Marfo et al. BMC Health Services Research (2023) 23:1018 BMC Health Services Research https://doi.org/10.1186/s12913-023-09984-6 RESEARCH Open Access Evaluation of treatment patterns, healthcare resource utilization and cost of illness for sickle cell disease in Ghana: a private medical insurance claims database study Kwaku Marfo1, Yvonne Dei‑Adomakoh2,3, Catherine Segbefia2,3, Duah Dwomoh3, Adeline Edgal4, Nancy Ampah5, Badarinath Chickballapur Ramachandrachar6*, Kumaresan Subramanyam7, Ashok Natarajan6, Olufolake Egbujo8 and Kenneth I. Ataga9 Abstract Background Sickle cell disease (SCD) is a major public health concern in sub‑Saharan Africa, accounting for nearly 75% of the global disease burden. The current analysis evaluated patient characteristics, treatment patterns, health‑ care resource utilization (HCRU) and associated costs in patients with SCD based on a Private Medical Insurance Database in Ghana. Methods This retrospective longitudinal cohort study was conducted using an e‑claims database from Ghana (01 January 2015 to 31 March 2021). Patients were stratified by age (0 month to < 2 years, ≥ 2 years to ˂6 years, ≥ 6 years to < 12 years, ≥ 12 years to < 16 years; ≥16 years), vaso‑occlusive crisis (VOC) (< 1, ≥ 1 to < 3, and ≥ 3 per year), and con‑ tinuous enrolment. Study outcomes related to patient characteristics, comorbidities, treatment pattern, HCRU were evaluated for pre‑ and post‑index period (index period was between July 2015 to March 2020). Descriptive analysis was used to analyse different study variables. Results The study included 2,863 patients (mean age: 20.1 years; Min age: 0; Max age: 83; females 56.1%). Overall, 52.2% (n = 1,495) of SCD patients were ≥ 16 years and 17.0% (n = 486) were in the ≥ 2 to ˂6‑years age group. The majority of patients aged ≥ 16 years (62.5%) in the database did not have reported VOC episodes, 35.9% of patients had 1 to 3 VOCs per year and 1.5% had ≥ 3 VOCs per year during the follow‑up period. Consultation‑based prevalence of SCD was 0.5% [95% confidence interval (CI): 0‑1.3%] − 1.4% [CI: 0.6‑2.2%]. Malaria, upper respiratory tract infection (URTI) and sepsis were the common complications of SCD. Analgesics were the most frequently prescribed medi‑ cations followed by anti‑infectives, hematinics, and antimalarials. Hydroxyurea, a routine standard of care for SCD was under‑utilized. SCD patients had median cost incurred for consultation/hospital services of $11.3 (Interquartile range [IQR] $6.2 ‑ $27.2). For patients with VOC, maximum median cost was incurred for medications ($10.9 [IQR $5.0‑ $32.6]). Overall median healthcare cost was highest for individuals with ≥ 3 VOCs per year during the follow‑up period ($166.8 [IQR $70.3‑$223.5]). *Correspondence: Badarinath Chickballapur Ramachandrachar BCRamachandrachar@ae.imshealth.com Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom‑ mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Marfo et al. BMC Health Services Research (2023) 23:1018 Page 2 of 14 Conclusion In this retrospective private insurance claims database analysis, SCD imposes a significant healthcare burden, especially in patients with VOC. There is a need for reimbursed treatment options that could reduce the long‑ term burden associated with SCD and VOC. Keywords Sickle cell disease, Vaso‑occlusive crisis, Healthcare resource utilization, Hydroxyurea, Claims database Background efficacy and safety risk profile, as hydroxyurea therapy Sickle cell disease (SCD) is a group of monogenetic is associated with risk of developing infection, caus- autosomal recessive disorders attributable to point ing myelosuppression and hepatotoxicity [13–15]. mutations in the beta-globin gene [1, 2]. SCD leads to In recent years, the treatment landscape of SCD has progressive organ dysfunction and failure due to vaso- slowly expanded with the advent of novel therapeutic occlusion, a chronic inflammatory state and endothelial approaches. These therapeutic options target differ- dysfunction [1, 3]. There are many SCD genotypes, with ent categories of pathobiology – (i) inhibition of sickle the most common in sub-Saharan Africa being homozy- hemoglobin polymerization (voxelotor), (ii) targeting gous SCD and compound heterozygous β-globin S and sickle red blood cells (RBCs) - and white blood cells β-globin C [4]. SCD is the most frequent genetically (WBCs) endothelial adhesive events (crizanlizumab), inherited life-threatening disorder, primarily affecting and (iii) antioxidant agents (L-glutamine) [12]. Other the African, Indian, Caribbean, and Arab populations therapeutic agents used in SCD include antibiotics, [5]. According to the systematic analysis of the Global antimalarial agents or antimalarial prophylactics and Burden of Disease Study, 3.2 million people are affected blood transfusions [12, 16]. Besides the diagnostic and by SCD globally and 176,000 people die per year therapeutic challenges, another major hurdle in the due to SCD-associated complications [3]. The high- management of patients with SCD is the lack of estab- est prevalence of the disease is in sub-Saharan Africa lished practices for transition from pediatric to adult where 240,000 people are born with SCD annually [6] care which adds to the healthcare resource utilization and mortality rate is high, with an estimated 50–90% (HCRU) in terms of emergency room visits, higher of children dying before the age of 5 [4]. In Ghana, inpatient stays and acute care visits [2]. SCD accounts for about 6.3% of the total disease bur- Although significant progress has been made in the den in sub-Saharan Africa, with nearly 2% of neonates treatment of SCD, it still imposes a substantial eco- (~ 15,000) being diagnosed with SCD annually [7]. nomic burden in terms of cost, HCRU and out-of-pocket The clinical manifestations of SCD are broad, and expenditure. VOC episodes further add to the economic include vaso-occlusive crisis (VOC), hemolytic anemia, burden of SCD as they are the most common cause of acute aplastic crisis, infections including bacterial sepsis, hospitalization and emergency department visits [17]. respiratory complications, acute splenic sequestration, In the United States (US), the annual mean cost for and psychosocial morbidity [5, 8]. The burden of malaria SCD treatment was United States dollars [US$] 20,206, is high in sub-Saharan Africa [9]. VOCs are the primary the highest in patients with more than 3 VOC episodes cause of health care encounters in patients with SCD and [18]. In addition, apart from the direct economic bur- increased VOC burden is associated with increased risk den, SCD also levies an indirect economic burden in of mortality [10]. terms of loss in work productivity that amounts to US$ In the management of SCD, hydroxyurea, approved 3,145,862 in adult SCD patients with VOC episodes for by the United States Food and Drug Administration a period of one year [19]. (USFDA) and European Medicine Agency (EMA), Sickle cell disease management requires an integrated remains a key therapeutic option. In 2018, the and holistic approach. However, there are many chal- Ghana Food and Drug Authority approved the use lenges with the provision of SCD care in sub-Saharan of hydroxyurea in treatment of both adults and chil- Africa, such as lack of newborn screening, and diagnos- dren with SCD [11]. Hydroxyurea exhibits multimodal tic tools, inequities in access to healthcare, including action – it induces fetal hemoglobin production and novel therapeutic options, absence of standard treat- reduces inflammation and cell adhesion. Long-term ment guidelines, significant stigmatization, the need use of hydroxyurea is safe and effective in both pedi- for well-resourced and equipped laboratories, few dedi- atric and adult SCD patients [12]. However, labora- cated SCD treatment centers, lack of appropriate pre- tory monitoring (complete blood count with white ventive and curative services, lack of disease awareness, blood cell differential and reticulocyte count) is war- weak public health systems, financial and emotional ranted with the use of hydroxyurea to balance the cost burden [20, 21]. M arfo et al. BMC Health Services Research (2023) 23:1018 Page 3 of 14 According to World Bank classification, Ghana is cat- sex), date of attendance, encounter type (inpatient or out- egorized as a lower middle-income country, with inci- patient), activity type (drugs, consumables [medical/sur- dence of poverty being 45.6% [22]. In the year 2016 (the gical supplies], procedures [medical/surgical procedures most recent year for which World Bank estimates are or diagnostic investigations], services [consultation or currently available), the poverty headcount ratio at $2.1 hospital services] and others [administrative services]), a day was 25.3% in the Ghanaian population [23]. As per claimed amount, reimbursed amount, and diagnostic recent reports, the gross living wage per month in Ghana information. is $257, while the minimum wage has remained $2 past 2 decades [24]. In a study conducted by the Consortium for Study population the Advancement of Sickle Cell Research, SCD patients The study population was identified based on Interna- in Ghana visited emergency or outpatient departments tional Classification of Diseases, Tenth Revision, Clini- more frequently for their pain episodes (annualized cal Modification (ICD-10-CM) codes (ICD-10 codes mean 2.0) compared to SCD patients in the US, United for diagnosis of SCD [D57: Sickle cell disorders; D57.0: Kingdom (UK), and Italy [25]. In a country like Ghana Sickle cell crisis/VOC with acute chest syndrome; D57.1: with high poverty levels, frequent hospitalization and Sickle cell anemia without crisis; D57.2: Double heterozy- other healthcare expenditures associated with SCD, can gous sickling disorders; and D57.8: Other sickle cell dis- impose a substantial economic burden on the affected orders]). The study population was stratified by age group families and healthcare facilities. In this context, the cur- (0 month to < 2 years, ≥ 2 years to ˂6 years, ≥ 6 years rent study was conducted to determine the treatment to < 12 years, ≥ 12 years to < 16 years; ≥16 years). Sub- pattern and financial burden of SCD in Ghana. The aim group analysis was also conducted based on the number of the current analysis was to evaluate the patient char- of episodes of VOC per year and VOC claims among acteristics, treatment patterns, hospitalizations, HCRU, SCD patients aged ≥ 16 years (< 1 VOC episode per year, total cost incurred in patients with SCD and its subsets, ≥ 1 to < 3 VOC episodes per year, ≥ 3 VOC episodes per based on the analysis of a private medical insurance year). In the study, discrete VOC-related claims within a (Nationwide Medical Insurance) database in Ghana. 3-day gap were combined and recorded as a single VOC episode. VOC episodes were identified based on ICD-10 Methods codes (D57.0, D57.1, D57.2) or prescription of medica- Study design tions (non-steroidal anti-inflammatory drugs [NSAIDs]/ This was a longitudinal, secondary database, retrospec- Opioids). tive, single-cohort study performed using insurance The study included patients with follow-up data of at claims data from January 1, 2015 to March 31, 2021. least 12 months, for ≥ 1 diagnosis claims with SCD dur- The index date for each patient was defined as the date ing the index period. Continuous medical enrolment of first record of diagnosis of SCD, identified during the data for at least 1 claim (any service) during the 6-month index period (from 01 July 2015 to 31 March 2020) in baseline period and 12-month follow-up period were the database. Patients with at least 1 SCD-related diag- assessed. There were no explicit exclusion criteria for nosis claim in the index period and a minimum follow- patient selection in the study; however, the patients with up period of 12 month were included in the study. The no follow-up data or continuous medical enrolment data pre-index period (refers to specified period prior to index were excluded. Out of 3,980 potentially eligible patients date i.e., 6-month baseline before the index period) and identified from the database, 2,863 (71.9%) patients met post-index period (refers to specified period after index the inclusion criteria and were included in the analysis. date i.e., 12-month follow-up after the index period) were required to assess the study outcomes. Ethical considerations Ethics committee approval or obtaining informed con- Data source sent from patients was not required for this study as it did The Nationwide Medical Insurance Claims Database is not involve the collection, use or transmittal of individual an anonymized patient-level database of all insurance identifiable data. Patient identity or medical records were claims generated from their subscribers across Ghana. not disclosed in this study. The database uses anonymized The database includes manually processed claims from data. Anonymization refers to the process of protecting the hospital. Each patient has a unique identifier (ID) in private or sensitive information of patient by complete the database and using this ID, patients are linked to mul- removal of identifiers such as name of the patient, date of tiple visits and other services. birth, email address etc., that can connect the individual In the current study’s context, the database provided to the data. The study conformed to the ethical principles comprehensive data on patient demographics (age and outlined in the Good Pharmacoepidemiology Practices Marfo et al. BMC Health Services Research (2023) 23:1018 Page 4 of 14 Guidelines, Declaration of Helsinki 1964 and its later The patients were not mutually exclusive. All-cause amendments, Good Epidemiological Practice guidelines HCRU and associated costs were also analyzed for issued by the International Epidemiological Association, the 6-month baseline period prior to the IDD, only Good Practices for Outcomes Research issued by the by visit type. The overall HCRU and associated costs International Society for Pharmacoeconomics and Out- were calculated for the VOC-related claims by the comes Research and other applicable guidelines/laws. adolescent and adult SCD patients (≥ 16 years). This The dataset and the security of the office where the data was for the 12-month follow-up period from the IDD set were kept met the requirements of the Health Insur- and by the VOC episodes. ance Portability and Accountability Act of 1996. • Number and percentage of SCD patients visiting The data used for the current study was not publicly different specialties were evaluated based on claims available. This data was obtained from Nationwide Medi- during the study period after the IDD. cal Insurance following all necessary legal procedures to • Different diagnostic methods, procedures and tech- acquire and use this anonymized patient claims data. niques used in the management of SCD during the study period were assessed based on the number and Study outcome measures percentage of patients who underwent the diagnostic tests. • Demographics and patient characteristics compris- ing of age, gender and VOC episodes per year were extracted from the claim records. Statistical analysis • The consultation-based prevalence was calculated Descriptive analysis was used to analyze the different for the patients with SCD and those with VOC dur- study variables throughout the pre-index and post-index ing the study period (01 January 2015 to 31 March periods. Continuous variables were summarized as num- 2021) considering the overall population registered in ber of observations, mean, standard deviation, median, Nationwide’s Database. interquartile range (IQR), minimum and maximum, as • Number of patients with each SCD genotype were appropriate. Categorical variables were summarized as analyzed based on the ICD-10-CM codes, by year frequency and percentages (n, %), and by subgroups of and overall time periods. VOC episodes, where appropriate. Demographics, preva- • The comorbidities/complications were assessed dur- lence estimates and SCD types were reported with 95% ing the study period for patients based on age groups confidence interval (CI). and having ≥ 1 SCD claim in the index period. • Prescription patterns of SCD treatment (includ- Results ing VOC crisis) in terms of number of patients and Demographics and baseline characteristics of patients claims were evaluated based on different drug cat- with SCD egories. The mean age of eligible patients was 20.1 ± 16.0 years • The time to first hospitalization (refers to the period with the majority being females (n = 1,607, 56.1%). from index date to first hospitalization date) dur- About 52.2% (n = 1,495) of the patients belonged to the ing the study period and annual rate of hospitaliza- age group of ≥ 16 years (Table 1). With respect to VOC tion during the 12-month follow-up period were also episodes in adolescent and adult patients (n = 1,495), assessed. The assessment was done for both SCD and 935 patients (62.5%) had zero VOC episodes per year, VOC episodes based on the ICD-10-CM codes for 537 patients (35.9%) had ≥ 1 to < 3 VOC episodes per VOC episodes (D57.0, D57.1 and D57.2). year, while 23 patients (1.5%) had ≥ 3 VOCs episodes per • Claims data for patients were analyzed for baseline year. At least 1 episode of VOC was reported by a total all-cause, SCD-related and VOC–related HCRU, of 1,211 SCD patients and around half (46.2%) of these and associated costs (all-cause costs refers to the patients were aged ≥ 16 Years (Table 2). healthcare costs incurred for all the claims that the patient encountered during the follow-up period; Consultation‑based prevalence of patients with SCD SCD-related and VOC-related costs refers to the and VOC healthcare costs incurred for claims that were spe- During the study period (January 2015-March 2021), cific to SCD and VOC, respectively, during the fol- year-on-year prevalence of patients with SCD and low-up period) in a 12-month follow-up period from VOC were analyzed using the claims database. A steady the index diagnosis date (IDD), based on visit type increase in prevalence of patients with SCD and patients (inpatient and outpatient) and activity type (drugs, with SCD and VOC episodes was observed from year consumables, procedures, services, and others). 2015 (0.6%; [95% CI: 0-1.6%] and 0.2%; [95% CI: 0-1.1%], M arfo et al. BMC Health Services Research (2023) 23:1018 Page 5 of 14 Table 1 Demographic characteristics of patients with SCD 2015-March 2021), of the 2,863 study patients, 89% (January 2015‑March 2021) (n = 2,562; [95% CI: 88−91%]) of patients reported with Baseline Characteristics Patients With SCD diagnosis code for sickle cell disorders (D57), 9% (n = 251; [95% CI: 5−12%]) for other sickle cell disorders (D 57.8) N % of Patients [95% CI] and 7% (n = 211; [95% CI: 4−11%]) of patients for sickle Overall Study Population 2863 cell crisis/VOC with acute chest syndrome (D57.0) (Table S1)). It should be noted that patient counts were N (Patient Counts) 2863 not mutually exclusive. Mean (SD) 20.1 (16.0) Median (IQR) 22.3 (3.9, 32.7) Age (As at Index Date) ‑ Number of Patients Comorbidities/Complications in patients with SCD 0 months to < 2 years 459 16.0% [13‑19%] The most common complications in ≥ 16 years age group ≥ 2 years to ˂6 years 486 17.0% [17‑20%] included malaria (n = 1,440; 96.3%), upper respiratory ≥ 6 years to < 12 years 306 10.7% [7‑14%] tract infection (URTI) (n = 1,071; 71.6%), sepsis/sep- ticemia (n = 445; 29.8%), acute chest syndrome (n = 214; ≥ 12 years to < 16 years 117 4.1% [0‑8%] 14.3%) and cellulitis (n = 108; 7.2%), and this trend was ≥ 16 years 1495 52.2% [50‑55%] Sex ‑ Number of Patients similar in patients of ≤ 16 years age group (Table  3). Other complications more commonly observed in the Male 1256 43.9% ≥ 16 years age group and not in the younger age groups Female 1607 56.1% were end-stage kidney disease requiring dialysis (n = 847; Abbreviations: CI Confidence interval, IQR Interquartile range, N Number of patients, SCD Sickle cell disease, SD Standard deviation 56.7%) and liver disease (n = 336; 22.5%). The most com- mon complications in patients with VOC episodes were malaria (< 1 VOC per year: n = 894, 95.6%; ≥  1 to Table 2 Age distribution of SCD patients with VOC (January < 3 VOCs per year: n = 523, 97.4%; ≥  3 VOCs per year: 2015‑March 2021) n = 23, 100%), URTI (< 1 VOC per year: n = 671, 71.8%; SCD Patients with VOC (Period: 1‑year Follow‑up from Index Date of ≥ 1 to < 3 VOCs per year: n = 383, 71.3%; ≥ 3 VOCs per SCD Diagnosis) year: n = 17, 73.9%) and end-stage kidney disease requir- Age N % of Patients [95% CI] ing dialysis (< 1 VOC per year: n = 552, 59.0%; ≥ 1 to < 3 VOCs per year: n = 287, 53.4%; ≥ 3 VOCs per year: n = 8, ≥ 16 years 1495 34.8%). Other complications observed in patients hav- < 1 VOC per year (no VOC episodes) 935 62.5% [59‑66%] ing ≥ 3 VOCs per year were gallstones (n = 4, 17.4%) and ≥ 1 to < 3 VOCs per year 537 35.9% [32‑40%] osteomyelitis (n = 4, 17.4%). ≥ 3 VOCs per year 23 1.5% [0‑7%] VOC patients with Either VOC 1211 Diagnosis Codes or VOC Drugs Treatment patterns 0 months to < 2 years 183 15.1% [10‑20%] Of the total study patients (n = 2,863), 1,500 patients ≥ 2 years to ˂6 years 260 21.5% [16‑26%] (52.4%) were treated with different drug classes. The ≥ 6 years to < 12 years 153 12.6% [7‑18%] most common drug classes prescribed to patients were ≥ 12 years to < 16 years 55 4.5% [0‑10%] NSAIDs (n = 1,134, 75.6%), anti-infectives (n = 783, ≥ 16 years 560 46.2% [42‑50%] 52.2%), hematinics (n = 419, 27.9%), antimalarial (n = 398, 26.5%), opioids (n = 146, 9.7%), non-opioids (n = 19, 1.3%) Abbreviations: CI Confidence interval, N Number of patients, SCD Sickle cell disease, VOC Vaso-occlusive crisis and hydroxyurea (n = 4, 0.3%). Out of 1,497 patients ≥ 16 years of age, 738 patients (49.4%) were treated with dif- ferent drug classes. The most common drug classes pre- respectively) till the year 2019 (1.4% [95% CI: 0.6-2.2%] scribed for patients more than ≥ 16 years were NSAIDs and 0.7% [95% CI: 0-1.5%], respectively). However, a dip (n = 501, 67.9%), anti-infectives (n = 308, 41.7%), hema- in the prevalence to 0.5% [95% CI: 0-1.3%] for SCD and tinics (n = 271, 36.7%), antimalarial (n = 158, 21.4%), 0.3% [95% CI: 0-1.1%] for SCD patients with VOC epi- opioids (n = 117, 15.9%) and non-opioids (n = 16, 2.2%) sodes was noted for the year 2020 (Fig. 1). (Table 4). Hospitalization during 12‑Month follow‑up period Types of SCD Overall, 80 patients were hospitalized with 109.5 (IQR The study patients (n = 2,863) were categorized based on 39.0-198.0) median days of time to first hospitaliza- the clinical type of SCD reported, using the ICD-10-CM tion and a median annual rate of hospitalization of 1.0 diagnosis codes. During the study period (January (IQR 1.0–2.0). For the patients who experienced VOC Marfo et al. BMC Health Services Research (2023) 23:1018 Page 6 of 14 Fig. 1 Comparison of consultation‑based prevalence in patients with SCD and VOC. Abbreviations: SCD: Sickle cell disease; VOC: Vaso‑occlusive crisis. episodes (n = 37), the median time to first hospitalization Healthcare resource utilization and cost during 12‑month was 162.0 (IQR 48.0253.0) days and median annual rate follow‑up period by visit type of hospitalization was 1.0 (IQR 1.0–2.0) (Table S2). Assessment of disease-specific HCRU and associated costs for 12-month follow-up period among all SCD Healthcare resource utilization and associated costs patients showed that despite median HCRU outpatient Healthcare resource utilization and cost during the 6‑month claims and inpatient claims (1.0 claims) being same, the baseline period by visit type median healthcare cost incurred due to inpatient claims During the baseline period of 6 months, for patients ($92.6) was higher than the cost of outpatient claims with SCD, the total number of claims was higher for ($25.8). A similar observation was noted in SCD patients outpatient visits (3.0 [IQR 2.0–6.0]) compared to inpa- with VOC episodes. The median HCRU cost was higher tient visits (1.0 [IQR 1.0–1.0]), however, the median due to the inpatient visits ($95.2) than the outpatient inpatient cost was higher compared to outpatient cost visits ($24.6). A higher median overall cost was noted to ($576.4 [IQR $291.9-$1,129.2] and $49.9 ([IQR $25.5- be incurred by SCD patients with VOC episode ($32.9) $91.4], respectively). Similarly, for SCD patients expe- than all SCD patients ($30.8) despite the number of all riencing VOC episodes, the median number of claims SCD patients (n = 406) being twice as more than the SCD for outpatient visit was higher than inpatient visits (3.0 patients with VOC (n = 206) (Table 5). [IQR2.0-5.0]) and 1.0 [IQR 1.0–1.0], respectively), while the inpatient cost was higher than outpatient cost ($70.4 Healthcare resource utilization and cost during 12‑month ([IQR $36.8-$141.6] and $43.4 [IQR $23.2-$81.2], respec- follow‑up period by activity type tively). Higher overall healthcare costs were incurred by The median number of claims was same for differ- SCD patients compared to SCD patients experiencing ent activity types for SCD patients and SCD patients VOC episodes ($55.4 (IQR $27.7-$107.9) and $48.8 (IQR with VOC episodes. In patients with SCD, the highest $25.0-$100.9), respectively) (Table S3). This could be cost incurred was for consultation or hospital services attributed to the fact that SCD patients group included ($11.3 [IQR $6.2-$27.2]) and lowest cost was for admin- the overall population while SCD patients experiencing istrative services ($5.1 [IQR  $2.4-$13.8]). However, for VOC episodes included only the patients above 16 years patients with VOC episodes, cost incurred was highest of age. Additionally, the HCRU cost assessed during the for medications ($10.9 [IQR $5.0-$32.6]) and lowest for baseline period also included the costs incurred for all administrative services ($6.8 [IQR $2.8-$13.8]) (Table comorbidities-related claims for patients with SCD and S4). Availability of free health care in the USA or Europe SCD with VOC; while the HCRU cost evaluated during compared to sub-Saharan Africa could explain overall the follow-up period included only costs specific to SCD reported relative higher rates of hospital admission ver- and SCD with VOC claims. sus VOC managed in an outpatient setting [26]. M arfo et al. BMC Health Services Research (2023) 23:1018 Page 7 of 14 Table 3 Complications/Comorbidities in patients with sickle cell disease (January 2015‑March 2021) Complications/ Comorbidities Number of Patients Age subgroups VOC episodes by Comorbidities/ N (%) N (%) Complications, Age Subgroups and VOC episodes 0 Months to < 2 Years ≥ 2 Years to ˂6 Years ≥ 6 Years to < 12 ≥ 12 Years to < 16 ≥ 16 Years < 1 VOC Per Year ≥ 1 to < 3 VOCs ≥ 3 VOCs per Years Years per Year Year Overall population 459 (16.0) 486 (17.0) 306 (11.0) 117 (4.0) 1495 (52.0) 935 (62.5) 537 (35.9) 23 (1.5) Malaria 440 (95.9) 483 (99.4) 298 (97.4) 115 (98.3) 1440 (96.3) 894 (95.6) 523 (97.4) 23 (100.0) URTI 412 (89.8) 449 (92.4) 265 (86.6) 85 (72.6) 1071 (71.6) 671 (71.8) 383 (71.3) 17 (73.9) Dialysis 17 (3.7) 24 (4.9) 30 (9.8) 21 (17.9) 847 (56.7) 552 (59.0) 287 (53.4) 8 (34.8) Sepsis/Septicemia 264 (57.5) 277 (57.0) 141 (46.1) 37 (31.6) 445 (29.8) 258 (27.6) 174 (32.4) 13 (56.5) Liver 6 (1.3) 10 (2.1) 7 (2.3) 7 (6.0) 336 (22.5) 210 (22.5) 121 (22.5) 5 (21.7) Acute chest syndrome 140 (30.5) 148 (30.5) 69 (22.5) 18 (15.4) 214 (14.3) 123 (13.2) 83 (15.5) 8 (34.8) Cellulitis 26 (5.7) 34 (7.0) 16 (5.2) 12 (10.3) 108 (7.2) 56 (6.0) 48 (8.9) 4 (17.4) Acute kidney disease 2 (0.4) 3 (0.6) 2 (0.7) 3 (2.6) 58 (3.9) 34 (3.6) 16 (3.0) 3 (13.0) Acute kidney injury 1 (0.2) 6 (1.2) 2 (0.7) 4 (3.4) 53 (3.5) 34 (3.6) 23 (4.3) 1 (4.3) Central nervous 11 (2.4) 12 (2.5) 6 (2.0) 2 (1.7) 54 (3.6) 29 (3.1) 23 (4.3) 2 (8.7) system Gall stones 0 (0.0) 0 (0.0) 3 (1.0) 2 (1.7) 48 (3.2) 20 (2.1) 24 (4.5) 4 (17.4) Osteomyelitis 8 (1.7) 10 (2.1) 7 (2.3) 0 (0.0) 12 (0.8) 7 (0.7) 1 (0.2) 4 (17.4) Stroke 1 (0.2) 0 (0.0) 1 (0.3) 0 (0.0) 9 (0.6) 7 (0.7) 2 (0.4) 0 (0.0) Heart failure 3 (0.7) 3 (0.6) 0 (0.0) 0 (0.0) 18 (1.2) 6 (0.6) 11 (2.0) 1 (4.3) Cardiomyopathy 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 10 (0.7) 4 (0.4) 5 (0.9) 1 (4.3) Leg ulcer 1 (0.2) 3 (0.6) 3 (1.0) 1 (0.9) 12 (0.8) 4 (0.4) 7 (1.3) 1 (4.3) Abbreviations: N Number of patients, SCD Sickle cell disease, URTI Upper respiratory tract infection, VOC Vaso-occlusive crisis Marfo et al. BMC Health Services Research (2023) 23:1018 Page 8 of 14 Table 4 Drug/Treatment patterns for patients with SCD (January 2015‑March 2021) Patients with SCD (Overall population) Patients with SCD (age ≥ 16 adult population) Drug Classes Patients; N (%) Claims; N (%) Patients; N (%) Claims; N (%) Analgesics (NSAIDs) 1134 (75.6) 1764 (70.4) 501 (67.9) 750 (65.8) Anti‑infectives 783 (52.2) 1186 (47.3) 308 (41.7) 428 (37.5) Hematinic 419 (27.9) 837 (33.4) 271 (36.7) 428 (37.5) Antimalarial 398 (26.5) 536 (21.4) 158 (21.4) 217 (19.0) Opioids 146 (9.7) 271 (10.8) 117 (15.9) 208 (18.2) Anti‑inflammatory 54 (3.6) 67 (2.7) 20 (2.7) 32 (2.8) Antihypertensive/Vasodilators 46 (3.1) 57 (2.3) 45 (6.1) 56 (4.9) Antiasthmatics 21 (1.4) 21 (0.8) 6 (0.8) 6 (0.5) Vaccine 21 (1.4) 21 (0.8) 20 (2.7) 20 (1.8) Non‑opioid Analgesics 19 (1.3) 19 (0.8) 16 (2.2) 16 (1.4) Anti‑platelet 17 (1.1) 22 (0.9) 16 (2.2) 21 (1.8) Antidepressants 6 (0.4) 7 (0.3) 6 (0.8) 7 (0.6) Anticoagulants 4 (0.3) 4 (0.2) 3 (0.4) 3 (0.3) Hydroxyurea 4 (0.3) 20 (0.8) ‑ ‑ Abbreviations: N Number, NSAID Non-steroidal anti-inflammatory drugs, SCD  Sickle cell disease Numbers are not mutually exclusive By VOC episodes and age groups: for 12‑month follow‑up Discussion In terms of VOC episodes, maximum number of visits SCD is a global public health concern due to substantial was reported for patients with ≥ 1 to < 3 VOC episodes morbidity, mortality, and socioeconomic burden. The sub- per year (n = 216); however, median was higher in case Saharan Africa region accounts for more than 75% of global of ≥ 3 VOCs per year (4.0 [IQR 2.0–7.0]). The median SCD burden [20, 21, 27–29]. Despite this considerable dis- healthcare cost was highest for patients with ≥ 3 VOCs ease burden, there is a dearth of real-world data published per year ($166.8 [IQR $70.3-$223.5]) (Table 6). on the disease burden, treatment patterns and economic The healthcare costs pertaining to visit type and activ- burden of SCD from the sub-Saharan Africa region and ity type in SCD patients were higher compared to those could be attributed to the lack of a national database on costs in SCD patients with VOC episodes, during the patients with SCD care in regions of sub-Saharan Africa 12-month follow-up period. [30]. Hence, this cost of illness study was conducted to eval- uate the HCRU for patients with SCD and VOC episodes Specialties visited by patients with SCD in Ghana using Nationwide Medical Insurance Database. Of the total 2,863 patients in the study, 2,408 patients The study also assessed diagnostic investigations, treatment visited physicians of different specialties for treatment patterns and specialties visited for treatment advice among advice. General physician (GP) visits were the highest patients with SCD and VOC, in a real-world setting. with patient visits of 1,810 (75.2%) and claims of 2,867 The yearly prevalence of patients with SCD as well as (69.7%). This was followed by pediatric and gynecol- the SCD patients with VOC episodes during the study ogy consultations (Table S5). Around 5.7% (n = 137) period exhibited an increasing trend, suggestive of the patients had specialist consultation with a total of 252 growing disease burden in Ghana. However, a dip in claims (6.1%). prevalence was observed in the year 2020 which could be attributed to the under-reporting of the claims due to coronavirus disease (COVID-19) pandemic. Majority Diagnostic investigations of the patients were ≥ 16 years of age (52.2%) with a pre- Of the overall study population (n = 2,863), 96% of dominantly female population and having VOC episodes. patients (n = 2,759) underwent diagnostic investiga- These findings are consistent with the real-world study tions with total 4,185 claims. The most frequently used by Foundation for Sickle Cell Disease Research [31]. In diagnostic investigations with the highest number of the current study, 33% in of  the patients belonged to 0 claims were full blood count, hemoglobin electrophore- months to < 6 years age group. A systematic review and sis, blood smear for malaria parasites, sickling test, and meta-analysis reports highest prevalence and mortality of routine urine examination (Table S6). SCD in children under 5 years of age, in Africa [32]. M arfo et al. BMC Health Services Research (2023) 23:1018 Page 9 of 14 Table 5 Healthcare resource utilization and costs by visit type (12‑Month Follow‑up period) Sickle Cell Disease SCD‑Related Healthcare Resource Utiliza‑ VOC‑Related Healthcare tion and Cost Resource Utilization and Cost Number of patients in 12‑month follow‑up 406 206 Number of claims in 12‑month follow‑up 971 359 Healthcare Utilization: Number of Visits (Claims) Overall N (patient count) 406 206 Total 971 359 Mean 2.4 1.7 SD 2.8 1.5 Median 1.0 1.0 Minimum 1.0 1.0 Maximum 23.0 11.0 Q1 (lower quartile) 1.0 1.0 Q3 (upper quartile) 2.0 2.0 Inpatient Visits N (patient count) 80 71 Total 133 120 Mean 1.7 1.7 SD 1.4 1.4 Median 1.0 1.0 Minimum 1.0 1.0 Maximum 8.0 8.0 Q1 (lower quartile) 1.0 1.0 Q3 (upper quartile) 2.0 2.0 Outpatient Visits N (patient count) 384 71 Total 838 120 Mean 2.2 1.7 SD 2.4 1.4 Median 1.0 1.0 Minimum 1.0 1.0 Maximum 21.0 8.0 Q1 (lower quartile) 1.0 1.0 Q3 (upper quartile) 2.0 2.0 Healthcare Costs (Reported in US$) Overall costs N (patient count) 406 206 Total 31891.1 19995.7 Mean 78.6 97.1 SD 185.0 233.0 Median 30.8 32.9 Minimum 0.0 0.0 Maximum 2029.8 2000.1 Q1 (lower quartile) 17.6 20.1 Q3 (upper quartile) 74.5 91.0 Marfo et al. BMC Health Services Research (2023) 23:1018 Page 10 of 14 Table 5 (continued) Sickle Cell Disease Inpatient Cost N (patient count) 80 71 Total 15635.4 14400.5 Mean 195.4 202.8 SD 344.3 360.2 Median 92.6 95.2 Minimum 14.7 18.1 Maximum 2000.1 2000.1 Q1 (lower quartile) 49.4 51.8 Q3 (upper quartile) 188.2 177.6 Outpatient Cost N (patient count) 384 174 Total 16255.7 5595.2 Mean 42.3 32.2 SD 45.1 26.5 Median 25.8 24.6 Minimum 0.0 0.0 Maximum 293.6 169.3 Q1 (lower quartile) 15.3 16.7 Q3 (upper quartile) 52.0 35.5 Abbreviations: N: Number of patients; SCD: Sickle cell disease; SD: Standard deviation; US$: United States dollar; VOC: Vaso-occlusive crisis Note: Currency conversion rates Source for conversion of Cedi to US$ currency: https:// www. unitc onver ters. net/ curre ncy/g hs- to-u sd. htm; Accessed on 11August 2022 14:52:0 1 Ghanaian Cedi=0.1132 United States dollar (currency values in US$ rounded off to one decimal point) Q1 (lower quartile) - Q1 is the median (the middle) of the lower half of the data Q3 (upper quartile) - Q3 is the median (the middle) of the upper half of the data. In the current study, number of VOC episodes were of sub-Saharan Africa with high incidence of SCD are evaluated only in patients with SCD aged ≥ 16 years and also associated with highest density of malaria. Although not in patients with SCD < 16 years. The probable rea- the sickle cell mutation at one allele of beta-globin gene sons could be difficulty in characterizing VOC episodes confers a survival advantage in malaria endemic areas, in children. Diagnosis of VOC in children is complicated inheritance of the mutation at both alleles, predisposes by the fact that VOC affecting the bone is the most com- individuals to severe malaria and increased mortal- mon acute clinical manifestation of SCD in this popula- ity from other complications of SCD [38]. Studies have tion. Furthermore, VOCs are often confused with the reported that VOC in SCD patients accounts for 95% of much less frequently occurring osteomyelitis [33, 34]. A emergency department visits and inpatient admissions recent Phase 3 study reported that a shorter duration of [34, 39, 40]. This analysis also evaluated the annual rate VOC episode was observed in patients < 16 years of age of hospitalization admissions which was found to be [35]. Additionally, the grouping was done in line with the 1.6 ± 1.1. A study conducted in Ghana on patients (with previous trials conducted on patients with SCD (SOL- SCD), aged > 13 years reported the annual hospitalization ACE trial and SUSTAIN trial [36, 37]. Moreover, the rate to be 2.6%, attributed mostly to the acute complica- demographic data obtained during the analysis also rep- tions [27]. resented the high disease burden in patients < 16 years of Our analysis identified a greater number of prescrip- age (47.8%). Hence, the patients were stratified into sub- tions for analgesics, anti-infectives, and hematinics as population < 16 years and ≥ 16 years. compared to hydroxyurea, the standard of care treat- In the current study, majority of SCD patients had ment for SCD. Despite hydroxyurea being included in common sequelae of SCD – VOC episodes, infections, the World Health Organization model list of essential malaria, sepsis, and acute chest syndrome among others medications for children and the large body of evidence in accord with other studies [5, 8]. Furthermore, regions for its established efficacy in terms of reduced frequency M arfo et al. BMC Health Services Research (2023) 23:1018 Page 11 of 14 Table 6 Healthcare Resource Utilization and Costs by VOC and Patient Association Groups to increase access to Episodes and Age Groups (12‑Month Follow‑up) hydroxyurea including a pediatric-friendly formulation. VOC‑Related Healthcare Resource Utilization and Cost Comprehensive management of SCD requires effec- tive healthcare systems and necessitates healthcare pro- < 1 VOC per ≥ 1 to < 3 VOCs ≥ 3 VOCs Year per Year per Year fessionals to have appropriate knowledge of the disease. The current study noted that the treatment of SCD was ≥ 16 ≥ 16 ≥ 16 largely by GP practice compared to specialized care [47]. Healthcare Utilization: Number of Visits (Claims) Considering the limited number of specialist physicians Overall such as hematologists and pediatricians in the region, N (patient counts) 61 110 23 upskilling community practice physicians such as GPs Total 101 216 127 and internal medicine doctors could help strengthen the Mean 1.7 2.0 5.5 care delivery for SCD patients. SD 1.5 1.8 4.7 In the current study, cost due to inpatient claims for Median 1.0 1.0 4.0 SCD patients was significantly higher compared to cost Minimum 1.0 1.0 2.0 due to outpatient claims; the cost incurred on consulta- Maximum 8.0 10.0 23.0 tion/hospital services was highest compared to other Q1 (lower quartile) 1.0 1.0 2.0 HCRU costs (drugs, consumables, procedure, and admin- Q3 (upper quartile) 1.0 2.0 7.0 istrative services). The SCD patients who experienced ≥ 3 Overall Healthcare Costs (Reported in US$) VOC episodes per year incurred nearly 3 times more N (patient counts) 61 110 23 healthcare costs than those with lesser VOC episodes Total 3077.8 8374.1 4891.2 per year [48]. A retrospective cohort analysis of patient- Mean 50.5 76.1 212.7 level data from Medicaid database reported that patients SD 82.1 198.9 305.1 with > 3 VOC episodes had the highest annual SCD cost Median 21.8 34.1 166.8 across all settings (mean: US$ 58,950); suggesting that Minimum 0.3 0.0 18.3 HCRU costs increased with the increase in number of Maximum 554.5 2029.8 1535.8 VOC episodes [18]. Few studies which have assessed the Q1 (lower quartile) 11.8 20.9 70.3 economic burden of SCD in countries within sub-Saha- Q3 (upper quartile) 49.6 74.5 223.5 ran Africa show that households spend a considerable proportion of their income on direct costs (hospitaliza- Abbreviations: N Number of patients, SD Standard deviation, VOC Vaso-occlusive crisis, US$ United States dollar tion, medications, outpatient visits) associated with SCD Currency conversion rates [49]. The Economic Intelligence Unit 2020 reported that Source for conversion of Cedi to US$ currency: https:// www. unitc onvert ers.n et/ Nigeria had the highest annual costs (direct and indi- curre ncy/ ghs- to- usd.h tm; Accessed on 11August2022 14:52:0 rect costs) of SCD (US$ 6.5  billion per year), followed 1 Ghanaian Cedi=0.11328 United States dollar (currency values in US$ rounded by Angola (US$ 719.6 million per year) and Ghana (US$ off to one decimal point) 472.8  million per year) among other sub-Saharan coun- Q1 (lower quartile) - Q1 is the median (the middle) of the lower half of the data tries [50]. The report highlighted that in Ghana, medi- Q3 (upper quartile) - Q3 is the median (the middle) of the upper half of the data cation was the major cost driver for patients aged 5–14 and ≥ 15 years (US$ 346 per year and US$ 526 per year, of VOC episodes, transfusions, and hospitalizations respectively) [51]. [41–44], its use is sub-optimal in the sub-Saharan African Our study noted higher healthcare costs incurred by region. Minimal use of hydroxyurea in the region could SCD patients with VOC episodes than SCD patients be attributed to lack of data on magnitude and impact without VOC episodes, despite the number of SCD of SCD in the region, lack of evidence-based guidelines patients without VOC being twice as many as SCD on feasibility, safety, and benefits of hydroxyurea in the patients with VOC. region. Other barriers to use of hydroxyurea in the region Our major limitation for this analysis is based on its include drug availability, cost of treatment and labora- retrospective design and analysis from a claims data- tory monitoring. Another study in the region emphasized base. The study sample size includes only a subset of the on wider access to hydroxyurea which provides a cost- privately insured population of Ghana with continuous effective therapeutic approach to deter the progression of enrolment during the study period whose demographic disease in SCD patients [45, 46]. Through public-private data mapping was available; thus, the results might not partnerships, Novartis is working with Ministry of Health be applicable for the entire population with SCD in of Ghana, Ghana Health Service, Sickle Cell Foundation Ghana. Analysis of Ghana Demographic health survey Marfo et al. BMC Health Services Research (2023) 23:1018 Page 12 of 14 dataset suggested that economic and educational sta- patients with SCD in Ghana. The study findings indicate tus, marital status (single/widowed), and geographical an increased disease burden on patients with SCD and disparity are the major determinants for not enrolling a substantial impact on the healthcare costs, especially in the private insurance in Ghana. The financial status in the sub-group of patients with VOC episodes. In our determined the insurance status, with poorest, poorer, study VOC episodes were seen in less than half of the and middle-income groups being less likely to pay them- SCD patients. The most common complications were selves for insurance. Women (single/widowed) were less malaria, URTI and sepsis. Hydroxyurea use was sub-opti- likely to be covered relative to married women although mal in this cohort of patients. We hypothesized that bar- this group was more likely to pay the insurance premi- riers relating to drug availability, cost of treatment, and ums themselves. Geographic disparities and educational laboratory monitoring could have contributed although status also accounted for inequity in the insurance enrol- this is a cohort of patients with private health insurance. ment [52]. Clinical and disease-specific parameters (e.g., Understanding these barriers and efforts to increase duration or severity of the disease) could not be obtained access both in private and public sectors of Ghana is from the claims data. Emergency department visits have paramount for reducing the disease and economic bur- not been included or may have been combined with the den associated with SCD. The study also reported a sig- inpatient visit, leading to information bias. There could nificantly higher HCRU in the treatment of VOC. The be a possibility of missing data due to patients not follow- VOC cost burden equals the cost burden of SCD treat- ing up at the same hospital or group of hospitals or not ment, which warrants the need for better management being able to follow-up at all. The medications filled over of VOC. However, the limitations of the current study, as the counter, provided by the physicians or obtained out- listed above, make it likely that the costs of SCD in Ghana of-pocket could not be ascertained in the claims data. are higher than the cost estimates stated here. Addition- Only direct healthcare costs were evaluated; indirect ally, the direct medical expenses and societal costs have costs such as work productivity and quality of life were disproportionately larger impact on low-income families. not analyzed for SCD. The database also does not allow In 2021, the Ghana Food and Drug Authority one-to-one mapping between diagnosis and medications/ approved registration of crizanlizumab for prevention procedures/consumables. Hence, some of the reported of VOC in SCD patients >16 years and over. Addition- SCD specific medications, services and costs may not be ally, Ghana is participating in the ongoing Phase 3 clini- related directly to SCD. VOC admission within a gap of cal trial (STAND) with crizanlizumab, the first time a 3 days was taken as a single episode to validate the accu- clinical study has been conducted with a biologic agent rate capture of VOC episode and to overcome under- or for managing SCD. Innovative treatments with disease over-representation of VOC episodes. Additionally, VOC modifying modalities such as crizanlizumab, targeting episodes managed at home were not captured. Moreover, VOC episodes could be considered in SCD patients who VOC data for children under 16 years of age were not are intolerable to hydroxyurea or with recurring VOCs captured during the analysis. Our study was designed to despite maximum tolerable doses of hydroxyurea. capture only VOC data above 16 years of age. The high prevalence and mortality rate associated with children has been noted in previous studies [53, 54]. Hence the AbbreviationsSCD Sickle cell disease VOC sub-group in our study cohort could have been VOC Vaso‑occlusive crisis under-represented which has implications on the cost USFDA United States Food and Drug Administration distribution and our findings around this major compli- EMA European Medicine AgencyRBC Red blood cell cation of SCD. WBC White blood cell However, the strength of the study lies in the fact that HCRU H ealthcare resource utilization it is the first-of-its-kind being conducted in Ghana using US United StatesUS$ United States dollar the National Private Insurance Claims database. It cap- UK U nited Kingdom tures information for the population covered by Nation- ID Identifier wide Medical Insurance Claims Database representing ICD‑10‑CM International Classification of Diseases, Tenth Revision, Clinical Modification 10–15% of the Ghanaian population. NSAID Non‑steroidal anti‑inflammatory drugs IDD Index diagnosis date IQR Interquartile range Conclusion CI C onfidence interval To the best of our knowledge, the current study is the N Number of patients URTI Upper respiratory tract infection first-of-its-kind analysis conducted using e-claims data- GP General physician base to evaluate the disease and economic burden on COVID‑19 C oronavirus disease M arfo et al. BMC Health Services Research (2023) 23:1018 Page 13 of 14 Supplementary Information Author details 1 Novartis Pharma AG, Basel, Switzerland. 2 University of Ghana Medical School, The online version contains supplementary material available at https://d oi. Korle Bu Teaching Hospital, Accra, Ghana. 3 University of Ghana Legon, Accra, org/1 0. 1186/s 12913‑ 023‑ 09984‑6. Ghana. 4 Novartis Ghana Limited, Accra, Ghana. 5 Nationwide Medical Insur‑ ance, Accra, Ghana. 6 IQVIA, 11th Floor Convention Tower, DWTC, Al Saada Additional file 1: Table S1. Type of Sickle Cell Disease (January 2015‑ Street, Dubai 33083, UAE. 7 IQVIA, Bengaluru, India. 8 Novartis Pharmaceuticals March 2021). Table S2. Hospitalization in All the Patients Having SCD Corporation, East Hanover, USA. 9 University of Tennessee Health Science Diagnosis and Inpatient Visit (12‑Month Follow‑up period). Table S3. Center, Memphis, USA. Healthcare Resource Utilization and Costs by Visit Type (6‑Month Baseline Period). Table S4. Healthcare Resource Utilization and Costs by Activity Received: 14 October 2022 Accepted: 29 August 2023 Type (12‑Month Follow‑up). Table S5. Specialities Visited by Patients with SCD (January 2015‑March 2021). Table S6. Diagnostic Investigations Conducted on Patients With SCD (January 2015‑March 2021) References Acknowledgements 1. Ogu UO, Billett HH. Comorbidities in sickle cell disease: adult providers Medical writing and editorial support were provided by Dr Kavitha Ganesha needed! Indian J Med Res. 2018;147(6):527–9. (Senior Consultant, IQVIA, India), Sharda Kandwal (Senior Consultant, IQVIA, 2. Ogu UO, Badamosi NU, Camacho PE, Freire AX, Adams‑Graves P. Manage‑ India) and Bushra Nabi (Associate Consultant, IQVIA, India) and assistance with ment of Sickle Cell Disease Complications Beyond Acute chest syndrome. data analysis was provided by Prashant Pandey from IQVIA, India. Support for J Blood Med. 2021;12:101–14. this assistance was funded by Novartis. 3. Sundd P, Gladwin MT, Novelli EM. Pathophysiology of Sickle Cell Disease. Annu Rev Pathol. 2019;14:263–92. Authors’ contributions 4. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle Conception or design of the work: KM, YD‑A, CS, DD, AE, NA, KS, OE, KA; cell disease in Africa: a neglected cause of early childhood mortality. Am J Conception or design of the work and analysis: BR, AN. All authors read and Prev Med. 2011;41(6 Suppl 4):398–405. approved the final manuscript. 5. Inusa BPD, Hsu LL, Kohli N, Patel A, Ominu‑Evbota K, Anie KA, et al. Sickle Cell Disease‑Genetics, Pathophysiology, clinical presentation and treat‑ Funding ment. Int J Neonatal Screen. 2019;5(2):20. This study was funded by Novartis. 6. Paintsil V, Amuzu EX, Nyanor I, Asafo‑Adjei E, Mohammed AR, Yawnumah SA, et al. Establishing a Sickle Cell Disease Registry in Africa: experience Availability of data and materials from the Sickle Pan‑African Research Consortium, Kumasi‑Ghana. 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Database contains anonymized Clinical outcomes and Healthcare utilization in patients with Sickle Cell structured insurance e‑claims data of the patients. Patients’ identity or medical Disease: a Nationwide Cohort Study of Medicaid beneficiaries. Blood. records were not disclosed for the purposes of this study, except where dis‑ 2019;134(Supplement1):3459. closure was allowed as per applicable law. The study conformed to the ethical 11. Allotey‑Babington GLSO, Williams AA, Asiedu EA, Amuakwa MK, Nettey principles of the Declaration of Helsinki of 1964 and its later amendments. H. Hydroxyurea granules for the management of sickle cell disease in The data used for the current study was not publicly available. This data was children. Sci Afr. 2022;16:1–8. obtained from Nationwide Medical Insurance following all necessary legal 12. Matte A, Zorzi F, Mazzi F, Federti E, Olivieri O, De Franceschi L. New procedures to acquire and use this anonymized patient claims data. According Therapeutic Options for the treatment of Sickle Cell Disease. Mediterr J to data sharing agreement between Nationwide Medical Insurance and IQVIA, Hematol Infect Dis. 2019;11(1):e2019002. IQVIA was granted a perpetual, non‑exclusive license to use only the elements 13. Okocha EC, Gyamfi J, Ryan N, Babalola O, Etuk E‑A, Chianumba R, et al. of the data described in the agreement. IQVIA was permitted to use the data Barriers to therapeutic use of Hydroxyurea for Sickle Cell Disease in Nige‑ after anonymizing and standardizing for health insurance claims data‑based ria: a cross‑sectional survey. Front Genet. 2022;12:765958. analysis and research studies and was allowed to share the anonymized and 14. LiverTox: Clinical and Research Information on Drug‑Induced Liver Injury standardized data with its client for health insurance claims databased analysis [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and research studies. IQVIA agreed to adhere to measures to comply with and Kidney Diseases; 2012‑. Phenotypes Of Drug Induced Liver Injury. applicable laws, including those related to data protection. [Updated 2019 May 4]. Available from: https:// www. ncbi. nlm. nih.g ov/ books/ NBK54 8473/. Consent for publication 15. McGann PT, Ware RE. Hydroxyurea therapy for sickle cell anemia. Expert Not applicable. Opin Drug Saf. 2015;14(11):1749–58. Novartis has no conflict of interest to declare related to patents, products in 16. Adepoju P. Ghana takes on sickle‑cell disease. The Lancet. development and marketed products. 2020;395(10222):402. The authors have no conflict of interest to declare. 17. Rizio AA, Bhor M, Lin X, McCausland KL, White MK, Paulose J, et al. The All Novartis Employees were full‑time employee of Novartis during the relationship between frequency and severity of vaso‑occlusive crises and conduct of the study. 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Heeney MM, Rees DC, De Montalembert M, Odame I, Brown RCC, Wali Y, et al. Initial safety and efficacy results from the phase II, Multicenter, open‑label Solace‑Kids Trial of Crizanlizumab in Adolescents with Sickle Cell Disease (SCD). Blood. 2021;138(Supplement 1):12. Ready to submit your research ? Choose BMC and benefit from: 38. McAuley CF, Webb C, Makani J, Macharia A, Uyoga S, Opi DH, et al. High • fast, convenient online submission mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya. Blood. 2010;116(10):1663–8. • thorough peer review by experienced rese archers in your field 39. Lee S, Vania DK, Bhor M, Revicki D, Abogunrin S, Sarri G. Patient‑reported • rapid publication on acceptance outcomes and economic burden of adults with Sickle Cell Disease in the • support for research data, including large and complex data types United States: a systematic review. Int J Gen Med. 2020;13:361–77. 40. Oladapo A, Swallow E, Briggs A, Zichlin ML, Mellgard BL. Prevalence of • gold Open Access which fosters wider collaboration and increased citations Vaso‑Occlusive crises in patients with Sickle Cell Disease: a retrospective • maximum visibility for your research: over 100M website views per year US claims database analysis. Blood. 2020;136(Supplement 1):8–9. 41. Le PQ, Gulbis B, Dedeken L, Dupont S, Vanderfaeillie A, Heijmans C, At BMC, research is always in progress. et al. Survival among children and adults with sickle cell disease in Belgium: benefit from hydroxyurea treatment. Pediatr Blood Cancer. Learn more biomedcentral.com/submissions 2015;62(11):1956–61.