Increasing Visibility of Sickle Cell Disease in Indiana: Establishing Baseline Prevalence Using Integrated Data From Multiple Sources

Abstract

Objective:

The Indiana Sickle Cell Data Collection (IN-SCDC) program aims to provide timely, reliable, and locally relevant information on the sickle cell disease (SCD) population in Indiana to inform public health interventions, research, and policy development. We describe the development of the IN-SCDC program and report the prevalence and geographic distribution of people with SCD in Indiana using an integrated data collection approach.

Methods:

Using multiple integrated data sources and case definitions established by the Centers for Disease Control and Prevention, we classified cases of SCD in Indiana during 2015-2019. We calculated the prevalence and incidence of SCD and described characteristics of people with SCD.

Results:

We identified 1695 people living with SCD in Indiana during the study period. The median age of people living with SCD was 21 years, and 1474 (87.0%) were Black or African American. Most (n = 1596, 91%) resided in metropolitan counties. The age-adjusted prevalence of SCD was 24.7 cases per 100 000 people. The prevalence of SCD among Black or African American people was 209.3 per 100 000 people. The incidence was 1 in 2608 live births overall and 1 in 446 live births among Black or African American people. Eighty-six deaths were confirmed in this population during 2015-2019.

Conclusions:

Our results establish a baseline for the IN-SCDC program. Baseline and future surveillance program efforts will help accurately inform standards of care for treatments, identify gaps in coverage and access to care, and provide guidance for legislators and community-based organizations.

Sickle cell disease (SCD), the most common monogenic disorder in the United States, is a collection of inherited red blood cell disorders that affect approximately 100 000 people in the United States. ¹ The polymerization of sickle hemoglobin (HbS) leads to abnormally stiff, often sickle-shaped red blood cells, common to all forms of SCD. These abnormal red blood cells damage and obstruct blood vessels and cause complications, including chronic anemia; pulmonary, cardiac, and renal damage; acute pain due to ischemia of bone marrow and bones (vaso-occlusive pain episodes); stroke; splenic infarction; and a reduction in life expectancy. ² Universal newborn screening and preventive treatments have effectively eliminated early childhood mortality from SCD complications in the United States, although patients with SCD continue to experience increased morbidity and early mortality.^3,4 Adults with SCD score significantly worse than the general US population on quality-of-life scales, ⁵ reflecting the complexity of this disorder and its effects on multiple facets of an individual’s life.

Public health surveillance is the ongoing, systematic collection, analysis, and interpretation of data along with the dissemination of findings to partners capable of preventing or controlling disease progression. ⁶ SCD surveillance is crucial to improved understanding and outcomes and important for clinical management, translational research, therapy development, public health planning, and education. ⁷ SCD surveillance may also attenuate geographic differences in adherence to quality-of-care indicators, ⁸ which can affect survival and quality of life.

Comprehensive surveillance studies for SCD did not exist until 2010, when the Centers for Disease Control and Prevention (CDC) created the Registry and Surveillance System for Hemoglobinopathies (RuSH), a pilot project in 7 states (California, Florida, Georgia, Michigan, New York, North Carolina, and Pennsylvania) using data from multiple administrative and clinical sources. Participating states have a sizable portion of the African American, Asian, and Hispanic populations (populations with ancestry from areas of the world where hemoglobin disorders are most prevalent) in the United States. ⁹ RuSH aimed to identify and collect data on all living people with a diagnosis of hemoglobinopathy from 2004-2008. Data sources included newborn screening records, hospital discharge data, emergency department records, death records, clinical records, and state Medicaid claims. Overall, reported SCD case numbers were similar to estimates using prior prevalence data and census data.^1,10 Improved infrastructure and access to community-based organizations (CBOs) and clinical care are benefits of initial surveillance efforts. ¹¹

Indiana created its Sickle Cell Data Collection (SCDC) program with 3-year grant funding from CDC to enhance surveillance efforts, joining a growing network of states with SCDC programs. The program aims to create a longitudinal surveillance system to provide timely, reliable, and locally relevant information on the Indiana population with SCD to inform public health interventions, research, and policy development. In this analysis, we describe the development of the Indiana SCDC (IN-SCDC) program, calculate the prevalence of SCD in Indiana by using an integrated approach to data collection, and compare the prevalence of SCD calculated by using the integrated approach with the prevalence of SCD calculated by using previous methods.

Methods

Using statewide medical and administrative records integrated across multiple sources, we sought to describe the prevalence of SCD in Indiana. This descriptive analysis establishes a baseline for the IN-SCDC program. We determined that the Indiana Department of Health would be the agency to request and store the data because of its role as a public health agency with the legal authority via the Health Insurance Portability and Accountability Act to conduct surveillance and obtain medical records. Because of the Indiana Department of Health’s legal authority to conduct surveillance, institutional review board oversight was not required.

The IN-SCDC Program

The Indiana Hemophilia and Thrombosis Center established a multidisciplinary, cross-sector team in Indiana in 2019 to create and manage the IN-SCDC program. The team consists of members from clinical settings who care for people with SCD, including the Indiana Hemophilia and Thrombosis Center, Riley Children’s Hospital, and Lutheran Hospital. The team also includes partners from the Regenstrief Institute, a nonprofit health services research organization that brokers access to statewide electronic medical record data; the Indiana Department of Health; patient representatives; and individuals who work at 3 CBOs: Martin Center Sickle Cell Initiative, North Central Indiana Sickle Cell Initiative, and SCACURE Networks, Inc. Working together, the team identified potential data sources, created lists of variables (eg, age, sex, race and ethnicity, SCD genotype) for data collection, and designed approaches for linking, interpreting, and disseminating data collected. The full team met quarterly via video conference, and subteams held additional video conference meetings as needed.

Case Definitions

The case definitions used for this program were previously established by the RuSH Project Surveillance Design Work Group.^12,13 Patients with a confirmed positive newborn screening identified through the newborn screening follow-up program or a physician diagnosis from a clinical encounter with laboratory testing are considered confirmed cases. Probable cases include patients with an initial positive newborn screening without confirmatory test results from the follow-up program or SCD International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes ¹⁴ (eTable in Supplemental Material) from 3 or more separate health encounters within a 5-year period from administrative claims. We excluded cases that were physician diagnosed as having sickle cell trait in clinic encounter data or had ICD codes for sickle cell trait in their administrative claims data. We did not exclude cases based on sex or race and ethnicity.

Data Acquisition

We gathered, linked, and integrated data from 4 sources: (1) Indiana Family and Social Services Administration (FSSA), the state’s Medicaid program; (2) the Indiana Network for Patient Care (INPC), a statewide network of electronic medical records; (3) Indiana Hemophilia and Thrombosis Center, a clinical setting that cares for people with SCD; and (4) the Indiana Department of Health, the state’s public health agency. IN-SCDC created and executed data-sharing agreements to allow for data exchange for the duration of the program. IN-SCDC agreed to collect data on an annual basis through completion of CDC’s 3-year grant, with the first year of collection to include historical data from 2015-2019.

The Indiana FSSA provided data from the state Medicaid program. Medicaid used the SCD International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) ¹⁵ and ICD-10-CM ¹⁴ codes from January 1, 2015, through December 31, 2019, to retrieve claims data. We obtained state death records for patients with underlying cause-of-death or additional cause-of-death ICD-10-CM codes for SCD from January 1, 2008, through December 31, 2019. We limited mortality analysis to this period because of time-restricted availability of electronic data. We did not use death certificate data to identify new cases but to provide mortality information on this population.

The INPC is managed by the Indiana Health Information Exchange. INPC contains data on more than 18 million patients and is one of the longest continuously operated statewide electronic health information exchange networks in the United States, consisting of data from 23 health systems and 93 hospitals. ¹⁶ Data in the INPC are routinely used to support clinical care delivery and public health and research activities.^16-18 Data include clinical observations from physical examinations, diagnostic imaging interpretations, laboratory results, hospitalization encounters, and other treatment data. The Regenstrief Institute is responsible for brokering access to data in the INPC. The Regenstrief Institute provided clinical encounter data for patients with ICD-9-CM and ICD-10-CM^14,15 diagnostic codes for SCD during January 31, 2015, through December 31, 2019.

Since 1985, all infants born in Indiana have been screened for SCD. The Indiana Department of Health provided newborn screening data from January 1, 2007, through December 31, 2020, including the infant’s date of birth, sex, race and ethnicity, and diagnosis and the mother’s demographic characteristics, and these data were used to link potential or probable cases and determine the approximate incidence of SCD. The state’s newborn screening follow-up program, Sickle SAFE, provided data from January 1, 2009, through December 31, 2020. Sickle SAFE has been administered by the Indiana Hemophilia and Thrombosis Center since 2009 and links children with a presumptive diagnosis of a hemoglobinopathy with hematology care. ⁸ Data from the follow-up program provided diagnostic confirmation. We requested clinical data from medical records from the Indiana Hemophilia and Thrombosis Center for all years available in its electronic health records.

Data variables requested included demographic characteristics, SCD diagnosis, comorbidities, physician information, medications, and hospital utilization. All of our data sources sent their data to the data analyst at the Indiana Department of Health for linkage and deduplication. The Indiana Department of Health conducted the linkage by using R version 4.0.2 (R Foundation for Statistical Computing), using custom algorithms. The analyst constructed and matched full names from first name, middle name (where available), and last name to date of birth. Of the remaining unmatched subset, the analyst constructed names from first name, last name, and date of birth; then first initial, last name, and date of birth; then full first name and last initial and date of birth, with each entry hand inspected to make sure the full name matched reasonably. Deduplication occurred in several steps: first by checking for the uniqueness of name and date of birth pairings, then by checking for uniqueness of assigned numbers. Deterministic linkage and manual inspections found any inaccuracies. The Indiana Department of Health housed data securely on its servers.

After data cleaning, linkage, and deduplication, we used the case definitions to classify cases into 2 groups: confirmed and probable. We estimated prevalence rates by dividing the number of confirmed and probable cases by the estimated 2019 Indiana total and African American populations and then multiplied by 100 000 to calculate the estimated number of cases per 100 000 people. We calculated age-adjusted rates by using 2010 US Census population estimates. ¹⁹ We calculated county prevalence rates similarly by using the total population in each county as the denominator. We calculated incidence rates by dividing the number of new cases, based on the dates of birth within the given year, by the total number of live births in Indiana and in the African American population in Indiana during the given year. Then we multiplied this number by 100 000 to calculate the rate per 100 000 live births. The Indiana Department of Health provided live birth data used to calculate incidence. ²⁰ We calculated frequency, relative frequency, and other descriptive statistical analyses on the combined confirmed and probable case groups. We performed all analyses using SAS version 9.4 (SAS Institute Inc) and R version 4.0.2 (R Foundation for Statistical Computing).

Results

Data collected from 2015-2019 identified 1695 unique people with SCD from all data sources using SCDC case definitions; 717 (42.3%) were classified as confirmed SCD cases and 978 (57.7%) were classified as probable cases. Most people with SCD were Black or African American (87.0%, n = 1474), were non-Hispanic (82.7%, n = 1402), and had Medicaid as their primary health insurance (69.2%, n = 1173) (Table). The mean (SD) age of this population was 24 (18.3) years, and the median age of the population was 21 years.

Table.

Characteristics of the population with sickle cell disease (SCD) in Indiana, 2015-2019

Characteristic	No. (%)
Total	1695 (100.0)
Age, y
<5	232 (13.7)
5-14	396 (23.4)
15-24	269 (15.9)
25-34	311 (18.3)
35-44	200 (11.8)
45-54	150 (8.8)
55-64	82 (4.8)
≥65	55 (3.2)
Sex
Female	881 (52.0)
Male	813 (48.0)
Unknown	1 (0.1)
Race
Black or African American	1474 (87.0)
White	65 (3.8)
Other	5 (0.3)
Unknown	151 (8.9)
Ethnicity
Hispanic	32 (1.9)
Non-Hispanic	1402 (82.7)
Unknown	261 (15.4)
Health insurance
Private	198 (11.7)
Medicaid	1173 (69.2)
Medicare	69 (4.1)
Self-pay	34 (2.0)
Other/unknown	221 (13.0)
Confirmed SCD genotype a
HbSS or HbSβ0-thalassemia	447 (62.3)
HbSC	196 (27.3)
HbSβ+-thalassemia	46 (6.4)
Other	28 (3.9)
Total confirmed	717

^aIncludes only cases with confirmed genotype via newborn screening or clinical laboratory confirmation.

Of cases with a confirmed genotype, most (n = 447, 62.3%) had the genotype HbSS or HbSβ⁰ thalassemia, followed by genotype HbSC (n = 196, 27.3%) and HbSβ⁺-thalassemia (n = 46, 6.4%) (Table). Twenty-eight (3.9%) cases were classified as having another SCD genotype.

The age-adjusted prevalence of SCD in Indiana in 2019 was 24.7 cases per 100 000 people. The age-adjusted prevalence of Black or African American people living with SCD in Indiana in 2019 was 209.3 per 100 000 people. The overall incidence of SCD in 2019 was 38.3 per 100 000 live births or 1 in 2608 live births. By race and ethnicity, the incidence in 2019 was 224.3 per 100 000 live births among Black or African American people or 1 in 446 live births among Black or African American people.

The number of SCD births increased steadily during the study period, with a noticeable increase of 17 SCD births from 2016 to 2017 (Figure 1). During 2015-2019, a total of 116 deaths from all causes within the SCD population were reported, and 86 deaths were confirmed via death certificate data. Of those confirmed deaths, the number of deaths was highest among people aged 35-44 and 55-64 years, with 19 deaths reported for each age group (Figure 2).

Figure 1.

Number of births with sickle cell disease in Indiana, 2008-2019. Data collected via newborn screening and provided by Indiana Department of Health, Maternal & Child Health Division, Genomics & Newborn Screening Program (unpublished).

Figure 2.

Age at death of people with sickle cell disease, Indiana, 2015-2019.

Most people with SCD resided in metropolitan communities in Indiana (Figure 3). Most of these people (63.3%) resided in 2 counties: Marion County (n = 820, 48.4%) and Lake County (n = 253, 14.9%). These 2 counties also had the highest rates of SCD in the state: Lake County had 225.1 cases of SCD per 100 000 people and Marion County had 83.9 cases of SCD per 100 000 people.

Figure 3.

Prevalence of sickle cell disease (SCD), by county, and location of SCD clinics, Indiana, 2015-2019. The data show that patients with SCD are concentrated in urban and suburban areas yet reside in 55% (51 of 92) of Indiana’s counties, meaning that SCD treatment and care resources are necessary statewide. Black diamonds indicate SCD care clinics, and counties that are blank (white) indicate that no people with SCD reside there.

Discussion

This is the first study to examine SCD prevalence in Indiana using integrated data from multiple sources. CDC recently added Indiana to its SCDC program, enabling the state to take a comprehensive look at SCD prevalence for the first time. SCD has been included in newborn screening programs in all 50 states since 2006, although Indiana has been screening newborns for SCD since 1985. Aside from newborn screening, the only multiple-data-source surveillance of SCD in the United States occurred as part of the RuSH project. ²¹ Ongoing or recent surveillance initiatives in the United States include Public Health Research, Epidemiology, and Surveillance for Hemoglobinopathies (PHRESH) during 2012-2014 and SCDC from 2015 to the present. PHRESH aimed to establish health profiles among people with SCD and track health outcomes over time. SCDC aims to collect health information on people with SCD to study trends in diagnosis, treatment, and health care utilization.^21,22 Other surveillance-related initiatives include using electronic health records across multiple health systems to create a learning health system to better identify and track SCD patients ²³ and improving the administrative case definition for SCD to better identify SCD patients. ¹³

Previously published estimates from the National Newborn Screening Information System using birth cohort data suggest that more than 1600 people in Indiana live with SCD; correcting for early mortality suggests a range of 1000-1200 people. ¹ Data from 2015-2019 identified 1695 cases of SCD in Indiana, which aligns with estimates from the National Newborn Screening Information System but is higher than previous estimates. ¹ This estimate was based on pooled correction estimates for African American and Hispanic birth cohorts, because Indiana did not have data available for 2008. Therefore, the total cohort numbers from 2005-2007 were carried over and, thus, may underestimate the state-specific population. Compared with the Hassell ¹ estimate using newborn screening cohort data, we found more cases of SCD. Efforts to create a comprehensive SCD surveillance program resulted in better accuracy of prevalence estimates. We hypothesize that the increased incidence may be due to population growth in racial and ethnic minority populations in Indiana. Increased SCD births support this hypothesis, as does Indiana’s reported downward trend for all live births since 2015. ²⁴ Increased case estimates could also be related to increased survival due to improved newborn screening follow-up in Indiana, increased use of hydroxyurea, recommended penicillin prophylaxis in children aged 0-5 years, pediatric transcranial Doppler screenings, and standard use of pneumococcal conjugate vaccine (PCV-13) rather than PCV-7 for infants. The number of deaths we observed by age group are in line with previous studies showing that people aged >35 years had the highest occurrence of death in this population using multiple linked data sources. ⁷

Of the population living with SCD in Indiana, 48% reside in Marion County (83.9 cases of SCD per 100 000 people), which has 3 comprehensive sickle cell centers. Conversely, Lake County, which has the highest rate of people living with SCD in the state (225.1 cases of SCD per 100 000 people), has an outreach clinic available in the county only 8 times per year. Both counties have high racial and ethnic minority populations. Vanderburgh County, which is the fourth-largest metropolitan area in the state, has 4 SCD outreach telemedicine clinics per year, and Evansville serves as a regional, tristate hub for health services for residents of Indiana, Kentucky, and Illinois. Although Vanderburgh and Lake counties have outreach clinics, no consistent structure for SCD care exists. As such, people with SCD who live in these counties will either travel long distances for comprehensive sickle cell care or seek care out of state. The other 2 SCD clinics are in Allen and St. Joseph counties, which comprise 4.4% and 4.9% of the SCD population, respectively. That leaves 27% of the population without a clinic in their resident counties, and the only comprehensive sickle cell centers are in Marion County. Shankar et al ²⁵ demonstrated that emergency department utilization rates are higher among people who do not live near a comprehensive sickle care center than among people who do live near a comprehensive sickle care center. People living with SCD also cite the lack of accessible comprehensive care centers as a barrier to care. ²⁶ Surveillance efforts can illustrate the need for more comprehensive sickle care centers to provide expert care and decrease emergency department utilization.

Strengths

A strength of this program was the use of multiple linked data sources to identify SCD cases. Data from administrative claims, newborn screening, and clinics have been used separately in the past to estimate the number of people living with SCD and observe health care utilization and health outcomes.^1,10,13,27 However, using all these sources together creates a complex system with the ability to capture a complete picture of SCD in Indiana and identify where improved access to SCD specialty care is needed. IN-SCDC illustrates the move toward public health intelligence (Public Health 3.0), in which public health agencies leverage an array of health information systems that complement traditional methods.^28-30 Integration of data across multiple sources (eg, Medicaid, electronic health records, SCD programs) illustrates a broader evolution in public health surveillance and the type of infrastructure that has proven beneficial for patient identification and care delivery.

Limitations

This study also had several limitations. First, data on genotype were collected but were unreliable from the administrative claims data sources. Only cases with confirmed genotypes were included in analysis on genotype. Second, initial testing data from newborn screening were collected from 1985, and the data received were limited and difficult to link to other data because of incomplete identifiers such as patient name. A patient’s full name may not be included in newborn screening data or may be different than what was used in other data sources. Third, clinical data for this program were obtained from only 1 clinic site. Data from additional sites would have increased the number of confirmed cases because confirmed clinical patients have accurate genotype data. We will collect clinical data from additional sites in the upcoming years of the program.

Conclusion

We ascertained a more precise baseline number of people with SCD in Indiana than previous estimates by using multiple linked data sources. The CBOs in our state developed a communication plan to inform the SCD community of the IN-SCDC. An infographic with results from the first year of the program is also being created as a tool to illustrate what we are doing and how we are working to increase awareness of the importance of SCD surveillance to partners, legislators, physicians, care providers, and people with SCD in the community. A public-facing online dashboard is also being created so the public can see current data and submit data requests for additional research. These surveillance data help us not only identify where people with SCD live but also understand what their health behaviors are, what resources they need, and how best to model their care and reduce the use of acute care. IN-SCDC provides opportunities to expand access to SCD experts, including telehealth, remote monitoring, and teleECHO (video conference sessions and telemonitoring for health care providers that provide additional education by subject matter experts). IN-SCDC will provide up-to-date, credible data to help accurately inform standards of care for treatments, identify gaps in coverage and access to care, and provide guidance for legislators and CBOs.