Vicki Anastasi

Mobile health devices are poised to transform medical care-and with it the medical device market.

	mHealth devices including motion sensors, wearable heart and blood sugar monitors, and patient-reported outcome apps can provide a wealth of real-time patient data previously unavailable. When networked with electronic health records (EHR), advanced analytics, call centers, and telemedicine technologies, mHealth devices are making possible a complete redesign of patient care, an emerging model known as the continuous safety monitoring paradigm.

	Instead of relying on periodic clinic checkups, mHealth allows continuous monitoring of patient vital signs, symptoms, and activity in the real world. The data can be used to adjust treatment for chronic conditions such as diabetes, heart failure and COPD, and monitor patients after surgery. This enables highly personalized care that is more responsive to patient needs, resulting in better clinical and functional outcomes. It also gives patients more control over their lives and their health.

	The continuous safety monitoring care model will be a bonanza for medical device manufacturers. According to BCC Research, global mHealth revenues from mHealth devices will reach $46.2 billion by 2021.

	Savvy medical device manufacturers have an opportunity to benefit by positioning themselves as early pioneers. However, mHealth device development involves many technical and economic challenges, and these must be addressed early in the development cycle. Among them:

-Payers and regulators increasingly require device developers to demonstrate the benefits of their products in terms of how they improve patients’ lives, and their effect on patients’ need for other services. To address these requirements, device developers must think early in the development process about how they can demonstrate the value of mHealth products.

	For example, payers might ask for evidence that a mobile network-connected spirometer not only accurately measures lung capacity, but also ensure that its use helps improve COPD or cystic fibrosis patients’ ability to do daily tasks such as walking to the grocery store, or that it reduces the need for emergency room or hospital treatment. In response, mobile device and app developers must think of their products in terms of how they can promote positive patient outcomes alone, and in combination with systems that enable continuous safety monitoring.

-Realizing the promise of mHealth will require developing new outcome measures that quantify meaningful real-world benefits. One challenge will be proving the accuracy of devices or mobile apps in measuring the target outcome under real-world conditions. For example, demonstrating the reliability and concurrent validity of a pedometer for measuring the daily activity of COPD or heart failure patients could require months of field testing under a wide range of conditions, especially for devices that are connected to or installed on patients’ existing smartphones, tablets or other consumer electronics.

	A second challenge will be demonstrating that the measured clinical outcome relates to meaningful aspects of how patients feel, function or survive or related economic outcomes. For example, it won’t be enough to arbitrarily set, say, walking 1,000 steps daily as a clinically desirable endpoint. You may also need to show that walking a specific distance daily provides a measurable and meaningful change for patients, for example making patients more independent in activities of daily living, or reducing emergency room visits, which will require extensive validation and economic modeling studies.

	Combining data from wearable devices with clinical measures and patient perceptions of how their progress affects their lives makes it possible to determine thresholds for change that can be used to construct robust, statistically validated, and patient-centered endpoints. An industry group, the Critical Path Institute’s Electronic Patient-Reported Outcome Consortium, has developed guidelines for ensuring the validity and reliability of new patient-centered outcome measures and endpoints derived from wearables data [1].

-Many mHealth devices and apps depend heavily on electronic communication-between mobile sensors and apps; apps and central servers; servers and EHR systems; and among physician offices and support centers, and patients’ apps and devices. Safety and privacy requires that these communication channels are secure at every step from both known and emerging cybersecurity threats including:

	â     Ransomware, in which hackers threaten to interrupt a device or app’s function unless a ransom is paid

	â     General malware, such as viruses or bots for launching denial-of-service attacks, interfering with device or app function

	â     Privacy breaches, in which protected patient data is exposed

	â     Device takeovers, in which a cardiac pacemaker or other device is taken over

	â     Financial blackmail, in which the vulnerability of a device is exposed by parties trying to manipulate stock prices

	Protections against these threats must be built in from the earliest design stage and updated for the life of the device or app as part of an overall risk management approach. It involves continuously monitoring emerging threats, assessing device vulnerabilities, developing and deploying countermeasures such as software patches, and backing up data to restore devices that have been compromised. This requires technical expertise and experience that exceed the capabilities of individual device developers. Collaborating with device industry coalitions and commercial IT security firms are essential for success.

Developing patient-friendly mHealth devices

	As with any therapeutic product, developing effective mHealth devices requires a clear understanding of patient needs and preferences. Beyond addressing clinical needs, a successful device also must be patient-friendly, provide value to the patient and be engaging.

	For example, a heart failure mHealth solution may include a passive heart monitor, a wireless link to a connected scale, an active patient-reported outcomes app, a medication and exercise reminder system, a telemedicine link to an on-call nurse, and an app to schedule office visits. However, patients will not tolerate five or six separate log-ins, so these all must be integrated into a single easy-to-use interface. Coordinating multiple developers to create such integrated solutions may be as big a challenge as developing the devices and apps themselves. Providing data to the patient in simple, understandable and (where appropriate) actionable formats is important to ensure ongoing value and engagement.

	In addition, many mHealth devices take advantage of existing mobile platforms, including smartphones and laptops using Mac, Android, and Microsoft operating systems. Patient preferences for these platforms also must be considered, and this may vary considerably by the condition and patient population to be treated. For example, a solution appropriate for managing diabetes will be very different from one for monitoring a cardiac pacemaker or recovery from pneumonia. The goal is always to engage the patient to meet their needs.

	Involving patients in program design through social media, patient and stakeholder interviews, analysis of real-world data from patient records, pharmacy and claims history, and reviews of literature and existing treatment guidelines and pathways is a good place to start. From these, potential channels for engaging and serving patients can be identified. These include mobile devices and sensors, and more conventional approaches such as call centers and educational brochures.

	Multiple mHealth and related products can be integrated into a product ecosystem, linking patients, providers, and device developers through integrated apps. In addition to providing patients with a seamless array of services, establishing a coordinated ecosystem can generate many strategic and financial benefits-notably, a more reliable and potentially larger, long-term revenue stream. Furthermore, an established ecosystem with dedicated customers creates a platform for seamlessly introducing new products and services, giving manufacturers an edge in competitive markets.

	The ecosystem concept is also flexible, presenting many opportunities to participate.

	One way is to develop all the parts needed to build an ecosystem that addresses a specific condition, such as cardiac arrhythmia. These might include a treatment device integrated with mobile sensors to communicate with clinicians about symptoms and device performance, and a smartphone app that informs patients when they need an appointment, connects them to call centers when they have questions, and provides information on what they need to do to stay healthy.

	Another way to participate in a digital health ecosystem is through partnerships. Many mHealth and other technologies that were developed separately can and are being connected. A mobile device that tracks a body function or symptoms might be combined with an app that shares the information with patients or alerts healthcare professionals. Apps that connect with many devices and incorporate analytics could help patients and clinicians choose the best option among a wide range of therapies, or alert when a better option might be available as a patient’s condition changes. This could create a powerful system for improving healthcare awareness and delivery, while opening up opportunities for developers of every size and type to participate.

	By participating in and contributing to a digital health ecosystem, manufacturers can gain a competitive edge though building stronger partnerships with providers and patients, and demonstrating real-world value to regulators and payers. However, making the most of the market opportunities mHealth presents will take planning and significant expertise.

	A robust EHR-centered infrastructure and patient engagement strategy is needed to successfully integrate mHealth into product development. Extensive experience with incorporating real-world evidence into clinical trials, including developing and validating new outcome measures, also is needed. And making the case for value-based reimbursement purposes, requires expertise in analyzing claims and service-use data. Collaborating with partners experienced in medical device development, use and commercialization, as well as in IT development and security, may be the best place to start.

	[1] Byrom B, Watson C, Doll H, Coons SJ et al. Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium. Value in Health (in press)

, Vice President and Global Head, Medical Device and Diagnostics Research, ICON plc

Articles

Get Ready for mHealth to Revolutionize the Device Market

	Big changes are coming to European Union legislation for medical and in vitro diagnostic devices. Launching a major transition effort to the new regulations now is critical for remaining in the 27-country EU market-and will give organizations a competitive edge over the next three to five years. This transition effort should include assessing the financial viability of your pipeline under the new rules, expanding data collection capabilities, and locking in soon-to-be-scarce notified body resources.

	The new regulations replace earlier EU directives and add stringent new requirements for CE Marking of new and existing devices. On May 26, 2020, any new medical device certified in the EU must comply with the new requirements of the Medical Device Regulation (MDR). On the same date in 2022, any new in vitro diagnostic device must be certified under the new In Vitro Diagnostic Device Regulation (IVDR). In 2024, any device sold, and in 2025 any device put into service, must comply with the new regulations.

	While the deadlines seem far off, significant lead-time and resources will be needed to meet the new requirements. Among these are:

	â     Certification for about 90% of IVDs, up from about 10% today

	â     Reclassification of some medical devices, requiring certification for the first time for some types, and recertification under different rules for others

	â     Increased clinical data reporting for certification and recertification for most devices, and pre-approval clinical studies rather than equivalency statements for many new implants

	â     Post-market surveillance and performance assessment for most devices

	â     Unique device identifier numbers on labelling

	â     Increased liability for defective devices for manufacturers and distributors, meaning more insurance and greater scrutiny of outsourced production

	Additionally, the new rules change the role of notified bodies (NB) and what types of devices they may certify. Fewer NBs are likely to be available to review devices above Class I, or IVDs above Class A. As the deadlines approach, NB processing for both new and existing product applications likely will slow, possibly delaying market entry in some cases.

	Getting ahead of the curve is essential to protect existing revenues and market share, and presents an opportunity to grow.

	New clinical testing requirements for new and existing products will be expensive and time-consuming. So, will it be worthwhile?

	Conducting a “gap analysis” of the existing pipeline and product portfolio will help with this decision. The goal is to identify the additional costs and resources needed to certify or recertify products under MDR or IVDR.

	The first step is determining what risk class each product will be certified in under MDR or IVDR. Then determine what, if any, additional clinical testing, production process, technical file documentation, labelling or other changes will be required to conform.

	In most cases more clinical testing will be needed. This may be challenging for makers of IVDs, most of which did not require clinical testing under previous EU rules.

	IVDR introduces a new, risk-based classification system, from A through D. It requires clinical testing for all IVDs above the lowest-risk Class A-which includes only products for general laboratory use, lab instruments, and specimen receptacles. As a result, about 90% of IVDs will now need clinical testing, compared with about 10% today.

	IVD manufacturers that have not done clinical testing before will have to develop the capability to do so. Further complicating the issue, the clinical evidence required for IVDs is more complex than for most medical devices. In addition to documenting that the test itself is valid, it must show that the test is necessary for making a medical decision that can significantly affect treatment decisions and patient outcomes. Developing this evidence will take time, money and expertise, adding cost to development programs.

	MDR requires clinical testing for most medical devices, including a proactive post-market surveillance program. Also, it entails clinical testing for re-certification of devices already on the market, if the current clinical data does not meet the new requirements. This will increase the cost of introducing new devices and maintaining legacy devices.

	Next, the second step of a gap analysis is to assess the cost of these changes and how they will affect profitability, allowing manufacturers to reconfigure portfolios accordingly. An analysis may indicate it’s time to drop marginal products with ample competition and focus on preparing packages for new, more targeted and profitable devices.

	There are many opportunities in testing as well. MDR and IVDR require uniform performance data reporting to a central database, making it easier for insurers and health system buyers to compare product performance head-to-head. As a result, any product that can show a clear performance edge could gain a decisive market advantage. Insurers, national health plans and other payers require this kind of real-world evidence to approve coverage of new devices and tests. Given growing payer preference for data submitted early to certify under MDR and IVDR could give organizations a market edge.

	However, it could expose the weakness of certain offerings, and is important to consider in deciding which portfolio and pipeline projects to pursue.

	Tailoring products to defined needs of specific patient populations and indications, and developing clinical test strategies that clearly demonstrate effectiveness for these populations, will help to gain and press market advantage under MDR and IVDR.

	The new EU regulations will create backlogs with Notified Bodies and may result in delayed certification reviews. This lag is caused by the MDR and IVDR change in the role of NBs, and their relationships with manufacturers, national competent authorities and EU officials.

	Previously, NBs functioned as consultants, helping manufacturers meet CE Mark requirements. Now they will act as the primary enforcers of the new regulations. Among other responsibilities, they will be tasked with reviewing clinical data submissions, submitting clinical evidence packages to expert panels, and conducting occasional unannounced inspections of manufacturer’s facilities, suppliers, and subcontractors.

	Furthermore, NBs will be designated by the European Commission to evaluate any device above Class I or IVD above Class A. The designation process begins in November 2017 and is scheduled to last six months. However, given the volume and complexity of the task, and the European Commission’s limited resources, it could take significantly longer, delaying the date on which some NBs can begin reviewing products.

	NBs will be restricted to evaluating only specific categories of devices for which they show expertise. As a result, there will be fewer NBs available to approve some devices, particularly those in higher risk classes. This could delay approvals. So, if a manufacturer currently uses NBs not redesignated for their devices, they will need to find new ones.

	The greater volume of data NBs must review will lengthen reviews, and will make them more expensive. The bottleneck created by fewer NBs with higher workloads could lead to long waits before reviews even begin.

	Therefore, the best strategy is to move early. Assess NB needs based on the types of devices produced. Ensure prospective NBs are or will be designated to review specific products. Coordinate a development plan with NBs to ensure timely access. This strategy will not only ensure products get to market and remain there, but also could result in slower competitors losing out at the back of the queue.

	Beyond jumping on certification planning and securing NB resources early, several other strategies can help keep medical and IVD device development on schedule, while meeting the new clinical testing and performance reporting requirements. These include:

	â     Integrating performance testing with early stage development. For example, parallel open-label testing of devices in broader populations for clinical and economic outcomes, such as the impact of a device on the use of other medical services, alongside any narrower clinical study needed for CE approval

	â     Incorporating adaptive design elements into clinical trials that may accelerate development by combining trial stages, and may enable a continuous learning development process in which data from earlier device versions support applications for new variations

	â     Automated data collection using electronic health records, which can reduce data collection costs while broadening the scope of data collection, especially for post-market surveillance

	â     Risk-based monitoring of trials and post-market surveillance, which can help spot protocol deviations or device performance issues early, enabling quick corrections to bring trials and the entire development process back on track

	MDR and IVDR have profound implications for device manufacturers that will affect every aspect of development, production, distribution and follow up. While a complex undertaking, developing an action plan that addresses these issues early will pay big dividends in the end.

 is Senior Manager, Regulatory Affairs, both with the Medical Device and Diagnostics Research division of ICON plc.

	1. Regulation (EU) 2017/745 Of The European Parliament And Of The Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. Official Journal of the European Union, May 5, 2017. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32017R0745

	2. Regulation (EU) 2017/746 Of The European Parliament And Of The Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU. Official Journal of the European Union, May 5, 2017. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32017R0746

The EU is launching a major transition within their legislation for medical and in vitro diagnostic devices. This transition is important and should include assessing the financial viability of the pipeline, expanding data collection, and locking in soon-to-be-scarce notified body resources.

Vicki Anastasi

Articles

Get Ready for mHealth to Revolutionize the Device Market

Big Changes for EU Medical and In Vitro Diagnostic Device Regulations