Cuffless Blood Pressure Monitoring – Not for the Faint-of-Heart (Pun Intended)

The following is a guest article by Steven LeBoeuf, Ph.D., Co-Founder & President at Valencell

Over the past decade, a motley bouquet of press releases [1, 2, 3], media reports [4, 5, 6], and peer-reviewed articles [7, 8, 9] has led to excitement, confusion, and disappointment regarding the alluring prospects of cuffless, calibration-free blood pressure (BP) monitoring in wearables. The excitement has been largely fueled by the renowned public health benefits of, and the seductive commercial opportunity for, a seamless hypertension management solution that is virtually invisible – part of what people are already wearing, such as smartwatches, earbuds, smart rings, and apparel. The impetus driving R&D efforts for cuffless, calibration-free BP monitoring is the guiding principle that such a solution would enable nearly effortless measurements of BP taken throughout daily living, enabling the seamless diagnosis and management of hypertension, free from the burdens associated with properly porting and donning a BP cuff. However, this excitement has been tempered by well-publicized commercial setbacks [10, 11, 12], potentially misleading medical claims [13], and somewhat disparaging peer-reviewed articles authored by experts in the field [14, 15, 16], suggesting that existing solutions may be missing the mark.

Indeed, the growing public health crisis of hypertension is well-documented beyond the need for belaboring [17, 18], and the positive impact of regular monitoring has been widely championed by leaders in cardiorespiratory health [19, 20, 21]. Moreover, the market for FDA-approved BP monitoring solutions that encourage routine measurements is well into the billions [22, 23]. Yet despite the estimated hundreds of millions of collective R&D dollars that have been directed towards the goal of cuffless BP monitoring [24], to date, there are no over-the-counter (OTC) FDA-approved cuffless BP monitoring solutions that have been proven to successfully address the public health use case of seamless hypertension management. The existential question remains: What gives? With the massive amount of investment directed towards this one specific goal, why do we still not have such a commercial solution in our hands (or on our wrists) today?

For some R&D efforts, the answer is quite simple – FDA approval has simply not been achievable due to the inability to pass critical performance standards. This has been the case for well-popularized reports documenting the shortcomings of leading smartwatch consumer brands [10, 25]. However, in many cases, the answer is substantially more complex. For example, even when a prescription-only FDA clearance has been reportedly granted for some cuffless BP monitoring solutions, the public health value of these solutions remains questionable in light of the reported complexity of product usage or lack of independently reported clinical success.

In the end, there is no single reason an FDA-cleared OTC cuffless blood pressure monitoring solution is unavailable in the marketplace today. Rather, there are many disparate challenges that, acting together, have pushed out the realization of seamless hypertension management further into the future. This article will summarize these challenges and also provide optimism for the refreshingly near future. Namely, while the progress towards FDA-cleared cuffless BP monitoring may feel protracted, significant technological advances, regulatory modernization, and clinical use case validation are rapidly advancing and aligning. 

Key Challenges Confronting OTC Cuffless Blood Pressure Monitoring

Scientific Risks

At the most fundamental level, the jury’s still out on whether sufficiently accurate noninvasive, cuffless, calibration-free blood pressure monitoring is physically realizable at all. Namely, “Do the laws of nature even allow for this?” This scientific risk is bolstered by the fact that, at least as of the date of this article’s publication, there have been no peer-reviewed independent clinical studies proving that any such technology can definitively meet the critical performance targets required by the current regulatory “gold standard” — ISO 81060-2:2018 [26].

At the heart of scientific risks is that cuffless BP monitoring solutions intrinsically do not directly measure blood pressure but rather measure proxies for BP. For example, devices employing pulse transit time (PTT) focus on accurately measuring the time it takes a pulse wave from the heart to reach the measurement site (such as an extremity). Typically an ECG sensor is used to mark the time when the heart starts beating, and a PPG sensor is used to mark the time when the pulse wave reaches the measurement site. Under steady conditions, PTT is a proxy for BP in that it is inversely proportional to one’s blood pressure (the faster the pulse wave velocity, the higher the blood pressure), and computational models have been developed to translate PTT into an estimation of one’s BP. The challenge is that many factors other than blood pressure can affect PTT, such as (but definitely not limited to) changing hemodynamics and blood viscosity. Thus the transfer function between PTT and BP is dynamic, such that accurate BP estimations using this technique require painfully frequent calibrations with a BP cuff.  

This example should not be mistaken to imply that, fundamentally, cuffless proxies for BP monitoring can never be sufficiently accurate for hypertension management. In fact, proxies can sometimes provide more reliable measurements than can gold standards. As just one example, the gold standard for monitoring the speed of a car by state troopers is often considered to be handheld radar. As a proxy, estimating car speed can also be achieved by counting the time it takes a vehicle to move past the standard 10-foot white lines along the highway. Although not technically as accurate as the gold standard, eyeballing speed can be more reliable in that it never requires calibration, never suffers electronic glitches, and can work sufficiently well under a broader set of conditions (e.g., where radar cannot be properly positioned).      

Scientific risk is perhaps the most uncomfortable challenge of them all, as it can only be addressed by definitive experimental proof. Absent this proof, there is only scholarly faith by which to justify the hundreds of millions of R&D dollars that have been spent in the pursuit of the “holy grail.” Alongside the escalation in peer-reviewed publications showcasing steady progress towards the prized goal of meeting critical regulatory standards, the good news is that new machine learning approaches have provided a “reason to believe” that is getting stronger with each passing year [27, 28].

Engineering Risks

Once the aforementioned scientific risks are effectively “put to bed”, such a noteworthy achievement would not imply that the engineering risks would be “zero”. Scientific feasibility is often demonstrated through one-off, wall-plugged prototypes sending raw data sent to cloud-based machine learning algorithms, which may not directly translate into a viable consumer product. Powering considerations and critical use case considerations are often just an afterthought for biomedical scientists. In contrast, marketable consumer use cases require an affordable, portable, easy-to-use product that isn’t rough around the edges. One can imagine that the most accurate cuffless BP monitor in the world wouldn’t provide much consumer value if its battery were to die after a few days of use if it were too uncomfortable to wear or too difficult to properly don. 

A good way to mitigate engineering risks is to begin the product development phase with a clear product vision, having a well-defined and precise user experience and target audience in mind. Medical solutions that try to achieve too much for too many use cases ultimately achieve neither. Fortunately, by starting with a well-defined product vision at the outset, engineering teams can do what they do best – build the right product within the right timeline.   

Use Case Risks

As any experienced product team will affirm, a viable product requires more than a functionally working solution; rather, all of the critical product goals must be met for a given use case. For illustration, a key use case for hypertension management is to enable seamless BP measurements throughout the day, enabling at least 16 BP measurements every 30 days. This number is based on reimbursement code criteria, which enable reimbursements to healthcare clinics for remote (telehealth) BP monitoring only when a sufficient number of self-measured BP measurements per month are recorded by patients and monitored by physicians [29]. Indeed, the development of a high-adherence solution encouraging numerous BP measurements each month is perhaps the most commonly cited justification for the sizable R&D investments directed towards cuffless BP monitoring over recent years. But if the product is too complex, uncomfortable, or inconvenient to use, adherence will be poor regardless of whether the solution is cuffless and calibration-free. 

Use case risks can be among the most challenging to predict, but their importance cannot be overemphasized. A cursory online survey of operating manuals for FDA-cleared cuffless BP monitors (each requiring calibration and a medical prescription) makes it self-evident that the benefits gained by eliminating BP cuffs are tempered by the burden of complex calibrations. The thought, “Just cuff me already!” comes to mind when reading these instructions. The bottom line is that a revolutionary new technology that does not enable a compelling new use case or that does not significantly enhance an existing one will not generate a revolutionary product. 

Regulatory Risks

Regulatory approval/clearance is intrinsic to medical devices – without it, there is literally no commercial product. Thus, it is important to be aware that even if a cuffless BP monitor meets accuracy requirements within the desired engineering specs, and even if it engages end-users for high adherence, the FDA’s blessing is still not guaranteed. One must start the medical product development process with a regulatory documentation mindset at the outset, such that the resulting documentation is sufficient to prove that the product is sufficiently safe for the intended use. 

To provide helpful context, Valencell has been developing a cuffless, calibration-free BP monitoring solution over the course of several years, and the company has taken the approach of engaging the FDA early in the development cycle. Yet even with this high level of preparation, it has reportedly taken the company approximately nine months from the point of its first supplemental FDA submission to receive acceptability for its proposed 510(k) validation plan. Moreover, even with a validation plan accepted by the FDA, there are many more months of work to be completed before the company can submit a formal 510(k). 

The key takeaway is that the regulatory process for a new technology takes significant time, even when the regulatory strategy is well-formulated and when the documentation is well-prepared. Thus, it is important to hold glam-media press releases of “cuffless BP wearables” to the fire with pointed questions regarding FDA submissions. Namely, if the entity making the grandiose cuffless blood pressure claim has not yet submitted anything to the FDA – not even a pre-submission – then it is likely that an FDA clearance is (at the absolute minimum) 2 years away. 

Commercial Risks

From the outset, it is important to make sure the proposed medical solution can meet a significant market need. Often the allure of a scientific/engineering achievement — a “world’s first” medical solution — can distract visionary scientists and engineers from confirming the existence of a commercially viable market need. 

As just one example, no biometric smartwatches can accurately and passively track beat-to-beat blood pressure during exercise, and the associated technical challenges and R&D investment toward this goal would be quite substantial. But is there any significant reason to track beat-to-beat BP during intense exercise? What problem would be solved by such a solution that couldn’t be solved with existing technology today? Would solving that problem justify the required level of investment? From the beginning of product development, such a product concept should be vetted for commercial viability. If commercial viability isn’t clear, the R&D investment should be adjusted accordingly.

In other cases, the market need may be well-established, and the product scoping and goals may be quite clear, but over the course of development, new scientific and engineering limitations may emerge. As regulators push back on broad medical claims, the final commercial product resulting from years of R&D may no longer meet a real market need. One such example of a useless medical wearable would be a truly noninvasive glucometer that was FDA-cleared only for those patients whose blood glucose levels never fluctuated out of a desirable range. One could literally develop such a product today, with virtually no scientific or engineering risk, in a simple wearable form-factor (e.g., a smartwatch) that meets the stated medical claims, but the market need for such a product is patently nonextant. 

Many players in the field of cuffless BP monitoring have focused their resources on developing passive wearable solutions, such as a wrist-worn BP monitoring device (e.g., a fitness band or smartwatch). A major benefit of this type of solution is that users would be able to collect numerous BP readings throughout the day, in the background, without having to take time out of their day for a BP spot-check. However, one key limitation is that many consumers simply do not want to wear a wrist device for such a purpose. While wearable adoption is impressively high, it is still an order of magnitude less than that of smartphones. Moreover, the medical community has not yet converged on a compelling argument for such a device to be continuously worn. Namely, continuous measurements risk providing data overload for physicians with no definitive public health value [30, 31].

Fortunately, there are alternative, very attractive commercialization pathways for cuffless BP monitoring that do not require continuous monitoring. For example, after pursuing a wearable solution for cuffless BP monitoring for several years, Valencell painfully realized that commercialization of this type of solution would require substantial market education and a lengthy clinical evaluation period in order to earn commercial adoption. In response, instead of building its own passive wearable monitoring solution, Valencell has focused its product goal on addressing the well-known commercial need for a substantially more convenient, less-burdensome BP spot-check – a cuffless BP fingertip sensor in the form-factor of a traditional pulse oximeter. Valencell believes this will bypass the aforementioned commercialization risks associated with a traditional wearable device, as educating consumers and the medical community on how to use and benefit from a pulse-oximeter-style spot-check is substantially simpler than an education on continuous BP monitoring in a medically unconventional form-factor. 

Medical Acceptance Risks

One of the most painfully overlooked risks of any new blood pressure monitoring solution is medical acceptance. Indeed, although automated oscillometric BP cuffs were first invented in the 1970s and first popularized for home use in the 1980s, widespread acceptance by physicians and clinics was not realized until more than a decade later. While modern-day technology adoption rates in the medical community are arguably more favorable than in the past, some level of clinical skepticism and resistance should be appreciated. 

A key challenge for those developing new medical solutions is that while the largest growth opportunities often reside within the medical community, the lowest-risk go-to-market approach frequently does not. The medical community, by its nature, can be extremely resistant to change – and especially to disruptive technology. This is not to disparage the medical profession – it is simply that while chemistry may be instantaneous, biology takes time. What this means for OTC medical product developers is that business plans for cuffless BP monitoring solutions should avoid (if at all possible) placing the medical community in the critical path of the go-to-market plan. It may make better sense to reach out to end users first, to help shape product development and demonstrate the value proposition, in preparation for a future growth opportunity within the medical marketplace as peer-reviewed success stories build steam.  

A relatively recent example of successfully navigating this space may be that of Livongo, which started first with a direct-to-consumer (B2C) diabetes and hypertension management solution for type-2 diabetics [32], followed by rather explosive B2B growth in employer-sponsored benefit plans [33]. The company benefited substantially from demonstrating B2C market adoption by its target end-users before optimizing their solution and pursuing a more scalable B2B growth opportunity.  

A parallel approach has also demonstrated success. Alivecor, for example, began launching its first consumer product, an ECG monitoring accessory to the iPhone, as its prototypes were being studied by cardiologists for arrhythmia monitoring. As the company continued to advance its roadmap with increasingly more scalable products, a crescendo of flattering peer-reviewed publications [34] from leading cardiologists across the world helped fuel Alivecor’s product sales in the OTC marketplace. 

In Summary

The promise of seamless hypertension management via cuffless BP monitoring, while extremely alluring for both the marketplace and public health at large, is also extremely challenging to achieve. This R&D endeavor is not for the faint-of-heart (pun intended). At the time of this article, to the best of the author’s knowledge, there is still not a single cuffless BP monitoring solution cleared by the FDA for OTC use, despite the collective hundreds of millions in R&D spending, from companies large and small, directed towards this goal. The risks are wide and deep but not insurmountable, with a well-engineered solution having a clear intended use for a specific, medically impactful, and commercially viable use case. New technological developments, compelling, realistic use cases, and parallel success stories provide great reasons for optimism. Indeed, by overcoming these challenges, hypertension management will change more in the next 5 years than it has in the past 100.   

About Steven LeBoeuf, Ph.D.

Inventor of more than 100 granted patents in the field of wearable biomedical sensing, Dr. Steven LeBoeuf is one of the foundational innovators in wearable PPG sensors that are now embedded in millions of wearables on the market today. Before founding Valencell in 2006, Dr. LeBoeuf pioneered innovations in solid state materials, multiwavelength optoelectronic devices, high-power electronics, nanostructured materials and devices, and biochemical sensor systems while serving as a Senior Scientist and Biosensor Project Lead for General Electric. LeBoeuf has developed dozens of strategic partnerships with industry leading consumer technology brands, medical professionals, research institutions, medical device manufacturers, health and fitness companies, and start-ups. One of the most broadly quoted scientists and entrepreneurs in the field of wearable PPG sensing, LeBoeuf has served as a speaker in 50+ events around the world and is routinely interviewed by journalists, industry analysts, venture capitalists, and academic researchers.  As a founding pioneer in modern wearables, LeBoeuf has managed Valencell’s foundational patent portfolio, which has been licensed to dozens of companies around the world and implemented in 40+ wearable devices, ranging from earbuds, hearing aids, wristbands, legbands, smartwatches, virtual reality systems, headbands and more. LeBoeuf holds a PhD in Electrical Engineering from North Carolina State University, where he has been inducted into the Electrical and Computer Engineering (ECE) Hall of Fame, and BS degree in Electrical Engineering and Mathematics at Louisiana Tech University.

   

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