12 min reading time

Good or bad?

The US House-approved “21st Century Cures Act” (now on its way to the Senate) tries to reduce the costs of bringing treatments to the patients that need them.

Here’s a link to the short US Energy and Commerce Committee paper which recommends action: http://medgroup.biz/21cures

A New York Times opinion piece at http://medgroup.biz/cures-act is staunchly against the Act.

“This would allow a device to be approved based on even lower standards of evidence than are currently used, on the theory the need outweighs the risk…. The device industry may stand to benefit from this legislation, but the health of the public does not.”

Group member and former CEO of MELA Sciences Joseph Gulfo is also a detractor. See http://medgroup.biz/against-cures-act

He says, “FDA doesn’t need 21st Century Cures. It has already been empowered to the fullest extent possible…. FDA has not been performing… with respect to review and approval times… despite mounting regulations.”

A piece in the New England Journal of Medicine at http://medgroup.biz/21-NEJM explains,

“The new law would redefine the evidence on which high-risk devices can be approved to include case studies… rather than more rigorous clinical trials…. [It allows] device makers to pay a third-party organization to determine whether the manufacturer can be relied on to assess the safety and effectiveness of changes it makes to its devices, in place of submitting an application to the FDA.”

What do you think?

Is a lower reliance on clinical trials before market introduction a good thing?

Will the tradeoff help more people than it hurts?

Is “hurting anyone” an acceptable risk?

And what about that “third-party organization” clause?

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Make it a great week.

Joe Hage
Medical Devices Group Leader

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Harry Knuth
Retired
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⭐️🌟Laura T. Smith, BSN, RN🌟⭐️
Manager Product Safety/PMS Clinician, Device/Drug/ SSCP CERs EU MDR, Product complaints compliance #EUMDR
There will be faster approval for pharma-and in general a focus on speed up of the approval process.

Julie Omohundro
Principal Consultant at Class Three, LLC
Actually, FDA was quite on target in the early years of the program, and clearances of 510(k)s via the third-party route were initially faster than 510(k)s submitted directly to FDA. This might have reflected mostly the fact that companies were sending mostly their plain-vanilla “me too” 510(k)’s for third party review, which FDA probably reviewed faster too, but still, the early results supported the claim that third-party review would expedite time to market.

The costs are unknown, since those are negotiated directly between the third party and company, with no fee for FDA review. Some of the answer may lie there. Third parties would set their fee appropriate to the amount of time it took them to review the 510(k)s. Industry may have concluded that it just wasn’t worth paying the price to reduce review time by, at best, a couple of week.

In any case, Industry just doesn’t seem to want to use the program, for whatever reason. An interesting question at this point in time would be whether those who also work with Notified Bodies are more likely to used third-party review when submitting a 510(k) to FDA, compared to companies who only work with FDA.

Arthur Brandwood
Medical devices and IVD regulatory expert with a global perspective
Hi again Julie,

I agree with your perspective on the 510k third party process: lack of uptake was primarily due to the fact that it cost more and didn’t actually deliver on the promised faster review times (partially because the final FDA check step took longer than promised).

The accredited persons however where almost all the very same organisations accredited as Notified Bodies, Canadian Registrars and Japanese 3rd party reviewers.

I’ve also seen variable quality of review – both with FDA and Notified bodies, but i wouldn’t go so far to say that Notified Bodies are too engineering focussed. Far from it and the 2007 MDD revision and the recently proposed changes in Europe have led to a continuing shift of emphasis towards clinical.

That’s not to say the 3rd party system is perfect. However I do believe that it’s an approach that merits serious consideration in the US.

Julie Omohundro
Principal Consultant at Class Three, LLC
The quality of regulatory review varies from review to review based on a number of factors. However, having had experience with both FDA and EU review of Class III devices, I have found FDA’s review to be more thorough.

I do think there is merit in the suggestion that NB review may focus more the design than on the data supporting the safety and performance of the product for its intended use. All of the NBs of whose history I am aware have their roots in technology, not healthcare, and therefore are probably inherently predisposed to focus on the technical aspects of the device, rather than on its clinical use.

Julie Omohundro
Principal Consultant at Class Three, LLC
Arthur, politically speaking, third-party review in the US appears to have been promoted by lobbyists and politicians trying to make a name for themselves by pushing through a process that industry probably never much wanted and largely ignored once it was available.

At the time, the common wisdom was that US companies did not trust third parties to protect their confidential and proprietary information. Thus, third-party review was considered to be, at most, a viable option only for truly “me too” 510(k)s, with little to no such information to protect. Whether this attitude has changed with the advent of Notified Bodies, I cannot say, but I think at this point, the issue is probably moot. This is probably why such scant attention was paid to third-party assessment.

From an article prepared by MDDI staff:

“The vast majority of 510(k) submissions between 2008 and 2012 were submitted directly to FDA for review. On November 21, 1998, FDA began accepting 510(k) reviews from accredited persons. This program has had limited use because only select devices are eligible, and companies have reported mixed experiences with their accredited persons. However, recent data show that the effective rate for the third-party 510(k) review process has steadily declined (from 16% in 2008 to 9% in 2012). There have not been any recent changes to this program, so this decrease appears to be attributable to industry’s disuse—perhaps due to lack of interest, dissatisfaction with the program, and added expense—rather than agency policy.

… it is worth noting that third-party-reviewed 510(k)s have seen longer review times by FDA, increasing from 46 days with FDA after the third-party has reviewed the submission in 2008 to 62 days in 2012. We have no way of knowing how long the third party took to review the submission (or the quality of the review) before making its recommendation to FDA, but these average review times all appear to be in excess of the 30 days FDA is allowed to make its decision after receiving the third party’s recommendation under Section 523 the Federal Food, Drug, and Cosmetic Act.”

http://www.mddionline.com/article/510k-statistical-patterns-12-02-2014

Arthur Brandwood
Medical devices and IVD regulatory expert with a global perspective
Reading the various comments here and the referenced Op-eds, it’s interesting to see how the third party assessment proposal has been quite glibly dismissed by most commentators.

Yet that’s exactly the model that’s been used successfully in Europe and Canada and Australia and to some extent in Japan for the last 10-20 years. A CE mark is actually a certification that attests to a manufacturer’s competence to design and improve devices within the scope of the Cert. There’s a requirement to go back to the certifier for significant changes – and they are pretty well defined in guidance. There’s also a much more detailed design review for the highest risk devices, and under the new regulations under development a presumption of direct clinical trials for all high risk devices.

It’s pretty well established that Europe gets technology to market faster than the US – and there’s no evidence that Europeans are harmed more by devices than Americans.

For sure Europe are tightening up and centralizing their system, but the fundamental regulatory model (including use of 3rd parties) at the core of the CE system is unchanged. What has changed is higher expectations for clinical evidence and much more rigorous scrutiny and checks and balances over third parties.

The result in Europe will be the weeding out of the long tail of smaller third party assessors who have created much of the concern about the European system. The biggest 8-10 will still be there, they always accounted for >90% of the assessments.

Amongst all this noise – note:

1. FDA already accepts third party reviews (with a final FDA check) for many 510(k)s

1. FDA is leading the Medical Device Single Audit Program – which is aimed to allow international regulators to share audit findings and audit on behalf of each other. That will involve FDA accepting reviews from the very same 3rd party assessors who are auditing for Europe, Canada, Japan and Australia.

I don’t know if full third party assessment will fly politically in the US, but it’s not something that should be dismissed out of hand.

Gerry Poe
Enterprise Project Specialist at Santa Clarita Consultants
The name of these acts tends to be the opposite of the content.

You can be sure of these things:
Industry will make money
Politicians will get their campaign donations
Patients will be monetized

Erik Jessen
Manager 3 and UVM SME at Raytheon
Julie O, in all industries, people make the decisions that are personally best for themselves – there’s management books that talk about that. There are very few early adopters – and if the risk or amount of work to try something new is high, then few of them will take the chance. So very quickly the number of people open to trying something new goes down so close to zero that it makes no sense to even start clinicals.

Once early adopters have adopted something, there is a long lag before the mass of people are willing to try something new. That lag can be years in some industries. Of course, as a medical company, one has to keep the staff around while waiting out that long period.

So the sooner trials get started, the sooner the long gap starts/ends and the volume sales start.

Erik Jessen
Manager 3 and UVM SME at Raytheon
There are two ways to lower medical costs:
a) new products that inherently have lower costs (more automation, drugs with fewer side effects or easier administration, etc.)
b) lower costs of approval (both elapsed time before product is available for sale, as well as cost to complete approval cycle).

So shortening approval cycle improves both, and when companies see a lower barrier to entry for products, they’ll bring to market products that otherwise wouldn’t have made financial sense to bring to market.

I’m not proposing laissez-faire, but I saw significant opportunities to do the same quality of work faster and cheaper. Also, I believe that one could widen preliminary testing with the terminally ill (or people close to it), which would also bring in release cycles without endangering the general population.

Whether you like him or hate him, Obama made the point that regulatory costs have significant (if not absolute) control over business, when he said that using regulations, he’d make sure that anybody who tried to build a coal-powered power-plant would go bankrupt. Medical is no different.

Erik Jessen
Manager 3 and UVM SME at Raytheon
I will respectfully will disagree with Julie O. Our device was mainly used in children (youngest that could use it was about 10) who had congenital heart defects. We all tried to figure out how to get the device out there faster. Yet the FDA required us to spend months refuting claims made in papers written the 1970s, that had already been refuted because of flawed data, outdated theories of how the heart worked and how electrical signals propagated in the human body. It drove us crazy.

Clearly the FDA had absolutely no clue what they were doing, and so were operating in CYA mode. Imagine a regulatory agency requiring you to do the equivalent of reproving that the Earth goes around the Sun, before they’d license your rocket?

I don’t blame the individual at FDA – it’s the organization’s management that’s not been able to figure out how to adapt to new technology, and it’s been going on long enough that it’s the fault of the last few people in the White House.

Kelly Bryant
Talent Acquisition Business Partner | Recruiter, US
Strongly agree with everyone here, especially Mark! Great article!

Robert Christensen
Medical Consultant
It’s about time. My TMJ devices in use for 40 years before FDA called for a costly and corrupt PMA process should have walked through an approval process that would have cost me nothing instead of millions of dollars. It truly was criminal.

Julie Omohundro
Principal Consultant at Class Three, LLC
Generally clinical trials are required because in vitro and in vivo animal studies are not 100% predictive of clinical experience. Whether that is the case here, I cannot say.

Typically the problem with letting the market determine clinical benefit is that “the market” consists of people who will determine the benefit by finding out firsthand whether they are harmed by the product or not. “The market” frequently has limited enthusiasm for this approach to design validation, and even if they are game, they are still not so happy if it turns out “the market” decided the product not only had no clinical benefit, but a good bit clinical risk, perhaps even class-action worthy. This is why I think of the first few years post-market as the litigation phase.

In this case the other problem with letting the market decide is the statistical problem you cite. Large samples are needed when the target market is rarely seen (i.e, device-related infections are uncommon) or the expected difference between infection rates with and without the coating is expected to be small. The market consists of individual physicians and patients who, under these circumstances, are in no position to determine if this type of product is actually effective. Not a bad scenario in which to pitch a post-market trial, though.

Often the reak sticking point is that the market has already decided that the product isn’t going to have enough clinical benefit to be willing to buy enough of the product in a short enough period of time at a price that will provide an attractive ROI from a multi-million dollar clinical trial. Otherwise, savvy investors would be lined up ready to pay for one. Moreover, the market (doctors who would use the coated products and the device makers who would coat their devices with it) would be at the front of the line. If they aren’t, why not?

Richard Terry
Principal Research Scientist Ι Coatings & Materials Consultant
That is exactly my point, Julie. If a new antimicrobial coating is safe, and both in vitro data and animal studies show it to be effective (so it is obviously not “snake oil”), why not let the market determine its clinical benefit? But safety and efficacy are absolutely not the same thing. There are mild levels of efficacy that cannot be proven clinically without multi-million dollar clinical trials. The safer technologies are more expensive because you need a larger number of patients to see statistical benefits. And devices with low incidence of infection, like hip implants, do not have protection from infection because the clinical study to prove efficacy would be cost-prohibitive. We are tolerating much higher rates of device-related infections in this country because of the clinical efficacy requirements of the FDA. As an example, it has been over 20 years since antimicrobial Foley catheters first entered the market. Now, over 20 years later, this same first generation antimicrobial technology is still the market leader! Safe and effective new technology exists but is not on the market today solely because the FDA requires a multi-million dollar efficacy clinical to gain device approval.

Julie Omohundro
Principal Consultant at Class Three, LLC
Richard for any device where efficacy is the ability to prevent infection, efficacy and safety are essentially the same thing. It doesn’t do a patient any good to know that a new type of coating wouldn’t have killed them, if the infection if failed to prevent does.

In any case, in this scenario, what I might be asking myself is not so much what FDA will accept as “adequate” demonstration of efficacy, but what the market will accept as adequate, since healthcare providers (and payors) will almost certainly focus on whether the “new and improved” device really does prevent infection more effectively, than on the safety of the new material per se.

Erik Jessen
Manager 3 and UVM SME at Raytheon
I recently completed Class-3 certification with FDA. Active-implant, life-critical. Clearly the FDA wasn’t capable of technically understanding what was going on, so they simply substituted in-depth understanding with requiring enormous amounts of paperwork that didn’t prove the device was either good or bad – it was simply irrelevant. Which made it feel like CYA-work, rather than patient-protection work.

A friend was at a conference and two FDA officials told him unofficially that the FDA knows how to regulate drugs, simple mechanical devices and software databases (like patient records). But they don’t understand digital electronics or embedded devices, or HW/SW systems. So practical experience was confirmed by statements by FDA employees.

I’ll point out that UL has done a satisfactory job since 1894 – why not take use the same model and allow the UL to approve medical devices? They currently approve even nano-technology, and everybody seems to be happy, both on their effectiveness and efficiency. Everybody agrees that the FDA fails on both counts.

I’d also observe that we have a tremendous number of people getting older – that means a large number of people are going to die without new treatments – so it would make sense to expand programs allowing early trials on people who will suffer without the new product. It’ll help the general population (should the product be approved) as well as the individual.

Mark McCarty
Regulatory Editor at Clarivate Analytics
Another fly in the Cures ointment; FDA says it will need close to or in excess of $900 million for its part of the Cures lift, but the House bill offers only $500 million. But let’s see what the Senate does. We may be jumping the gun.

Look, I’m all for feel-good moments in Washington so long as the consequent legislation makes sense, but I didn’t see anything even remotely close to half a billion additional dollars for FDA in either the House or Senate appropriations bills for FY 2016.

To me, this is a money grab for NIH that will at best clog operations at FDA and leave CMS with no way to review the slew of biomarkers that an accelerated biomarker review process at FDA would presumably churn out, assuming (rather hopefully) that Congress does indeed send FDA anything close to the required appropriations.

Stephen Glassic
Available: Biomedical Equipment Technician, Field Service Engineer, Electronic/Electromechanical Technician
Richard Terry@ I understand what you are saying but at the same time the FDA can’t be approving safe snake oil. It could cause a lot of wasted time and money on quick, cheep or easy treatments that do not work as well, rather than on more effective (but maybe more difficult or expensive) treatments. But I do understand that in the case of what you are working on, this might be a practical approach.

Julie Omohundro
Principal Consultant at Class Three, LLC
I haven’t read it yet either. Mostly I’ve been cringing at the shallow and useless opinion pieces (both pro and con) that are being cranked out. I will say generally that I think the healthcare community is pretty happy with the levels of protection for patient safety built into the current process, and, while they would like to see new SAFE AND EFFECTIVE products made available more quickly…who wouldn’t, they appreciate that there are practical limits on how fast you can assure the safety of a new drug or device, and on how much you can assure effectiveness at all.

I think the sense of urgency in getting new medical technologies to market is one felt almost entirely by industry, and is fare more of an urgent business need than an urgent healthcare need. (Healthcare urgently needs anything that will reduce their costs.) I don’t think healthcare providers lie awake nights thinking how many of their patients could be saved if only FDA would move faster.

Chuck, I don’t think the lack of cures has much of anything to do with FDA. FDA does not find cures, and there are not hundreds of cures sitting around in any pipelines, nor in queue at FDA.

Michael, this is the nature of government agencies, I’m afraid. It is the natural result of being funded by tax dollars, and therefore having several hundred million watchdogs waiting to get a piece of you if you make a single misstep.