Systematic literature searches for literature based submissions

Why do a systematic literature search?

A key requirement of evidence based medicine is that, as far as possible, all potentially relevant published literature should be scrutinised.

What is a systematic literature search?

It is a conceptually logical, explicit, and reproducible approach to identifying and retrieving all authoritative published material which contains evidence (both positive and negative) for issues raised in the submission.

There should be a demonstrated and unbroken line of reasoning from the search strategy through the:

• references retrieved
• selection or filter criteria applied
• subsequent appraisal of the evidence identified.

What are the requirements?

As a minimum, a well-conducted systematic search of Medline or Embase with reporting of any additional searching, such as:

• systematic
• non-systematic
• searching by hand.

No single literature search strategy will fit all cases and requirements will vary according to the specific nature of the application.

Frame your systematic search strategies to address each issue in an application for prescription medicines.

In particular, search nonclinical (non-human) toxicology and pharmacokinetic data separately from clinical (human) data.

Note:In planning and conducting systematic literature searches, you may find it useful for an information retrieval expert to be involved in the process.

Requirements for the search strategy

Your search strategy needs to be transparent, of sufficient quality, and reproducible.

For this reason:

• The quality of the Medline and/or Embase search is paramount.
• You should not substitute 'in-house' databases for Medline and/or Embase searches.
• Do not use non-native interfaces to search Medline and/or Embase, (i.e. an internet search engine or a federated search engine), as the search algorithms are not robust or transparent enough for systematic searches.
• Pre-established authoritative search strategies ("hedges") should be used with caution, and only if they are justified by fully matching your search parameters.
• You may include other appropriate databases, as long as the searches are fully recorded.
• Do not use internet search engines as a primary search platform.
• Additional relevant references can be identified through:
  • bibliographies
  • hand searching
  • expert consultation
  • internet searches etc
  • and must be fully reported as part of the methodology.

Using Embase and Medline for searches

Embase now contains the majority of records which were formerly unique to Medline.

Because of the potential for substantial duplication in retrieval, you should note that:

• You can use Embase as the sole source for database searches, provided the search strategy clearly demonstrates that all potential MeSH terms have been used.
• You should not rely on the Embase algorithm for mapping MeSH terms, as the terms may not strictly correlate. Appropriate MeSH and Embase subject headings must both appear.
• It's not sufficient to use free text words and phrases alone, and you should show appropriate use of:
  • subject headings
  • subheadings
  • limits
  • publication types.
• You may apply duplicate detection where Embase and Medline are searched on the same platform.
• Show the duplicate detection strategy as part of the reported search strategy.
• You are encouraged to use a bibliographic reference management tool for the detection of duplicates where Embase and Medline are searched on different platforms.
• You should report this as part of the search strategy, together with number of duplicate items detected.

Documenting the search methodology

Include a report of the methodology used for your systematic literature search with the application (at CTD Module 1: Administrative information and prescribing information for Australia).

The report should include:

• a rationale for the conduct of the systematic search(es) in relation to clinical and nonclinical issues identified in the submission
• a detailed, unedited, 'line by line' output of each systematic database search undertaken, including the:
  • number of references retrieved at each line of the search
  • details of the database platform used
  • time period covered by the database
• annotations showing which retrieved database sets were retained for appraisal and selection
• details of how any additional references were retrieved - for example, from in-house databases, lists of references, or hand searching
• dates on which searching was performed
• sufficient detail to ensure that the search strategy is transparent and reproducible.

For more information on documenting literature searches, please refer to Appendix 3 of Systematic Reviews - external site: CRDs guidance for undertaking systematic reviews in health care.