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When Kissinger won the Nobel Peace Prize, Tom Lehrer promptly declared that satire had become obsolete. I had much the same emotion on reading the letter by Stansby et al (BMJ 2012;345:e5098) where the authors of the NICE guidance in relation to timing of ultrasound in cases of suspected DVT justified their decision on the grounds of “protecting people from being exposed to potential harm from receiving unnecessary low molecular weight heparin.”
As a result of the way the DoH decided to implement NICE guideline CG92 (prophylaxis of venous thromboembolism), there is now an industry devoted to ensuring that as many medical inpatients as possible are exposed to potential harm from receiving unnecessary low molecular weight heparin (LMWH). Physicians are obliged to complete a risk assessment on every inpatient using an unvalidated screening tool that is in essence designed to ensure that all medical inpatients with “ongoing reduced mobility” (not defined) should be given prophylaxis unless contraindicated. This outcome is clearly not evidence-based, a fact that was eloquently discussed in this journal by Welfare (BMJ 2011;343:d6452) and more recently by Snee (BMJ 2012;345:e4940).
The justification for the conclusion reached by NICE (that LMWH prophylaxis was cost-effective in medical inpatients) appears to rest on the guideline development group’s (GDG) stance that there is a continuum of risk between asymptomatic VTE events and serious VTE complications and that a reduction in the former would be accompanied by reduction in the latter. The referenced justification for this approach is a paper written in the 1930s on prevention of industrial accidents. However, at the time CG92 was written there was already enough trial and meta-analysis evidence in relation to the outcomes of VTE prophylaxis in medical inpatients for the authors to be absolutely certain that mortality was not in fact reduced by anything like 60%, and that their theory of a continuum of risk was therefore incorrect1. It is not credible that the guideline authors were ignorant of this evidence. The question is therefore begged: why did they choose to model the cost effectiveness of LMWH on the basis of premises they knew to be false? This question has been repeatedly put by clinicians to the GDG: we are yet to receive an answer.
Whatever one thinks of the process leading up to the development of CG92, and I think it unlikely that satisfactory answers to the concerns of clinicians will ever be provided, new evidence is now available and has been for nearly a year in the shape of the entirely negative results of the LIFENOX study, which in its design closely replicated the application of the NICE guidance2. To this we can add the results of the scrupulous meta-analysis conducted by Lederle et al to underpin the current American College of Physicians guideline3.
It is time for NICE to re-evaluate the evidence underpinning CG92, and in doing so it should remind itself to remind itself of the basic principle of the null hypothesis that if an effect cannot be demonstrated to be present, it is safer to assume it is absent. On current evidence it seems probable that most of the more serious complications of venous thromboembolism are not preventable by LMWH in medical inpatients, and that the small benefits that do accrue are approximately balanced by harms resulting from excess bleeding. The policy of universal risk assessment with a default outcome of prescription of prophylaxis should also be abandoned in favour of research designed to produce a validated tool for risk assessment on the one hand, and better strategies for VTE prophylaxis on the other.
References
1. Dentali F Douketis JD Gianni M. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical inpatients. Ann Intern Med 2007; 146: 278-288
2. Kakkar AK, Cimminiello C, Goldhaber SZ. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011;365:2463-72.
3. Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice guideline. Ann Intern Med 2011;155:602-15
Competing interests:
No competing interests
19 August 2012
Andrew J Leonard
Consultant Acute Physician
East Sussex Healthcare NHS Trust
Conquest Hospital, St Leonards on Sea, E Sussex TN37 7RD
Re: Authors’ reply to Makowska-Webb, Byatt, D’Costa, and Hart
When Kissinger won the Nobel Peace Prize, Tom Lehrer promptly declared that satire had become obsolete. I had much the same emotion on reading the letter by Stansby et al (BMJ 2012;345:e5098) where the authors of the NICE guidance in relation to timing of ultrasound in cases of suspected DVT justified their decision on the grounds of “protecting people from being exposed to potential harm from receiving unnecessary low molecular weight heparin.”
As a result of the way the DoH decided to implement NICE guideline CG92 (prophylaxis of venous thromboembolism), there is now an industry devoted to ensuring that as many medical inpatients as possible are exposed to potential harm from receiving unnecessary low molecular weight heparin (LMWH). Physicians are obliged to complete a risk assessment on every inpatient using an unvalidated screening tool that is in essence designed to ensure that all medical inpatients with “ongoing reduced mobility” (not defined) should be given prophylaxis unless contraindicated. This outcome is clearly not evidence-based, a fact that was eloquently discussed in this journal by Welfare (BMJ 2011;343:d6452) and more recently by Snee (BMJ 2012;345:e4940).
The justification for the conclusion reached by NICE (that LMWH prophylaxis was cost-effective in medical inpatients) appears to rest on the guideline development group’s (GDG) stance that there is a continuum of risk between asymptomatic VTE events and serious VTE complications and that a reduction in the former would be accompanied by reduction in the latter. The referenced justification for this approach is a paper written in the 1930s on prevention of industrial accidents. However, at the time CG92 was written there was already enough trial and meta-analysis evidence in relation to the outcomes of VTE prophylaxis in medical inpatients for the authors to be absolutely certain that mortality was not in fact reduced by anything like 60%, and that their theory of a continuum of risk was therefore incorrect1. It is not credible that the guideline authors were ignorant of this evidence. The question is therefore begged: why did they choose to model the cost effectiveness of LMWH on the basis of premises they knew to be false? This question has been repeatedly put by clinicians to the GDG: we are yet to receive an answer.
Whatever one thinks of the process leading up to the development of CG92, and I think it unlikely that satisfactory answers to the concerns of clinicians will ever be provided, new evidence is now available and has been for nearly a year in the shape of the entirely negative results of the LIFENOX study, which in its design closely replicated the application of the NICE guidance2. To this we can add the results of the scrupulous meta-analysis conducted by Lederle et al to underpin the current American College of Physicians guideline3.
It is time for NICE to re-evaluate the evidence underpinning CG92, and in doing so it should remind itself to remind itself of the basic principle of the null hypothesis that if an effect cannot be demonstrated to be present, it is safer to assume it is absent. On current evidence it seems probable that most of the more serious complications of venous thromboembolism are not preventable by LMWH in medical inpatients, and that the small benefits that do accrue are approximately balanced by harms resulting from excess bleeding. The policy of universal risk assessment with a default outcome of prescription of prophylaxis should also be abandoned in favour of research designed to produce a validated tool for risk assessment on the one hand, and better strategies for VTE prophylaxis on the other.
References
1. Dentali F Douketis JD Gianni M. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical inpatients. Ann Intern Med 2007; 146: 278-288
2. Kakkar AK, Cimminiello C, Goldhaber SZ. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011;365:2463-72.
3. Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice guideline. Ann Intern Med 2011;155:602-15
Competing interests: No competing interests