Wearables in Clinical Trials

Where we are & where we are going

Xavier Flinois, President PAREXEL Informatics

As real world evidence becomes an integral part for many clinical trials, wearables allow for monitoring and data collection anywhere the patient is located – freeing researchers of the location barrier of real world evidence.With the demand for wearables and sensors in clinical trials on the rise, pharmaceutical companies are increasingly faced with the challenges of both rising costs and market saturation of similar drugs – and that is where Clinical Research Organisations (CROs) come into play. From both a technology perspective and a processes perspective, CROs can leverage remote medical devices, unleashing an opportunity to collect novel endpoints and supplemental data that may improve the regulatory case. This also opens the door for CROs to make the case for reimbursement more compelling, open up trial participation to a wider population and/or reduce site visits for patients who may not live close to an investigative site. Although medical devices like spirometers and activity monitors have been used in clinical trials for almost a decade, modern wearable technology is improving the patient experience and lessening the data management burden. Outdated spirometers or activity monitors had to be transported back to the clinical site, where the data was then transcribed into an Electronic Data Capture (EDC) system, and downloaded – a process prone to transcription and human errors. Now wearables are more scalable and allow clinical sites to digitally collect the information without transporting or transcribing. These updates improve both trial efficiency and data accuracy. Regulating Medical Devices The use of medical devices for study endpoints has yet to receive regulatory guidance, but at a Drug Information Association Meeting in December 2016, the Federal Drug Administration (FDA) expressed cautious optimism that these devices could provide better and more timely insight into a patient’s health status. FDA speakers went so far as to say that researchers need not necessarily use medical devices with a 510(k) approval or CE stamp; consumer grade devices can be used as long as they are ‘fit for purpose.’ As regulators and drug companies accept the use of wearables, medical devices will play a more prominent role in clinical trial data collection, particularly in Phase II and III trials. Wearables by Phase: Phase I With the initial influx of information gathering in Phase I, wearables fit well into the protocol of the early clinical stage. One instance of this was a trial that added remote sensors into Phase I. The objective of adding this technology was to both pilot the new sensors as well as to compare the sensor data to the in-clinic data for a diabetes trial. With successful collaboration, the trial facilitators were able to produce a trial design that minimised the impact on the core protocol while maximising the number of devices. In all, six remote medical devices were added to the study –spirometer, blood pressure, pulse oximeter, blood glucose monitor, weight scale and activity monitor. Site and subject acceptance was high. It is expected that Sponsors developing new biologics where the benefit is best measured by sensors and/or where sensors provide valuable health status information to subjects, will begin piloting the applicable sensors in Phase I in parallel to their first in human clinical trials. Wearables by Phase: Phase II-III Because of the lack of regulatory guidance, the validated use of specific mobile health devices to deliver primary endpoint data is expected over the next 12–24 months. In Phase II and III trials, clinical trial sponsors will likely use medical devices as exploratory endpoints to mature their understanding of the utility of sensor-based endpoints. For some disorders, medical devices will be used across all phases as combination products. According to the FDA, “Combination products are therapeutic and diagnostic products that combine drugs, devices, and/or biological products. FDA expects to receive large numbers of combination products for review as technological advances continue to merge product types and blur the historical lines of separation between FDA’s medical product centers, which are made up of the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Center for Devices and Radiological Health (CDRH).” Wearables by Phase: Phase IV The growing demand for wearables in clinical trials is also being seen in Phase IV studies. The post-marketing demands and remote connectivity make wearables an ideal Phase IV component. Sponsors have the opportunity to make a strong case to regulators, especially in regard to why certain drugs should move to an over-the-counter status since the general population has the ability to use commonly available medical devices to either self-diagnose or monitor a particular health condition. Thanks to the maturation of this technology medical devices can now securely and wirelessly transfer data, increasing the integrity of clinical trial data. For example, once a reading is taken on a blood pressure monitor, that data is automatically downloaded to a hub (a device plugged into an electrical outlet). The patient then plugs in the hub once and takes his or her readings on the prescribed schedule. All of the data transfer is handled seamlessly and securely without the need for manual intervention – reducing the chance of human error. If the patient forgets to plug in the hub, the data is stored on the medical device until it’s plugged in. Alternatively, there is an option to securely transfer data via a companion app on a smartphone. What Else can Wearables Enable? Medical devices offer a multitude of possibilities for researchers that go far beyond collecting blood pressure. Using the data collected from wearables, predictive analytics may allow medical devices to alert researchers of future medical events. The application of predictive analytics to connected medical device data may enable the identification of subjects who are who are not protocol compliant such that the sites can intervene to increase subject retention. A predictive analytics for sensor-based data will enable increased patient retention and safety. Wearables not only simplify data collection and improve patient safety; this technology allows for the advancement of international partnerships where multiple teams can be connected in real-time. Remote and in-clinic data can be “fused” together for sites and study teams to view side-by-side in Phase I-IV clinical trials. This takes away the barrier of geographic location for multiple sites working across the globe, and allowing this increased comparison of diverse data will increase the integrity of the results on an international scale. The value of wearables is not limited to trials sites. As Real World Evidence (RWE) becomes an integral part for many clinical trials, wearables allow for monitoring and data collection anywhere the patient is located – freeing researchers of the location barrier of RWE Wearables have created a structure where data collection is aboundary-free factor in clinical trial management. End-to-End Medical Device Components It is critical that Sponsors leverage a medical device solution that securely and wirelessly transmits the data with the ability to store, visualise and alert from the big data time series data; however, the application of medical devices is not just a technology exercise. The performance of medical devices must be evaluated prior to use for study endpoints to understand if the device generates data within acceptable parameters and in comparison to the manufacturer\'s claims. Informed Consent Forms must be adapted for the collection of personal data and there are data storage and data transmission/re-use implications, particularly in the European Union. There are health economic and outcomes research considerations that must be taken into account to ensure that the associated endpoints are fit for purpose for regulatory submissions. Logistics also plays an important role on the front end, when devices are acquired, kitted and distributed to sites in a timely manner that accommodates the storage limitation at the sites. At the end of a trial, the devices need to be returned; cleansed or destroyed; and all data deleted from the device. Effective medical device use requires best-in-class medical, HEOR, biostatistics, logistics, technology and clinical trial conduct capabilities. Where does this Go Next? So where can wearables take the industry? The shrinking size of medical devices and connected implantable device along with evolving technology will further enable the collection of novel and complementary data to support regulatory submissions and reimbursement. With experience and regulatory acceptance, the potential for connected medical devices is extraordinary. These devices have the potential to change the way clinical trials are conducted; to broaden participation in clinical trials at a time when subject recruitment is major barrier; to enable virtual trials; and to reduce clinical trial costs. The challenge today is not deciding on whether to use a mobile health device, but the effective integration into drug development programmes.

With the demand for wearables and sensors in clinical trials on the rise, pharmaceutical companies are increasingly faced with the challenges of both rising costs and market saturation of similar drugs – and that is where Clinical Research Organisations (CROs) come into play. From both a technology perspective and a processes perspective, CROs can leverage remote medical devices, unleashing an opportunity to collect novel endpoints and supplemental data that may improve the regulatory case. This also opens the door for CROs to make the case for reimbursement more compelling, open up trial participation to a wider population and/or reduce site visits for patients who may not live close to an investigative site.

Although medical devices like spirometers and activity monitors have been used in clinical trials for almost a decade, modern wearable technology is improving the patient experience and lessening the data management burden. Outdated spirometers or activity monitors had to be transported back to the clinical site, where the data was then transcribed into an Electronic Data Capture (EDC) system, and downloaded – a process prone to transcription and human errors. Now wearables are more scalable and allow clinical sites to digitally collect the information without transporting or transcribing. These updates improve both trial efficiency and data accuracy.

Regulating Medical Devices

The use of medical devices for study endpoints has yet to receive regulatory guidance, but at a Drug Information Association Meeting in December 2016, the Federal Drug Administration (FDA) expressed cautious optimism that these devices could provide better and more timely insight into a patient’s health status. FDA speakers went so far as to say that researchers need not necessarily use medical devices with a 510(k) approval or CE stamp; consumer grade devices can be used as long as they are ‘fit for purpose.’ As regulators and drug companies accept the use of wearables, medical devices will play a more prominent role in clinical trial data collection, particularly in Phase II and III trials.

Wearables by Phase: Phase I

With the initial influx of information gathering in Phase I, wearables fit well into the protocol of the early clinical stage. One instance of this was a trial that added remote sensors into Phase I. The objective of adding this technology was to both pilot the new sensors as well as to compare the sensor data to the in-clinic data for a diabetes trial. With successful collaboration, the trial facilitators were able to produce a trial design that minimised the impact on the core protocol while maximising the number of devices. In all, six remote medical devices were added to the study –spirometer, blood pressure, pulse oximeter, blood glucose monitor, weight scale and activity monitor. Site and subject acceptance was high. It is expected that Sponsors developing new biologics where the benefit is best measured by sensors and/or where sensors provide valuable health status information to subjects, will begin piloting the applicable sensors in Phase I in parallel to their first in human clinical trials.

Wearables by Phase: Phase II-III

Because of the lack of regulatory guidance, the validated use of specific mobile health devices to deliver primary endpoint data is expected over the next 12–24 months. In Phase II and III trials, clinical trial sponsors will likely use medical devices as exploratory endpoints to mature their understanding of the utility of sensor-based endpoints. For some disorders, medical devices will be used across all phases as combination products. According to the FDA, “Combination products are therapeutic and diagnostic products that combine drugs, devices, and/or biological products. FDA expects to receive large numbers of combination products for review as technological advances continue to merge product types and blur the historical lines of separation between FDA’s medical product centers, which are made up of the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Center for Devices and Radiological Health (CDRH).”

Wearables by Phase: Phase IV

The growing demand for wearables in clinical trials is also being seen in Phase IV studies. The post-marketing demands and remote connectivity make wearables an ideal Phase IV component. Sponsors have the opportunity to make a strong case to regulators, especially in regard to why certain drugs should move to an over-the-counter status since the general population has the ability to use commonly available medical devices to either self-diagnose or monitor a particular health condition.

Thanks to the maturation of this technology medical devices can now securely and wirelessly transfer data, increasing the integrity of clinical trial data. For example, once a reading is taken on a blood pressure monitor, that data is automatically downloaded to a hub (a device plugged into an electrical outlet). The patient then plugs in the hub once and takes his or her readings on the prescribed schedule. All of the data transfer is handled seamlessly and securely without the need for manual intervention – reducing the chance of human error. If the patient forgets to plug in the hub, the data is stored on the medical device until it’s plugged in. Alternatively, there is an option to securely transfer data via a companion app on a smartphone.

What Else can Wearables Enable?

Medical devices offer a multitude of possibilities for researchers that go far beyond collecting blood pressure. Using the data collected from wearables, predictive analytics may allow medical devices to alert researchers of future medical events. The application of predictive analytics to connected medical device data may enable the identification of subjects who are who are not protocol compliant such that the sites can intervene to increase subject retention. A predictive analytics for sensor-based data will enable increased patient retention and safety.

Wearables not only simplify data collection and improve patient safety; this technology allows for the advancement of international partnerships where multiple teams can be connected in real-time. Remote and in-clinic data can be “fused” together for sites and study teams to view side-by-side in Phase I-IV clinical trials. This takes away the barrier of geographic location for multiple sites working across the globe, and allowing this increased comparison of diverse data will increase the integrity of the results on an international scale.

The value of wearables is not limited to trials sites. As Real World Evidence (RWE) becomes an integral part for many clinical trials, wearables allow for monitoring and data collection anywhere the patient is located – freeing researchers of the location barrier of RWE Wearables have created a structure where data collection is aboundary-free factor in clinical trial management.

End-to-End Medical Device Components

It is critical that Sponsors leverage a medical device solution that securely and wirelessly transmits the data with the ability to store, visualise and alert from the big data time series data; however, the application of medical devices is not just a technology exercise. The performance of medical devices must be evaluated prior to use for study endpoints to understand if the device generates data within acceptable parameters and in comparison to the manufacturer's claims.

Informed Consent Forms must be adapted for the collection of personal data and there are data storage and data transmission/re-use implications, particularly in the European Union. There are health economic and outcomes research considerations that must be taken into account to ensure that the associated endpoints are fit for purpose for regulatory submissions.

Logistics also plays an important role on the front end, when devices are acquired, kitted and distributed to sites in a timely manner that accommodates the storage limitation at the sites. At the end of a trial, the devices need to be returned; cleansed or destroyed; and all data deleted from the device.

Effective medical device use requires best-in-class medical, HEOR, biostatistics, logistics, technology and clinical trial conduct capabilities.

Where does this Go Next?

So where can wearables take the industry? The shrinking size of medical devices and connected implantable device along with evolving technology will further enable the collection of novel and complementary data to support regulatory submissions and reimbursement.

With experience and regulatory acceptance, the potential for connected medical devices is extraordinary. These devices have the potential to change the way clinical trials are conducted; to broaden participation in clinical trials at a time when subject recruitment is major barrier; to enable virtual trials; and to reduce clinical trial costs. The challenge today is not deciding on whether to use a mobile health device, but the effective integration into drug development programmes.

--Issue 29--

Author Bio

Xavier Flinois

Xavier Flinois leads PAREXEL’s Informatics division, which provides innovative technology solutions to help optimise patient engagement, clinical and regulatory processes. He brings to PAREXEL more than 25 years of experience in technology and healthcare, including senior leadership positions with global companies in the clinical software, consulting and IT services areas.

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