NICE process and methods

5 Production

5 Production

5.1 Equality and diversity considerations

'Evidence summaries: new medicines' (ESNMs) are developed in accordance with the NICE equality scheme.

5.2 Process and timescales

ESNMs are not formal NICE guidance and therefore are not subject to the same intensity of process as other NICE products.

Table 1 shows the key steps in the development of ESNMs.

Table 1 Key steps for developing an ESNM with timelines

Key step

Timescale

Scope topic

Week 1

Contact manufacturer for data

Week 1

Literature search

Searching for evidence

Sifting and selecting the evidence

Appraising and categorising the evidence

Week 2

Week 3

Week 3

Authoring the ESNM

Produce initial draft

Internal check of initial draft

Week 4

Week 4

Review of draft ESNM

Initial draft sent to manufacturers, specialist commentators, NICE Clinical Guidelines team and NICE Technology Appraisals team for review

Week 5

Review comments received and produce revised draft

Week 8

Quality assurance of the ESNM

Technical check of content by senior adviser

Editorial check of content by NICE publishing team

Manufacturer invited to check for any remaining factual errors

Final check of content by Medicines and Prescribing Centre Programme Director, Associate Director or Consultant Clinical Adviser

Week 9

Week 9

Week 10

Week 11

Sign off and publication of the ESNM

Guidance Executive sign off

Manufacturer informed of date that ESNM will be published

Publication on NICE website

Week 12

Week 12

Week 13

5.3 Scoping of individual topics

The NICE Medicines and Prescribing Centre holds an internal scoping meeting for each ESNM topic to:

  • confirm key contacts at the pharmaceutical manufacturer

  • identify specialist commentators (through the NICE Medicines and Prescribing Associates and other existing NICE networks)

  • identify terms for a literature search to identify published clinical trial data that reflect the possible indication for the medicines (usually phase III trials)

  • confirm arrangements for identifying:

    • proposed or likely indication

    • relevant published trials

    • likely licensing and marketing timeline

    • proposed cost and course of treatment

    • evidence of clinical effectiveness

    • safety issues

    • treatment alternatives

    • likely place in therapy

    • incidence and prevalence of (likely) indication (to inform an estimation of use).

5.4 Contacting the manufacturer

NICE asks the manufacturer to support the production of the ESNM by providing the following data (within 10 working days):

  • Key published clinical trials relating to the indication being reviewed in the ESNM that have been published in full.

  • Key relevant clinical trials that are ongoing or that have been completed but not yet published in full.

  • The licence status within the UK, including whether a positive opinion or a marketing authorisation has been granted, and an indication of when the medicine will become available.

  • The presentation of the medicine, including form, strength and pack size.

  • The expected cost (for medicines not yet available).

  • The expected or licensed dose.

5.5 Literature search

5.5.1 Searching for evidence

A literature search is conducted by the NICE Guidelines Information Service. The literature search is intended to locate the best (highest quality) available published evidence relating to the efficacy and safety of the medicine. In addition, explicit reference is made to information in the summary of product characteristics (if one exists) relating to precautions, warnings and undesirable effects and also to published advice from the Medicines and Healthcare products Regulatory Agency (MHRA). Cost information is obtained from the current Drug Tariff, or if the product is not listed there, the current edition of MIMS, or if the product is not listed there, the manufacturer.

5.5.2 Sifting and selecting the evidence

The NICE Medicines and Prescribing Centre sifts the final set of search results using the title and abstract of each article, applying first exclusion and then inclusion criteria. These include the basic criteria as set out below.

First sift

This process removes evidence based on the following exclusion criteria:

  • articles of poor relevance against search terms

  • publication types that are out of scope:

    • non-English language studies

    • articles if neither the abstract nor full text is freely available online

    • conference abstracts[2]

    • studies that have not been published in full[2].

Second sift

This sift of evidence includes relevant randomised controlled trials (RCTs) that address the use of the medicine within the defined indication under review. The reasons for inclusion and non-inclusion based on the second sift are recorded as well as a 'long list' of those studies that are excluded from the first sift.

Up to 3 RCTs can be reviewed for an ESNM. If more than 3 RCTs have been identified for possible inclusion, they are prioritised taking into account the following considerations:

  • whether patient-oriented outcomes[3] were reported and if so, whether these were primary or secondary outcomes

  • whether an active comparator was used, and whether this reflects usual UK practice

  • whether the population in the study reflects the typical UK population for which this medicine is likely to be used (bearing in mind the licensed or proposed indication and NICE guidance)

  • the size of the available studies.

5.5.3 Appraising and categorising the prioritised evidence

The NICE Medicines and Prescribing Centre prioritises the evidence for critical appraisal and records the reasons for non-inclusion of evidence. The full text of the prioritised evidence is appraised using an assessment form suitable for the type of evidence. If a European public assessment report (EPAR) has been published, it is used to supplement the information included in the published study report, if this is necessary.

5.6 Authoring of the ESNM

The NICE Medicines and Prescribing Centre drafts the ESNM using a standard template, which includes sections relating to the following:

  • synopsis of key points from the evidence

  • relevance to NICE guidance programmes

  • general information about the disease or condition

  • product overview, including drug action, licensed or proposed indications, course and cost

  • review of the available evidence, with relative strengths and weaknesses of evidence for clinical effectiveness and safety

  • context, including treatment alternatives and their cost

  • estimated impact for the NHS, including likely place in therapy and estimated usage

5.7 Review of the draft ESNM

The NICE Medicines and Prescribing Centre sends the draft ESNM to the identified external specialist reviewers, the manufacturer, the NICE Clinical Guidelines team, and the NICE Technology Appraisals team for review. Any comments received are considered within the production of the revised draft. Actions are also recorded. Feedback to commentators is available on request to NICE.

5.8 Quality assurance of the ESNM

Quality assurance of the ESNM is carried out by the NICE Medicines and Prescribing Centre. This involves a detailed check of all content, to ensure all sections of the document contain statements and conclusions that are fair and balanced. They must accurately reflect the evidence reviewed and be substantiated by an explicit and appropriate source of evidence. This is carried out to a standard checklist. A further check for clarity, grammar, spelling and style is also undertaken by the NICE Medicines and Prescribing Centre. All drafts and any changes to drafts are recorded for audit purposes.

In conjunction with the NICE publishing team, the NICE Medicines and Prescribing Centre produces a near-final draft. The manufacturer is given the opportunity to review the near-final draft to check for any factual errors and any necessary corrections are made by the Medicines and Prescribing Centre. Once sign-off is received from the Medicines and Prescribing Centre Programme Director, Associate Director or Consultant Clinical Adviser, NICE Guidance Executive reviews the ESNM, and if appropriate, approves the ESNM for publication, ensuring that due process has been followed in its development. The manufacturer is informed of the scheduled publication date, and may request an embargoed copy of the ESNM to be sent to them 24 hours before publication.

5.9 Publication of the ESNM

The final ESNM is uploaded and made available online through the Medicines and Prescribing Centre page of the NICE website.

The NICE Communications team develops a communications plan for the ESNM, together with the Associate Director within the Medicines and Prescribing Centre, and is responsible for disseminating the ESNM once it has been published.


[2] Studies that have been reported only as conference abstracts or otherwise not reported in full are excluded because they cannot be critically appraised. However, the ESNM may indicate if key clinical trials are ongoing or have been completed but not yet published in full.

[3] Patient-oriented outcomes are those that are of direct clinical importance, such as mortality, rates of cardiovascular events, or quality of life. This is in contrast to disease-oriented, surrogate outcomes, such as changes in blood pressure or biochemistry.