Wearables and Digital Self-Reporting in Sickle Cell Disease | A Real-World Exploration of Novel Sleep and Patient-Reported Outcomes Insights.

It can be a disheartening landscape for patients with rare diseases, the emergence of new and innovative therapies where few, if any were available before often marred by the question: “will I have access?” Over the past 4 years alone, two novel therapies received initial approvals for treatment in sickle cell disease (SCD), and with them came a renewed hope for patients for whom existing options may already have been exhausted.

However, recent months have once again shed doubt on whether these treatments will ultimately be able to reach the wider patient populations that truly need them. Phase 3 trials of crizanlizumab have seen preliminary results that show no improvement in the rate of pain crises leading to healthcare contacts in comparison to the placebo group, despite positive results in a previous study. Similarly, NICE feedback for voxelotor was plagued by queries around the availability of real-world evidence that demonstrate how published improvements to haemoglobin levels translate to improvements in long-term outcomes, quality of life, and complications, as well as how this compares to current standards of care such as hydroxycarbamide and transfusion.

A common theme across not only these treatments, but many others in the rare disease pipeline, is the need to generate a greater depth and follow-up duration for the evidence base that supports their regulatory assessment. It is all too clear that there is a gap in the available data that urgently needs to be filled in order to meet the criteria for safe and cost-effective treatments, with direct measurements of improvement to patient wellbeing across multiple domains. 

As many of us in the rare disease space consider what we can do to help advance the therapeutic landscape and the patients these innovations are designed to support, a core question persists: how do we apply technology and optimised data capture to strengthen evidence bases in the face of such regulatory hurdles?

Enriching the knowledge base in rare diseases through real-world evidence.

Our recent work with the SCD clinical and patient communities has seen us drive research that addresses key missing gaps in what is known about the disease. Indeed, sleep is an area frequently flagged by patients and their care teams as an important factor in daily wellbeing and the potential onset of a pain crisis, and yet it remains under-described in the literature. While links between sleep quality and pain, quality of life (QoL), overall physical health, functional disability, and clinical depression have previously been reported, data surrounding the detailed impacts of specific sleep metrics remains limited in SCD. As a result, our recent work explored associations between such metrics and patient-reported outcomes as a first step in measuring any impact these may have on QoL.

To achieve this, we provided consenting patients who had joined the Sanius ecosystem with a clinically validated, CE-marked and FDA-cleared wearable monitoring device. This smartwatch was worn day and night, with automated capture of key biometrics. For the purposes of this particular piece of work, this focused on a number of sleep quality metrics and heart rate. Alongside this, patients were given access to a mobile app through which QoL-linked measures, the EQ-5D-5L instrument and basic 0-10 pain scores were manually self-reported via a digital patient-reported outcomes (PRO) portal.

For those patients with an overlap of available QoL metrics and sleep data, their mean values across the project period were compared to the rest of the patient group and stratified into low, average, or high categories. Across each of these categories, patients’ mean EQ-5D-5L scores were compared to identify any potential differences in QoL between them, supported by a direct correlation analysis of these sleep metrics and a number of key variables.

While a host of sleep metrics are indeed captured by the wearable, our analysis found that statistically significant differences in EQ-5D-5L were only seen when comparing different 'deep sleep' levels. Perhaps counterintuitively to what may have been assumed prior to this work, patients within the lower ranges of deep sleep (0-39%) in fact had significantly better EQ-5D-5L scores than those in the higher range (50-83%). Additional correlations identified a statistically significant link between increasing deep sleep levels and both decreasing haemoglobin (Hb) levels and increasing pain scores. As such, it is clear that further work will be critical in understanding the causality of these associations and whether there is value in their inclusion as future endpoints when exploring the impacts of different treatment pathways.

Overall, these insights highlighted clear associations between the levels of deep sleep in patients with SCD and their EQ-5D-5L, Hb levels, and pain scores. With a potential implication for longer periods of deep sleep in lower patient-perceived wellbeing, our key next steps with clinical and research colleagues will investigate any potential causal or confounding relationships, such as medication, and their role in our findings. As a key factor in better understanding the interplaying factors in patient health and their potential value in long-term monitoring, this next phase seeks to establish whether patients may enter longer periods of deep sleep as a result of poorer QoL, or whether it is an excess of deep sleep itself that impacts patient QoL in SCD.

Translation of real-world insights into disease management and therapeutic innovation.

Truly understanding what is happening to a patient after beginning a new treatment and the resulting impacts on their wellbeing, requires a depth of insight beyond what is often captured in early trials. Integrating methods for remote and more longitudinal monitoring is by no means a new one, but it remains a resource that is rarely fully utilised in the clinical trials and post-approvals space.

As we continue to work with patient communities to address the key unmet needs, our core focus is to ensure better outcomes for patients – a common thread being the need for new therapeutic options as part of their disease management. From ongoing collaborations with clinical and life science colleagues across the rare disease space in identifying the most appropriate endpoints for trial settings and the key drivers in predictive alert systems to supporting patients with a full wraparound support ecosystem, enrichment of the underlying knowledge base needed to facilitate this remains a central part of our work.

Each day, this grows what is available in terms of real-world evidence from the current limitations of clinic and follow-up point snapshots, into a single longitudinal ecosystem across multiple sources. Be it physiological wearable-collected metrics captured in real-time, the lived patient experience delivered by QoL-linked PROs, or the more traditional endpoints of healthcare utilisation from medical records, Sanius Health continues to support partners navigating the post-approval landscape with a greater depth of evidence from which to drive therapeutic innovation. We welcome anyone who wishes to know more about our ecosystem or how it could support you to contact us at info@saniushealth.com.