A study designed to help prepare the ground for a larger, more definitive piece of research should either improve the chances of the subsequent study producing valuable evidence, or help to avoid wasting resource on large studies that are unlikely to answer the intended research question.
Studies of this type funded by the Research for Patient Benefit (RfPB) programme are usually intended to inform a randomised controlled trial (RCT), but we also welcome proposals for studies in preparation for other research designs such as surveys, data linkage studies, or investigations of how best to access seldom heard groups.
When applying to RfPB for studies in preparation for a RCT to evaluate an intervention, applicants need to demonstrate the promise of the proposed intervention and identify the specific uncertainties that need to be addressed before the main study. RfPB funding committees will assess applications against these criteria, paying particular attention to the rationale for the specific uncertainties and the robustness of the plan to address them.
This document presents revised guidance for applying for funding for feasibility studies, for applicants to the RfPB programme.
A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale.
As a subset of feasibility research, pilot studies may or may not be randomised. In a randomised pilot the future RCT design is first conducted on a smaller scale. This is intended to check that the study processes (e.g. recruitment, randomisation, treatment, follow-up assessments) all run smoothly. In some cases, this will be the first phase of the main study, and data from the pilot phase may contribute to the final analysis; this is referred to as an internal pilot. A non-randomised pilot has similar aims but without randomisation of participants.
These definitions are agreed by the Programme Grants for Applied Research (PGfAR), Efficacy and Mechanism Evaluation (EME), Health Technology Assessment (HTA) and RfPB programmes. This is in line with MRC guidance and follows Eldridge et al (2016).
The promise of the intervention
When applying for studies in preparation for an RCT of an intervention, applicants will be required to demonstrate, at Stage 1, that there is convincing evidence making a case to support the promise of the particular intervention. This might include:
- existing trials of effectiveness included in systematic reviews of small underpowered trials
- existing trials of efficacy
- observational, and before and after studies
- a convincing explanation for how an intervention might produce the postulated effect
- evidence that the intervention is being used in practice, in the NHS or elsewhere
- a promising signal that the intervention may be more cost effective than current practice
The programme acknowledges the potential challenge in generating a case for the promise of some complex interventions or for underrepresented groups. Judgements about the extent to which an intervention is ready for RfPB evaluation are made on a case-by case basis and are proportional to likely impact, importance to patients and the NHS, and potential costs of the feasibility work. However, applicants should be aware that even if preparatory work suggests that the proposed study design for a definitive trial is broadly feasible, funding is unlikely if a convincing case for the promise of the intervention has not been marshalled to support that wider-scale and costly research.
The specific uncertainties
All preparatory research, be it a pilot, feasibility study, proof-of-concept or exploratory qualitative research, assesses uncertainties in relation to the conduct of a larger study including whether the full study is likely to be possible. Depending on the nature of the specific uncertainties that need to be resolved, different research designs may be appropriate. For example, interviews or observations might ascertain the acceptability of an intervention, willingness to take part or be randomised, or to refine particular components of an intervention.
RfPB considers pre-RCT preparatory studies to be good value for money, as they improve the chances of success for a full RCT. However, after funding a substantial number of feasibility studies, we observe that ‘formulaic’ designs may not be efficient in resolving the uncertainties that really matter. We therefore require that preparatory work should identify the uncertainties for the conduct of the particular RCT and address them in the appropriate field and settings.
For example, uncertainty could concern:
- Acceptability of the intervention to the users
- Adherence to an intervention
- Ways to ensure representative recruitment and engagement
- The willingness of patients to be randomised
- The willingness of clinicians to randomise patients
- The choice of primary outcomes and their characteristics
- The choice of an adequate comparator
- Follow-up rates, response rates to questionnaires, adherence/compliance rates, ICCs in cluster trials, etc.
- The time needed to collect, clean and analyse data
- Practicality of delivering the intervention(s) in the proposed setting(s)
- Variation in use or delivery of the intervention in each setting
If the applicant team considers that there are no, or very few, uncertainties to be resolved, and it Is thought that the remaining uncertainties could be addressed in an internal pilot then it may be appropriate to apply directly for a RCT and plan an internal pilot, with minor feasibility questions as part of the stated progression criteria.
Here we provide examples from previously funded RfPB studies on how uncertainty can be addressed.
Testing the acceptability of the intervention in the setting
A study used mixed methods to test the feasibility of conducting a cluster randomised RCT of a fall prevention intervention in care homes. The research team tested uncertainties relating to acceptability (would enough care homes be willing to take part?), tolerability and adherence (would enough residents take part? Would they tolerate the techniques involved?) as well as implementation facilitators and barriers for the intervention. The study also explored whether it would be possible to collect valid and reliable data.
Funding awarded: £143,322
Testing the feasibility of implementing an intervention
A study in preparation for a large evaluation assessed whether a problem solving intervention for people at risk of self-harm and suicidal behaviour could be implemented in prisons and what length of follow up would be possible after the participants were released from prison. Interviews were conducted to assess the acceptability of the intervention while an interrupted time series analysis was used to examine whether an evaluation was feasible.
Funding awarded: £248,635
Testing the safety of an intervention and the feasibility of collecting data
A cohort study tested the tolerance of intravenous iron administration in patients with cystic fibrosis in preparation for a multicentre RCT. The study also tested the feasibility of collecting and measuring preliminary data on patient-focused clinical outcomes and informing sample size calculations.
Funding awarded: £148,367
Testing the acceptability of the intervention to the users
A preparatory study built on findings from a previous trial of training videos for first time users of hearing aids. The research team used a mixed-methods approach, including semi-structured interviews, to address uncertainties about adaptation of the intervention (including greater personalisation) for use with mobile technologies. Usability, delivery, accessibility, acceptability and adherence were assessed to inform the development of a definitive multi-centre RCT.
Funding awarded: £149,906
Testing the willingness of patients and clinicians to participate in a trial
A preparatory study informed the development of a fully powered RCT of treatment for patients with Barret’s Oesophagus. Qualitative interviews with a purposive sample were used to examine acceptability, to patients and clinicians, of a trial comparing surgery to endotherapy. Uncertainties included barriers to recruitment and retention and how to ensure equivalent treatment and histology interpretation in the different centres.
Funding awarded: £224,773
Pathway to RCT
RfPB Committees consider the pathway to a RCT as part of their assessment. Therefore, a clear route (e.g. progression criteria) should be included in the research plan. Applicants are expected to identify the potential funder and the anticipated time frame to the subsequent RCT. To encourage faster progression into RCTs, applicants are expected to include writing the proposal for the RCT, if shown to be feasible, within the timeframe of the RfPB feasibility study. Where the full trial is not considered to be feasible the results should be submitted for publication within the study time frame.
RfPB does fund full RCTs, although it is recognised that our current limit of £500,000 will preclude many multi-centre studies. RfPB has occasionally fast tracked preparatory studies to consideration for a full RCT within the programme and we work closely with other NIHR programmes that fund larger studies. RfPB feasibility studies have led to RCT funding from HTA, PGfAR, RfPB, EME, PHR, HS&DR, and NIHR Academy Fellowships and also from charity and other funders. Each funding programme has a specific remit. Advice about programme remits are available on their websites. Applying for funding is, or course, a highly competitive process and while our programme managers (and colleagues in the Research Support Service) will help guide applicant teams there are no guarantees of future funding, even for those preparatory studies that appear promising.
For HTA studies that undertake national evaluations of the effectiveness and cost-effectiveness of interventions, NIHR has published guidance on whether an intervention ready for HTA researcher-led evaluation. Generally, an intervention is ready for HTA evaluation if:
- There is a reasonable chance that it will be effective
- It has already been tested in a typical NHS or social care setting
- There is a reasonable chance it will be used across the NHS if shown to be effective.
HTA evaluation may also be appropriate if the intervention is already widely used in the NHS, but evidence of benefit and harms is lacking.
RfPB policy on funding studies in preparation for future research
RfPB welcomes applications for preparatory work resolving uncertainties in relation to RCTs and other large studies. Depending on their complexity and the scale of the uncertainties most studies would cost less than £300,000, while those that test an individual uncertainty (e.g. identifying a core outcome set) would cost less than £200,000. Costs higher than this will need to be fully justified with a strong case for the trajectory to patient benefit.
RfPB continues to welcome proposals for studies in preparation for future research. We are looking for a clear statement of the specific uncertainties, a sound justification for the preparatory study design and an indication that the intervention (where applicable) has promise. By funding more appropriately designed preparatory work RfPB envisages that the programme can improve the transition to large studies, including RCTs for promising interventions, within NIHR and to other funders.
Eldridge SM, Lancaster GA, Campbell MJ, Thabane L, Hopewell S, Coleman CL, et al. (2016) Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework. PLoS ONE 11(3): e0150205.
Many of the RfPB preparatory studies seek funding for follow on studies from the HTA programme. NIHR has published guidance on whether an intervention ready for HTA researcher-led evaluation and hints and tips for a good HTA study design. For more information, contact email@example.com.