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

1. SUMMARY .................................................................................................................................. 7
1.1 Scope of the manufacturer submission ................................................................................ 7
1.2 Summary of clinical effectiveness evidence submitted by the manufacturer ......................... 7
1.3 Summary of cost effectiveness submitted evidence by the manufacturer .............................. 8
1.4 ERG commentary on the robustness of evidence submitted by the manufacturer ................. 8
1.4.1 Strengths .................................................................................................................... 8
1.4.2 Weaknesses and areas of uncertainty .......................................................................... 9
1.5 Summary of additional work undertaken by the ERG .......................................................... 9
2 BACKGROUND .................................................................................................................... 10
2.1 Critique of manufacturer’s description of underlying health problem. .............................. 10
2.2 Critique of manufacturer’s overview of current service provision ..................................... 11
3 Critique of manufacturer’s definition of decision problem ....................................................... 12
3.1 Population ....................................................................................................................... 12
3.2 Intervention...................................................................................................................... 12
3.3 Comparators .................................................................................................................... 12
3.4 Outcomes ......................................................................................................................... 13
3.5 Other relevant factors ...................................................................................................... 13
4 CLINICAL EFFECTIVENESS ............................................................................................... 14
4.1 Critique of the methods used by the manufacturer to systematically review clinical
effectiveness evidence .................................................................................................................. 14
4.1.1 State objective of systematic review. Provide description of manufacturers search
strategy and comment on whether the search strategy was appropriate. If the manufacturer did
not perform a systematic review, was this appropriate?............................................................ 14
4.1.2 State the inclusion/exclusion criteria used in the study selection and comment on
whether they were appropriate. ................................................................................................ 17
4.1.3 What studies were included in the clinical effectiveness review and what were
excluded? Provide a table of identified studies. Please identify the most important clinical
effectiveness studies. ............................................................................................................... 18
4.1.4 Provide details of any relevant studies not discussed in the submission? Why were
these studies excluded and how were these studies identified by the ERG? .............................. 20
4.2 Summary and critique of submitted clinical effectiveness evidence.................................... 21
4.2.1 Summary of submitted clinical evidence for each relevant trial. ................................ 21
4.2.2 Describe and critique the manufacturer’s approach to validity assessment for each
relevant trial. ........................................................................................................................... 24
4.2.3 Describe and critique the statistical approach used within each relevant trial. ............ 25
4.2.4 Describe and critique the manufacturer’s approach to outcome selection within each
relevant trial. ........................................................................................................................... 27
4.2.5 To what extent does each relevant trial include the patient population(s),
intervention(s), comparator(s) and outcomes as defined in the final scope? .............................. 27
4.2.6 Where appropriate, describe and critique any meta-analysis, indirect comparisons and/
or mixed treatment analysis carried out by the manufacturer. ................................................... 28
4.2.7 Additional clinical work conducted by the ERG........................................................ 31
4.3 Conclusions ..................................................................................................................... 32
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