Sleep is a complex and multifaceted physiological process. In humans, not only is sleep required for survival, but a growing volume of research is revealing an important link between disordered or inadequate sleep and poor health outcomes. Sleep deficiency is associated with increased risk for cardiovascular¹ and metabolic diseases², cancer^3,4, immune functioning⁵, mood disorders⁶, neurodegenerative disorders⁷, accidents⁸, and social isolation⁹. This evidence has led to sleep being recognized as a central pillar of population health along with nutrition and exercise^10,11, underscoring its significance to our overall wellbeing.

Further, sleep problems are common comorbidities of many chronic conditions, such as chronic pain, obesity, Parkinson’s disease, Alzheimer’s disease, depression, neuromuscular disorders, cancer, and many more.

For example, patients with chronic pain reported fatigue and difficulty sleeping as a primary way their condition manifests as symptoms in their daily life. They describe a significant overlap between chronic pain and difficulty sleeping, with one participant sharing,

“My pain has kept me up at night for most of my adult life.”¹²

This is only one example of the significant and interwoven relationship between many chronic diseases and sleep disturbances. Overall, sleep is an increasingly common health problem in our society where approximately 35% of US adults are reported to sleep less than the AASM recommended 7 hours per night¹⁵.

Sleep is Overlooked in Clinical Trials

Given the importance of sleep to overall health and the prevalence of disordered or inadequate sleep, it’s surprising to see only a small percentage of clinical trials include sleep as an outcome measure. Of course, clinical trials that target sleep disorders or symptoms include sleep outcome measures. The most common sleep disorders include insomnia, narcolepsy, and sleep apnea. Sleep is often the core concept of interest in such trials and sleep measure(s) are positioned as the primary endpoints. However, clinical trials specifically focusing on sleep disorders only make up a small percentage of all trials conducted. Moreover, these trials could benefit from real-world sleep measures derived from wearable DHTs (which you can read more about in our recent white paper).

The scenario in which sleep should be included, but is largely overlooked, is clinical trials that target chronic diseases where sleep problems are well known to affect patients’ quality of life.

This mismatch between the clinical importance of sleep and its inclusion as a study outcome in clinical trials has recently been systematically examined in two chronic conditions: 

Knee Osteoarthritis: Feda et al¹⁶ studied this paucity of sleep outcomes in clinical trials in knee osteoarthritis (OA). Among the 926 randomized control trials conducted between 2000 and 2022, only 19 (2.1%) recorded some form of sleep assessment. This is an astonishingly low number given that multiple international guidelines have recommended knee OA clinical trials include sleep assessment as a core outcome due to the established relationship between sleep disturbances and pain¹⁷ and patients report sleep disturbance as a significant symptom with a daily impact on their lives¹⁸.

Major Depressive Disorder: Peerenboom et al¹⁹ advocate for a qualified digital outcome measure to provide sleep assessments in depressive disorder. As mentioned above, sleep is a core symptom contributing to the clinical diagnosis of depression, with 92% of patients reporting sleep disturbance as a symptom²⁰. When patients were asked about the impact of comorbid health conditions, sleep disorders were a prominent topic during the discussion, as patients indicated that management of sleep disorders such as sleep apnea and insomnia significantly impacted management of their depressive symptoms²¹.

These two recent publications are just two examples of how sleep is being overlooked in clinical trials. Other peer-reviewed articles have made similar recommendations to include sleep assessments in clinical trials for cancer^22,23, substance use disorder²⁴, and chronic low back pain²⁵.

Consistent with these reports in the peer-reviewed literature, our analysis of industry-sponsored Phase 2 and 3 trials on clinicaltrials.gov revealed that most of them do not include sleep outcomes. 

Over the decade between 2013 to 2023, sleep was assessed in only 3% of trials in osteoarthritis, 8% in chronic pain, 11% in Parkinson’s disease, and 16% in depressive disorder. Across all the chronic conditions we examined, sleep assessments were most common in fibromyalgia trials, but this still represented only one third of trials. Overall, only a small minority of clinical trials included sleep as an outcome measure.

By omitting sleep assessments from clinical trials, researchers are missing a valuable opportunity to demonstrate the value of their treatment interventions.¹⁶

Where Do We Go from Here?

In the case of sleep measures, decades of research have provided sufficient validation that at-home objective sleep assessments can be obtained via wearable devices at scale. Fit-for-purpose, medical-grade wearable DHTs provide the level of validation and compliance required by regulatory scrutiny, but just as any other tools, deploying them properly in clinical trials and care requires robust documentation of verification and validation, operational excellence, sound scientific rationale, and statistical rigor.

We strongly believe that wearable sleep assessments can help us gain insights into sleep wellbeing not only in sleep disorders, but also key aspects of quality of life in chronic conditions, closing the gap between what is being measured in clinical research and what is meaningful in patient’s everyday life.

For more information about measuring sleep in clinical trials using wearable devices, including an overview of the regulatory perspective, read our white paper, “Closing the Gap in Our Understanding of Sleep Health with Fit-For-Purpose Wearable Digital Health Technologies.”

References

1. Cappuccio, F. P., Cooper, D., D’Elia, L., Strazzullo, P. & Miller, M. A. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J 32, 1484–1492 (2011)
2. Luyster, F. S., Strollo, P. J., Zee, P. C. & Walsh, J. K. Sleep: A Health Imperative. Sleep 35, 727–734 (2012).
3. Wu, A. H. et al. Sleep duration, melatonin and breast cancer among Chinese women in Singapore. Carcinogenesis 29, 1244–1248 (2008).
4. Kakizaki, M. et al. Sleep duration and the risk of prostate cancer: the Ohsaki Cohort Study. Br J Cancer 99, 176–178 (2008).
5. Ranjbaran, Z. et al. Impact of sleep disturbances in inflammatory bowel disease. J Gastroenterol Hepatol 22, 1748–1753 (2007).
6. Lyall, L. M. et al. Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91 105 participants from the UK Biobank. Lancet Psychiatry 5, 507– 514 (2018).
7. Zhou, G. et al. High prevalence of sleep disorders and behavioral and psychological symptoms of dementia in late-onset Alzheimer disease. Medicine 98, e18405 (2019).
8. Williamson, A. et al. The link between fatigue and safety. Accid Anal Prev 43, 498–515 (2011).
9. Worley, S. L. The Extraordinary Importance of Sleep: The Detrimental Effects of Inadequate Sleep on Health and Public Safety Drive an Explosion of Sleep Research. P T 43, 758–763 (2018).
10. American Academy of Sleep Medicine. Sleep Well, Be Well: A national health priority. https:// sleepeducation.org/get-involved/campaigns/ sleep-well-be-well-a-national-health-priority/.
11. Perry, G. S., Patil, S. P. & Presley-Cantrell, L. R. Raising Awareness of Sleep as a Healthy Behavior. Prev Chronic Dis 10, 130081 (2013).
12. CDER & FDA. Chronic Pain: The Voice of the Patient: A Series of Reports from the U.S. Food and Drug Administration’s Patient-Focused Drug Development Initiative. https://www.fda.gov/ media/124390/download (2019).
13. Haroz, E. E. et al. How is depression experienced around the world? A systematic review of qualitative literature. Soc Sci Med 183, 151–162 (2017).
14. Tandberg, E., Larsen, J. P. & Karlsen, K. A community-based study of sleep disorders in patients with Parkinson’s disease. Movement Disorders 13, 895–899 (1998).
15. Centers for Disease Control and Prevention. CDC Behavioral Risk Factor Surveillance System (BRFSS). https://www.cdc.gov/sleep/data-andstatistics/adults.html (2020).
16. Feda, J., Miller, T., Young, J. L., Neilson, B. & Rhon, D. I. Measures of sleep are not routinely captured in trials assessing treatment outcomes in knee osteoarthritis - A scoping systematic review and call to action. Osteoarthr Cartil Open 5, 100400 (2023).
17. Dworkin, R. H. et al. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain 113, 9–19 (2005).
18. Arthritis Foundation. Osteoarthritis: The Voice of the Patient: A Summary Report from ExternallyLed Patient-Focused Drug Development Meeting. https://www.arthritis.org/science/ events-publications/oa-vop (2017).
19. Peerenboom, N. et al. The Case for the PatientCentric Development of Novel Digital Sleep Assessment Tools in Major Depressive Disorder. Digit Biomark 7, 124–131 (2023).
20. Geoffroy, P. A. et al. Insomnia and hypersomnia in major depressive episode: Prevalence, sociodemographic characteristics and psychiatric comorbidity in a population-based study. J Affect Disord 226, 132–141 (2018).
21. Foxworth, P. Report of the Externally-Led PatientFocused Medical Product Development Meeting on Major Depressive Disorder. https://www. dbsalliance.org/wp-content/uploads/2019/10/ final-Externally-led-VOPR.pdf (2019).
22. George, G. C. et al. Sleep quality and its association with fatigue, symptom burden, and mood in patients with advanced cancer in a clinic for early-phase oncology clinical trials. Cancer 122, 3401–3409 (2016).
23. Howell, D. et al. Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice. Annals of Oncology 25, 791– 800 (2014).
24. Huhn, A. S. et al. Patient-reported sleep outcomes in randomized-controlled trials in persons with substance use disorders: A systematic review. Drug Alcohol Depend 237, 109508 (2022).
25. Neilson, B. D., Dickerson, C., Young, J. L., Shepherd, M. H. & Rhon, D. I. Measures of sleep disturbance are not routinely captured in trials for chronic low back pain: a systematic scoping review of 282 trials. Journal of Clinical Sleep Medicine 19, 1961–1970 (2023).