Appendix table

What is the clinical and cost effectiveness of lifelong anticoagulation in specific ‘subgroups’ of patients with unprovoked VTE?
PICO questionPopulation: Patients with unprovoked VTE who have completed 3 months of anticoagulation successfully.
Intervention: Continued oral anticoagulation throughout trial (as an approximate to lifelong therapy).
Comparison: Stop oral anticoagulation
Outcomes: Outcomes should be measured at 3 months, 12 months and then annually.
Importance to patients or the populationIt is very important to understand the benefits of lifelong anticoagulation in specific subgroups to be able to accurately determine the balance of the benefits compared with the risk of bleeding, or death, in these patients.
Relevance to NICE guidanceDetailed information would enable recommendations specific to different underlying risks in the identified subgroups. The comparison of lifelong anticoagulation therapy to 3 months supports the recommendation made in the current guideline.
Relevance to the NHSThe results of this study would enable accurate prescribing of anticoagulation therapy and reduce costs associated with adverse events due to either inappropriate continuation or discontinuation of treatment.
National prioritiesVTE has been identified as an important area at a national level (House of Commons Select Committee on Health Second Report, 2005194) because of the number of deaths related to it.
Current evidence baseEvidence reviewed for duration of pharmacological interventions. There was no evidence relating to duration in the specific subgroups.
Study designA randomised controlled trial (RCT) is required. Power calculations should be conducted to establish the required sample size of the trial. It is important that the study is adequately powered to detect a clinically important effect size. The investigators should do a thorough review on the recurrence rate of the specific subgroup of interest in the study.
Economic considerationsAny reduction in VTE recurrence or unnecessary risk of bleeding will have an impact improving quality of life, life expectancy, reducing costs of treating the VTE and reducing hospital admissions and deaths.
FeasibilityIdeally a double blinded RCT should be conducted, however the GDG considered the practicalities of conducting a double blinded RCT for 5 years and the cost implications of funding such a study. Therefore an open label RCT with intention to treat analysis would be a pragmatic approach. The study could consider only addressing a specific subgroup of patients of interest (for example males, patients with elevated D-dimer, or patients with PTS) as the main inclusion criteria; it is recognised that a study with multiple groups will need a larger sample size so that further analysis could be done to identify the risks within each subgroup. Timescales would need to gain an approximation of lifelong anticoagulation therapy; the GDG felt that follow up for 5 years from randomisation would be sufficient. The length of follow-up must be equal for both arms of the study.
Individual patient data analysis is also considered a possible alternative. However, prior investigations need to be conducted to ensure that existing trial data already included patients with risk factors of interest and that these data could be accessed.
EqualitiesThe study should include women of childbearing age but make appropriate provisions for pregnancy and breast-feeding events.
Other commentsNew medications, if approved, will not influence the value of the study. The study will still provide very important information on whether certain subgroups could benefit from secondary prophylaxis to prevent VTE recurrence.

From: Appendix J, Research Recommendations

Cover of Venous Thromboembolic Diseases
Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing [Internet].
NICE Clinical Guidelines, No. 144.
National Clinical Guideline Centre (UK).
Copyright © 2012, National Clinical Guideline Centre.

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