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. 2020 May 26;4(10):2351-2365.
doi: 10.1182/bloodadvances.2020001768.

Methodology for the American Society of Hematology VTE guidelines: current best practice, innovations, and experiences

Wojtek Wiercioch  1   2   3 , Robby Nieuwlaat  1   2   3 , Elie A Akl  3   4 , Robert Kunkle  5 , Kendall E Alexander  5 , Adam Cuker  6   7 , Anita Rajasekhar  8 , Pablo Alonso-Coello  9 , David R Anderson  10 , Shannon M Bates  11 , Mary Cushman  6   12 , Philipp Dahm  13   14 , Gordon Guyatt  3 , Alfonso Iorio  3   11 , Wendy Lim  11 , Gary H Lyman  15   16 , Saskia Middeldorp  17 , Paul Monagle  18   19   20 , Reem A Mustafa  3   21 , Ignacio Neumann  22 , Thomas L Ortel  6   23 , Bram Rochwerg  3   11 , Nancy Santesso  1   2   3 , Sara K Vesely  24 , Daniel M Witt  25 , Holger J Schünemann  1   2   3   11
Affiliations

Methodology for the American Society of Hematology VTE guidelines: current best practice, innovations, and experiences

Wojtek Wiercioch et al. Blood Adv. .

Abstract

Background: Methods for the development of clinical guidelines have advanced dramatically over the past 2 decades to strive for trustworthiness, transparency, user-friendliness, and rigor. The American Society of Hematology (ASH) guidelines on venous thromboembolism (VTE) have followed these advances, together with application of methodological innovations.

Objective: In this article, we describe methods and methodological innovations as a model to inform future guideline enterprises by ASH and others to achieve guideline standards. Methodological innovations introduced in the development of the guidelines aim to address current challenges in guideline development.

Methods: We followed ASH policy for guideline development, which is based on the Guideline International Network (GIN)-McMaster Guideline Development Checklist and current best practices. Central coordination, specialist working groups, and expert panels were established for the development of 10 VTE guidelines. Methodological guidance resources were developed to guide the process across guidelines panels. A methods advisory group guided the development and implementation of methodological innovations to address emerging challenges and needs.

Results: The complete set of VTE guidelines will include >250 recommendations. Methodological innovations include the use of health-outcome descriptors, online voting with guideline development software, modeling of pathways for diagnostic questions, application of expert evidence, and a template manuscript for publication of ASH guidelines. These methods advance guideline development standards and have already informed other ASH guideline projects.

Conclusions: The development of the ASH VTE guidelines followed rigorous methods and introduced methodological innovations during guideline development, striving for the highest possible level of trustworthiness, transparency, user-friendliness, and rigor.

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Conflict of interest statement

Conflict-of-interest disclosure: A.C. has served as a consultant for Synergy and CRO, and received institutional research support on his behalf from Alexion, Bayer, Novo Nordisk, Pfizer, Sanofi, Spark, and Takeda. A.R. has served on an advisory board for Alexion, Baxter, Bayer, Kedrion Biopharma, and Octapharma Plasma, and has received institutional research support on her behalf from Alnylam (Sanofi Genzyme), Baxalta (Shire), Biomarin, Dimensions Therapeutics, Genetech, Janssen Pharmaceuticals, and Roche. D.M.W. has served as a consultant for, and received institutional research support on his behalf from, Roche Diagnostics. E.A.A. has served as a guideline methodologist on other guidelines related to VTE, and has led a number of systematic reviews on VTE. G.H.L. is a principal investigator on a research grant from Amgen to the Fred Hutchinson Cancer Research Center, and has consulted within the past 2 years for the following companies on other topics: Biotheranostics, Beyond Spring, G1 Therapeutics, Invitae, Mylan, Partners Therapeutics, Samsung, and Spectrum. H.J.S. was cochair of the ASH VTE guidelines and is cochair of the GRADE Working Group; has developed methods, tools, and approaches for guideline development; has coauthored the background papers for the IOM report on trustworthy guidelines, the GIN-McMaster guideline development checklist, and other tools; is a consultant to ministries of health, the World Health Organization, and professional societies on guideline methodology; and is director of Cochrane Canada (Cochrane methods have served for this guideline). R.K. and K.E.A. are employed by ASH, which has funded and disseminated the guidelines discussed in this paper. S.M.B. reports honoraria from Leo Pharma. S.M. reports research grants and honoraria from Aspen, Bayer, Bristol-Myers Squibb–Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, Portola, and Sanofi; all fees were paid to the author’s institution. T.L.O. has served as a consultant for Instrumentation Laboratory, and has received institutional research support on his behalf from Instrumentation Laboratory, Siemens, Stago, the National Institutes of Health, the Centers for Disease Control and Prevention, and the Patient-Centered Outcomes Research Institute. The remaining authors declare no competing financial interests.

Figures

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Graphical abstract
Figure 1.
Figure 1.
Development process for the ASH VTE guidelines. ASH and the McMaster GRADE Centre collaborated to organize, plan, and coordinate the different steps of the guideline-development process. ASH had primary responsibility for budget, topic selection, guideline panel membership, COI management, public consultation, organizational approval, and dissemination. The Systematic Review Working Group (SRWG) worked with guideline panels to prioritize guideline questions and to synthesize and assess the evidence. Guideline panels formulated recommendations and were responsible for writing the guideline reports. The Methods Advisory Group (MAG) advised on and guided methodology for evidence synthesis, formulation of recommendations, and reporting. PICO, population, intervention, comparisons, and outcomes. Adapted from Schünemann et al with permission.
Figure 2.
Figure 2.
ASH organization, oversight, and VTE guidelines project timeline. Process and progress of the American Society of Hematology VTE guidelines. In 2014, the ASH Committee on Quality proposed the project as a collaboration with the McMaster GRADE Centre. After approval of the budget by the ASH Executive Committee in May 2014, the Committee on Quality formed an ASH VTE Guideline Coordination Panel in 2015, composed of 11 individuals with expertise in the clinical management of VTE, guideline methodology, or both. The VTE Guideline Coordination Panel prioritized 10 guideline topics on VTE, determined the general scope for each topic, and recommended panel appointments. This work was accomplished via teleconference calls and an in-person meeting held in June 2015, which was also attended by chairs of the 10 guideline panels. Simultaneously, the ASH Committee on Quality proposed ASH policies and procedures relevant to the project, including a COI policy, which were approved by the Executive Committee. The Executive Committee also approved all proposed panel appointments. By 2016, appointments to the 10 VTE guideline panels were finalized, and the general questions to be addressed by the panels had been proposed by the chairs and coordinated by the VTE Guideline Coordination Panel. This panel therefore stopped meeting. Simultaneously in 2016, in response to member demand, the Committee on Quality proposed, and the Executive Committee approved, new guideline projects on other topics, including immune thrombocytopenia and sickle cell disease, as well as collaborative guideline projects with other medical specialty societies. These multiple projects soon demanded more attention than the Committee on Quality could provide. In late 2015, a Guideline Oversight Subcommittee was formed, reporting to the Committee on Quality. Thereafter, the Guideline Oversight Subcommittee assumed responsibility for executing ASH policies and procedures relevant to the VTE guidelines project, including implementation of the ASH COI policy and review of draft guidelines for ASH organizational approval.
Figure 2.
Figure 2.
ASH organization, oversight, and VTE guidelines project timeline. Process and progress of the American Society of Hematology VTE guidelines. In 2014, the ASH Committee on Quality proposed the project as a collaboration with the McMaster GRADE Centre. After approval of the budget by the ASH Executive Committee in May 2014, the Committee on Quality formed an ASH VTE Guideline Coordination Panel in 2015, composed of 11 individuals with expertise in the clinical management of VTE, guideline methodology, or both. The VTE Guideline Coordination Panel prioritized 10 guideline topics on VTE, determined the general scope for each topic, and recommended panel appointments. This work was accomplished via teleconference calls and an in-person meeting held in June 2015, which was also attended by chairs of the 10 guideline panels. Simultaneously, the ASH Committee on Quality proposed ASH policies and procedures relevant to the project, including a COI policy, which were approved by the Executive Committee. The Executive Committee also approved all proposed panel appointments. By 2016, appointments to the 10 VTE guideline panels were finalized, and the general questions to be addressed by the panels had been proposed by the chairs and coordinated by the VTE Guideline Coordination Panel. This panel therefore stopped meeting. Simultaneously in 2016, in response to member demand, the Committee on Quality proposed, and the Executive Committee approved, new guideline projects on other topics, including immune thrombocytopenia and sickle cell disease, as well as collaborative guideline projects with other medical specialty societies. These multiple projects soon demanded more attention than the Committee on Quality could provide. In late 2015, a Guideline Oversight Subcommittee was formed, reporting to the Committee on Quality. Thereafter, the Guideline Oversight Subcommittee assumed responsibility for executing ASH policies and procedures relevant to the VTE guidelines project, including implementation of the ASH COI policy and review of draft guidelines for ASH organizational approval.
Figure 2.
Figure 2.
ASH organization, oversight, and VTE guidelines project timeline. Process and progress of the American Society of Hematology VTE guidelines. In 2014, the ASH Committee on Quality proposed the project as a collaboration with the McMaster GRADE Centre. After approval of the budget by the ASH Executive Committee in May 2014, the Committee on Quality formed an ASH VTE Guideline Coordination Panel in 2015, composed of 11 individuals with expertise in the clinical management of VTE, guideline methodology, or both. The VTE Guideline Coordination Panel prioritized 10 guideline topics on VTE, determined the general scope for each topic, and recommended panel appointments. This work was accomplished via teleconference calls and an in-person meeting held in June 2015, which was also attended by chairs of the 10 guideline panels. Simultaneously, the ASH Committee on Quality proposed ASH policies and procedures relevant to the project, including a COI policy, which were approved by the Executive Committee. The Executive Committee also approved all proposed panel appointments. By 2016, appointments to the 10 VTE guideline panels were finalized, and the general questions to be addressed by the panels had been proposed by the chairs and coordinated by the VTE Guideline Coordination Panel. This panel therefore stopped meeting. Simultaneously in 2016, in response to member demand, the Committee on Quality proposed, and the Executive Committee approved, new guideline projects on other topics, including immune thrombocytopenia and sickle cell disease, as well as collaborative guideline projects with other medical specialty societies. These multiple projects soon demanded more attention than the Committee on Quality could provide. In late 2015, a Guideline Oversight Subcommittee was formed, reporting to the Committee on Quality. Thereafter, the Guideline Oversight Subcommittee assumed responsibility for executing ASH policies and procedures relevant to the VTE guidelines project, including implementation of the ASH COI policy and review of draft guidelines for ASH organizational approval.
Figure 2.
Figure 2.
ASH organization, oversight, and VTE guidelines project timeline. Process and progress of the American Society of Hematology VTE guidelines. In 2014, the ASH Committee on Quality proposed the project as a collaboration with the McMaster GRADE Centre. After approval of the budget by the ASH Executive Committee in May 2014, the Committee on Quality formed an ASH VTE Guideline Coordination Panel in 2015, composed of 11 individuals with expertise in the clinical management of VTE, guideline methodology, or both. The VTE Guideline Coordination Panel prioritized 10 guideline topics on VTE, determined the general scope for each topic, and recommended panel appointments. This work was accomplished via teleconference calls and an in-person meeting held in June 2015, which was also attended by chairs of the 10 guideline panels. Simultaneously, the ASH Committee on Quality proposed ASH policies and procedures relevant to the project, including a COI policy, which were approved by the Executive Committee. The Executive Committee also approved all proposed panel appointments. By 2016, appointments to the 10 VTE guideline panels were finalized, and the general questions to be addressed by the panels had been proposed by the chairs and coordinated by the VTE Guideline Coordination Panel. This panel therefore stopped meeting. Simultaneously in 2016, in response to member demand, the Committee on Quality proposed, and the Executive Committee approved, new guideline projects on other topics, including immune thrombocytopenia and sickle cell disease, as well as collaborative guideline projects with other medical specialty societies. These multiple projects soon demanded more attention than the Committee on Quality could provide. In late 2015, a Guideline Oversight Subcommittee was formed, reporting to the Committee on Quality. Thereafter, the Guideline Oversight Subcommittee assumed responsibility for executing ASH policies and procedures relevant to the VTE guidelines project, including implementation of the ASH COI policy and review of draft guidelines for ASH organizational approval.
Figure 3.
Figure 3.
Example health-outcome descriptors for proximal DVT. Pairs of methodological and clinical experts from the panels drafted the descriptors to create common definitions for outcomes with respect to symptoms, time horizon, testing and treatment, and consequences. The health-outcome descriptors serve to differentiate outcomes with respect to consequences and severity for patients, and aid in making decisions about desirable and undesirable health effects (available at https://ms.gradepro.org/).
Figure 4.
Figure 4.
Use of PanelVoice for online voting. Use of the PanelVoice app in GRADEpro allowed us to obtain input from panel members and prevoting on judgements for the EtD frameworks. Prevoting ahead of in-person panel meetings helped to identify areas of agreement and highlight criteria for more in-depth discussion with the panel. As some panels required additional online meetings after their in-person panel meetings to complete recommendations, use of PanelVoice also allowed us to obtain input prior to discussions and agreement on draft recommendations to optimize efficiency. Panel members were able to provide input and agree on recommendations through the PanelVoice surveys, including those who were unable to attend certain online meetings. CI, confidence interval; RR, relative risk.
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