intervention, if known. Applications which include recruitment from populations which have been historically under-served by research activity in this field or access to treatments are encouraged.
Intervention/technology: Any add-on intervention or technology to improve the effectiveness of the primary treatment, which has human clinical proof of concept to suggest a signal of efficacy, but where efficacy remains an uncertainty. This may include novel treatments with adequate supporting evidence, as well as those already offered. Several research uncertainties are highlighted on the HFEA website.
Applicants are encouraged to note current provision and uptake of the add-on(s) to be evaluated, as well as the potential for the intervention to be used in routine practice, if efficacious.
Comparator: Treatment as usual (no add-ons)
Setting: NHS; Fertility Treatment Centres (may include the private sector)
Study Design: An appropriate randomised design, which may aim to evaluate one or more add-on technology. Applicants are encouraged to embed mechanistic studies that are relevant to the intervention within any study design.
Applicants should provide details regarding the anticipated trial and supplementary intervention/technology to be evaluated, including the study team, research design and governance structures where known, however full details are not required at this stage and some elements may be defined as part of the application development work.
Applications to this call must define and justify the specific challenges which will be addressed within the award and how they will ultimately enable a complete application to be made. Examples of the types of work which may be supported include, but are not limited to:
- Developing networks or collaborations to support the set-up and delivery of the study.
- Defining, justifying and standardising the interventions or technologies which will be evaluated.
- Defining and agreeing a study protocol that may be followed across all collaborating centres.
- Addressing challenges relating to industry assets and/or private practices participating in the study.
- Work to ensure the proposed study follows need and recognises health disparities, including reaching disproportionately affected and under-served groups.
- Targeted work to clarify the ‘signal of efficacy’ for technologies to be included at the outset (this may use existing data but should not involve any recruitment or primary research).
- Further understanding the anticipated effectiveness of the study design, including any necessary modelling.
- Defining and validating elements of the full study design, such as the comparator, sample size or most important health outcome measures.
- Establishing the feasibility of a study in the proposed setting, including Patient and Public Involvement and Engagement (PPIE).
It is anticipated that teams may require up to £200,000 for complex awards, such as platforms or international studies, over a maximum of 12 months. Project cost and duration is expected to be commensurate with the complexity of the study and the level of development work required.
The Application Development Award must deliver the following key outputs:
- Development of a Post-Development Application (PDA) to EME for a trial evaluating supplementary interventions and/or technologies that aim to improve the effectiveness of fertility treatments. Details below.
- A written report in the form of a single Research Article covering the commissioned work, two weeks after the contract end date, for publication in one of the NIHR publication platforms.
In addition, NIHR supports teams to produce audience-appropriate outputs, such as a variety of digital formats (e.g., podcast, video, social media) including related articles to third-party journals, but the publication of the research article cannot be delayed to accommodate this.
Post-Development Application
For successful awards, a Stage 1 PDA must be submitted to the EME Programme by the end of the award. A submission deadline will be set based on the duration of the ADA.
The application will be required to:
- detail an efficacy study within remit of the EME Programme.
- include one or more technologies or interventions to be evaluated. The study design may evaluate the combination of interventions as appropriate.
- build on engagement with proposed recruitment centres (which may span the NHS and private sector) to propose a standardised and feasible study.
- demonstrate that the proposal builds on and incorporates feedback from Patient and Public Involvement and Engagement (PPIE).
- demonstrate that the proposed research will include historically underserved communities.
- take account of further application guidance and feedback arising through the funding process.
The research team must:
- demonstrate experience in delivering multi-centre interventional studies in the UK.
- demonstrate a track record in working with members of the public, people who draw on services and in locations of greatest need to perform inclusive studies.
- evidence ability to establish and coordinate data input from a variety of sites.
Out of scope
This call is for application development work only. An application for the full study will be invited from the successful team(s).
If you wish to apply for a full evaluative study of supplementary interventions and technologies intended to improve the effectiveness of fertility treatments, please refer to the EME Researcher-Led call. However, applicants should note that the Funding Committee will take into consideration any overlapping development applications.
Application process
To enable quicker funding decisions, this is a straight to Stage 2 (single stage) funding opportunity.
A key deliverable within this award must be the development of a Stage 1 Post-Development Application (PDA), by the agreed deadline. This will represent a milestone for the award.
Any PDA which is shortlisted by the EME Funding Committee will be invited to submit a Stage 2 application