Their pedigrees and their scholarship couldn’t be faulted—two deeply researched studies emerged in the dog days of August when most Washington policymakers were away, each providing potent reasons for speeding up the FDA approval process for medical devices.
The first, with no fewer than 26 authors from diverse professional settings in academia, industry, clinical practice, informatics and government, came from FDA with far-reaching recommendations to integrate existing and developing data systems and registries to “promote continuous accrual of benefit/risk and safety knowledge from invention to obsolescence.”
Entitled Recommendations for a National Medical Device Evaluation System—Strategically Coordinated Registry Networks to Bridge Clinical Care and Research, the 146-page FDA task force report foresees ultimate deliverables that “should include better, more efficient regulatory science-based decisions in conjunction with device information dissemination customized to stakeholder groups, including patients, clinicians, professional societies, regulators, manufacturers, payers and others . . .”
The second, an unrelated 56-page working paper from Harvard Business School assistant professor of business administration Ariel Dora Stern aided by 23 acknowledged collaborators from other schools, industry and FDA, provides a compelling case for getting on with those recommendations.
Blaming “regulatory uncertainty” at FDA, her research finds that early mover medical device innovators spend 34% (7.2 months) more time getting FDA approval than do follow-on imitators that come along later—the opposite of what market entrants experience when introducing new drug products.
“Back-of-the-envelope calculations suggest that the cost of this delay is upwards of 7% of the cost of bringing a new high-risk device to market,” Stern writes, observing that this deters small companies from even trying.
The voluminous extramural FDA report builds on a 2012-published agency overview, Strengthening Our National System for Medical Device Postmarket Surveillance and in the process seemingly opts for a dash of political correctness, eschewing forever the prickly word “surveillance” in favor of the less polarizing word “evaluation.”
But the name change is more than just semantics, the report insists. By broadening surveillance into evaluation, the national system could “organically both add efficiency and better inform the ability for manufacturers to use [safety signals] as engineering targets and to convincingly demonstrate signal mitigation with newer, better device designs that reach the public faster . . .”
Critical to the national system’s success will be strategically integrating existing device registries, electronic health records, administrative claims data and mobile device outputs “to produce a complementary network whose whole data composite in fact could support ongoing and robust device evaluation.”
Such structures have been called “coordinated registries networks” or CRNs—even though not all of their members are actual registries, the report notes.
“Functionality of CRN structure and governance should be guided with the objective of meeting the needs of multiple stakeholders including patients, clinicians, healthcare systems, FDA, registry owners, and industry partners,” it says.
“Functionality, leveraging and linking of participating registries and other entities,” the report goes on, “should promote ongoing device evaluation, increase patient and device data and outcome information quality, modulate added work load through dual-purposing existing workflow, and so reduce cost and enhance overall efficiencies and timeliness associated with regulatory milestones.”
Examples of contemporary devices that could be profiled by CRNs, the report says, include hip and knee replacement devices, spine surgery procedures/devices, vascular procedures/devices (peripheral, abdominal aortic aneurysm repair, carotid and vascular access/catheters), cardiac valves, atrial fibrillation ablation procedures/devices, implantable rhythm and heart failure devices, coronary stents, robotic and other minimally invasive surgery devices, ophthalmic procedures/devices, and surgical mesh.
“The success and sustainability of CRNs, and of the national system itself,” the report concludes, “will depend on the actively promoted transformation of the contemporary medical device innovation ecosystems from a landscape of fragmentation, skepticism, and distrust to a culture of good will and partnering in every aspect of the CRN and national system’s development and operations.”
All of this adds up to efficiency gains in a regulatory system that now is far from that. Another word for efficiency is “speed”—in this context, speed of processes that currently don’t work together well. The FDA report wants these processes to become a smooth “continuum.”
As an authoritative description of how badly everyone needs this, Stern’s Harvard Business School working paper discovers that, contrary to many expectations, technological novelty is largely unrelated to FDA approval time for a high-risk device.
Instead, she says, approval time is “meaningfully reduced by the publication of objective regulatory guidelines.”
PMA content and format uncertainty at FDA, Stern writes, “is easiest to think about in a scenario in which a product and its functionality are known to the regulator, but evaluation criteria have not been formally articulated or informally established by precedent. This can be seen in the case of drug eluting stents (DESs), which were first sent to the FDA for approval in 2002.
“It was not until 2008, however, after five different DESs had submitted applications for regulatory approval and four had already been cleared, that the FDA published a formal guidance document, detailing what criteria it would use to evaluate DESs moving forward.”
This document and others on another eight unique medical devices (pacemakers, implanted cardioverter defibrillators, electrodes, heart valves, lasers, occluders, catheters and stents) provided objective regulatory guidance that allowed average approval times for subsequent entrants to fall by about 40% (6.1 months), Stern’s paper says.
“These findings,” she writes, “have implications for other emerging categories of medical technology such as tissue engineered products and the applications gene therapies, as these are all contexts in which there is a large degree of uncertainty about the content and format of new product applications and, as a corollary, around how to evaluate new products.
“This uncertainty is the result of both a short (or nonexistent) regulatory history for these types of products and a dearth of formally or informally established regulatory criteria. In these new product categories, regulatory approval times for a given product are similarly likely to be substantially protracted until a time when objective product evaluation criteria are formalized and made available to innovators.”
Stern cites a 2010 survey of the medical device industry by Josh Makower et al that found that for roughly 20% of companies the average cost of bringing a high-risk medical device to market was about $94 million.
“Assuming a discount rate of 11.5%,” she writes, “the results suggest that the opportunity cost of the delay associated with being the first entrant in a product code is probably around $6.7 million, or more generally, upwards of 7% of the total cost of new device development.”
Stern’s analysis of FDA data suggests, she says, that by even the most conservative estimate “the resolution of procedural uncertainty through the publication of formal guidance is associated with a 6.1 month (approximately 185 day) reduction in regulatory approval times”—or an average 41% reduction.
In other words, as others have also found, familiarity with FDA protocols is more important than technical knowledge for predicting a medical device firm’s successes.
Moreover, Stern and the FDA task force together make it obvious that fusing diverse knowledge systems need not further retard the route to market but should actually have the opposite effect.