Recommendations for research
The guideline committee has made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.
What is the accuracy of individual risk assessment tools in predicting the risk of venous thromboembolism (VTE) and risk of bleeding in people admitted to hospital?
Risk assessment is a mandatory for all people admitted or having day procedures in hospital. Since 2010, the National VTE Risk Assessment Tool has been widely used in the NHS to assess a person's risk of VTE. This tool has not been validated or tested against other tools to evaluate its diagnostic accuracy or effectiveness at correctly identifying people at risk of VTE. There is concern that the tool may not accurately identify those who are most likely to get VTE.
According to national figures, over 70% of medical patients in the UK have prophylaxis when the national tool has been used, with some trusts offering prophylaxis to over 90% of medical patients. Around 40% of medical patients have prophylaxis in largely US‑based populations when other tools are used (although this may partially relate to different indications for hospital admission). It is not known if this means that the national tool identifies too many people or the other tools do not identify enough. The potential impact of giving unnecessary prophylaxis is that people may be at increased risk of bleeding and discomfort through repeated injections. There is also the potential for reducing the cost of thromboprophylaxis by better defining 'at risk' populations, so that the number of those given thromboprophylaxis is reduced.
What is the clinical and cost effectiveness of weight-based dose-adjustment strategies of low-molecular-weight heparin (LMWH) compared with fixed-dose strategies of LMWH for preventing VTE in people who are very obese (BMI over 35) who are admitted to hospital or having day procedures (including surgery and chemotherapy)?
Obesity is on the rise in England. The prevalence of obesity increased by 11% between 1993 and 2014 (15% in 1993 and 26% in 2014), which has resulted in more obese people being admitted to hospital. Obesity may as much as double a person's risk of developing hospital-acquired VTE, therefore most obese people will need prophylaxis. There is much uncertainty about what dose to use and the clinical and cost effectiveness of using weight-based dose-adjustment versus fixed-dose strategies. In current practice, a higher than usual dose is given but this may not be necessary, especially if the person has obesity-related liver disease. Several studies have reported effectiveness in terms of biological measures rather than clinical outcomes such as deep vein thrombosis (DVT) and bleeding events. It is important that there is a clearer understanding of the effects that different dose strategies can have in terms of clinical outcomes. This is because they can directly influence the quality of life of obese people admitted to hospital and help inform clinical decisions on patient care.
What is the clinical and cost effectiveness of direct oral anticoagulants for preventing VTE in people with lower limb immobilisation?
The Computerized registry of patients with venous thromboembolism (RIETE) study, a multicentre prospective cohort study of 30,886 patients with acute VTE, estimated that 5.7% of VTE events were associated with lower limb immobilisation for non-major orthopaedic surgery. Estimates of DVT risk in people with lower limb immobilisation, based on meta-analyses of trials comparing chemothromboprophylaxis with placebo, range between approximately 4% and 40%. Given that lower limb immobilisation following trauma or non-major orthopaedic surgery is so common, the consequent burden of disease from VTE from this cause in the whole population is very considerable. For example, the annual incidence of ankle fracture is 187 per 100,000, translating to over 120,000 incident fractures per year in the UK. If 10% of these fractures are complicated by VTE, then we might expect approximately 12,000 events per year only related to immobilisation following ankle trauma.
Despite this burden of ill-health, no randomised studies comparing modern anticoagulants that are available in oral preparations (perhaps more suitable for outpatient treatments) with established treatments such as LMWH or fondaparinux were identified in the evidence review. The committee were unable to make a recommendation to consider oral anticoagulants for this patient group given this lack of evidence.
What is the clinical and cost effectiveness of aspirin alone versus other pharmacological and/or mechanical prophylaxis strategies (alone or in combination) for people with fragility fractures of the pelvis, hip or proximal femur?
Fragility fractures are the greatest burden of musculoskeletal disease in hospitals in the UK. There are approximately 70,000 fragility hip fractures per year in England alone leading to 1.5 million bed days being used each year, which equates with the continuous occupation of over 4,000 NHS beds.
Current evidence supports a recommendation for prophylaxis with LMWH or fondaparinux. Both involve a subcutaneous injection for 28 days requiring either self-injection at home or a community nurse attending to deliver the injection. Patient adherence to treatment may be improved with an oral rather than injectable treatment.
A large but controversially reported trial suggests that aspirin may be at least as effective as currently recommended treatments. However, because of methodological and reporting limitations, the evidence for the effectiveness of aspirin alone is not clear. There is potentially a large cost saving if aspirin is clinically effective because it is very inexpensive.
What is the clinical and cost effectiveness of standard versus extended duration pharmacological prophylaxis for preventing VTE in people undergoing elective total hip replacement surgery?
In 2015, there were 84,462 hip replacements in England, Wales and Northern Ireland. The current recommended duration of prophylaxis is 28 days in the elective total hip replacement population. This extended duration of prophylaxis is based on few, small and older trials. The quality of the evidence supporting extended duration prophylaxis is very low. Modern pharmaceutical trials of newer interventions use extended duration prophylaxis based on these historical data, with the added incentive of more expensive prophylaxis strategies. There is a large potential cost saving if a shorter duration of prophylaxis is as clinically effective, given the considerable cost of prophylaxis and the number of people for whom it is prescribed.