Background
Sickle cell disease (SCD) refers to a group of inherited disorders caused by mutations in the gene that encodes the β-subunit of adult hemoglobin (HBB). These mutations lead to the production of abnormal, sickled hemoglobin and chronic hemolytic anemia, resulting in chronic and episodic pain, progressive clinical disease, end-organ damage, and reduced life expectancy [1].
SCD is characterized by multisystem acute and life-long complications, including vaso-occlusive crises (VOCs), acute chest syndrome, avascular necrosis, and cardiopulmonary and renal complications [1, 2]. These clinical complications can reduce health-related quality of life (HRQoL) and impact financial well-being [3, 4]. Previous reports highlight impaired HRQoL in people with SCD compared to those without SCD, reflecting the debilitating pain associated with VOCs, frequent clinical complications that impact daily life (including reduced school achievement or work hours), and an increased prevalence of depression and anxiety [3, 4]. Living with SCD can also impart economic burden, primarily due to direct and indirect costs associated with frequent hospitalizations, physician or emergency department visits, and use of prescription drugs [5]. Furthermore, people with SCD often report significant absenteeism, presenteeism, and loss of productivity due to time spent managing the disease [5].
Health access and equity barriers create additional challenges for people living with SCD. A recent cross-sectional analysis illustrated longer emergency department wait times for people with SCD than for people with bone fractures or other painful conditions, despite those with SCD presenting with higher degrees of pain and being assigned priority at triage [6, 7]. Results from this study reflect ongoing healthcare challenges people with SCD face, in part due to race, and the need to reduce wait times for all patients in need of immediate care. Further, despite current guideline recommendations on opioid analgesia in SCD [8], many people with SCD may be under treated for pain associated with SCD (i.e., for VOCs), potentially due to ongoing concerns around opioid use amidst the opioid epidemic in the US [9]. These challenges underscore the complexities and nuanced obstacles people with SCD experience day-to-day as they manage a disease associated with significant pain.
To date, many studies have focused broadly on the overall SCD patient population and therefore, limited data are available to describe HRQoL and economic impacts associated specifically with SCD with recurrent VOCs [3, 4]. To address this gap in evidence in a patient population with high clinical disease severity and overall burden, we conducted a prospective longitudinal real-world study to characterize HRQoL and economic impacts in adults with SCD and recurrent VOCs.
Methods
Study design and data source
A mixed-methods study, consisting of two phases, was developed to describe and quantify HRQoL and economic impacts in people living with SCD with recurrent VOCs.
Phase 1 involved completion of a targeted literature review, designed to inform the creation of a conceptual framework and moderation guide for semi-structured focus group discussions. These discussions aimed to characterize the symptomatic experiences and humanistic burden associated with living with SCD, including clinical symptoms, HRQoL, and work/school productivity impacts. Findings from focus groups then informed an evidence gap assessment, which led to the development of bespoke questions included in Phase 2 of this study. Further details and results from Phase 1 have previously been reported [10].
Phase 2 included a multi-country prospective longitudinal observational survey, designed to better understand the impact of SCD with recurrent VOCs on the HRQoL of those living with this disease. A global scientific advisory team included clinical experts, academics with significant experience in patient-reported outcomes research and representatives from SCD patient advocacy groups collaborated to design the study. The survey comprised validated PRO instruments and finalize bespoke questions. The wording, response options and formatting of bespoke questions were further refined by the scientific advisory team to ensure that the patient voice was appropriately incorporated into the research process.
The study was administered online at three different time points over a six-month period (0 months [baseline], 3 months, and 6 months), and data were collected prospectively between May 2022 and November 2022. This study is reported in accordance with guidelines for Strengthening and Reporting of Observational studies in Epidemiology (STROBE) checklist [11].
Study population
Adults (aged ≥ 18 years) with SCD with recurrent VOCs in the US and Europe (France, Germany, Italy, and the UK) were invited to participate through patient advisory groups, including Sick Cells in the US, Sickle Cell Care Manchester in the UK, SOS Globi in France, and the European Sickle Cell Federation in France, Germany, and Italy. Eligibility was based on a self-reported clinical diagnosis of SCD, with a history of ≥ 2 VOCs per year in each of the 2 years before enrolment that required a visit to a medical facility and administration of pain medication and/or red blood cell transfusion. People with prior hematopoietic stem cell transplantation, gene therapy, and/or gene editing were excluded. In addition, people were excluded if they were currently enrolled in a clinical trial to treat SCD or if they were unable to provide informed consent. A convenience sampling approach was used to facilitate study recruitment in Phase 2.
Study outcomes
The primary outcome was to describe HRQoL impacts among people with SCD over three time points (baseline (0), 3, 6 months).
As outlined, findings from the evidence gap assessment and feedback from the scientific advisory team informed the identification of generic and disease-specific patient-reported outcome measures (PROMs) and development of bespoke questions for inclusion in the study: EuroQoL Five-Dimensions Five Level (EQ-5D-5 L) and Visual Analogue Scale (EQ-5D-5 L VAS) [41], Functional Assessment of Cancer Therapy – General (FACT-G) [42], Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) [43], Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) [46], Work Productivity and Activity Impairment Questionnaire (WPAI) [45], and 11-point numerical rating scale (NRS) of pain [44]. For each participant, health utilities were calculated using country-specific value sets for the EQ-5D-5L responses [36‐40]. A brief description of these PROMs, with references supporting their validity, and bespoke questions is provided in Supplementary Table 1.
Bespoke questions were focused on the financial impacts associated with managing SCD with recurrent VOCs, including estimates of money spent covering the costs associated with managing their condition per month, burden of out-of-pocket expenses, and financial distress experienced. The bespoke questions were structured as follows “On average, how much do you spend every month out-of-pocket to manage your sickle cell disease?”, “How much of a financial burden are out-of-pocket expenses to manage your sickle cell disease for you and/or your family?” and “How often do out-of-pocket expenses to manage your sickle cell disease cause you distress?” Additional bespoke questions on stigma/prejudice and time burden were also included. Survey materials were developed in English and translated into the local language of the location the study was carried out; all translated surveys were reviewed by a native speaker. For the PROMs, where there were relevant validated translations, these were used instead of translating the English version. Participants were invited to provide a response for all questions; however, “not applicable” and “do not know” options were provided where appropriate.
Participants were asked to complete a background survey once, immediately following enrolment. The background survey asked participants about their demographic information (i.e., age, sex, residence, race/ethnicity, marital status, employment, and gross annual household income), clinical characteristics, and diagnosis and treatment of SCD (i.e., medical history, number of VOCs managed in the hospital setting and at home during the 12 months prior to enrollment), and medical treatments received during the month prior to enrollment.
Statistical analysis
All data were aggregated and pseudonymized prior to analyses. Descriptive statistics, including frequencies and proportions, were used to describe participant demographics, clinical symptoms, and treatment characteristics. PROMs were scored according to their respective scoring manuals. Minimal clinically important differences (MCIDs) were only available for changes in EQ-5D, FACT-G, and FACIT-F and reported alongside US general population normative data [12‐14]. To compare mean values of PROMs between participants and the US general population, a Welch’s t-test was conducted. PROMs were also analyzed by age subgroups (18–35 years, 36–55 years and > 55 years), gender (male and female, to note non-binary was not presented due to < 5 individuals) and assessed for stability over time (at month 0, 3, and 6), using ANOVA and repeated measure ANOVA, respectively. Statistically significant differences were assessed at a 0.05 level for all analyses; p-values were two-sided. All analyses were performed using R (version 4.3.1) and R Studio (version 2023.06.1 + 524) software.
Ethics
This study was conducted in accordance with the ethical standards of the institutional or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Exemption for this study was granted by WIRB-Copernicus Group Institutional Review Board. Informed consent was obtained from all participants included in this research. Recruitment was conducted through patient advocacy groups, with no interactions occurring within hospital settings or involving healthcare professionals. This study was deemed exempt from NHS Health Research Authority research ethic committee review. This study was conducted in accordance with the Association of the British Pharmaceutical Industry, British Healthcare Business Intelligence Association and European Pharmaceutical Market Research Association codes of conduct [15‐17].
Results
Demographics and clinical characteristics
Overall, 142 adults with SCD with recurrent VOCs were enrolled in this study (Table 1). The mean (standard deviation [SD]) age of participants was 35.5 (10.4) years. Most participants were female (71.8%), residents of the US (59.9%) or the UK (23.2%), ‘Black or African American’ or ‘Black/African/Caribbean/Black British’ (93.2%) and had gross annual household incomes < 25,000 USD per year (55.4%) (Table 1).
Table 1
Participant self-reported demographics (N = 142)
n (%) | |
|---|---|
Age (years) | |
Mean (SD) | 35.5 (10.4) |
Median (IQR) [range] | 35.0 (28.3–41.8) [18–62] |
Age (years) | |
18–35 | 76 (53.5) |
36–55 | 59 (41.5) |
55+ | 7 (4.9) |
Sex | |
Female | 102 (71.8) |
Male | 39 (27.5) |
Non-binary | 1 (0.7) |
Residence | |
US | 85 (59.9) |
UK | 33 (23.2) |
Italy | 15 (10.6) |
France | 8 (5.6) |
Germany | 1 (0.7) |
Race/ethnicity (n = 118)a | |
Black or African American | 82 (69.5) |
Black/African/Caribbean/Black British | 28 (23.7) |
Mixed/multiple ethnic groups | 4 (3.4) |
Other | 3(2.5) |
Prefer not to say | 1 (0.8) |
Current marital status | |
Single | 75 (52.8) |
Married/domestic partner | 30 (21.1) |
In a committed relationship | 20 (14.1) |
Separated/divorced | 12 (8.5) |
Prefer not to say | 5 (3.5) |
Employment | |
Unemployed | 52 (31.9) |
Receiving/awaiting disability payments or on leave due to SCD | 38 (23.3) |
Other | 28 (18.1) |
Part-time | 23 (14.1) |
Full-time | 22 (13.5) |
Gross annual household income (n = 130)b | |
Less than 10,000 USD per year | 33 (25.4) |
10,000 to 25,000 USD per year | 39 (30.0) |
25,000 to 50,000 USD per year | 31 (23.8) |
50,000 to 75,000 USD per year | 5 (3.8) |
75,000 to 100,000 USD per year | 1 (0.8) |
100,000 to 200,000 USD per year | 5 (3.8) |
200,000 USD per year and greater | 1 (0.8) |
refer not to say | 15 (11.5) |
The mean (SD) number of VOCs requiring a hospitalization or management at home in the past 12 months were 5.9 (4.8) and 7.5 (7.7), respectively (Table 2). In the same period, 61.3% of participants reported ≥ 4 severe VOCs that required admission to a hospital and administration of pain medication and/or a red blood cell transfusion, and 69.3% reported having ≥ 4 VOCs that were managed at home (Table 2); these two populations overlapped, with some participants experiencing a range of severity in VOCs.
Table 2
Participant self-reported clinical characteristics (N = 142)
n (%) | |
|---|---|
Number of VOCs managed in hospital in past 12 months (April 2021-22)a, | |
Mean (SD) | 5.9 (4.8) |
Median (IQR) [range] | 5.0 (3–7) [2–26] |
Proportion of patients with VOCs managed in hospital in past 12 months (April 2021-22)a categorized by number of VOCs | |
2–3 VOCs | 55 (38.7) |
4–6 VOCs | 44 (31.0) |
7–9 VOCs | 20 (14.1) |
≥ 10 VOCs | 23 (16.2) |
Number of VOCs managed at home in the past 12 months (April 2021-22) | |
Mean (SD) | 7.5 (7.7) |
Median (IQR) [range] | 5.0 (3–9) [1–70] |
Proportion of patients with VOCs managed at home in the past 12 months, categorized by number of VOCs | |
0–1 VOCs | 5 (3.6) |
2–3 VOCs | 38 (27.1) |
4–6 VOCs | 40 (28.6) |
7–9 VOCs | 23 (16.4) |
≥ 10 VOCs | 34 (24.3) |
Medical historyb | |
Daily pain medication | 103 (72.5) |
Hip or shoulder damage due to SCD | 70 (49.3) |
Regular blood transfusions | 67 (47.2) |
Spleen removal | 58 (40.8) |
Retinopathy | 38 (26.8) |
Lung damage | 32 (22.5) |
Stroke | 25 (17.6) |
Kidney damage | 23 (16.2) |
Leg ulcers | 19 (13.4) |
Current treatments (received in the last month) | |
Prescription pain medication | 102 (71.8) |
Hydroxyurea | 88 (62.0) |
Hydration infusions | 75 (52.8) |
Exchange transfusions | 31 (21.8) |
RBCT | 30 (21.1) |
Frequent clinical complications and procedures reported by participants were hip and shoulder damage (49.3%), regular red blood cell transfusions (47.2%), spleen removal (40.8%), and retinopathy (26.8%). Most participants (72.5%) reported daily use of pain medications, and 71.8% and 62.0% of participants used prescription pain medications and hydroxyurea during the past month, respectively (Table 2).
Impact of SCD on HRQoL
At month 0, participants had significantly lower mean (SD) EQ-5D-5 L utility scores (0.59 [0.27]) than the US general population (0.85 [0.21]; group difference: p < 0.001; MCID: 0.078) (Table 3) [18]. Most participants reported feeling slightly to extremely anxious or depressed (74.1%), as well as slight to extreme problems with mobility (71.2%), usual activities (79.9%), and self-care (46.8%). Similarly, the mean (SD) EQ-5D-5 L VAS score at month 0 was significantly lower among participants (58.7 [19.4]) than among the US general population (80.4 [15.6]; group difference: p < 0.001; MCID: 7–10 [19]) (Table 3). EQ-5D-5 L VAS scores remained consistent from month 0 to month 6, with the largest fluctuation (3.6) being below the MCID (7–10) [19] (Fig. 1A).
Fig. 1
EQ-5D-5 L VAS (A) and FACT-G total (B) scores reported over time in participants with SCD with recurrent VOCs (n = 118)a, b. EQ-5D-5 L, EuroQol Five-Dimension Five-Level; FACT-G, Functional Assessment of Cancer Therapy – General; MCID, minimal clinically important difference; VAS, visual analogue scale; VOC, vaso-occlusive crisis. aThe increase in EQ-5D-5 L VAS score did not reach the MCID of 7–10. bThe largest fluctuation in FACT-G total score did not reach the MCID of 3–7
×
![]()
Table 3
Patient-reported EQ-5D-5 L, FACT-G, FACIT-F, ASCQ-Me, and WPAI scores collected at 0 months (N = 142)
Score range | Mean (SD) | US general population | p-value | |
|---|---|---|---|---|
EQ-5D-5La, b | ||||
EQ-5D-5 L utility (n = 139) | 0–1 | 0.59 (0.27) | 0.85 (0.21) | < 0.001 |
EQ-5D-5 L VAS (n = 137) | 0-100 | 58.7 (19.4) | 80.4 (15.6) | < 0.001 |
FACT-G (n = 138)c | ||||
Physical well-being | 0–28 | 15.6 (5.7) | 22.7 (5.4) | < 0.001 |
Social and family well-being | 0–28 | 16.6 (6.7) | 19.1 (6.8) | < 0.001 |
Emotional well-being | 0–24 | 15.0 (5.4) | 19.9 (4.8) | < 0.001 |
Functional well-being | 0–28 | 15.2 (5.8) | 18.5 (6.8) | < 0.001 |
FACT-G Total | 0-108 | 62.5 (18.1) | 80.1 (18.1) | < 0.001 |
FACIT-F (n = 103)d | ||||
FACIT-F Subscale | 0–52 | 24.2 (10.2) | 43.6 (9.4) | < 0.001 |
ASCQ-Me (n = 138) | ||||
Emotional Impact | 0-100 | 43.5 (7.6) | ||
Social Functioning Impact | 0-100 | 47.3 (8.3) | ||
Pain Impact | 0-100 | 41.5 (9.0) | ||
Sleep Impact | 0-100 | 49.3 (5.6) | ||
Stiffness Impact | 0-100 | 41.1 (8.2) | ||
WPAI | ||||
Absenteeism (n = 47) | 0-100 | 24.7 (27.1) | ||
Presenteeism (n = 44) | 0-100 | 42.0 (27.8) | ||
Work productivity loss (n = 44) | 0-100 | 53.4 (27.5) | ||
Overall activity impairment (n = 137) | 0-100 | 52.6 (26.0) |
The total mean (SD) FACT-G score at month 0 was lower among participants (62.5 [18.1]) than the US general population (80.1 [18.1]; p < 0.001; MCID: 3–7 [20, 21]). Participants had significantly reduced mean (SD) FACT-G domain scores compared to published information about the US general population, with a 31% relative reduction in physical well-being (15.6 [5.7] vs. 22.7 [5.4]) and 25% reduction in emotional well-being (15.0 [5.4] vs. 19.9 [4.8]; MCID: 1–2 points) (Table 3) [20, 21]. A substantial proportion of participants reported having a lack of energy (43.1%; “quite a bit” or “very much”) in the past 7 days and having trouble meeting the needs of their family because of their physical condition (40.7%). FACT-G scores were stable from month 0 to month 6 (Fig. 1B), with the largest fluctuation (2.8) being below the MCID (3–7) [20, 21].
The mean (SD) FACIT-F subscale score (24.2 [10.2]) further illustrated the significant fatigue experienced by adults with SCD and recurrent VOCs, with participants reporting significantly lower scores than the US general population (43.6 [9.4]; p < 0.001; MCID: 3-8.3) and scores similar to those previously reported in anemic patients with cancer (23.9 [12.6]) (Table 3) [13, 22].
Current pain, pain at its worst, and pain at its best were measured with the 11-point NRS, wherein the mean (SD) scores were 4.2 (2.6), 9.5 (1.0), and 2.8 (2.3), respectively. When asked to assess an acceptable level of pain, participants reported a mean (SD) score of 3.4 (1.6). A total of 60.0% of participants reported their current pain as “moderate” or “severe” (NRS scale range: 4–10) (Fig. 2), which is consistent with findings from the EQ-5D-5 L (Table 3), wherein 89.9% of participants reporting living with slight to extreme pain/discomfort “today”. Nearly all participants (96.5%) rated their pain at its worst as “severe” (NRS scale range: 7–10), and 31.0% of participants rated their pain at its best as “moderate” or “severe” (NRS scale range: 4–10) (Fig. 2). 23.5% and 8.0% reporting their current pain and pain at its best as “severe” (Fig. 2).
Fig. 2
Pain NRS responses in patients with SCD with recurrent VOCs (n = 115). NRS, Numerical Rating Scale; SCD, sickle cell disease; VOC, vaso-occlusive crisis. Note Sample sizes for these end points are lower than the total sample size as the NRS of pain is only available in English
×
![]()
On the ASCQ-Me, participants reported increased pain, stiffness, and emotional impacts compared to the reference sample of US adults with SCD (mean [SD] score: 50 [10] across all ASCQ-Me domains) (Table 3) [23, 24]. Over one third of participants reported that their health “made it hard to do things” (40.6%) or “kept [them] from going out” (37.7%) often or always in the past 30 days. Additionally, in the past 7 days, 20.3% of participants reported often or always feeling “completely hopeless” because of their health, and 27.3% reported often or always having “pain so bad that [they] could not do anything” for a whole day. Over one quarter of participants reported that, during their last VOC, they were unable to do most things they usually do (27.3%) or could not take care of themselves and needed some help from others (26.6%).
Employment and financial burden
Employed participants (n (%); 47 [33.1%]; (Table 1) reported an average of 9.8 h of missed work in the past 7 days and had an overall work productivity loss of 53.4% (Table 3). Most participants (58.5%) reported having insufficient money to cover the costs associated with managing their disease and estimated that they would need an additional median of 433 USD per month (interquartile range: 200 to 800 USD). Out-of-pocket expenses were reported as a moderate-to-major burden for 61.9% of participants (Fig. 3A), and 45.7% of participants reported frequently or very frequently experiencing financial distress due to out-of-pocket expenses needed to manage their SCD (Fig. 3B).
Fig. 3
Financial burden of out-of-pocket expenses (n = 118) (A) and frequency that out-of-pocket expenses cause distress (n = 118) (B) in patients with SCD with recurrent VOCs. SCD, sickle cell disease; VOC, vaso-occlusive crisis. Note: The sample sizes for these end points are lower than the total sample size as data were collected at M3 (dropouts) and not all participants responded to this question
×
![]()
Subgroup and longitudinal analyses
Overall, mean scores across all PROMs were consistent when analyzed by age subgroups (18–35 years, 35–55 and > 35 years) [Supplementary Table 2] and gender (male and female, to note non-binary was not presented due to < 5 individuals) (Supplementary Table 3). Results for these measures were also stable over time, from month 0 to month 6 (Fig. 1 and Supplementary Table 4).
Discussion
This study demonstrated the HRQoL and economic impacts associated with living with SCD with recurrent VOCs. Participants with SCD with recurrent VOCs reported significantly reduced HRQoL compared to published information about the US general population, which was captured across all PROMs. Mean EQ-5D-5 L utility and VAS scores were considerably lower than those reported in the US general population and the decrements were two-to-three times the respective MCIDs [18]. FACT-G scores were also consistently lower across the physical, social and family, emotional, and functional domains of well-being compared to published information about the US general population, confirming the multi-faceted impact of SCD on HRQoL that has previously been reported [3, 25, 26]. When asked about experiences with their most recent VOCs, up to 27.3% participants reported not being able to take care of themselves, needing some help from others, and being unable to do things that they usually do, which are examples of the profound day-to-day impacts that living with SCD has on physical and mental health.
Pain (e.g., from VOCs) is widely reported to have meaningful impacts on HRQoL in people with SCD [4, 25]. Participants consistently reported increased pain on the 11-point NRS and ASCQ-Me, with 23.5% and 8.0% reporting their current pain and pain at its best as “severe”, respectively (NRS scale range: 7–10). Further, the reported mean level of current pain and pain at its worst was 1.2-fold and 2.8-fold higher than what participants deemed an acceptable level of pain (3.4 [1.6]). Considering that other researchers have reported a mean pain score of 8.5 in adults with SCD upon hospital admission for painful VOCs [4], results from this study emphasize the ongoing clinical burden of managing SCD with recurrent VOCs, especially for those living with severe and daily pain.
Pain scores reported in this study were also consistent with other studies conducted in people with SCD with frequent VOCs [26]. When compared to participants with SCD experiencing 0–3 VOCs per years, those with ≥ 4 VOCs per year had a significantly lower pain impact score (i.e. worse pain impact) on the ASCQ-Me, representing overall lower functioning [26]. Therefore, it is not surprising that 71.8% of participants in the current study reported current use (within the last month) of prescription pain medication and 72.5% reported previous daily use to manage their ongoing pain. As most people with SCD manage chronic pain and pain episodes at home [4], the high rate of pain medication reported in the current study suggests that the frequency of VOCs reported from hospital datasets may underestimate the total number of VOCs, and potential magnitude of pain experienced by people with SCD.
SCD is characterized by anemia, fatigue, and weakness [27] and, as expected, fatigue scores reported in this study were lower than the US general population scores (43.6) [13] but were comparable to scores reported among anemic people with cancer (23.9) [13]. As an independent predictor of HRQoL [28] and one of the most commonly reported symptoms in people with SCD [3], fatigue was not only widespread in this patient population but a clear reflection of the overall disease pathophysiology. Addressing the underlying mechanisms of SCD to improve fatigue, among other clinical symptoms, is critical – especially when considering its impact on HRQoL and the potential financial implications associated with reduced productivity at work or school.
Management of SCD with recurrent VOCs is associated with considerable direct and indirect costs in the US [29]. In a recent claims-based analysis, people with SCD with recurrent VOCs incurred higher annual ($67,282 vs. $4,134) and lifetime ($3.8 million vs. $229,000 over 50 years) healthcare costs compared to matched controls [29]. In the current study, indirect costs associated with managing SCD with recurrent VOCs were considerable, with participants reporting needing a median of 433 USD more per month. Many participants were unable to work due to their disease, leaving them financially dependent upon their family and employed participants reported high levels of presenteeism and absenteeism, likely associated with managing chronic pain, anemia, and other SCD complications. Results from the current study are consistent with others noting high absenteeism, presenteeism, and lost work productivity in people with SCD [5, 26], with some estimating that 15,103 USD annual absenteeism and presenteeism costs are attributable to pain-related events (e.g., VOCs) [5]. Previous reports have estimated approximately 33,816 USD in costs among people with SCD due to lost productivity [30] and 700,000 USD in lost lifetime income [31]. Considering participants report considerable impairments to their work productively and activity and nearly half of participants in this study (45.7%) experienced frequent or very frequent financial distress due to out-of-pocket expenses, there is a significant lifetime financial burden for people living with SCD with recurrent VOCs.
Disparities in health care access and equity concerns remain an ongoing concern among people with SCD [6, 7, 9]. Racial prejudice and accessibility barriers exist in communities with high prevalence of SCD, and challenges in trust and relationship building with the healthcare system remain [32]. Initiatives to reduce structural racism within the healthcare system and educational programs focused on building trust between the SCD and medical community could be particularly beneficial as novel and functionally curative therapies become available in order to ultimately reduce the clinical and economic burden of SCD [33, 34].
As improving HRQoL remains a key treatment goal for people with SCD [3], a growing number of large cohort studies have highlighted the health impact and impaired productivity of people with SCD within the last 5 years [3, 35]. While findings from cross-sectional studies support the significant burden among people with SCD, the stability of the longitudinal findings reported here demonstrate that daily impacts of SCD persist over time. Furthermore, the use of validated questionnaires in addition to the development of bespoke, patient-centered questions in this study further underscore the complex humanistic and financial impact of managing SCD. Given that has been reported it is imperative to reduce the overall burden associated with managing SCD, particularly in people with recurrent VOCs.
Limitations
There are several limitations that should be considered when interpreting results from this study. Participants were self-selected and part of a patient advocacy group email list, which may impact the generalizability of these results. Additionally, although the associated risks to data quality were minimized by asking participants specific eligibility questions, and performing data checks (e.g., identification and potential removal of outliers) prior to analysis. Further, all data were self-reported, and eligibility as well as data accuracy were not independently verified by a clinician, which could introduce potential bias or inaccuracies. Although extensive, the data on economic burden is not comprehensive, as some components of direct and indirect costs are not covered. Data from this study were compared to published US general population scores, which may not fully reflect the normative population scores of participants from other countries (e.g., the UK, Italy, Germany, and France). However, the US population was chosen as a reference because it represents the largest proportion of our study sample. Furthermore, this study employed online surveys, which may have limited participation to people with internet access and potentially excluded some potential participants with low digital literacy. Moreover, comparisons to the general population, and use of MCIDs, were limited to US population values. Although these may vary across regions, considering the HRQoL impact of SCD in individuals with recurrent VOCs noted in this study, we would anticipate that similar differences if these data were compared to published information about general population scores from other countries.
Conclusions
SCD with recurrent VOCs is associated with significant impairments in HRQoL, as measured by multiple PROMs and bespoke questions. Most participants reported having difficulty paying for costs associated with managing SCD, and nearly half of participants experienced frequent financial distress due to out-of-pocket expenses. Overall, these survey results highlight the humanistic and economic burdens and unmet needs in adults with SCD and recurrent VOCs.
Acknowledgements
Medical writing was provided by Rosalba Satta, PhD, Jenifer Li, MSc, and Matthew Williams, PhD, and editing support was provided by Nicholas Strange of Complete HealthVizion, IPG Health Medical Communications, Chicago, IL, USA, funded by Vertex Pharmaceuticals Incorporated. This study would not have been possible without our patient advocacy group partners and survey participants living with sickle cell disease who kindly provided their time and shared their experiences.
Declarations
Ethical approval
Ethical approval was not required for this study and exemption for this study was granted by WIRB-Copernicus Group Institutional Review Board.
Consent to publish
The authors affirm that human research participants provided informed consent for publication.
Competing interests
Jennifer Drahos, Adriana Boateng-Kuffour, and Nanxin Li are employees of Vertex Pharmaceuticals Incorporated and may hold stock or stock options in the company. Melanie Calvert is Director of Birmingham Health Partners Centre for Regulatory Science and Innovation and Centre for Patient-Reported Outcomes Research and a National Institute for Health and Care Research (NIHR) senior investigator; has received funding from Anthony Nolan, European Regional Development Fund-Demand Hub and Health Data Research UK, Gilead, GlaxoSmithKline, Janssen, Macmillan Cancer Support, Merck, NIHR, NIHR ARC WM, NIHR Birmingham BRC, NIHR BTRU Precision and Cellular Therapeutics, UCB Pharma, UKRI, and UK SPINE; and has received consultancy fees from Aparito, Astellas, Boehringer Ingelheim, CIS Oncology, Daiichi Sankyo, Gilead, Glaukos, GlaxoSmithKline, HalfLoop, Merck, Patient-Centered Outcomes Research Institute, Pfizer, Takeda, and Vertex Pharmaceuticals Incorporated. Ashley Valentine has received consulting fees for Atlas Clarity Consulting Firm and Vertex Pharmaceuticals Incorporated; acted as Board of Director for IVI; and acted as an advisory board member for PCORI. Anthony Mason has received consulting fees for Vertex Pharmaceuticals Incorporated. Zahra Pakbaz has received research grants from Amgen, Forma Therapeutics, Global Blood Therapeutics, Novartis, Novo Nordisk, and Pfizer; received consulting fees from Agio, Alexion, Amgen, Dova, Global Blood Therapeutics, Novartis, Sobi, and Vertex Pharmaceuticals Incorporated; received speaker fees from Apalstic Anemia MDS Foundation and from Cayenne Wellness Center and Child Foundation, and acted as a CME course director for the Cayenne Wellness Center and Child Foundation and planning committee member for their annual education symposium; and received honorarium as a speaker from GBT, Agio, Sobi. Farrukh Shah has received research grants from IQVIA, Novartis Pharma AG, Pharmacosmos, and Vertex Pharmaceuticals Incorporated; received honoraria from Biologix FZ co, Bristol Myers Squibb, Chiesi Ltd, and Novartis Pharma AG; served as an advisory board or committee member for Agios, bluebird bio, Bristol Myers Squibb, Silence Therapeutics Plc, and Vertex Pharmaceuticals Incorporated; and acted as Chair for the UK Forum on Haemoglobin Disorders. Nick Ainsworth is an employee of QC Medica and Antony P. Martin is a partner of QC Medica who was funded by Vertex Pharmaceuticals Incorporated to perform this research.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.