A Scoping Review of Transition Interventions for Young Adults with Sickle Cell Disease

Abstract

Standardized programming for individuals with sickle cell disease (SCD) transitioning from pediatric to adult-centered care does not currently exist, resulting in high rates of mortality and morbidity. This scoping review examines and evaluates the current literature on SCD transition programs and interventions. Eligible studies described an existing program for individuals with SCD aged 12–29 years preparing to transition. The Evidence Project risk of bias tool was used to assess article quality. We identified 30 eligible articles, of which, only 2 were randomized controlled trials. Many studies have incomplete reports of feasibility information, such as completion rates, patient characteristics, and attrition; all studies were limited to a single institution; and most studies were rated high for risk of bias. Progress has been made in designing and gathering initial evaluation data for SCD transition programs; however, there is a need for higher quality studies, consistent assessment, and better dissemination of programs.

Introduction

Sickle cell disease (SCD) is an inherited blood disorder caused by a mutated gene that results in polymerization of red blood cells that distorts them into a crescent shape.¹ These red blood cells adhere to each other and block blood vessels, impeding the flow of oxygenated blood to parts of the body; and leading to infections, debilitating pain, and tissue and organ damage. Treatment regimens involve medications and chronic blood infusions to reduce stroke risk.¹ SCD affects approximately 100,000 individuals in the United States and is experienced by approximately 3 million people worldwide, with the majority of the burden of the disease occurring in sub-Saharan Africa and India.² Historically, individuals with SCD were not surviving into adulthood, but due to advancing medical options, over 95% of youth with SCD in the United States are now expected to reach adulthood.³ Therefore, work to ensure successful transition to adult care is essential.

For individuals managing SCD, the transition period is marked with several barriers, such as poor preparedness, differences between pediatric and adult health systems, and insurance changes.⁴ As adolescents with SCD age, they experience more disease progression; thereby requiring more specialized care.⁵ Notably, young adults aged 18–30 have higher rates of health care utilization and mortality compared to other age groups.^6,7 Further, there is a lack of adult providers familiar with the everyday management of SCD and poor infrastructure of the health care system limiting coordinated care, which is necessary as patients tend to experience end organ damage as they get older.⁸ Youth are not only transitioning their medical care but are experiencing other transitions in academic and vocational aspirations; family and social relationships; and independent living.

The 2011 joint statement from the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Physicians on transitioning of youth,⁹ and the creation of the Got Transition/National Center for Healthcare Improvement has spurred investigations about healthcare transition in all chronic illnesses.¹⁰ Global recommendations to support the transition process for youth with SCD transitioning to adult care (SICKLE recommendations) have been proposed.¹¹ These recommendations highlight six priorities: skills transfer, increasing self-efficacy, coordination of transition, knowledge transfer, linking to adult services, and evaluating readiness. Of note, these recommendations were generated based on consensus from a task force of experts from a multi-country consortium and not based on empirical evaluation of existing literature.¹¹ A 2013 systematic review of the literature searched for publications on transition to adult care for individuals with SCD, transition of other chronic diseases to identify potential alternative programs, and evidence-based guidelines and meta-analyses.¹² The search identified 23 publications and found that the majority (N=14) focused on barriers to care in SCD; and six examined the continuity of care of other chronic illnesses.¹² Three articles identified in the review focused on transition program development, components, and goals for individuals with SCD; but due to the early stage of development, program effectiveness and efficacy outcomes were not available.¹² Based on the systematic review results, the authors recommended a flexible, patient-centric transition plan to develop independence that includes caregivers and families, and pediatric and adult medical teams.¹² The authors also identified a need for more rigorous investigation of best practices in transition care.

Since this 2013 review, SCD transition programming and research has continued to expand, with a particular focus on transition program development and implementation. The purpose of this scoping review was to examine and evaluate the current literature on SCD programs and interventions designed to support the transition from pediatric to adult-centered care. This information is vital for establishing evidence-based guidelines and directing future research in this area.

Methods

Guided by the Scoping Review guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), a scoping review of the literature was conducted to identify studies that described programs or interventions for adolescents and young adults with SCD preparing to transition from pediatric to adult care. Databases (PubMed, PsychINFO, Web of Science) were searched from inception to October 2020. We combined Medical Subject Heading terms and free text words for sickle cell disease, sickle cell anemia, pediatric, adolescent, young adult, youth, transition, and transition readiness. In addition, reference lists and title pages from key journals were hand-searched for any additional references. The results of the search strategy are included in Figure 1.

Figure 1:

Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) flow diagram

Retrieved records were filtered for language (English) and subject (human). Studies were eligible if they reported or described an existing program or intervention designed specifically for individuals with SCD who were preparing to transition from pediatric to adult care. Participants of interest were between the ages of 12–29, defined as teenagers, adolescents, or young adults. For the purposes of this scoping review, full text manuscripts, development or protocol papers, and peer-reviewed conference abstracts were included. No attempt was made to locate unpublished studies. In instances where conference abstracts were published followed by a full-text manuscript, only the full-text publication was included in the review.

Two authors screened the titles, abstracts, and full texts of all studies identified during the search process (Figure 1). Any instances of disagreement were resolved through discussion. Data extraction was conducted by the authors to capture information of interest including sample characteristics, study design, study outcome (including feasibility if this was the stated primary outcome), and primary results of the study. In addition to data abstraction, article quality was assessed for risk of bias using the Evidence Project risk of bias tool. The Evidence Project risk of bias tool is a scoring system applicable for both randomized and non-randomized study designs. The tool includes a checklist of eight items, each of which is rated as either present (yes), not present (no), not reported, or not applicable. Ratings were completed independently by two authors and any disagreements were resolved by discussion.

To organize the review, we categorized publications by type of evidence including 1) development studies (i.e., those providing program descriptions but no evaluation data), 2) case series, 3) retrospective observational studies, 4) single arm, pre-post studies, and 5) randomized controlled trials (RCTs). We describe intervention/program components, order of development procedure/process of the intervention/program (if applicable) the target population, the setting where the program or intervention took place, any outcomes, and pertinent results of the interventions.

Results

Our search yielded 30 articles (4 conference abstracts and 26 full text manuscripts) referring to unique studies. Of these, 8 were papers describing the development of an intervention or program, 2 were case series, 7 were retrospective observational studies, 11 were single arm pre/post studies, and 2 were randomized clinical trials. All studies were conducted within a single institution. Details of included studies are reported in Table 1 and Supplementary Table 1.

Table 1.

Overview of development studies selected for review.

Reference	Intervention/Program	Order of Development Procedure/ Process	Results
Baskin (1998)	Psychoeducational group intervention	Literature review Application of Stress-Coping Model Program development	A group intervention was designed for AYA ages 16–21. The intervention includes 8 group sessions targeted to provide support and education.
Cerns (2013)	Pediatric SCD clinic based interdisciplinary team transition program (includes patient tours)	Inter-disciplinary team led program development	Patients and families report satisfaction with the tours Young adults indicated less apprehension about the transition as a result of the tours
Crosby (2017)	Mobile app	Acceptability surveys and interviews Co-creation sessions Prototype evaluation	Study included 5 AYA App was easy to use AYAs found the app beneficial for tracking health behaviors
Doulton (2010)	Pediatric SCD clinic transition program medication cards, preparation for transition binder, communication education	Community needs assessment Pediatric/adult provider collaboration Program development	At age 13 patients are given a transition binder. At 18 years transition is completed.
Kulandaivelu (2018)	Home-based digital self-management and transition program	Qualitative semi- structured interviews Focus groups with healthcare providers	Study included 19 participants (66% female) A digital self-management program should include disease–related education; guidance on developing self-advocacy and communication skills; and provide social support Features for better engagement should be considered
Melita (2019)	Community-based problem-solving education	Focus groups (needs and preferences) Adaptation of problem-solving education models	Study included 17 AYA Endorsed as an acceptable intervention Desired group problem-solving sessions
Porter (2017)	Programming within a pediatric SCD clinic	Focus groups (needs assessment) Program and tool evaluation Program refinement	Study included 14 AYA ages 12–18 years, 64.3% female Programs should include specific disease knowledge and self-management skills Patient-specific considerations should be made surrounding all transitions
Viola (2020)	Home-based mentor-led transition education	Needs assessment Program development and refinement (stakeholder feedback)	Study included 20 AYA over age 18, 70% female Needs and recommendations for programming aligned with the SMART framework. AYAs were receptive to working with a medical student mentor.

Development studies

Eight of the identified studies reported on the development of a transition program or intervention. Three of these studies did not include any outcome measures and simply described the development process and program description.^13–15 Most development processes followed a similar approach, which involved an initial needs assessment with the patient population, followed by iterative development involving providers and patient stakeholders. Only one study did not include patient input in the development process.¹⁴ Of the five studies that reported on development outcomes, three addressed the results of the needs assessment that led to program development^16–18 while two reported initial feasibility and usability data.^19,20

Needs assessments in the development process yielded similar results across studies, revealing needs including disease-specific knowledge, self-advocacy and communication skills, self-management skills, and more support regarding the transition process. Programs and interventions targeted these needs using different modalities, including group education,¹³ comprehensive multi-year transition programming,¹⁵ adult facility tours,¹⁴ a self-management mobile app,¹⁹ remote problem-solving skills training,²⁰ mentors,¹⁸ and a digital self-management program.¹⁷

Case series

Two studies were identified that reported the results of cases series.^21,22 One described the impact of a structured transition program on the health and transition outcomes of two patients.²² Based on the 6 principles of the GOT Transition guidelines, the transition program included a formal transition policy, a collaborative pain management plan, and quarterly multidisciplinary reviews of transitioning patients.²² The authors concluded that their approach of early involvement of a multi-disciplinary care team improved patient outcomes. The second case series described a community-based mentor program offered to recently transitioned adults to help with goal attainment and self-management.²¹ The case series only included two patients, and the authors reported that the program was not feasible as designed due to the low participation and interest of the patients.

Retrospective observational studies

Seven studies utilized historic cohorts to evaluate the impact of transition programs and interventions. Sample sizes from these studies were moderate, ranging from 34 to 112 participants receiving the new programs. Outcomes from these studies included measures of feasibility,^4,23 psychosocial outcomes (e.g., feelings and concerns about transition, disease knowledge),²⁴ and healthcare utilization measures (e.g., loss-to-follow-up, appointment attendance, and transfer).^23,25–28 Notably, all seven of these transition programs took place within a clinic setting. Four^24–27 utilized separate transition clinics, and three took place within the patient’s regular pediatric clinic appointments.^4,23,28 Of the retrospective studies, the programs described by Allemang²⁸ and Saulsberry⁴ demonstrated the highest quality of evidence. Allemang²⁸ found that a transition program with transition navigator reduced loss to follow up and improved medication adherence, while Saulsberry⁴ demonstrated increase in adult care matriculation and a decrease in care abandonment.

Single arm, pre/post studies

Eleven pre/post single arm studies were identified. Of these, four were primarily designed to assess feasibility of web modules,²⁹ virtual mentoring,³⁰ genetic education sessions,³¹ and online patient portal.³² Six studies assessed the impact of transition programs on psychosocial outcomes (self-efficacy, disease knowledge, transition readiness),^33–38 and one study looked at rate of transfer as a primary outcome.³⁹ Among the studies designed to test feasibility, four assessed the feasibility of electronic or mobile health-based programs, while the other two programs were conducted in-person. Both electronic and in-person interventions demonstrated high acceptability among participants. Only two studies reported completion rates, making it hard to compare rates of program completion among modalities. Four studies (one web-based and two in person) demonstrated improvements in disease knowledge post-intervention,^29,36–38 a program that utilized take-home worksheets demonstrated significant improvements in skill-building,³⁴ and a six-month transition navigator program increased transition readiness among participants.³⁶

Randomized controlled trials

Two randomized controlled trials were identified. The first was a conference abstract that provided the results of an intervention testing the impact of a 30-minute DVD and corresponding educational website compared to a CD containing educational music in thirty patients with SCD ages 12–21.⁴⁰ The authors reported that self-efficacy and knowledge did not increase with the age of the patient, and also reported difficulties with uptake of the program. The other study was a protocol paper for an RCT with no published results.⁴¹ The program is described as a hospital-based transition program to be delivered to patients when they are 16–17 years older. The authors hypothesize that those participating in the transition program will have lower rates of hospital admissions and emergency room visits, as well as demonstrate improvements in SCD knowledge and self-efficacy.

Quality of studies

Using the Evidence Project risk of bias tool, we found that the majority of studies demonstrated some potential risk of bias (see Table 2). However, this was largely attributed to the research design, with a large number of development, retrospective observational, and single arm, pre-post feasibility studies. Studies met the criteria for having a cohort if participants were followed over time pre-intervention to post-intervention or across multiple time points. Serial cross-sectional studies including different participants did not meet this criterion. Among the 30 studies included in this review, 16 studies included a cohort; five utilized a comparison or control group; and one reported on the equivalence of the groups by sociodemographic characteristics or outcomes at baseline. In regard to program retention, only two studies reported a follow-up rate of 80% or more, with a majority of studies not meeting (n = 3) or not reporting on this benchmark (n = 8).

Table 2.

Quality assessment of articles using the Evidence Project Risk of Bias Tool

	Cohort?	Control or comparison group?	Pre/post intervention data?	Random assignment of participants to the intervention?	Random selection of participants for assessment?	Follow-up rate of 80% or more?	Comparison groups equivalent on sociodemographics?	Comparison groups equivalent on outcomes at baseline?
Development Studies
Baskin (1998)	No	No	No	-	-	-	-	-
Cerns (2013)	No	No	No	-	-	-	-	-
Crosby (2017)	No	No	No	-	No	-	-	-
Doulton (2010)	No	No	No	-	-	-	-	-
Kulundaivelu (2018)	No	No	No	-	No	-	-	-
Melita (2019)	No	No	No	-	No	-	-	-
Porter (2017)	No	No	No	-	No	-	-	-
Viola (2020)	No	No	No	-	No	-	-	-
Case Series
Berg	Yes	No	Yes	-	No	-	-	-
Noronha	No	No	No	-	No	-	-	-
Retrospective Observational Cohort Studies
Allemang (2019)	Yes	Yes	Yes	No	No	N.R.	Yes	-
Andemariam (2014)	Yes	No	No	-	No	-	N.R.	-
Hankins (2012)	Yes	Yes	No	No	No	N.R.	N.R.	N.R.
Latzman (2011)	No	Yes	No	-	No	-	N.R.	-
Nolan (2018)	Yes	No	Yes	-	No	N.R.	-	-
Saulsberry (2019)	Yes	Yes	Yes	No	No	N.R.	N.R.	N.R
Single Arm, Pre-post Studies
Calhoun (2019)	Yes	No	Yes	No	No	No	-	-
Crosby (2017)	Yes	No	Yes	No	No	No	-	-
Griffin (2013)	Yes	No	Yes	No	No	N.R.	-	-
Kidwell (2019)	Yes	No	Yes	No	No	No	-	-
Rogers-Melnick (2017)	Yes	No	Yes	No	No	No	-	-
Porter (2014)	Yes	No	Yes	No	No	N.R.	-	-
Smith (2011)	Yes	No	Yes	-	No	N.R.	-	-
Smith (2019)	Yes	No	No	No	No	Yes	-	-
Saulsberry (2020)	Yes	No	No	-	No	-	-	-
Randomized Controlled Trials
Hoegy (2020)	Yes	Yes	Yes	Yes	No	N.R.	N.R.	N.R.

Note. N.R. = Not reported; “-“ = Not applicable

Note. Quality review was not conducted for conference abstracts.

Discussion

This scoping review builds on the work of a previous 2013 systematic review that focused on investigating the state of the literature on transition to adult care for individuals with SCD.¹² At that time, the majority of research was focused on identifying barriers to care transition, and there was a call for additional work on intervention and program development to aid in the transition process. The current scoping review was focused on reviewing the developing body of published research on SCD programs and interventions designed to support the transition from pediatric to adult-centered care. Results indicate that this topic is a growing area of research with 30 articles detailing unique programs since 2010. Notably, many programs are still in the early stages of evaluation, as the majority of studies were descriptive, retrospective observational, or single-arm pre/post studies. In addition, many of the published studies have incomplete reports of feasibility information such as completion rates, patient characteristics, and attrition; all studies were limited to a single institution; and most studies were low quality in relation to risk of bias.

However, despite limitations in this literature base, the results provide preliminary evidence concerning what modalities and components may be acceptable to individuals with SCD and promote certain transition outcomes. Specifically, facility tours, tailored education, and peer support were found acceptable to adolescents and young adults with SCD across studies. Both electronic and in-person interventions also demonstrated high acceptability among participants. Programs that were conducted within the same location and time of patient’s pediatric SCD appointments reported more significant improvements in healthcare utilization outcomes (e.g., transfer, loss to follow-up). As for the impact of the programs, both in person and within clinic programs demonstrated improvements in SCD knowledge. Of note, many of the studies that demonstrated improvements in knowledge tested for these effects immediately after the conclusion of the program; thus, limiting the ability to predict if this knowledge is lasting or how it will impact health behavior in the future.

Results should be interpreted with caution given the limitations with the studies included in the review and the variability among them. We found that the majority of studies demonstrated some potential risk of bias, which was largely due to research design issues. There were only two RCTs identified: a conference abstract and a protocol paper. The lack of RCTs weakens the evidence for any one program or its components. No research has been conducted to directly compare what types of program components are more effective than others; or to examine if specific program components are more or less effective given patient or health care setting characteristics, which would allow for the creation of targeted transition recommendations. Overall, this resulted in limited support for any one program or program component in relation to effectiveness for promoting transition.

The inconsistency in the measurement of disease-specific and non-disease-specific outcomes presents an additional challenge to evaluating these programs. There is currently no established consensus on appropriate benchmarks for a successful transition in SCD, though researchers are working to identify the most salient quality indicators.⁴² Of note, there are two published SCD-specific transition assessments: The Transition Intervention Program-Readiness for Transition⁴³ measure and The Sickle Cell Transition Intervention Program Skills Checklists^44,45; however, they are not regularly used. There is a need for consistent, standardized outcomes across studies to be able to compare effectiveness and make recommendations for best practices. Lastly, as mentioned previously, all studies included in this review were conducted at a single institution, and many failed to report on rates of attrition and/or lacked long-term follow-up data. Future studies need to be conducted across sites, provide clear information on attrition and possible factors impacting attrition, and collect and report long-term follow data to address issues of feasibility, effectiveness, and generalizability of interventions across populations and settings.

Beyond the areas mentioned above, our review highlighted the limited use of international¹¹ and national transition program frameworks¹⁰ to guide the development of transition programs for individuals with SCD. Only three of the identified programs used the Got Transition framework to design their programs.^4,22,39 Additionally, our review highlighted the need for better collaboration across sites to facilitate multisite studies. The American Society of Hematology SCD Clinical Network is a recently formed program designed to facilitate clinical trials across clinical sites and may be particularly useful for facilitating multisite RCTs focused on transition.⁴⁶ Clinically, our results indicate that there are many acceptable components that can be used to aid in the transition process; and based on outcome goals, there is also some information to help guide clinicians in choosing what program components may be particularly useful for their clinic population. To promote both more research in this area as well as clinical usefulness, more efforts should be focused on disseminating program details for those programs with solid preliminary evidence. This will allow researchers and clinicians to examine how to scale these programs appropriately given different resources and settings, patient characteristics, and barriers to care. Lastly, as highlighted by the few studies that did report retention rates, researcher and clinicians need to focus their efforts on addressing possible issues with attrition associated with transition programming. One avenue for doing so would be to partner with patients and other stakeholders to better identify and address factors contributing to attrition.

In conclusion, this study provides an updated summary of our knowledge of programs and interventions focused on SCD transition from pediatric to adult care, which is vital for establishing evidence-based guidelines and directing future research. Our findings indicate that there are a plethora of SCD intervention programs currently being implemented, and that these programs vary in components, modality, and quality of empirical evidence. Also, while progress has been made in designing and gathering initial evaluation data for SCD transition programs, there is a need for higher quality studies (i.e., randomized control trials); consistent assessment across intervention studies to allow for comparison; and better dissemination of programs across sites.

Abbreviations:

SCD

Sickle cell disease