Apixaban for the prevention of venous thromboembolism in people ...

Indirect and mixed treatment comparisons
Searches were carried out on all NICE required databases and used the same strategies as 9.2. 11 The
ERG noted a typographical error for Fondaparinux in the original submission which was subsequently
addressed in the manufacturer’s response (Response to Clarification Letter, A4, page 18) (see
Appendix 1A). The ERG noted that not all low molecular weight heparins were searched for as free
text and queried this omission with the manufacturers. The manufacturers responded that “At the
initial citation screening stage (on the basis of title and abstract), all LMWH RCTs which met the
inclusion criteria for the review were included. However, as stated in appendix 16 of the submission,
it was decided a priori that meta-analysis was restricted to licensed doses of LMWHs, since the NICE
appraisal is primarily focused on UK licensed doses of apixaban and its relevant comparison
treatments (Response to Clarification Letter, A6, page 19) In the original submission the ERG also
queried the omission of the abbreviation “LMWH” from the search strategy, this was addressed
satisfactorily in the manufacturer’s response (Response to Clarification Letter, A5, page 18).
Adverse events
The Manufacturer stated that searches created for sections 5.1 and 9.2 of the Industry submission,
were also designed to identify eligible studies for adverse events associated with Apixaban. 11 CRD
guidance recommends that if searches have been limited by an RCT filter, additional searches should
be undertaken to ensure that adverse events that are long-term, rare or unanticipated are not missed. 12
The ERG considered it was possible that some relevant evidence might not have been identified as a
consequence of the RCT limit.
Non-RCT Evidence (Apixaban)
Adequate searches were carried out on all NICE required databases, plus additional hand searches of
the bibliographies of relevant articles and unpublished data from the manufacturer’s own clinical trials
database. 11 The ERG noted the same limitations in the facets for hip/knee replacement as in earlier
searches (see Appendix 1B)
Cost effectiveness
Searches were carried out on all NICE required databases. The search date was reported for all
searches but no Issue date was reported for the Cochrane search. The searches were well reported and
reproducible. The ERG did notice a recurring typographical error on the word analysis in the Medline
and Embase search of the original submission, which the manufacturer addressed in their response
(Response to Clarification Letter, B7, page 56).
Embase
The ERG queried why a Medline cost filter was applied to the Embase search, the use of Medline
mesh such as “exp cost/” in Embase would also pick up unwanted terms such as Energy cost/. The
Manufacturer addressed this in their response (Response to Clarification Letter, B8, page 56). The
ERG reran the manufacturers search with all corrections (n=348) but noted some remaining
weaknesses and addressed this by conducting an additional search (n=485) (See Appendix 1A)
The manufacturer reported that additional searches were undertaken for relevant material by hand
searching reference lists of previous trials and systematic reviews and by searching conference
15
Copyright 2011 Queen’s Printer and Controller of HMSO. All rights reserved.