Specifying sickle cell disease interventions: A study protocol of the Sickle Cell Disease Implementation Consortium (SCDIC)

Abstract Background Sickle cell disease (SCD) is an inherited blood disorder that results in a lifetime of anemia, severe pain, and end-organ damage that can lead to premature mortality. While the SCD field has made major medical advances, much needs to be done to improve the quality of care for people with SCD. This study capitalizes on the Sickle Cell Disease Implementation Consortium (SCDIC), a consortium of eight academic sites aiming to test implementation strategies that could lead to more accelerated application of the NHLBI guidelines for treating SCD. This report documents the process to support the consortium by specifying the interventions being developed. Methods This study consists of three steps. The Principal Investigator of each site and two site representatives who are knowledgeable of the intervention (e.g., study coordinator or the person delivering the intervention) will answer an online survey aiming to capture components of the interventions. This survey will be completed by the site representatives three times during the study: during the development of the interventions, after one year of the interventions being implemented, and at the end of this study (after 2 years). A site visit and semi-structured interview (Step 2) in the first year of the process will capture the context of the sites. Step 3 comprises of the development of a framework with the details of the multi-component SCDIC interventions at the sites. Discussion The outcome of this study, a framework of the SCDIC, will enable accurate replication and extension of published research, facilitating the translation of SCD studies to diverse populations and settings and allowing for theory testing of the effects of the intervention components across studies in different contexts and for different populations. Trial registration ClinicalTrial.Gov (#NCT03380351). Registered December 21, 2017

Impact of the COVID-19 pandemic on the implementation of mobile health to improve the uptake of hydroxyurea in patients with sickle cell disease: Mixed methods study

BACKGROUND: Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. OBJECTIVE: We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. METHODS: The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients\u27 daily app use. Adherence to hydroxyurea was calculated as the proportion of days covered (PDC) from prescription records over the first 12 and 24 weeks after implementation. A linear model examined the relationship between app usage and PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured interviews with patients, health care providers, administrators, and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed methods approach to investigate the convergence of qualitative and quantitative findings. RESULTS: The percentage of patients accessing the app decreased after March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: -8.2%; P=.14; 24 weeks: -10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B\u27s closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. CONCLUSIONS: We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may insulate the implementation of interventions to increase medication adherence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/16319

Identifying barriers to evidence-based care for sickle cell disease: Results from the Sickle Cell Disease Implementation Consortium cross-sectional survey of healthcare providers in the USA

OBJECTIVES: Sickle cell disease (SCD) leads to chronic and acute complications that require specialised care to manage symptoms and optimise clinical results. The National Heart Lung and Blood Institute (NHLBI) evidence-based guidelines assist providers in caring for individuals with SCD, but adoption of these guidelines by providers has not been optimal. The objective of this study was to identify barriers to treating individuals with SCD. METHODS: The SCD Implementation Consortium aimed to investigate the perception and level of comfort of providers regarding evidence-based care by surveying providers in the regions of six clinical centres across the USA, focusing on non-emergency care from the providers\u27 perspective. RESULTS: Respondents included 105 providers delivering clinical care for individuals with SCD. Areas of practice were most frequently paediatrics (24%) or haematology/SCD specialist (24%). The majority (77%) reported that they were comfortable managing acute pain episodes while 63% expressed comfort with managing chronic pain. Haematologists and SCD specialists showed higher comfort levels prescribing opioids (100% vs 67%, p=0.004) and managing care with hydroxyurea (90% vs 51%, p=0.005) compared with non-haematology providers. Approximately 33% of providers were unaware of the 2014 NHLBI guidelines. Nearly 63% of providers felt patients\u27 medical needs were addressed while only 22% felt their mental health needs were met. CONCLUSIONS: A substantial number of providers did not know about NHLBI\u27s SCD care guidelines. Barriers to providing care for patients with SCD were influenced by providers\u27 specialty, training and practice setting. Increasing provider knowledge could improve hydroxyurea utilisation, pain management and mental health support

What does it mean to be affiliated with care?: Delphi consensus on the definition of unaffiliation and specialist in sickle cell disease

Accruing evidence reveals best practices for how to help individuals living with Sickle Cell Disease (SCD); yet, the implementation of these evidence-based practices in healthcare settings is lacking. The Sickle Cell Disease Implementation Consortium (SCDIC) is a national consortium that uses implementation science to identify and address barriers to care in SCD. The SCDIC seeks to understand how and why patients become unaffiliated from care and determine strategies to identify and connect patients to care. A challenge, however, is the lack of agreed-upon definition for what it means to be unaffiliated and what it means to be a SCD expert provider . In this study, we conducted a Delphi process to obtain expert consensus on what it means to be an unaffiliated patient with SCD and to define an SCD specialist, as no standard definition is available. Twenty-eight SCD experts participated in three rounds of questions. Consensus was defined as 80% or more of respondents agreeing. Experts reached consensus that an individual with SCD who is unaffiliated from care is someone who has not been seen by a sickle cell specialist in at least a year. A sickle cell specialist was defined as someone with knowledge and experience in SCD. Having knowledge means: being knowledgeable of the 2014 NIH Guidelines, Evidence-Based Management of SCD , trained in hydroxyurea management and transfusions, trained on screening for organ damage in SCD, trained in pain management and on SCD emergencies, and is aware of psychosocial and cognitive issues in SCD. Experiences that are expected of a SCD specialist include experience working with SCD patients, mentored by a SCD specialist, regular attendance at SCD conferences, and obtains continuing medical education on SCD every 2 years. The results have strong implications for future research, practice, and policy related to SCD by helping to lay a foundation for an new area of research (e.g., to identify subpopulations of unaffiliation and targeted interventions) and policies that support reaffiliation and increase accessibility to quality care

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model.

PURPOSE: To examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains. METHODS: Participants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare. RESULTS: Higher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02-1.10, 95% CI range [1.004-1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58-3.28 95% CI range [1.18-4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46-0.64, 95% CI range [0.34-0.86]). CONCLUSIONS: Study results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes

Examining mental health, education, employment, and pain in sickle cell disease

IMPORTANCE: Pain related to sickle cell disease (SCD) is complex and associated with social determinants of health. Emotional and stress-related effects of SCD impact daily quality of life and the frequency and severity of pain. OBJECTIVE: To explore the association of educational attainment, employment status, and mental health with pain episode frequency and severity among individuals with SCD. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional analysis of patient registry data collected at baseline (2017-2018) from patients treated at 8 sites of the US Sickle Cell Disease Implementation Consortium. Data analysis was performed from September 2020 to March 2022. MAIN OUTCOMES AND MEASURES: Electronic medical record abstraction and a participant survey provided demographic data, mental health diagnosis, and Adult Sickle Cell Quality of Life Measurement Information System pain scores. Multivariable regression was used to examine the associations of education, employment, and mental health with the main outcomes (pain frequency and pain severity). RESULTS: The study enrolled a total of 2264 participants aged 15 to 45 years (mean [SD] age, 27.9 [7.9] years; 1272 female participants [56.2%]) with SCD. Nearly one-half of the participant sample reported taking daily pain medication (1057 participants [47.0%]) and/or hydroxyurea use (1091 participants [49.2%]), 627 participants (28.0%) received regular blood transfusion, 457 (20.0%) had a depression diagnosis confirmed by medical record abstraction, 1789 (79.8%) reported severe pain (rated most recent pain crises as ≥7 out of 10), and 1078 (47.8%) reported more than 4 pain episodes in the prior 12 months. The mean (SD) pain frequency and severity t scores for the sample were 48.6 (11.4) and 50.3 (10.1), respectively. Educational attainment and income were not associated with increased pain frequency or severity. Unemployment (β, 2.13; 95% CI, 0.99 to 3.23; P \u3c .001) and female sex (β, 1.78; 95% CI, 0.80 to 2.76; P \u3c .001) were associated with increased pain frequency. Age younger than 18 years was inversely associated with pain frequency (β, -5.72; 95% CI, -7.72 to -3.72; P \u3c .001) and pain severity (β, 5.10; 95% CI, -6.70 to -3.51; P \u3c .001). Depression was associated with increased pain frequency (β, 2.18; 95% CI, 1.04 to 3.31; P \u3c .001) but not pain severity. Hydroxyurea use was associated with increased pain severity (β, 1.36; 95% CI, 0.47 to 2.24; P = .003), and daily use of pain medication was associated with both increased pain frequency (β, 6.29; 95% CI, 5.28 to 7.31; P \u3c .001) and pain severity (β, 2.87; 95% CI, 1.95 to 3.80; P \u3c .001). CONCLUSIONS AND RELEVANCE: These findings suggest that employment status, sex, age, and depression are associated with pain frequency among patients with SCD. Depression screening for these patients is warranted, especially among those experiencing higher pain frequency and severity. Comprehensive treatment and pain reduction must consider the full experiences of patients with SCD, including impacts on mental health

An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model.

PurposeTo examine the relations between patient-reported outcomes (PROs) within a conceptual model for adults with sickle cell disease (SCD) ages 18 - 45 years enrolled in the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) registry. We hypothesized that patient and SCD-related factors, particularly pain, and barriers to care would independently contribute to functioning as measured using PRO domains.MethodsParticipants (N = 2054) completed a 48-item survey including socio-demographics and PRO measures, e.g., social functioning, pain impact, emotional distress, and cognitive functioning. Participants reported on lifetime SCD complications, pain episode frequency and severity, and barriers to healthcare.ResultsHigher pain frequency was associated with higher odds of worse outcomes in all PRO domains, controlling for age, gender and site (OR range 1.02-1.10, 95% CI range [1.004-1.12]). Reported history of treatment for depression was associated with 5 of 7 PRO measures (OR range 1.58-3.28 95% CI range [1.18-4.32]). Fewer individual barriers to care and fewer SCD complications were associated with better outcomes in the emotion domain (OR range 0.46-0.64, 95% CI range [0.34-0.86]).ConclusionsStudy results highlight the importance of the biopsychosocial model to enhance understanding of the needs of this complex population, and to design multi-dimensional approaches for providing more effective interventions to improve outcomes

Pregnancy outcomes with hydroxyurea use in women with sickle cell disease

Hydroxyurea reduces pain crises, acute chest syndrome, and blood transfusions in sickle cell disease (SCD), but potential detrimental effects on fertility and birth outcomes impede its use. Data on the effects of hydroxyurea taken for SCD during conception and pregnancy are scarce. The Sickle Cell Disease Implementation Consortium collected self-reported pregnancy history, corresponding hydroxyurea use, and pregnancy outcomes in women with SCD in the clinical setting. Among 1285 women 18-45 years of age, 737 (57.4%) reported 1788 pregnancies (1079 live births, 394 miscarriages, 40 stillbirths, 207 abortions, 48 current pregnancies, and 20 missing outcomes) of which 241 (15.9%) live births, miscarriages or stillbirths were conceived while on hydroxyurea. In univariate analyses, pregnancy number more than three, severe sickle genotype, history of stillbirth or miscarriage, and chronic kidney disease at enrollment were covariates significantly associated with a pregnancy ending in miscarriage or stillbirth. After adjustment for covariates and additional SCD severity markers in multivariate analyses, hydroxyurea use during conception and pregnancy, but not during conception only, was associated with an increase in the odds ratio (OR) of miscarriage or stillbirth (OR 2.21, 95% confidence interval [CI] 1.40-3.47). In analyses of live birth outcomes, hydroxyurea use during conception and pregnancy was associated with birth weight < 5.5 pounds in full-term infants (OR 2.98, 95% CI 1.09-7.38) but not with prematurity or serious medical problems at birth. These findings suggest that hydroxyurea use may be safe up to the time of conception, but that clinicians should continue to advise caution regarding use during pregnancy

What does it mean to be affiliated with care?: Delphi consensus on the definition of "unaffiliation" and "specialist" in sickle cell disease.

Accruing evidence reveals best practices for how to help individuals living with Sickle Cell Disease (SCD); yet, the implementation of these evidence-based practices in healthcare settings is lacking. The Sickle Cell Disease Implementation Consortium (SCDIC) is a national consortium that uses implementation science to identify and address barriers to care in SCD. The SCDIC seeks to understand how and why patients become unaffiliated from care and determine strategies to identify and connect patients to care. A challenge, however, is the lack of agreed-upon definition for what it means to be unaffiliated and what it means to be a "SCD expert provider". In this study, we conducted a Delphi process to obtain expert consensus on what it means to be an "unaffiliated patient" with SCD and to define an "SCD specialist," as no standard definition is available. Twenty-eight SCD experts participated in three rounds of questions. Consensus was defined as 80% or more of respondents agreeing. Experts reached consensus that an individual with SCD who is unaffiliated from care is "someone who has not been seen by a sickle cell specialist in at least a year." A sickle cell specialist was defined as someone with knowledge and experience in SCD. Having "knowledge" means: being knowledgeable of the 2014 NIH Guidelines, "Evidence-Based Management of SCD", trained in hydroxyurea management and transfusions, trained on screening for organ damage in SCD, trained in pain management and on SCD emergencies, and is aware of psychosocial and cognitive issues in SCD. Experiences that are expected of a SCD specialist include experience working with SCD patients, mentored by a SCD specialist, regular attendance at SCD conferences, and obtains continuing medical education on SCD every 2 years." The results have strong implications for future research, practice, and policy related to SCD by helping to lay a foundation for an new area of research (e.g., to identify subpopulations of unaffiliation and targeted interventions) and policies that support reaffiliation and increase accessibility to quality care

Evaluating the implementation of a multi-level mHealth study to improve hydroxyurea utilization in sickle cell disease

BackgroundSickle Cell Disease (SCD) is a progressive genetic disease that causes organ damage and reduces longevity. Hydroxyurea is an underutilized evidence-based medication that reduces complications and improves survival in SCD. In a multi-site clinical trial, part of the NIH-funded Sickle Cell Disease Implementation Consortium (SCDIC), we evaluate the implementation of a multi-level and multi-component mobile health (mHealth) patient and provider intervention to target the determinants and context of low hydroxyurea use. Given the complexity of the intervention and contextual variability in its implementation, we combined different behavioral and implementation theories, models, and frameworks to facilitate the evaluation of the intervention implementation. In this report, we describe engagement with stakeholders, planning of the implementation process, and final analytical plan to evaluate the implementation outcomes.MethodsDuring 19 meetings, a 16-member multidisciplinary SCDIC implementation team created, conceived, and implemented a project that utilized Intervention Mapping to guide designing an intervention and its evaluation plan. The process included five steps: (1) needs assessment of low hydroxyurea utilization, (2) conceptual framework development, (3) intervention design process, (4) selection of models and frameworks, and (5) designing evaluation of the intervention implementation.ResultsBehavioral theories guided the needs assessment and the design of the multi-level mHealth intervention. In designing the evaluation approach, we combined two implementation frameworks to best account for the contextual complexity at the organizational, provider, and patient levels: (1) the Consolidated Framework for Implementation Research (CFIR) that details barriers and facilitators to implementing the mHealth intervention at multiple levels (users, organization, intervention characteristics, broader community), and (2) the Technology Acceptance Model (TAM), a conceptual model specific for explaining the intent to use new information technology (including mHealth). The Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM) framework was used to measure the outcomes.DiscussionOur research project can serve as a case study of a potential approach to combining different models/frameworks to help organize and plan the evaluation of interventions to increase medication adherence. The description of our process may serve as a blueprint for future studies developing and testing new strategies to foster evidence-based treatments for individuals living with SCD