Chest
Volume 141, Issue 2, Supplement, February 2012, Pages 53S-70S
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Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.11-2288Get rights and content

Background

To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists.

Methods

Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion.

Results

One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance.

Conclusions

AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review.

Section snippets

Composition and Selection of Topic Panel Members

The ACCP AT9 Executive Committee selected panel members for each article. A topic editor and a deputy editor led each of the AT9 panels issuing recommendations. The topic editor was the person primarily responsible for each article and was required to be a methodologist without serious financial or intellectual conflict of interest for any of the article's recommendations. In all but one case, the topic editor also was a clinician. The Executive Committee chose these individuals on the basis of

Ensuring Consistency Across Articles

We used a number of strategies to ensure consistency across articles, and one of us (M. C.) participated extensively in the formulation of clinical questions for each article. To ensure consistency of judgments regarding bleeding, one of us (S. S.) was responsible for standardizing the approach to bleeding outcomes and participated in multiple topic panels (described in more detail later in this article). Additionally, to ensure consistency in the trade-offs between thrombotic and bleeding

Defining the Clinical Questions—Population, Intervention, Comparator, and Outcome

The thrombosis expert on the Executive Committee (M. C.) along with the deputy editors took primary responsibility for defining the scope of the clinical questions that each article would address. For each question, the topic editor and deputy editor defined the relevant population, alternative management strategies (intervention and comparator), and the outcomes (ie, population, intervention, comparator, and outcome [PICO] format). Each clinical question provided the framework for formulating

Evaluating Risk of Bias in Individual Studies

We developed and applied uniform criteria for evaluating the risk of bias associated with individual RCTs based on the criteria recommended by the Cochrane Collaboration11 (Table 1). Although all authors assessed risk of bias for individual studies, because of resource limitations, we summarized the results of the risk of bias (eg, Table 112) for only a minority of the recommendations. Readers can find these assessments in the online data supplements. For most recommendations for which we did

Values and Preferences

Making trade-offs between desirable and undesirable consequences of alternative management strategies—the fundamental process of making recommendations—requires making value and preference judgments. For antithrombotic therapy guidelines, this trade-off involves, in most instances, a reduction in thrombotic events compared with an increase in bleeding events. Ideally, the values and preferences applied to this decision would be the average values and preferences of the patient population. We

Resource Use Issues

In addressing resource use (cost) issues in AT9, we followed previously developed principles.27 In particular, we restricted economic evaluation to recommendations in which it was plausible that resource use considerations might change the direction or strength of the recommendation and in which high-quality economic evaluations were available. When this was not the case, we did not consider resource use in the recommendations.

Six clinicians with the requisite expertise in decision and economic

Disclosing and Managing Conflicts of Interest

All panelists were required to disclose both financial conflicts of interest, such as receipt of funds for consulting with industry, and intellectual conflicts of interest, such as publication of original data bearing directly on a recommendation. Financial and intellectual conflicts of interest were classified as primary (more serious) or secondary (less serious).38 The operational definition of primary intellectual conflicts of interest included authorship of original studies and

Formulating Recommendations

Following approaches recommended by the GRADE Working Group,23 the topic editor, in some cases aided by a panelist without conflicts, formulated the draft recommendations. The formulation of recommendations considered the balance between the desirable and undesirable consequences of an intervention; the quality of evidence; the variability in patient values and preferences; and, on occasion, resource use issues. The recommendations were graded as strong when desirable effects were much greater

Review by ACCP and External Reviewers

The ACCP HSP Committee established a process for the thorough review of all ACCP evidence-based clinical practice guidelines. After final review by the AT9 Executive Committee, the guidelines underwent review by the Cardiovascular and Pulmonary Vascular NetWorks of the ACCP, the HSP Committee, and the ACCP Board of Regents. The latter two groups had the right of approval or disapproval but usually worked with the topic panelists and editors to make necessary revisions prior to final approval.

Organization of Articles

In order to provide a transparent, explicit link among PICO questions, evidence, tables, and recommendations, the section numbering in each article corresponds to numbers in Table 1 in each article, which specifies the patients, interventions, and outcomes for each question. The section numbering also corresponds to the numbering of the recommendations themselves. Evidence Profiles and other tables include these corresponding numbers in brackets in the title, as is true for the online data

Revisions in the Process Since AT8

AT9 includes improvements from AT8 that reflect the evolution of the science of systematic reviews and clinical practice guidelines. In this supplement,40 some of these improvements include augmented provisions to decrease the likelihood of conflict of interest influence, more stringent application of GRADE criteria for evidence and recommendations (both facilitated by methodologists without primary conflicts taking the role of topic editor), and a systematic review of values and preferences to

Limitations of Methods

Although encouraged to use Evidence Profiles and Summary of Findings tables for all recommendations, there were some for which the authors were unable to produce such tables. However, those recommendations used an evidence-based systematic review and assessment of relevant studies. Some recommendations would have benefited from meta-analyses that would have clarified aspects of the evidence. Although panelists were instructed in completing the value and preference rating exercise to estimate

Plans for Updating AT9

We plan to continue the tradition of the antithrombotic guidelines to update recommendations when important new studies are published that might change the current recommendations. In March 2011, the ACCP Board of Regents approved a proposal to revise the guideline development and updating process to a “living guidelines” process, whereby the evidence-based guidelines will be periodically assessed and updated as the literature warrants. From 1 year after the publication of this ninth edition

Conclusion

For AT9, we used an explicit, transparent process that seeks to produce highly relevant and unbiased recommendations for clinical practice. This process involved the a priori specification of clinical questions in the PICO format along with study inclusion and exclusion criteria, an exhaustive search for relevant literature, an evaluation of the risk of bias of included studies, and a rigorous and standardized assessment of the quality of the body of evidence and its translation into

Acknowledgments

Author contributions: Authors contributed to the AT9 guideline process in the roles described in the article. As Topic Editor and Chair of the guideline, Dr Guyatt oversaw the development of this article.

Dr Guyatt: produced the first draft and was responsible for the final article.

Dr Norris: undertook a major revision of a late draft of the article.

Dr Schulman: took responsibility for sections relevant to their role in AT9 and reviewed and approved the final article.

Dr Hirsh: took

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    Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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