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The evidence synthesis, modelling and decision making processes may identify uncertainties and gaps in the evidence base. Summarise these in a clearly identifiable 'uncertainties' section in the guidance. The summary is not intended to be exhaustive, but is used to help select the most important uncertainties (step 2) for prioritisation.
There are different types of uncertainties, and they may relate to any aspect of clinical, health, public health, or social care practice. Examples include clinical- and cost-effectiveness, diagnosis, test accuracy, prognosis, modes of delivery, optimal service design, quality of life, outcomes that are important to users, and user preferences and values.
Uncertainties may arise for many reasons. The 2 primary reasons are that there is no published evidence available, or the available evidence is not sufficient, robust, or conflicting (see box 1 for more detailed examples).
There is no evidence available because:
the relevant research has not been done
the relevant research has been done, but not published
the relevant research has been done and published, but it has not been identified Evidence is available but:
there is insufficient information on which to base a recommendation (for example, due to
inadequate reporting)
there are methodological limitations (for example, the study enrolled too few participants to be sure statistically that the results were not due to chance alone)
the results were inconclusive or inconsistent
the results cannot be applied to the population in question (for example, the setting or social and cultural context is not comparable, the user population differs, or a different dosage has been used)
it concerns a related but different question (for example, the comparator differs)
the research is out of date (for example, a systematic review needs updating with recent trials or practice has changed)
NICE reviews the summarised list of uncertainties and identifies and documents the most important ones. The uncertainties deemed most important are those that the NICE committees consider need to be resolved to inform future updates of guidance recommendations, and that will also give clear benefits and added value to the NHS, public health, social care and voluntary sectors. For example, uncertainties related to aspects of care or services that providers need to address as a priority. There are no limits to the number of important uncertainties identified and prioritised, and it may be that none are identified at all.
NICE committees lead the process of identifying and prioritising the most important uncertainties, with input from clinicians, researchers, patients and carers, service users or the target population, reviewers, health economists and NICE technical staff.
The committees may use any modelling that has been done to help select the most important uncertainties. For example, the results of an economic modelling exercise may be sensitive to specific parameter or structural assumptions that could be clarified by research.
Additional analysis (for example, 'value-of-information' methods) using the same models as in the decision-making are a possible method for establishing the value for money of additional research to reduce evidence gaps and help prioritise future research. There is no requirement to routinely undertake such evaluations, but they may help identify the most important uncertainties.
Translate prioritised uncertainties into a research recommendation applying a framework with 2 components (see box 2 for an example):
a structured stand-alone statement that sets out the questions that need to be answered (see table 1 for an example format)
a structured rationale explaining why the research is important and is being recommended to research funders and researchers (see table 2 for an example format).
| Criterion | Explanation |
|---|---|
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Population |
Define the population that the research needs to be undertaken in. Where appropriate, specify any of the following:
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Intervention |
Specify the intervention that needs to be evaluated. This can be:
For public health this may also refer to risk factors that the service user or population is exposed to. Also consider providing information on:
For public health interventions, the context, setting and method of delivery of the intervention may also need to be specified. |
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Comparators |
If appropriate, state what the intervention needs to be compared with. For example, placebo, routine care, alternative treatment, or management strategy. Also consider providing information on:
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Outcome |
What will the researcher need to measure, improve, influence, or accomplish to assess whether the intervention is effective? What clinical outcomes or patient or user-related outcomes of the intervention should be measured to demonstrate this? Consider providing information on:
For public health interventions, specify whether the causal pathway leads to individual or population level outcomes. |
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Study design |
In some cases, it may be appropriate to specify the study design to address the proposed question, but be aware that there may be several alternatives depending on timescale and context. In many cases, it may be more appropriate for the study design to be considered by the research funder after the research recommendation has been made by the NICE Committee. |
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Timeframe |
Is there a timeframe in which the study needs to be completed? For example, to inform a guidance review, or if the technology might be superseded before any studies are complete. |
| Potential criterion | Explanation |
|---|---|
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Importance to patients, service users or the population |
What would be the impact of any new or altered guidance on the population (for example, acceptability to patients or service users, quality of life, morbidity or disease prevalence, severity of disease, or mortality)? |
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Relevance to NICE guidance |
How would the answer to this question change future NICE guidance (that is, generate new knowledge or evidence)? How important is the question to the overall guidance?
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Relevance to the NHS, public health, social care and voluntary sectors |
What would be the impact on the NHS, public health, social care and voluntary sector and (if relevant) the public sector of any new or altered guidance (for example, financial advantage, or effect on staff, strategic planning, or service delivery)? |
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National priorities |
Is the question relevant to a national priority area (such as a national policy or parliamentary paper)? If so, specify the document. |
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Current evidence base |
What are the problems with the current evidence base? (That is, why is further research needed?) Is there any relevant ongoing research that may resolve the uncertainty? |
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Equality |
Does the research recommendation have any relevance to equality? For example, does it focus on groups needing special consideration, or on a technology, intervention or service that is not available for use by people with certain disabilities? What is known about the impact of the intervention on the health gradient? |
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Feasibility |
Can the proposed research be carried out within a realistic timescale? Would the sample size needed to resolve the question be feasible? Would the expense needed to resolve the question be warranted? Are there any ethical or technical issues? |
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Other comments |
Any other important issues that should be mentioned, such as potential funders, outcomes of previous attempts to address this issue, or methodological problems. |
Structured standalone statement:
A randomised-controlled trial should be undertaken to determine whether benzoyl peroxide or adapalene is more clinically and cost-effective at reducing the number of non-inflammatory lesions in the treatment of acne vulgaris in adolescents. The study should also consider the impact of treatments on quality of life.
Structured rationale:
Retinoids such as adapalene are currently recommended by many experts as first-line treatment for acne. The systematic review undertaken by NICE in 2009 did not identify any robust evidence comparing them with generic treatments, such as benzoyl peroxide, which have been demonstrated to be clinically and cost effective. Acne has a significant impact on quality of life. Acne is highly prevalent amongst teenagers, and therefore the preferential use of retinoids could have significant budgetary implications for the NHS. No ongoing trials have been identified.
The research recommendations need to be stand-alone statements because they will be abstracted into a database and may not be read in the context of the guidance. The recommendation must characterise the research that needs to be undertaken and convey why it is important, to ensure that readers will pick up the recommendation for further exploration.
Research recommendations can propose primary and secondary quantitative and qualitative research, for example, formative and summative evaluations, trials, longitudinal studies, secondary analysis and scoping papers of research needs. They may also recommend methodological research, epidemiological studies, and data collection exercises.
Some NICE committees make 'only in research' recommendations if the adoption of a technology should be considered only in the context of research. See the Guide to the methods of technology appraisal 2013 for details.
During guidance development the NICE committee may invite a research funding body to support the development of research recommendations. The funding body advises on the structure of clear and actionable research recommendations that fall within the remit of its specific research programmes. For example, NICE guidelines in public health increasingly apply this approach, working with the NETSCC. The research funding body can also ensure that the NICE committee is aware of any relevant ongoing research it is commissioning.
If a committee contacts a research funding body to support the development of research recommendations, it should do this at an early stage, before the guidance is sent for consultation, and before it is finalised and published. The NICE SP&R team can support this.
If NICE believes that a research recommendation is particularly important it has a special arrangement with NETSCC that enables the recommendation to be given, by agreement, a 'key priority' status.
A NICE key priority is a research recommendation that can be progressed rapidly through an identified research commissioning route. NICE key
priority research recommendations may bypass the NIHR HTA Advisory Panels and go directly to the NIHR HTA Prioritisation Group, which meets 3 times a year. Processes for other NETSCC programmes may vary.
The aim of the key priority designation is to resolve important uncertainties as rapidly as possible through research. The intended outcome is that the commissioned research will provide evidence that can be used to inform an update to the guidance or related guidance. This process can take place outside of formal guidance update timelines depending on the relevance and importance of the findings from the research evidence, which may require NICE to update the guidance as soon as possible.
The NICE key priority designation is made only if the NICE Committee Chair and Centre Director agree that special priority needs to be signalled. The designation should be made before the guidance is finalised and the SP&R team should be notified to facilitate discussion with NETSCC. This ensures that the final research recommendation is clear and actionable and takes account of any research started or commissioned since the systematic reviews were carried out for the NICE Committee. The details of the research in progress can then be added to the final guidance.
It has been agreed that NETSCC will accept for consideration up to 10 NICE key priority research recommendations each year. NICE's SP&R team maintains and manages the list across NICE and liaises with NETSCC and the NICE guidance producing centres.
Always include all research recommendations in the draft guidance for consultation in a separate 'Research recommendations' section. For guidelines, include this section in both the full and short versions. The recommendations may also be included in the body of the text.
NICE committees (with input from professionals and practitioners, researchers, patients, users of services, carers, the target population, reviewers, health economists and NICE technical staff) may be aware of research in progress that would support a research recommendation. Do not put information about these research activities in the 'Research recommendations' section, but in a separate 'Ongoing research' section.
Revise the draft research recommendations in light of any consultation comments and publish the final recommendations in the guidance.
The NICE SP&R team extracts all the important research recommendations that are published and adds them to the online NICE research recommendation database. The database is searchable and is monitored by research funders. For example, NETSCC actively reviews all NICE research recommendations and considers those that are within the remit of the programmes they manage.
It is important to check research recommendations as part of the guidance-review cycle to see if research has been undertaken that could feed into the updated guidance.
Carry out this check in conjunction with developing a review scope. The literature searches for the review scope process may identify whether research has been undertaken or is in progress. If the research has been undertaken, notify the NICE SP&R team so they can record the uptake of the research recommendation, and if necessary, remove the recommendation from the research recommendation database.
As part of the review process, guidance development teams may also be able to advise if partially updated guidance confirms amendments to, replacement or removal of existing research recommendations.
ISBN: 978-1-4731-6143-6