Healthcare Domain 1

On January 27, 2020, the U.S. Department of Health and Human Services declared a public health emergency because of confirmed cases of 2019 Novel Coronavirus. COVID-19 caused significant disruption to health care systems throughout the U.S., and many of the SCD providers in the SCDTDRCP were engaged in either front line care or planning and developing procedures and processes, or both, to respond to evolving needs. Healthcare systems and individual providers quickly implemented new workflows and approaches to provide essential care for people living with SCD — who were at high risk for serious complications of COVID-19. Appendix B contains additional information about the impact of COVID-19 on people living with SCD and on the Program.

Increase the number of providers treating individuals with SCD using the National Heart, Lung and Blood Institute (NHLBI) Evidence-Based Management of Sickle Cell Disease Expert Panel Report Domain 1 Highlights

• Robust frequency of HU prescription: On average, 70% of the pediatric population and 58% of the adult population served by this program received an HU prescription* • Increasing recognition and use of disease-modifying agents, other than

HU: On average, 14% of the pediatric population and 24.6% of the adult population served by this program received disease-modifying therapies (other than HU)* • Confirmation of the importance of immunizations and acknowledgment that the processes of immunization assessment and delivery must be improved: On average, the pediatric pneumococcal immunization rate was 82% and the adult pneumococcal immunization rate was 63.5%* • Demonstration of higher rates of TCD screening than some national findings, but recognition that efforts to increase rates should continue.

The average pediatric TCD rate was 65.5%* • Identification of barriers to care, including systemic bias and racism, and planning activities to address them Hydroxyurea (HU) prescribing, a disease-modifying medication effective in reducing pain crises and decreasing hospitalization and ER visits

Immunization, a prophylactic therapy that prevents life-threatening infections, with specific focus on pneumococcal vaccination

Transcranial Doppler (TCD) screening, a procedure that identifies children who are at higher risk for stroke

Importance of Hydroxyurea Use and Other Disease-Modifying Therapies for Individuals with SCD

Hydroxyurea has been shown to significantly reduce the frequency of SCD-related pain, need for blood transfusions, and common pulmonary complications, including ACS (National Heart Lung and Blood Institute, 2014). Left untreated, ACS has been shown to cause significant morbidity and is associated with a higher risk of death. HU has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of clinically severe SCD since 1998 for adults and since 2017 for children. Additional HU information and NHLBI guidelines for HU use can be found in the Recommendations. However, despite the strong NHLBI recommendation, uptake has been inconsistent and below recommended levels (Brousseau et al., 2019; Su et al., 2019). A discussion of factors that may contribute to low rates of HU is in Appendix B.

The Program assessed adherence to HU use recommendations by 1) reviewing health record information to measure the number of patients given a prescription for HU (CQIM, see Table 2 and Table 3); and 2) surveying providers to determine the percentage who report prescribing HU (PSPM). Results demonstrated high, consistent support of the use of HU among participating sites and higher percentages of HU usage compared to other available data on the national experience. Every RCC provided CQIM data on HU utilization within their regions. On average, 70 percent of the pediatric population served by this program received an HU prescription and 58 percent of the adult population served by this program received an HU prescription.

Table 3. Hydroxyurea Use Aggregated into Six-Month Increments for Adult Population Treated at RCCs and Participating Sites

Data from the Program’s PSPM also suggest high utilization of HU:

• In 2019 and 2020, between 18,000-20,000 patients out of approximately 26,000 total patients seen (both adult and pediatric populations) were given an HU prescription in the last year, with an average of 75 percent of the pediatric patients and 67 percent of adults given a prescription. • Almost 50-65 percent of providers surveyed reported prescribing HU in the past year (YR1 47.7 percent; YR2 65 percent).

RCC HU-Focused Work

Further assessment is needed to fully explain the relatively high utilization of HU use compared to national findings. Program work completed to develop infrastructure to track HU use and reduce burden and barriers associated with ordering a prescription may be a contributing factor. Several of the Program sites specifically programmed their Electronic Health Record (EHR) systems to track clinical care elements, including HU prescription, so that accurate counts of treatments can be obtained quickly. In addition, some sites instituted QI projects to improve the tracking of HU and, in turn, increase its use. Because this type of analysis is time- and resource-intensive, QI activities are not currently feasible for all programs. Additional discussion of national data, barriers to HU use and prescription, factors that may have contributed to the Program HU use, and examples of RCC activities can be found in the Appendix.

Two RCCs described QI projects to track when discussions are completed with patients about therapies and decisions to modify treatment plans. The tracking documents patient responses during discussions; if the patient or caregiver is turning down treatments, the site flags and reviews the notes to better understand the decision-making process and concerns so that the clinical team can provide the right information to the patient. Sites have found that patients and caregivers may need more information about the treatment and its side effects to dispel myths and clarify explanations. These include print or electronic resources; referrals to connect with families who decided to place their child on disease-modifying therapies; lived experiences of older patients on specific treatments; support from CBOs; and continued discussion at each clinic visit.

Beyond HU: Other Disease-Modifying Therapies

Most people with SCD meet the criteria for HU prescription. Providers in the Program agree that HU should continue to be one of the standards of care. However, because some patients have reached their maximum dosage or cannot take HU for other reasons, additional therapies are needed. RCCs are actively participating in research in this area, such as trials related to bone marrow transplantation and other alternative disease-modifying therapies. Transplant is currently the only cure for SCD and sites are trying to expand this treatment, though it is costly and requires donor matching that makes it uncommon. Additional information about bone marrow transplant is in Appendix B. Emerging and novel therapies will have a broader role in treatment options offered either in combination with HU or alone,

including: Adakveo (crizanlizumab), Oxbryta (voxelotor), and Endari (L-glutamine); and the use of erythrocytapheresis, a non-surgical treatment red cell exchange transfusion. Additional information about these emerging medications and advances in gene therapy can be found in the Appendix. With increased options, using combination therapies may be the solution to address the myriad health issues faced by people with this complex disease. RCCs have increased tracking the use of disease-modifying therapies other than HU. During the time of the Program, they elected to collect initial data about these other therapies though they were not a focus of the original measurement strategy. Data collected from the Program suggests some growth in utilization of disease-modifying therapies beyond HU among the adult population but use in pediatric populations is still emerging. The results from these data are modest and should be viewed only as an initial assessment. Continued work is needed to capture more information about specific types of therapies used and frequency of use at treatment sites.

Immunizations

People with SCD are at increased risk for invasive bacterial diseases, like pneumococcal disease. The NHLBI guidelines recommend that all patients, unless otherwise advised, be immunized based on the CDC’s Advisory Committee on Immunization Practices. Still, comprehensive rates are subpar. Appendix B contains immunization guidelines and national rates.

Immunization Data Collection Challenges

Although all RCCs strongly supported the routine and consistent administration of preventive immunizations, access to comprehensive immunization records were not available to many program sites, particularly subspecialty clinics without access to statewide immunization registries. This made data collection challenging. Additional discussion of the Program immunization data collection challenges is in Appendix C. Thus, during the Program, several teams focused on both the data collection process (access to data and data quality) and actual immunization utilization.

Tables 6 and 7 show information from the sites that reported immunization data. It is important to note that reporting across quarters was inconsistent, so these data should not be considered population-level information but rather select clinic representation. Although the overall results may be higher due to missing data, trends toward improving immunization coverage during the Program can be seen for many of the vaccine series.

RCC Immunization-Focused Work

To improve immunization data collection, several RCCs created elaborate dashboards, managed clinical EHR systems, or manually maintained spreadsheets to track immunization data. Pneumococcal Immunization (PCI) was a specific priority area for the Program, with some participating sites focusing on PCI in QI efforts. The PCI-specific data from the Program suggests increasing PCI rates across both pediatric and adult populations.

Table 4. Disease-Modifying Therapy Use Other Than HU Among Children/Adolescents

Percent of patients ≥9 months and <18 years of age prescribed disease-modifying therapy other than HU.

Table 5. Disease-Modifying Therapy Use Other Than HU Among Adults

Table 7. Immunizations Aggregated by Six-Month Increments for Adult Population Among RCCs and Participating Sites

*Vaccine priority for this project PCI = pneumococcal immunization PPSV = pneumococcal polysaccharide vaccine MenACYW = vaccine for 4 strains of the meningococcal bacteria – A, C, W, and Y Hib = Haemophilus influenzae type b vaccine Flu = influenza (quadrivalent) vaccine Men B = Meningococcal B vaccine

Transcranial Doppler Screening

People who live with SCD are at increased risk for stroke, both overt and silent. Adults who experience stroke have severe morbidity and high mortality rates. Transcranial Doppler (TCD) is a noninvasive ultrasound procedure that allows the clinician to clearly see how quickly blood is flowing through the brain over a set time. High blood flow is associated with an increased risk of stroke. The test is reliable, painless, and relatively inexpensive. While HU has helped reduce strokes, programs continue other methods to reduce stroke risk. Given these factors, per the NHLBI guidelines, TCD use with children aged 2-16 years is strongly recommended. Even so, it appears that less than half of eligible pediatric patients receive appropriate TCD screening (National Academies of Sciences Engineering and Medicine, 2020).

RCC Transcranial Doppler-Focused Work

The RCCs conducted extensive work to increase the use of TCD. During the Program, several sites implemented changes to their clinical flows and other processes to ensure that all eligible patients are scheduled for this life-saving preventive screening. Some RCCs implemented QI projects that tracked a patient’s last TCD to flag when they would be due again. This type of tracking has been essential in ensuring that programs do not allow more than a year between TCDs. One region is leading a comprehensive effort to create a “stroke-free generation.” Examples of other initiatives undertaken by RCC sites to improve TCD rates are in the Appendix. However, there are some serious barriers to care that RCCs continue to address in this area.

The myriad ways that RCCs and sites have focused work on the clinically supported guidelines for TCD appear to have led to progress, as data collected for the Program shows moderately high percentages of TCD completion. On average, 65 percent of eligible patients aged 2-16 years had a TCD screening in the last 15 months, as shown in Table 9.

Table 9. CQIM Transcranial Doppler Screening Completed Within the Last 15 Months for Patients Aged 2-16 Years in Six-Month Increments Among RCCs and Partner Sites