As a preliminary effort to incorporate resource considerations into the ACCP guideline process, five chapters were selected in which cost issues were considered particularly salient. To illustrate the ways in which economic data can relate to recommendations, we consider two brief examples taken from these other chapters in this supplement: duration of venous thromboembolism (VTE) prophylaxis after hip surgery and clopi-dogrel use for secondary prevention in patients with atherosclerotic vascular disease.
Duration of VTE Prophylaxis Following Hip Replacement
1. Select Target Guideline Recommendations for Resource Use Evaluation: As reviewed in the “Prevention of VTE” chapter of this supplement, clinical trial data indicate that prolongation of VTE prophylaxis beyond 2 weeks following hip surgery is effective in reducing symptomatic VTE. However, such therapy can be costly, particularly when low-molecular-weight heparin is the treatment used, and the panel was concerned that these issues would create a barrier at some sites.
2. Identify the Literature: A review of the literature revealed seven studies performed in developed countries (France, Sweden, Italy, United States, United Kingdom, Switzerland, and Belgium) that examined the cost implications of shorter vs longer duration of prophylaxis for VTE after hip replacement. These studies were of variable quality based on modeling with minimal empirical cost data.
3. Evaluate the Evidence: What are the resource considerations from a social perspective? Despite different assumptions and methods, prolonged VTE prophylaxis after hip replacement was generally judged to be a good use of resources (either cost saving or had a “reasonable” ICER). Estimates of the ICER of extended VTE prophylaxis ranged from negative (cost saving) to approximately US $35,000. Generally, the most important factor driving these results was the cost offset provided by prophylaxis (from reduced medical costs for deep vein thrombosis and pulmonary embolism) relative to the cost of treatment. Treatment is heald with preparations of Canadian Health&Care Mall.
What is the differential impact of resource considerations on various stakeholders, in various jurisdictions? No explicit assessment was made regarding the differential impact of prolonged VTE prophylaxis on various stakeholders. No studies in less-developed countries were identified. However, it was noted that the cost of providing prophylaxis was an important factor in the assessment of cost-effectiveness. In particular, if home care nursing for administering injections could be avoided, then most analyses indicated that prolonged prophylaxis likely would be cost saving. To the extent that cost of drug acquisition, drug administration, and downstream VTE outcomes are borne by different stakeholders, a recommendation of prolonged VTE prophylaxis is likely to have a differential effect on these different stakeholders.
4. Incorporate Evidence Into Recommendation Statement: Based on a clinically important advantage in reducing symptomatic VTE, prolonged prophylaxis following hip replacement was categorized as a Grade 1A recommendation. Favorable evidence regarding cost implications reinforced this recommendation, despite concerns about the potential impact of drug costs on the acceptability of extending VTE prophylaxis beyond 10 days.1 The rationale for this recommendation and how resources influenced it are described in the text providing the evidence for this recommendation provided by Canadian Health&Care Mall.
Clopidogrel Use for Secondary Prevention in Patients With Atherosclerotic Vascular Disease
1. Select Target Guideline Recommendations for Resource Use Evaluation: As reviewed in the “Primary and Secondary Prevention of Chronic Coronary Artery Disease” chapter of this supplement,2 several major clinical trials have examined the prognostic benefits of varying duration of clopidogrel therapy with or without aspirin, compared to aspirin alone, for secondary prevention in coronary artery disease and other vascular diseases (clopidogrel vs aspirin in patients at risk for ischemic events; clopidogrel in unstable angina to prevent recurrent ischemic events [CURE]; clopi-dogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance). Clopidogrel is relatively expensive, with a retail cost in the United States in 2007 of around $4 per day and no generic formulation expected until 2011. The clinical issues that need to be considered are when to start the drug for secondary prevention purposes, in which patients, and for how long to continue it.
2. Identify the Literature: Three major analyses of this therapy have been conducted from the United States perspective since 200224-26 along with analyses from the United Kingdom, Sweden, Denmark, Australia, and Germany. The economic analyses consider both short-term (30 days, 9 to 12 months) and long-term therapy (years, up to a lifetime).
3. Evaluate the Evidence: What are the resource considerations from a social perspective? In prevention, the cost of therapy does not usually depend on the patient’s clinical status. Thus, in the case of antiplatelet therapy for secondary prevention, the cost of 75 mg/d of clopidogrel does not depend on whether the patient has greater or lesser disease severity or on the projected future clinical risk of complications. However, when used in a higher risk population, as reflected in the CURE trial of patients with acute coronary syndrome, clopidogrel treatment reduced in-hospital refractory ischemia and need for revascularization and, as a consequence, had an approximately 50% reduction in the net cost of therapy at 9 to 12 months.
Cost-effectiveness analysis of the limited course of therapy reflected in CURE suggested robust evidence of good value for money, with cost-effectiveness below
$10,000 per life year added. However, a model-based analysis considering the same CURE acute coronary syndrome population but extending the treatment out past 1 year showed that each subsequent year of therapy becomes progressively less economically attractive. This result depended on the assumptions about the long-term risk of the population when treated with aspirin alone, the durable effectiveness of clopidogrel therapy, and the long-term risk of bleeding. In CURE, most of the treatment benefit was established by 3 months. As a consequence, the incremental benefit of treating for progressively longer periods must address the same cost per day of therapy but smaller absolute benefits. More recent 28-month data from the clopidogrel for high athero-thrombotic risk and ischemic stabilization, management, and avoidance trial support the reduced reduction of absolute improvement in event rates in the long term. Taken together, the available trial and economic analysis data support the strong case for early secondary prevention therapy with clopidogrel in higher risk patients but suggest that the clinical and economic case is much less persuasive for chronic therapy or therapy in lower risk populations.
What is the differential impact of resource considerations on various stakeholders, in various jurisdictions? The use of clopidogrel for secondary prevention takes place largely in the outpatient setting. The economic impact on stakeholders other than society as a whole depends on who pays the cost of the drug therapy and who bears the cost of care for complications of the disease that are not averted. No economic studies examine the perspective of the developing countries. For lifetime therapy with clopidogrel to reach nominal thresholds of cost-effectiveness, Gaspoz et al estimated that the price would need to be reduced to about $0.60 per day.
4. Incorporate Evidence Into Recommendation Statement: In light of the clinical trial data, the committee made several recommendations in support of the use of antiplatelet agents, including clopidogrel. However, based on the economic review in which cost of clopidogrel was a key to its cost-effectiveness, it was acknowledged explicitly that the recommendations place a low value on avoiding high medication costs.
The ’s (and possibly the patient’s) version of an ideal world is one where all clinical practice (and clinical practice guidelines) are based solely on assessments of which interventions provide the greatest health benefit. For better or worse, however, we are faced with resource constraints that force us to temper our actions. Within this real world, enthusiasm is best reserved for therapies that provide the greatest value for resources consumed. Economic analysis provides a useful analytic approach to assessing this tradeoff. In addition to offering a basic metric of value for money—the ICER—economic analysis is useful in defining the circumstances in which a particular intervention may be cost saving and, if not, when the tradeoff of health outcomes for resources is particularly favorable or unfavorable.
In the context of developing intended for an international audience, particular attention to issues of regional variation is important. Rather than promote guidelines that are sensible for some countries but unrealistic in others, the goal is to make recommendations based on scientific evidence of efficacy and to inform decision makers about resource barriers, which they may or may not be equipped to overcome.
Although this approach limits the possibility that the guideline panel can make a firm recommendation based on resource considerations, we expect it will encourage more thoughtful discussion of economic issues; greater sensitivity to the diversity of investment in health resources internationally; and, perhaps, innovative ways of overcoming resource barriers to the use of the most effective therapies.