NICE’s recommendations for thromboembolism are not evidence based

A Radio 4 Face the Facts programme earlier this year placed hospitals and doctors who do not assess patients for risk of venous thromboembolism (VTE) in the dock alongside fraudsters (www.bbc.co.uk/programmes/b012fqss). But do the facts support prophylaxis for the largest group at risk—medical inpatients? Deaths from VTE are important and tragic for individuals and families. I support government led safety initiatives, and actively participated in the Clostridium difficile reduction programme. But we need targets and treatments to be driven by evidence—not politics.

A House of Commons health committee report in 2005, partly in response to lobbying by the thrombosis charity Lifeblood, recommended prophylaxis, with an unreferenced claim that 25?000 people die each year from VTE that is contracted in hospital. A report from the National Institute for Health and Clinical Excellence (NICE) made almost the same recommendations. In the Radio 4 programme Bruce Keogh described the adoption of these recommendations his first priority as NHS director. NICE has a reputation for robust analysis of risk benefit and in particular cost benefit, and claims, “We always use the best available evidence in all our work and we are free from political influence” (www.nice.org.uk/aboutnice/howwework/how_we_work.jsp). In this case the evidence is not there for medical patients.

What can be wrong with the simple requirement to assess all (medical) admissions and prescribe preventive drugs for patients at high risk? Firstly, the scale of the problem looks inflated. Headlines claim that the policy will prevent 25?000 deaths. About 600?000 people die each year in the United Kingdom, so this suggests that one in 24 does so from preventable VTE. Only 6500 people a year are actually certified as having died from VTE (www.nice.org.uk/guidance/qualitystandards/vteprevention/vtequalitystandard.jsp), implying that deaths were under-recorded by more than four times, that all occurred after hospital admission, and that all were preventable. As a target for headlines, staff sense intellectual inconsistency (or, even worse, dishonesty) and react against it.

Secondly, there is no good evidence that drug prophylaxis in medical patients affects mortality or is cost effective. NICE’s meta-analysis showed an odds ratio of 0.99 (95% CI 0.78 to 1.24) for mortality (www.nice.org.uk/nicemedia/live/12695/47920/47920.pdf). Prophylaxis does not result in a statistically significant reduction in symptomatic pulmonary emboli (odds ratio 0.56; 0.11 to 2.13; 8/2027 v 13/1986). Surrogate end points are notoriously unreliable, so reliance on a reduction in asymptomatic, screened-for deep vein thrombosis at about 14 days, from 13% to 5.9% (odds ratio 0.46; 0.31 to 0.7; 63/479 v 29/488) should not be the basis for recommending treatment. Estimates of cost effectiveness rely on many, usually favourable, assumptions, such as those used in relation to postphlebitic leg syndrome. US guidelines also recommend prophylaxis but are based on a meta-analysis that includes two unblinded studies (Ann Intern Med 2007;146:278-88, www.annals.org/content/146/4/278.abstract).

Thirdly, the hand of big pharma is evident. Lifeblood is supported by industry: Boehringer Ingelheim even issued a press release on behalf of Lifeblood without itsconsent (www.nice.org.uk/nicemedia/live/12695/47200/47200.pdf) On the NICE committee recommending prophylaxis eight out of 13 members (nearly all the doctors) acknowledged a relationship with drug companies, but this was not thought to warrant their exclusion from discussions (www.nice.org.uk/nicemedia/live/12695/47200/47200.pdf). Big pharma was also formally represented in the stakeholder group.

Fourthly, there are three potential sources of increased cost. Low molecular weight heparins cost about £3 (€3.50; $4.70) a day and many patients take them. The cost of treatment to the NHS is unknown. Litigation costs will rise if people who experience VTE after admission to hospital have not been assessed or given prophylaxis. And trusts will be fined £350?000, the equivalent of about 10 nurses’ salaries, if they do not comply with the requirement to assess more than 90% of all admissions.

Fifthly, it skews practice. As I see 26 acute admissions on a morning ward round I have to make about 25 decisions for each patient. The dominant one has become checking whether the VTE assessment has been done to ensure that our trust is compliant. There are many better things I could be concentrating on.

Finally, the policy implies that this matter has been dealt with: the box has been ticked, and 25?000 lives have been saved. However, it almost certainly has not been resolved: further research ideas will not be pursued, and political and clinical momentum will be lost.

So, let’s really face the facts: prophylaxis against VTE will not save 25?000 lives. It may save no patients’ lives, but will cost millions of pounds in possibly unnecessary treatment and lost funds for trusts. It will prevent the development of policies that may actually prevent VTE. From the facts available, NICE could have drawn the conclusion that good evidence does not support prophylaxis and could have recommended a proper study with death as the end point, which would have answered the question once and for all. Here NICE has abdicated its responsibility.

VTE policy for medical inpatients promises something it is very unlikely to be able to deliver and may leave the NHS worse off. It should be rethought. The programme highlighted a case of clearly missed VTE. Lifeblood is now running a new campaign entitled “Spot the Clots.” Now that is a campaign to support.