Chest
Volume 133, Issue 6, Supplement, June 2008, Pages 123S-131S
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Antithrombotic and Thrombolytic Therapy, 8th ED: ACCP Guidelines
Grades of Recommendation for Antithrombotic Agents: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

https://doi.org/10.1378/chest.08-0654Get rights and content

This chapter describes the system used by the American College of Chest Physicians to grade recommendations for antithrombotic and thrombolytic therapy as part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Clinicians need to know if a recommendation is strong or weak, and the methodologic quality of the evidence underlying that recommendation. We determine the strength of a recommendation by considering the balance between the desirable effects of an intervention and the undesirable effects (incremental harms, burdens, and for select recommendations, costs). If the desirable effects outweigh the undesirable effects, we recommend that clinicians offer an intervention to typical patients. The uncertainty associated with the balance between the desirable and undesirable effects will determine the strength of recommendations. If we are confident that benefits do or do not outweigh harms, burden, and costs, we make a strong recommendation in our formulation, Grade 1. If we are less certain of the magnitude of the benefits and risks, burden, and costs, and thus their relative impact, we make a weaker Grade 2 recommendation.

For grading methodologic quality, randomized controlled trials (RCTs) begin as high-quality evidence (designated by “A”), but quality can decrease to moderate (“B”), or low (“C”) as a result of poor design and conduct of RCTs, imprecision, inconsistency of results, indirectness, or a high likelihood for reporting bias. Observational studies begin as low quality of evidence (C) but can increase in quality on the basis of very large treatment effects.

Strong (Grade 1) recommendations can be applied uniformly to most patients. Weak (Grade 2) suggestions require more judicious application, particularly considering patient values and preferences and, when resource limitations play an important role, issues of cost.

Section snippets

STRENGTH OF THE RECOMMENDATION

In determining the strength of recommendations, our grading system focuses on the degree of confidence in the balance between the desirable and the undesirable effects of an intervention (Table 1). Desirable effects or benefits can include beneficial health outcomes, decreased burden of treatment, and decreased resource use (usually measured as costs). Undesirable effects or downsides can include uncommon major adverse events, common minor side effects, greater burden of treatment, and more

INTERPRETING STRONG AND WEAK RECOMMENDATIONS

One way to interpret strong and weak recommendations is in relation to patient values and preferences. For decisions in which it is clear that benefits far outweigh downsides, or downsides far outweigh benefits, almost all patients will make the same choice, and guideline developers can offer a strong recommendation.

For instance, results from an extremely large high-quality randomized trial suggest that ASA reduces the relative risk of death after myocardial infarction by approximately 25%.

HOW METHODOLOGIC QUALITY CONTRIBUTES TO GRADES OF RECOMMENDATION

In our grading system, the highest-quality evidence comes from one or more well-designed and well-executed randomized controlled trials (RCTs) yielding consistent and directly applicable results. High-quality evidence can also come from well-done observational studies yielding very large effects (our guideline for a very large effect is an RRR of at least 80%) [Table 4 ]. RCTs with important limitations and well-done observational studies yielding large effects constitute the moderate-quality

INTERPRETING THE RECOMMENDATIONS

Clinicians, third-party payers, institutional review committees, and the courts should not construe these guidelines as absolute. In general, anything other than a Grade 1A recommendation indicates that the chapter authors acknowledge that other interpretations of the evidence and other clinical policies may be reasonable and appropriate. Even Grade 1A recommendations will not apply to all circumstances and all patients. For instance, we have been conservative in our considerations of cost, and

SUMMARY

The strength of any recommendation depends on two factors: the tradeoff between benefits, risks, burden, and cost, and our confidence in estimates of those benefits and risks. The American College of Chest Physicians grading system classifies the tradeoff between benefits and risks in two categories: strong (Grade 1 recommendations), in which the tradeoff is clear enough that most patients, despite differences in values, would make the same choice; and weak (Grade 2), in which the trade off is

CONLICT OF INTEREST DISCLOSURES

Dr. Guyattreveals no real or potential conflicts of interest or commitment.

Dr. Schünemannreports no personal payments from for-profit organizations, but he has received research grants and/or honoraria that were deposited into research accounts or received by a research group that he belongs to from AstraZeneca (research grant, honoraria), Amgen (research grant), Barilla (research grant), Chiesi Foundation (honorarium), Lily (honorarium), Pfizer (research grant, honorarium), Roche (honorarium),

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