Decision theoretical foundation of clinical practice guidelines: an extension of the ASH thrombophilia guidelines

• The ASH thrombophilia guidelines modeling was suboptimal.

• The use of appropriate decision methodology leads to more accurate recommendations.

Decision analysis can play an essential role in informing practice guidelines. The American Society of Hematology (ASH) thrombophilia guidelines have made a significant step forward in demonstrating how decision modeling integrated within GRADE (Grading of Recommendations Assessment, Developing, and Evaluation) methodology can advance the field of guideline development. Although the ASH model was transparent and understandable, it does, however, suffer from the certain limitations that may have generated potentially wrong recommendations. That is, the panel considered two models separately- after 3-6 months of index venous thromboembolism (VTE), the panel compared Thrombophilia Testing (A) vs. discontinuing anticoagulants (B) and Test (A) vs C (recommending indefinite anticoagulation to all patients) instead of considering all relevant options simultaneously (A vs. B vs. C). Our study aimed to avoid what we refer to as the omitted choice bias by integrating two ASH models into a single unifying threshold decision model. We analyzed 6 ASH panel's recommendations related to testing for thrombophilia in settings of "provoked" vs. "unprovoked" venous thromboembolism (VTE) and low vs. high-bleeding risk (total 12 recommendations). Our model disagreed with the ASH guidelines panels' recommendations in 4 of the 12 recommendations we considered. Considering all three options simultaneously, our model provided results that would have produced sounder recommendations for patient care. By revisiting the ASH guidelines methodology, we have not only improved recommendations for thrombophilia but also provided a method that can be easily applied to other clinical problems and promises to improve the current guidelines' methodology.