Graduated compression stockings for the prevention of deep-vein thrombosis in postoperative surgical patients: a systematic review and economic model with a value of information analysis

Background: Deep-vein thrombosis (DVT) can occur in surgical patients. Routine prophylaxis can be pharmacological and/or mechanical [e.g. graduated compression stockings (GCSs)]. GCSs are available in knee length or thigh length. Objective: To establish the expected value of undertaking additional research addressing the relative effectiveness of thigh-length GCSs versus knee-length GCSs, in addition to pharmacoprophylaxis, for prevention of DVT in surgical patients. Design: Systematic review and economic model, including value of information (VOI) analysis. Review methods: Randomised controlled trials (RCTs) assessing thigh- or knee-length GCSs in surgical patients were eligible for inclusion. The primary outcome was incidence of DVT. DVT complications and GCSs adverse events were assessed. Random-effects meta-analysis was performed. To draw on a wider evidence base, a random-effects network meta-analysis (NMA) was undertaken for the outcome DVT. A review of trials and observational studies of patient adherence was also conducted. A decision-analytic model was developed to assess the cost-effectiveness of thigh- and knee-length GCSs and the VOI. Results: Twenty-three RCTs were included in the review of effectiveness. There was substantial variation between trials in terms of the patient characteristics, interventions and methods of outcome assessment. Five trials comparing knee-length with thigh-length GCSs with or without pharmacoprophylaxis were pooled; the summary estimate of effect indicated a non-significant trend favouring thigh-length GCSs [odds ratio (OR) 1.48, 95% confidence interval (CI) 0.80 to 2.73]. Thirteen trials were included in the NMA. In the base-case analysis, thigh-length GCSs with pharmacoprophylaxis were more effective than knee-length GCSs with pharmacoprophylaxis (knee vs. thigh OR 1.76, 95% credible interval 0.82 to 3.53). Overall, thigh-length stockings with pharmacoprophylaxis was the most effective treatment, with a 0.73 probability of being the most effective treatment in a new trial of all the treatments. Patient adherence was generally higher with knee-length GCSs, and patients preferred knee-length GCSs. Thigh-length GCSs were found to be cost-effective in all but the subgroup with the lowest baseline risk, although the absolute differences in costs and effects were relatively small. The expected value of perfect information ranged from £0.2M to £178.0M depending on the scenario and subgroup. The relative effect parameters had the highest expected value of partial perfect information and ranged from £2.0M to £39.4M. The value of further research was most evident in the high-risk subgroups. Limitations: There was substantial variation across the included trials in terms of patient and intervention characteristics. Many of the included trials were old and poorly reported, which reduces the reliability of the results of the review. Conclusions: Given that the results from both the standard meta-analysis and the NMA lacked precision (CIs were wide) owing to the heterogeneous evidence base, a new definitive trial in high-risk patients may be warranted. However, the efficiency of any further research (i.e. whether this represents value for money) is dependent on several factors, including the acquisition price of GCSs, expected compliance with thigh-length GCSs wear, and whether or not uncertainty can be resolved around possible effect modifiers, as well as the feasibility and actual cost of undertaking the proposed research. Study registration: This study is registered as PROSPERO CRD42014007202. Funding: The National Institute for Health Research Health Technology Assessment programme