Development of a Severity Classification System for Sickle Cell Disease

Nirmish Shah,1 David Beenhouwer,2 Michael S Broder,2 Lanetta Bronte-Hall,3 Laura M De Castro,4 Sarah N Gibbs,2 Victor R Gordeuk,5 Julie Kanter,6 Elizabeth S Klings,7 Thokozeni Lipato,8 Deepa Manwani,9 Brigid Scullin,10 Irina Yermilov,2 Wally R Smith8 1Department of Medicine, Duke University, Durham, NC, USA; 2Partnership for Health Analytic Research (PHAR), LLC, Beverly Hills, CA, USA; 3Foundation for Sickle Cell Disease Research, Hollywood, FL, USA; 4Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 5Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 6Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 7Department of Medicine, Boston University School of Medicine, Boston, MA, USA; 8Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA; 9Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA; 10Department of Medicine, University of North Carolina, Chapel Hill, NC, USACorrespondence: Nirmish ShahDuke University, Department of Medicine, Duke South, Durham, NC 27710, USATel +1 (919) 668-5178Email nirmish.shah@duke.eduPurpose: There is no well-accepted classification system of overall sickle cell disease (SCD) severity. We sought to develop a system that could be tested as a clinical outcome predictor.Patients and Methods: Using validated methodology (RAND/UCLA modified Delphi panel), 10 multi-disciplinary expert clinicians collaboratively developed 180 simplified patient histories and rated each on multiple axes (estimated clinician follow-up frequency, risk of complications or death, quality of life, overall disease severity). Using ratings on overall disease severity, we developed a 3-level severity classification system ranging from Class I (least severe) to Class III (most severe).Results: The system defines patients as Class I who are 8– 40 years with no end organ damage, no chronic pain, and ≤ 4 unscheduled acute care visits due to vaso-occlusive crises (VOC) in the last year. Patients < 8 or > 40 years with no end organ damage, no chronic pain, and < 2 unscheduled acute care visits are also considered Class I. Patients any age with ≥ 5 unscheduled acute care visits and/or with severe damage to bone, retina, heart, lung, kidney, or brain are classified as Class III (except patients ≥ 25 years with severe retinopathy, no chronic pain, and 0– 1 unscheduled acute care visits, who are considered Class II). Patients not meeting these Class I or III definitions are classified as Class II.Conclusion: This system consolidates patient characteristics into homogenous groups with respect to disease state to support clinical decision-making. The system is consistent with existing literature that increased unscheduled acute care visits and organ damage translate into clinically significant patient morbidity. Studies to further validate this system are planned.Keywords: expert panel, disease severity, vaso-occlusive crises, organ damage, chronic pain