NICE process and methods
Appendix B: Identification, selection and synthesis of clinical evidence
Appendix B: Identification, selection and synthesis of clinical evidence
1.1 Identification and selection of relevant studies
This section provides guidance on identifying and selecting relevant studies that provide evidence for:
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the technology being evaluated
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comparator technologies, when an indirect or mixed treatment comparison is carried out.
To identify and select relevant studies, it is expected that a systematic literature search will be carried out in line with NICE's health technology evaluations manual, sections 3.4.2, 3.4.4 and 3.4.5.
In exceptional circumstances a systematic literature search may not be necessary. If a systematic literature search is not included in the submission, the company must confirm that no other additional relevant studies have been done outside its organisation.
Advise whether a search strategy was developed to identify relevant studies. If a search strategy was developed and a literature search carried out, provide details under the subheadings listed in this section. Key aspects of study selection can be found in Systematic reviews: CRD's guidance for undertaking reviews in health care (University of York Centre for Reviews and Dissemination).
Search strategy
Describe the search strategies used to retrieve relevant clinical data. The methods used should be justified with reference to the decision problem. Sufficient detail should be provided so that the results may be reproduced. This includes a full list of all information sources and the full electronic search strategies for all databases, including any limits applied.
Study selection
Provide details of the treatments to be compared. This should include all treatments identified in the final NICE scope. If additional treatments have been included, the rationale should be provided. For example, additional treatments may be added to make a connected network for a mixed treatment comparison.
Describe the inclusion and exclusion selection criteria, language restrictions and the study selection process in a table. Justification should be provided to ensure that the rationale for study selection is transparent. See the following suggested table format.
| Clinical effectiveness | Inclusion criteria | Exclusion criteria |
|---|---|---|
| Population | ||
| Intervention | ||
| Comparators | ||
| Outcomes | ||
| Study design | ||
| Language restrictions |
A flow diagram of the numbers of studies included and excluded at each stage should be provided using a validated statement for reporting systematic reviews and meta-analyses, such as the PRISMA flow diagram. The total number of studies in the statement should equal the total number of studies listed in section 2.1.
When data from a single study have been drawn from more than 1 source (for example, a poster and a published report) or when trials are linked (for example, an open-label extension to a randomised controlled trial [RCT]), this should be clearly stated.
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Provide a complete reference list of included studies.
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Provide a complete reference list of excluded studies.
For indirect and mixed treatment comparisons
Summary of trials included in indirect or mixed treatment comparisons
In a table, provide a summary of the trials used to carry out the indirect comparison or mixed treatment comparison. A suggested table format is presented at the end of this section. When there are more than 2 treatments in the comparator sets for synthesis, include a network diagram.
If the table or network diagram provided does not include all the trials that were identified in the search strategy, the rationale for exclusion should be provided.
| Intervention A | Intervention B | Intervention C | Intervention D | |
|---|---|---|---|---|
|
Trial 1 |
Yes |
Yes |
Yes |
|
|
Trial 2 |
Yes |
Yes |
Yes |
|
|
Trial 3 |
Yes |
Yes |
||
|
Trial 4 |
Yes |
Yes |
||
|
[Add more rows as needed] |
Methods and outcomes of studies included in indirect or mixed treatment comparisons
Provide the rationale for the choice of outcome measure chosen, along with the rationale for the choice of outcome scale selected.
Discuss the populations in the included trials, especially if they are not the same as the populations specified in the NICE scope. If they are not the same:
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provide a rationale to justify including the study
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describe the assumptions made about the impact or lack of impact this may have on the relative treatment effect
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explain whether an adjustment has been made for these differences.
Describe whether there are apparent or potential differences in patient populations between the trials. If this is the case, explain how this has been taken into account.
For each trial included, provide table(s) of the:
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methods
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outcomes and results
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participants' baseline characteristics.
Methods of analysis of studies included in indirect or mixed treatment comparisons
Provide a clear description of the indirect or mixed treatment comparison methodology. If the company considers that an indirect treatment comparison or mixed treatment comparison is inappropriate, the rationale should be provided and alternative analyses explored (for example, naive indirect comparison or a narrative overview).
For analyses of overall survival, provide and discuss the subsequent treatment data for each trial and how this informed the feasibility assessment for the indirect or mixed treatment comparison.
Refer to NICE's health technology evaluations manual, sections 3.4.11 to 3.4.21.
For studies which will be detailed in section 2.4 of the main submission (that is, studies assessing the intervention technology), cross reference the submission rather than repeating the information in appendix B.
Supply any programming language used (for example, the WinBUGS code).
Risk of bias of studies included in indirect or mixed treatment comparisons
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Provide a complete quality assessment of each trial.
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Identify any risk of bias within the trials identified, and describe any adjustments made to the analysis.
1.2 Participant flow in the relevant randomised controlled trials
Provide details of the numbers of participants who were eligible to enter the trials. Include the number of participants randomised and allocated to each treatment. Provide details of and the rationale for participants who crossed over treatment groups, were lost to follow up or withdrew from the RCT. Provide a CONSORT diagram showing the flow of participants through each stage of each of the trials.
See section 2.4 for full details of the information required here.
1.3 Critical appraisal for each study
See section 2.5 for more details of what should be included here.
For studies that will be detailed in section 2.5 of the submission (that is, studies assessing the intervention technology), cross reference the submission rather than repeating the information in appendix B.