Understanding Provider Barriers to Hydroxyurea Use for Pediatric Sickle Cell Disease
Authors: Oyeku Suzette O. , Green Nancy S. , Pashankar Farzana , Giardina Patricia , Mullen Craig A. , Driscoll Catherine 
Published: October 2019

Abstract
Abstract 255
Despite proven efficacy in clinical trials, hydroxyurea (HU) has not been uniformly adopted into the care of children with sickle cell disease (SCD). In 2008, the NIH Consensus Development Conference on Hydroxyurea Treatment for Sickle Cell Disease postulated that barriers to HU use may occur at the provider level. Limited evidence exists on barriers to the use of HU, and prior studies have largely focused on use in adults. HU use is rapidly expanding to different indications, to use in patients with less common hemoglobin genotypes and to young children. Initial data from the Pediatric Hydroxyurea Phase III Trial (BABY HUG) in very young children (ages 9–18 months) is also now becoming available. To better understand current provider barriers to effective translation of efficacy trial results into “real-world” clinical care of children with SCD, we surveyed pediatric hematology providers within several regional consortiums of pediatric hematology programs in the eastern US. The objectives of our study were to: 1) describe practice patterns related to HU use among providers of children and adolescents with SCD; 2) identify provider level barriers to HU use among SCD children; and 3) solicit provider recommendations to overcome the perceived barriers. A close-ended, self-administered web-based survey was sent to 230 pediatric hematology providers in June 2010. Provider demographics, practice characteristics, clinical indications to prescribe HU, concerns related to HU use and suggestions to improve HU use were assessed by this survey. Forty-two percent (N=97) of 230 surveys were completed by hematologists (84%), nurse practitioners (12%) and physician assistants (3.7%). The number of SCD patients in provider practices ranged from 2 to 1,200 patients. 57% of respondents were female. 42% of respondents were in practice for more than 20 years. The majority (72%) of providers were white. Many providers (83%) were somewhat/very familiar with the NHLBI guidelines about HU use in SCD. Among those surveyed, the most frequent indications to start HU were: 1) history of 3 painful episodes, 2) acute chest syndrome, 3) chronic pain use requiring narcotics, 4) priapism and 5) symptomatic anemia. A majority of providers (82%) reported using HU in children ages 3–5 years of age, with 41% of providers indicated using HU in children less than 3 years of age. Fewer than half of providers (28%) prescribe HU to patients with Hgb SC or other Hgb S variants. Only 74% of providers attempted to titrate HU to maximal tolerated dose. This goal dose ranged from 20 to 40mg/kg/day among our respondents. Major provider concerns about HU in children are: 1) patient compliance with taking HU, 2) compliance with attending drug monitoring visits, 3) compliance with taking contraception, 4) effects of HU on fertility and 5) long term side effects. Almost 50% of clinicians were concerned about the age of the patient when starting HU: 48.5% of clinicians considered patients less than 1 years of age too young to start HU, while 40% of clinicians felt patients' ages 1–2 years were too young. Some providers (39%) had concerns about the efficacy of HU in patients with Hgb SC, while 24.1% were concerned about efficacy in patients with Hgb S variants. Providers' suggestions to improve HU use included: 1) developing updated evidence based practice guidelines for HU use (89%), 2) developing culturally appropriate patient educational materials about HU (84%), 3) extending FDA approval for HU to children (80%), and 4) developing a national registry of patients on HU to monitor clinical outcomes and adverse events (74%). Our survey highlights that HU use varies among pediatric providers with respect to: 1) the broader clinical indications for HU use, 2) optimal maximal tolerated dose of HU, 3) appropriate lower age limit to prescribe HU, and 4) sickle cell genotype in which to use HU. Updated national evidence- based guidelines to assist clinicians in using HU in pediatric sickle cell care are indicated given the efficacy of HU for SCD over a wide range of indications, the logistical limits and tempo of clinical studies, the paucity of other widely available treatments, and persistent barriers to HU use at the provider level. Additional studies are warranted to examine alternative indications for HU, HU use in younger ages, optimum dosing, potential impact on fertility, teratogenicity and possible carcinogenicity, and use of HU for other sickle cell genotypes.

Disclosures:
Off Label Use: Hydroxyurea has not been FDA approved for use in children and adolescents with sickle cell disease, the topic of the submitted abstract.