DEVELOPMENT OF A TREATMENT DECISION-MAKING TOOL FOR SICKLE CELL DISEASE MANAGEMENT: THE MANAGE, MONITOR, REALIZE FRAMEWORK

Abstract

Objective: Remittive therapies for sickle cell disease (SCD) have increased over the past 7 years highlighting the need for standardized and quantifiable markers to monitor SCD, progression and treatment response. The aim was to develop an SCD treatment-decision framework that is well-defined, quantifiable, adaptable, personalizable, and clinically relevant for every stage of the individual patient journey. Methods: SCD experts worldwide, with extensive knowledge of organ systems commonly associated with SCD-related complications participated in an iterative series of advisory boards to identify and prioritize laboratory, clinical, and qualitative measures of SCD progression to see how these measures should be used for treatment decision making. The series were designed to 1) determine quantifiable goals for SCD treatment; 2) identify unmet needs and barriers to applying goal-oriented decision making in SCD clinical practice; and 3) introduce, refine, and validate an SCD treatment-decision framework and populate the framework with specific treatment targets. To aid implementation of a SCD treatment-decision framework in clinical practice, parameters identified were prioritized using a virtual survey and differentiated for pediatric or adult implementation. Results: Advisors focused on the significance of shared decision making between patient and clinician, treatment goals including of biological, social, and psychological dimensions, and the uniqueness of individual patients and their experiences. Advisors recommended that an SCD treatment-decision framework should invoke regular assessment, re-assessment, and proposed the monitoring of three key areas: markers of disease activity, markers of organ damage, and measures of health-related quality of life (HRQoL). Advisors agreed on the manage, monitor, perform (MMR) framework: 1) Manage: Are key SCD parameters managed? 2) Monitor: Are key aspects of disease progression monitored to prevent further organ complications? 3) Realize: Is the patient able to fulfill their potential? The MMR framework requires clinicians to consider and reassess the three pillars in parallel in the clinic to assess patient treatment. Advisors identified key assessment criteria: SCD parameters (hematological parameters, markers of hemolysis, presence of vaso-occlusive episodes, presence of acute chest syndrome, transfusion burden, risk of infection); presence and severity of organ complications (renal, cardiovascular, pulmonary, neurological, retinal, osteonecrosis, hepatobiliary, endocrine [growth and development], leg ulcers), and shared decision making (patient treatment goals, HRQoL, pain, fatigue, depression, anxiety, transition of care, reproduction and fertility, professional development). Discussion: Unity on SCD treatment measures, outcomes, and goals could improve SCD management and patient outcomes. Conclusions: The finalized MMR framework should aim to achieve the best clinical standard of care and address worldwide regional limitations. The MMR framework could also be used to guide the design of clinical trials. We plan to continually refine the MMR framework, in partnership with global SCD experts, to allow for customization to worldwide healthcare systems, application to patients based on developmental stage and/or disease status, and to allow piloting in clinical practice.