Severity Classification for Sickle Cell Disease: A RAND/UCLA Modified Delphi Panel

Background: The clinical course of sickle cell disease (SCD) varies greatly by patient depending on age, complications, comorbidities, and psychosocial health. While researchers have developed models to predict complications and mortality, there is currently no accepted classification system of overall SCD severity. Our goal was to develop a severity classification system that could be tested for its ability to predict clinical outcomes. Methods: Using a RAND/UCLA modified Delphi panel, a method that has content, construct, and predictive validity, we convened 10 expert clinicians (9 MDs, 1 DNP) from various backgrounds (5 hematologist/oncologists, 3 internists, 1 psychiatrist/public health practitioner, 1 pulmonologist) with an average of 20 years of experience caring for SCD patients. Experts were provided with a review of evidence drawn from the 2014 National Heart, Lung, and Blood Institute Expert Panel Report, focusing on factors associated with morbidity and mortality in SCD. They collaboratively developed then rated 180 patient scenarios with varying characteristics (age, HbSS/HbSβ0/HbSC/HbSβ+ genotype, no/mild or moderate/severe end organ damage, presence/absence of chronic pain, and number of unscheduled acute care visits per year due to vaso-occlusive crises (VOCs)) on multiple axes including risk of complications or death, quality of life impact, and overall disease severity using a 1 to 9 scale. Each scenario was a simplified patient history in which end organ damage was defined as either severe damage to organs fed by the circulatory system (e.g., congestive heart failure, ≥Stage 3 kidney disease, overt stroke); mild/moderate damage (e.g., hypoxia, Stage 1 or 2 kidney disease, transient ischemic attack in the absence of stroke); or no damage. Other characteristics were also categorized in a simplified fashion (e.g., present/absent chronic pain defined as ongoing pain on most days over the past 6 months). Ratings were completed independently by each expert before an all-day in-person meeting. Areas of disagreement were discussed. Median ratings were grouped into 3 categories (1-3, 4-6, 7-9) and disagreement was defined as ≥2 individual ratings outside the median category. At the conclusion, experts completed ratings again. These final round ratings were used to develop a 3-level severity classification system ranging from Class I (least severe) to Class III (most severe). Results: The proportion of items with disagreement decreased from 64% to