Mathini Ilancheran

	An actigraph is a wrist-worn activity monitor that is used to monitor movement, and sleep and wake patterns over an extended time period. They are used in clinical trials to evaluate medication sleep side effects among sleep disorders such as insomnia, sleep apnea, etc. They are typically a wearable device that falls under the diagnostic device category. 

	Actigraphs are typically worn around the wrist of the non-dominant arm, although there are several cases in which actigraphs can be worn around the ankle. Modern actigraphs have accelerometers built into their circuitry that detect movement. These detections are sampled several times per second and saved in storage bins called epochs. Epoch capacity (typically one minute) and memory size dictate the length of time that the actigraph is able to record.

	As per the view of Gary K. Zammit, PhD, President & CEO of Clinilabs*, the science of activity monitoring, actigraphy, has been around for decades and has been used to assess sleep and daytime activity levels (agitation, hyperactivity, daytime somnolence). The first commercial device came into clinical use in the late 1980s when Ambulatory Monitoring, Inc. introduced the original model Motionlogger®. The device was about the size and weight of a deck of cards and was attached to the wrist with two straps. This product used a sophisticated piezoelectric motion sensor, which had to be properly tuned in the manufacturing process. Now that accelerometers have become inexpensive and plentiful (they’re in every car airbag system to sense impacts and every smartphone that allows the screen orientation to change with position), the technology has been miniaturized and the market is being flooded with a multitude of activity recording wearables. However, not all actigraphy devices are the same, and it is critically important that reliable, validated systems are placed into use in the context of drug development.

	Along with cardiac and ECG monitoring devices, there is a need for continuous sleep and activity monitors during clinical trials. Actigraphs impact on clinical research has been significant. It has become a valuable resource as it provides information about a subject’s movement activity during the day, which may be pertinent to therapeutic outcomes. A reliable objective scale representing disease severity is necessary for appropriate management of these disorders. The International Classification of Sleep Disorders (ICSD-II) requires a clinical interview combined with video polysomnography (video-PSG) to diagnose. Video-PSG is time consuming and expensive and not always feasible in clinical practice. Whereas, wearable accelerometers such as actigraphs enable long-term recording of a patient’s patterns during daily activities and, hence, regarded as the best choice for quantitative assessment of the disease symptoms.

Actigraphs are widely utilized in behaviorial and mental disorders, neurological diseases such as Parkinson’s disease, Alzheimer’s disease and, cerebral infarction, seasonal affective disorder, restless leg syndrome, vascular dementia and also sleep disorders related to abnormal activity symptoms. It is necessary to evaluate the severity or the effects of drugs to treat these diseases in clinical practice.

 For example, studies of investigational drugs being evaluated for movement disorders such as Parkinson’s disease, or agitation associated with conditions like anxiety or dementia may utilize actigraphy as a hard measure of movement activity. Actigraphy also is a reliable middle ground between the inexpensive/inaccurate patient sleep diary and the costly night(s) in a sleep laboratory. It can provide objective, validated estimates of sleep at a fraction of the cost. Finally, actigraphy also has the value of providing information about activity and sleep in a subject’s own, real-world environment. The ease of use and high subject compliance allow for long-term outcome studies and repeat tests, which is something very costly or impossible to do with other technologies.

	The figure below shows the distribution of clinical studies utilizing actigraph by therapeutic area. It is evident that majority of the studies are being conducted within the behaviorial and mental disorders patients, followed by nervous system diseases.

	Out of the $1.994 billion global device market for sleep research, actigraphy devices contribute to an approximate share of $588 million in 2015, growing at a year-on-year CAGR of 7% until 2019.

	The growth of this market is a result of increased portability, mobility coupled with effective diagnosis. Within the sleep research devices market, actigraphy systems or devices is anticipated to grow at the highest CAGR of greater than 7% through the 2013--2019 period compared to other devices. The key reason for growth is the compact nature of these devices with increased portability hence supporting home testing with high reliability. The design in the form of a wrist watch also drives the most unobtrusive patient experience during trials with the ability to wear for weeks or months.

	Actigraphy as a technology is utilized mostly within the developed markets of North America and Europe. This eventually relates to use of actigraph for clinical studies in North America at 63% followed by Europe at 22%. Asia is still lagging in terms of usage of such technology during a clinical trial conduct

The figure below shows the distribution of clinical studies utilizing actigraph globally.

	Choosing an Actigraph for Clinical Trials

	While the risk to the patient using actigraphy is extremely low (possibility of mild skin irritation from the band, or mild social embarrassment due to the presence of the monitor), there is significant risk to the study in general if the wrong actigraph monitor is chosen; commented Zammit. The marketing of the new class of wearables or “sleep trackers” has left the general public under the impression that these devices have an acceptable level of accuracy. In general, this is certainly not true. Consumer sleep trackers come with no validity studies demonstrating their ability to correctly identify minutes of sleep or wake and are not FDA cleared to be marketed as a medical device. The other misconception is that all FDA-cleared actigraphs provide the same level of accuracy. This is also not true. FDA sets the bar very low when establishing “equivalency” to other FDA cleared devices. Even the most insensitive actigraph can do a good job detecting sleep (validation studies refer to this as the devices “sensitivity”) since it involves the ability to detect absence of motion. High levels of accuracy can be achieved in normal populations since they sleep through the night. However, the ability to detect small periods of wakefulness within a typical night (validation studies refer to this as the devices “specificity”) is much more difficult and many FDA-cleared devices do quite a poor job of this in sleep disturbed populations. It is recommended to always ask a potential actigraph provider for validation studies showing sensitivity and specificity values for night time sleep periods (some providers base their statistics over 24-hour periods which makes accuracy measures seem better due to the preponderance of easily-identified daytime wakefulness they are including in their calculations) in populations that include sleep disturbed individuals (normal subjects are easy to score accurately since they contain few awakenings). Also, checking with the provider to see if they have any validity papers in your target population is advised.

	Actigraphy has immense and untapped value in clinical drug development. It can be used to screen or assess subjects’ activity in trials conducted in multiple therapeutic areas. These areas include, but are not limited to affective disorders (e.g., psychomotor retardation in depression), fatigue, pain, cough, itch, attention deficit disorder, movement disorders, and sleep disorders. In each case, actigraphy provides objective data that complement other objective or self-report data collected in a clinical trial. Actigraphy data also may aid in the interpretation of therapeutic outcomes. For example, did an investigational drug reduce blood pressure because subjects were sedated and inactive, or did it demonstrate effects independent of activity level? Actigraphy offers an important “life sign.” While its utility has been overlooked in the past, pharmaceutical companies are increasingly seeking this technology for inclusion in clinical trials.

*Editor’s Note: Clinilabs is a provider of actigraphy core lab services, among many other clinical research services.

	Mathini Ilancheran is Lead Analyst, Clinical Research at Beroe Inc. and Gary K. Zammit, PhD is President & CEO for Clinilabs.

http://www.clinilabs.com/sites/www.clinilabs.com/files/Actigraphy_White_Paper.pdf

			Weidong Pan, Yu Song, Shin Kwak, Sohei Yoshida, and Yoshiharu Yamamoto, “Quantitative Evaluation of the Use of Actigraphy for Neurological and Psychiatric Disorders,” 

, vol. 2014, Article ID 897282, 6 pages, 2014. doi:10.1155/2014/897282

			Louter, Maartje , Johan BAM Arends, Bastiaan R Bloem, and Sebastiaan Overeem. "Actigraphy as a diagnostic aid for REM sleep behavior disorder in Parkinson’s disease." 

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http://www.medgadget.com/2015/09/sleep-apnea-devices-market-global-industry-analysis-size-share-growth-trends-and-forecast-2013-2019.html

			Zammit, Gary , interview by Mathini Ilancheran. 

Impact of Actigraphy in Clinical Research

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With all the buzz around wearables, actigraphs-which monitor sleep and daytime activity levels-have been around for decades.