Digital Health in Patients with Sickle Cell Disease

Sickle cell disease (SCD) is a disorder of red blood cells that is estimated to affect millions of people worldwide. It is an increasing global health problem; the number of live births with SCD is set to increase from 300,000 in 2010 to over 400,000 in 2050, making it the most common monogenetic disorder.

SCD is characterized by a mutation in the beta-globin gene that causes red blood cells to become sickle-shaped. It is a chronic debilitating illness that affects nearly every organ in the body. Complications including pain, stroke and organ failure are caused when these malformed sickled red blood cells pass through small blood vessels and become trapped.

The hallmark of SCD is pain. Many patients experience daily, chronic pain as well as intermittent, unpredictable acute painful episodes called vaso-occlusive crisis (VOC). VOCs are the leading cause of hospitalisations and emergency department visits for patients with SCD, with hospital stays sometimes lasting for weeks. Other serious complications include acute chest syndrome, pulmonary hypertension, cerebrovascular disease, and long-term end-organ damage. As well as costly healthcare burdens, these complications have a significant on patients’ health-related quality of life (HRQOL) due to the impact of mental health, social life, work and school.

Meeting a Growing Need

Patients with SCD are living longer than ever before and one of the growing challenges for the health care system is addressing the shift from acute to chronic disease management in this population. Providing care to patients with SCD is challenging, often including a complex and time-consuming regimen of daily medications and frequent healthcare contact. This presents a major logistical and healthcare burden on both the individual SCD and their caregivers.

Poor self-management of SCD is associated with increased health complications that require urgent and costly healthcare utilisation and worse HRQOL. A recent review of publications found high rates of low adherence to medications and clinic visits, as well as poor self-management skills among patients with SCD, across all ages. There is therefore an urgent unmet need for interventions and healthcare strategies to deliver effective SCD disease management, which also ameliorates the burden of care. One area of growing interest is the utility of digital health to improve care pathway management of patients with SCD, especially in children and young adults.

Digital health is a broad term that covers many different categories including mobile health, health information technology, wearable devices, telehealth and telemedicine, and personalized medicine. The use of digital technologies has become near-ubiquitous within households in the United States. Over 90% of the population under 44 years had access to broadband internet in 2018, including the majority of individuals with SCD. In addition, as of 2015, 96% of hospitals and 86% of physicians’ offices have adopted digital health records (EHR) and is likely to near 100% in 2022. The prevalent use of digital technology by healthcare providers, patients with SCD and their caregivers present opportunities to minimise barriers for access to healthcare, deliver interventions that promote self-management and optimise medication adherence, intervene before symptoms escalate, and ultimately improve overall health outcomes.

The aim of this narrative review is to briefly describe how digital health has been used to address the specific unmet needs of patients with SCD, identify gaps in the current literature and discuss possibilities for future work.

Three themes are included in this review: medication adherence, pain and symptom monitoring, and self-management and self-efficacy.

Medication Adherence

Medication adherence is associated with improved clinical outcomes and lower healthcare cost utilisation in patients with SCD. However, medication adherence is less than optimal. Non-adherence rates in SCD patients are reported to be 35-50%, compared to 25% in other chronic disease populations. Multiple reasons for medication non-adherence have been identified including; forgetfulness, concerns about side effects, lack of patient engagement, difficulties with obtaining refills, and perceived lack of efficacy.

Monitoring medication adherence, and identifying patients in need of an effective adherence intervention, are challenging. Established methods for monitoring adherence, including; pharmacy dispensing and insurance claims data, medication volume tracking, biomarkers and self-report surveys, have been found to be limited. Non-adherence to medication in patients with SCD can result in premature termination of therapy or inappropriate dosage increases, this limits therapeutic benefits and can also potentially increase the risk of toxicity. Therefore, accurate adherence data is required to ensure optimal care pathways and minimise healthcare costs.

Digital health medication adherence and monitoring tools include a combination; daily administration videos, electronic reminders and electronic medication tracking devices.

Daily administration videos, electronic reminders and messages from clinic staff have been used to support and reinforce medication adherence. Medication adherence measured by medication possession ratio (MPR) ranged from 0.67-0.91, whilst observed adherence ranged from 60% to 93%. Adherence increased in all interventions where it was measured, adding to the growing evidence that interventions that include daily administration videos can be used to increase medication adherence in patients with SCD. Anderson et al. also reported that participants that were compliant with the intervention had significantly better SCD-related functioning compared to non-completers (P<0.05).

A randomised trial conducted by Pernell et al found that using text messages alone improved medication adherence scores significantly in the intervention arm (P=0.002), but not the control (P=0.08). These findings are supported by another feasibility study that found that although text reminders alone did not result in significant improvements in MPR (P=0.86) or hospitalisations (P=0.79), participants improved laboratory parameters (P<0.05) and decreased clinic visits persisting for a year.

Electronic medication tracking devices can be used to measure adherence. Ingerski et al found that adherence using the device was 72%, lower than MPR (87%) and self-report (94%), but higher than pill count (26%), however, Inoue et al reported a concordant medication adherence rate of 85% for both electronic medication device and MPRs. In addition, Ingerski et al also found that in general participants lab values improved over the intervention. Whilst medication tracking devices provide a novel means of adherence measurement for clinical and research use in patients with SCD, further research is required to understand differences in medication tracking methodologies.  

Pain and Symptom Monitoring

Digital health has increasingly become an integral part of healthcare management assisting in the documentation of symptoms in SCD patients including; e-diaries, mobile phone apps, and wearable devices to record objective physiological metrics.

Currently, there is no cure for SCD and treatment is considered palliative. Approximately 90% of acute care visits are for pain events and the main therapeutic goal is to reduce VOCs and avoid hospitalisation.  

Effective monitoring and managing patient symptoms, including pain, is important to improve patient outcomes and avoid preventable healthcare utilisation. Traditional methods for reporting patient symptoms are recorded through paper diaries are associated with poor compliance and unreliable data. Recording pain electronically in patients with SCD have been associated with improved compliance (P<0.01), and reduced data entry errors and omissions (P<0.01). It is also reported to be well correlated with traditional paper VAS (ICC = 0.97%, 95% CI 0.92%–0.99%). In addition, subjective pain recorded using mobile phone apps have been developed into a predictive model that forecasts in patients with SCD in the community. These insights could be used to develop optimized, data-driven decisions balancing medication and pain for the patient in real-time.

The use of mobile technology is potentially an efficient method for measuring health outcomes, engaging participants in self-management interventions, and enabling timely communication between patients and healthcare providers. A major benefit of mobile phone applications is the automatic transfer of data which allows for early interventions in terms of screening, early detection and prevention of pain and symptoms.

Subjective pain measurements can be time-consuming and intrusive to patients, physiological measures of pain are easier to collect, cheaper and more consistent. These measures can include blood pressure, respiratory rate, oxygen saturation, temperature, pulse, and activity. Changes to vital signs have been reported to be correlated with acute pain. The collection of these physiological measures over time could lead to a richer understanding of pain, the causes of pain and can ultimately be used in pain forecasting models.

Digital wearable technology allows non-invasive monitoring of body movement and physiological signals in real-time, and can be used for automatic pain assessment, improved pain management, provide more personalised care for patients with SCD. Yang et al. and Johnson et al. demonstrated the feasibility of using physiologic measurements obtained from wearables to accurately predict patient-related pain scores in the acute setting.

The numerous healthcare visits associated with SCD has led to an abundance of EHR data, that can be leveraged to investigate relationships between SCD patient outcomes, including acute pain and organ failure. Several studies have demonstrated the feasibility of developing accurate predictive pain models using physiological data recorded in EHR. Mohammed et al leveraged machine learning techniques to accurately predict the development of organ failure SCD patients up to six hours before onset. These findings are significant because the early recognition of SCD complications in acute settings allows for more effective care pathway management and the implementation of earlier interventions.

Self-Management and Self-Efficacy

Living with a chronic condition like SCD requires the patient to have adequate self-management and self-efficacy skills, and to be an informed and active participant in their care. Poor self-management can precipitate health complications that require urgent and costly treatments. Previous research indicates that often adolescents and young adults with SCD lack the ability, confidence, and skills to manage their disease effectively.

Mobile health-based interventions that focus on improved self-management and self-efficacy have demonstrated promising feasibility and acceptability, especially in children transitioning into adulthood. These interventions are often multifaceted and include education modules, pain and symptom logging, as well as health coaching and formative feedback. Results from the SCThrive and ITP studies found that participants who engaged in these self-management and self-efficacy interventions demonstrated significantly better SCD-related functioning (P<0.05)). However, engagement in these interventions was variable. Further research is needed to understand how to effectively engage patients with SCD in these types of interventions, especially in adolescents and young adults.

Current standards of pain management primarily focus on the use of opioids, despite evidence of negative physical and psychological consequences associated with long term use in patients with SCD. Cognitive behavioural therapy (CBT) in adjunct to standard care that promotes pain self-management can lead to pain reduction, improved coping skills and HRQOL, and decreased healthcare utility for patients with chronic illness.

A major barrier to implementing CBT based interventions is access to office-based clinics (Barakat 2010). Mobile health-based interventions enable care providers to potentially overcome this barrier. In a randomised trial using the SMART mobile app, SCD patients using reported a marginal decrease in depression (P=0.06) and improved daily pain (P=0.014), however, no significant effects were found for anxiety. These results are supported by Schatz et al who reported that using CBT on days with higher pain was associated with reductions in next-day pain intensity. Guided audio-visual relaxation using mobile apps have also been found to be a promising self-management tool for patients with SCD and have been reported to significantly reduce immediate stress and pain compared to control groups.  

Key Findings

Digital health is increasingly being used in the management of SCD across a range of domains. Many of these interventions measured a variety of outcomes, which showed improvement across multiple components. Key benefits of digital health-based interventions in patients with SCD, compared to traditional methodologies included; reduced access barriers, less intrusive measurement techniques, and opportunities for health coaching and formative feedback. Evidence suggests there is significant promise for improving medication adherence, symptom control, self-management and efficacy using digital health in SCD. Furthermore, the development of predictive pain models and real-time patient feedback presents opportunities for more proactive interventions by both clinicians and SCD patients.

Many interventions were limited in sample size, conducted in the United States, and were mainly focused on children and adolescents. This limits the generalisability of inferences that can be gained from these studies.  In addition, many studies included multiple components that make it difficult to unravel the influence of specific components, otherwise known as confounding effects. Larger studies with strong study design, in more generalisable populations, are therefore required to establish the efficacy of these interventions.

Another challenge found with digital health interventions was maintaining long-term engagement. Many studies reported improved SCD-related outcomes, but only in patients who engaged with the intervention. Future studies should consider strategies to maximise engagement, including differentiating interventions to meet participants specific needs and involving participants in decision-making processes.

The use of wearable technology is a reliable and unobtrusive method of collecting objective outcomes in SCD patients to measure pain. However, many studies still rely on traditional subjective measurements. Furthermore, most studies that used physiological measures collected data in healthcare settings, after the pain had escalated. Only one study was found to collect objective measures in the community to predict pain. Accurately predicting pain in the community, has the potential to empower both patients and clinicians to adjust care pathways and mitigate pain, before the point of crisis. This has the potential to improve patient outcomes and avoid costly healthcare utility.

The widespread availability and frequent use of digital technology presents an opportunity to deliver interventions that promote better outcomes in patients with SCD. Given the increased risk of health complications that require urgent and costly healthcare utilisation in patients with SCD, there is a significant unmet need for digital health interventions to improve patients’ outcomes. However,  larger-scale interventions in populations representative of the socio-economic spectrum of SCD patients are required to establish efficacy and inform future health policy regarding the future of digital health care solutions in SCD globally.