Discrepancy between original and adapted ASH VTE guidelines: same clinical evidence but different recommendations Open Access

TO THE EDITOR:

Many factors affect the way guideline panels make recommendations. According to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology, the current state-of-art system for developing evidence-based guidelines, there are primary and secondary drivers of practice recommendations. Primary considerations include the strength of the recommendations (strong or conditional and in favor of or against a health intervention), their magnitude of benefits and harms, the quality (certainty) of the evidence, and the patient’s values and preferences (supplemental Table 1). Secondary factors depend on resource use (costs), feasibility, acceptability, and health equity.¹ Benefits, harms, and the certainty of evidence are based on a systematic review of the literature, evaluated according to scientific merits, irrespective of the geographical origin of the research studies. Secondary drivers affect recommendations by addressing resource considerations, feasibility, equity, cultural differences, or diverse moral or ethical judgments. However, the considerations that drive the decisions of guideline panels are theoretical and normative, rather than empirically based.

The aim of this report was to evaluate the drivers of changes of the recommendations in the adaptation of the American Society of Hematology (ASH) guidelines on venous thromboembolism (VTE) to the Latin American context. We present, to our knowledge, the first empirical assessment of how different settings and secondary drivers may influence guideline panels’ decision-making, even when primary drivers remain unchanged.

From 2017 to 2020, ASH collaborated with 12 hematology partner societies in Latin America to adapt the original ASH guidelines on VTE for the Latin America context following the GRADE-ADOLOPMENT approach. Both guidelines used the same methodological approach to rate certainty of evidence and used the Evidence to Decision framework.¹ We reused health effects from the original ASH VTE guidelines but conducted a search for novel or relevant data about baseline risk, resource use, accessibility, feasibility, and impact in health equity. A detailed description of the methodology is available in a previous study.² 

A total of 66 of 172 recommendations (38%) were adapted,^3-5 of which 23 (35%) changed either strength (n = 9 [39%]) or direction (n = 14 [61%]; Figure 1). Most changes (43%) resulted from resource constraints, followed by reinterpretation of baseline risk of the target population (33%) and cultural preferences or health equity (24%). A total of 8 of 14 recommendations (57%) that changed direction involved considerations about resource use/costs, accessibility, feasibility, or impact on health equity. The remaining recommendations that changed direction (6/14 [43%]) and all the recommendations that changed strength were attributed to the reinterpretation of baseline risk of thrombosis and/or bleeding in the targeted population, which was considered by the panel as having either higher or lower thrombotic or bleeding risk in the adapted guideline (Table 1).

No recommendation was based on high certainty of evidence. Most recommendations that changed direction were of very low certainty of evidence (11/14 [79%]). Most recommendations that changed strength were based on moderate certainty of evidence (5/9 [56%]).

Our findings confirm the theoretical view that evidence based only on primary drivers (strength of the recommendations and their magnitude of benefits and harms, the certainty of the evidence, and the patient’s values and preferences) is necessary but not sufficient for decision-making.⁶ Guidelines developed in 1 setting, in which considerations of resources, feasibility, or equity are context specific, may not be directly applicable to other socioeconomic settings. Such guidelines should undergo formal adaptation to account for these differences, as demonstrated by our study.

Contribution: S.M.R. drafted the manuscript and analyzed and interpreted the data; B.D. designed the work and interpreted the data; I.N. analyzed and interpreted the data; and all authors critically reviewed the manuscript and approved its final version.

Conflict-of-interest disclosure: S.M.R. and B.D. are members of the Guideline Oversight Subcommittee of the American Society of Hematology. I.N. has received payment from the American Society of Hematology to develop the adapted venous thromboembolism guidelines for Latin America.

Correspondence: Suely Meireles Rezende, Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, 190 Avenida Alfredo Balena, Room 255, Belo Horizonte, Brazil, 30130-100; email: suely.rezende@uol.com.br.