A Nuanced Opposition to the FDA and Similar Regulatory Agencies

As regular readers will know, I am no great admirer of medical regulation as it presently exists in the wealthier parts of the world. It is a burdensome system, in which whatever power good intentions have to make the world a better place has long been eroded away by the short-term human incentives present in any large bureaucratic organization. What is left is a system in which it costs multiples of what it should cost to bring medicine into the clinic at an appropriate level of risk, a system that acts primarily to suppress rather than encourage development of new medical technology, and a system that tramples upon the rights of patients to make their own informed choices.

In the past my prescription for a better future has been one in which medical tourism flourishes: the use of regulatory arbitrage to bring medicine to the clinic in a responsible way in places outside the US. The eminently dysfunction US medical system, in which no party is incentivized to control costs, the most influential parties collude to prevent cost discovery, and quoted costs have little relation to actual costs, leads to a situation in which it is cheaper to fly halfway around the world to another country to receive even modest procedures. So let medical tourism grow as a form of pressure upon the existing regulatory system, because competition from outside is the only thing that has a hope of resulting in significant reform.

Any number of people work within the system on initiatives to make it better. There are non-profits and high net worth individuals and patient advocates all calling for reform of the FDA in one way or another. All are distinguished by having had very little positive effect over the years of their efforts. Indeed, over the last decade the cost of FDA approval has doubled, the time lengthened, and the rate at which new medical technologies are approved is stagnating. This has happened over the course of a period of enormous, staggering progress in biotechnology, in which costs of the underlying technologies have fallen dramatically. How can this be the case? Cynically, I would say this was also a period of great progress in connectivity and media exposure. Thus the tendency of bureaucrats to prioritize the minimization of bad press and accountability leads to ever greater demands, costs, and delays placed on regulatory applications, in search of a mythical, non-existent minimum level of risk that can only really be obtained by preventing new technologies from arriving at all.

Medical tourism, however, has challenges, primarily that it remains a highly disorganized market. Few of the people who might benefit significantly in fact do so. It requires a fair amount of research and determination; there is no easy on-ramp. I think that it will require universally desired enhancement therapies, such as follistatin or myostatin gene therapies for muscle growth, to obtain a large enough number of potential customers to generate sufficient organization in this marketplace to build that on-ramp. The number of people with severe illnesses is simply too small for the self-organization of entrepreneurship and venture funding to snowball in medical tourism - if it was going to happen, it would have happened already.

Here is another question: how do new therapies become available via medical tourism? Just as medical tourism is disorganized, so too there are large challenges facing company founders who want to responsibly develop and offer a therapy outside the established mainstream regulatory systems. A clear path forward to this goal has not been built; there is no roadmap. It is the jungle of uncertainty, and investors fear uncertainty. The founders of a company heading in this direction, such as BioViva Sciences and a few others, are faced with not just the challenging of building a therapy that is safe and reliable, but also building the entire infrastructure - the relationships, the legal understandings, the third party validation of safety and effectiveness - to bring that therapy into a clinic. Then they must also survive the bombardment of negative press from organizations invested in the status quo, hostile to the idea that proving safety and responsibility really doesn't require more than a fraction of the costs that the FDA imposes. Further, the founders must successfully woo investors who are very used to the present beaten path and nervous regarding anything new.

Taken together, this is a tall order. It is a task suited to a non-profit, or more accurately a dedicated organization, or a distributed bootstrapping process of cultural change driven by many such groups. The prize is well worth it, in terms of an acceleration of progress towards many new classes of therapy, a removal of the dead weight cost that slows and suppresses advances in medicine. As is so often the case, it is far easier to articulate the change we'd like to see than to make it happen, however.

So if I started a medical biotech company, I'd have to say that I would take it through the current regulatory system, while (a) being an honest player by the rules of that system, because that is the best way through the gauntlet, and (b) continuing to hold the view that the whole thing should be replaced with a far less self-serving, onerous, expensive, and terrible option. Unfortunately, the standard regulatory path is the only fairly reliable way to put a therapy in the hands of large numbers of patients. The other, ethically far better paths, such as that pursued by BioViva, have the unfortunate outcome of great uncertainty in whether patients will ever be able to use the treatment in large numbers. I'm sure I'm not alone in having come to this position.

The change the world needs here is clear: a far more organized industry of medical tourism, and an infrastructure for responsible medical development and validation of therapies, outside the established regulatory systems, that is generally accepted by investors. These challenges are easy to state, but resistant to any sort of easy solution that can do better than reaching a fraction of the patients who might benefit. At present any one company might succeed against the odds in obtaining enough funding and support to set up an offshore clinic - but how many patients can they reach? Small heroic battles, one company at a time, will not be enough. Until greater change is achieved, near everyone who starts the process of medical development will likely look at the landscape and make the rational short-term choice to pass through the existing regulatory gauntlet.

Comments

It would be awesome if a heavy hitter like Amazon or Warren Buffet would create medical treatments (rejuv) off shore in a structured and efficient manner. I could see them making a ton of money with their cash and influance. Seems like a no brainer to me. Maybe in 5-10 years when Sencient treatment becomes common knowldege and being done in various places plus other treatments are within sight.

Maybe Peter Thiel and AudreydaGrey could connect with a few of these people/corp and make it happen?

Posted by: Robert at April 16th, 2018 3:41 PM

Bravo editor! Your awareness grows weekly. Regrettably, the same people who "HOW ROCKEFELLER FOUNDED MODERN MEDICINE AND KILLED NATURAL CURES", and profit from the American sickcare system, are not going to allow pervasive medical tourism. These are the same people who can arrange a Tomahawk missile strike as soon as a whiff of peace rises in the ME. Medical tourism will stay on the down low, or Governments will topple and facilities will be discredited or destroyed. And it will stay this way as long as it takes to create a majority autistic, drug addicted, fluoride-demented, and plastic and pesticide feminized population to relinquish their freedom to the globalists.

Posted by: Tom Schaefer at April 16th, 2018 3:58 PM

this is what concerns me the most about this field. how long will it take until the averge joe can get access to rejuvenation? if in 10 years from now things havent changed and we are still facing the challenges we have today then i dont see any hope for change in the regulatory system. we need to demand changes by making it known that we want reform in the system. it is insane that all these blockades exist, the whole system needs cleaing up fast.

Posted by: scott emptage at April 16th, 2018 6:36 PM

At Robert, the really really big downside to a large US concern getting involved in MT is that they would likely be subject to lawsuits in US courts. And thus it is apparent that the main reason US medical development costs are so high is not so much red tape but class action suits and such.

Posted by: JohnD at April 16th, 2018 7:14 PM

I haven't thought about this deeply, but I think mail order therapies may be a partial way forward. Traveling to other countries, even if you have south and central America in you back yard, is still a big ask.

Also creating a gene therapy to knock down myostatin is still a difficult technical process. Even Big Pharma and Biotechs struggle to produce sufficient volumes of virus particles to act as the vector. I'm not sure next gen lipid particles will be that much cheaper.

You could however produce a new Supramolecular Nanofiber Peptide Vaccine that raises an antibody B cell response to myostatin, but not a T cell response, which could cause an autoimmune reaction. You could then mail this thermally stable peptide from a developing country to places like the US.

Any anti aging therapy that can be replicated by injecting an antibody could be provided from overseas using this selective vaccine approach.

Posted by: Jim at April 17th, 2018 1:30 AM

Now cryptocurrencies and blockchain technologies allow completely new and efficient ways for investments. We can see as various no-name companies easily rise tens of millions dollars via ICO for clearly doubtful projects. There are thousands people out there who can invest from $1000 to $100,000 in cryptocurrencies and who believe that radical extension of healthy life is possible! Why don't many companies pursue this way? We need a someone who will break the ice and new market will emerge quickly. If you are not going to make FDA approval you can sell your therapy directly by your tokens!

Posted by: Ariel at April 17th, 2018 9:30 AM

Scott,

I have a hard time imagining drastic change in the regulatory system in 10 years. I'm hopeful, but not exactly holding my breath either.

Posted by: Ham at April 17th, 2018 10:13 AM

@Ham me neither. i asked aubrey about this and he said that because the therapies will arrive after a decade of feverish anticipation, it will drive a profound redesign of the system.

dont know what to make of that.

Posted by: scott emptage at April 17th, 2018 11:46 AM

Really good meat here today. Let's get started.

The regulatory meat grinder is killing thousands yearly. They know this, however the system is built to ensure that litigations are minimized for both the FDA itself and the pharma companies involved. The high cost and high failure rate of drugs go hand in hand. We are a pitifully fragile species, and it doesn't take much to damage or kill us. Only now are we getting better at building medicines that are made from Human cells and genes, not some foreign molecule. This is true medicine, and we have never had it before.

Government agencies will not change unless they absolutely HAVE to. The good news is, we are seeing it now. The FDA will change, probably in the next 10 years because if it doesn't, aging will become a threat to national security.

Japan has changed its version of the FDA with a progressive licensing system, specifically for regenerative medicine.

There's a lot of hand-wringing about this in the community right now. Rightly so. We could all right now be on Rapalogs and Metformin, however because of the dogma built into the regulatory and medical systems, millions suffer from age related illness. The good news is coming in a weird yet horrible twist in events.

The Japanese have adopted this new regulatory system out of desperation. The cost of their elderly is going through the roof, and they realize that unless they can get that cost down CONSIDERABLY, there won't be an economy. The best part is... the powers that be know it.

http://time.com/5233629/cbo-budget-deficit-one-trillion/

The CBO spills the beans as plain as day. 1 trillion in debt per year going forward in 2020. The US GDP is 18 trillion. Clicky on the link and have a good hard look at the numbers.

https://www.cbo.gov/system/files/115th-congress-2017-2018/reports/52480-ltbo.pdf

Yeah, that graph right there, by 2030 11.5 short years from now, Social Security/Medicare/Medicaid will crowd out all revenue growth. The 'silver tsunami' is going to wreck government budgets all across the planet.

There are only 3 ways of taming this beast.

1) Make the elderly live without medical care and pensions. They are on their own. Health care will be rationed, and with that, the demand for medicine and that entire industry hollow out. We have the technology, we have the people, but hordes of people can't afford it. So, the sector shrinks. This makes the problem even WORSE as the workers in these industries will be let go and not contributing to the tax base. Capitalism works great during times of growth, the way down however is a nightmareish slugfest. I out to know, I'm a rust-belt exile. Profits decline, we enter a new age of Breaking Bad survival as desperate people do desperate things to get medical care. We are already seeing it now.

http://www.nbcnews.com/id/8575712/ns/us_news-crime_and_courts/t/faced-debt-ga-man-shoots-postal-worker/

You won't want to live in this kind of world, so if we don't get Life Extension, death may be preferable especially for those of us getting up there in years. You may see this in the US, but just try this in Canada or the EU. Not a real option.

2) I like to call option 2 "Putting Grandma in the woodchipper". Forced death of the elderly when they become too sick/expensive to deal with. I doubt we will see this to be honest. It's been tried in the UK and it really backfired. Cost Theresa May her shot at a majority. Again, you might see this in the US, but try this in Canada or the EU. Not going to happen

3) I like to call this option "Putting Grandma in University". Grandma is well enough to be retrained for a new career, so she can be a contributor rather than a burden. Plus, it really beats the woodchipper. I know what world I would rather live in.

We have to tackle this.

If we don't do something about the costs associated with the age wave, there will be no economy, no future, nothing. The powers that be know this. Japan has started in making the changes it needs to survive. Will the US? Japan KNOWS it needs to build the infrastructure to assist its elderly. Its doing it already. Other countries will follow suit as they will be in the same boat in just a couple years.

Probably a better idea is for people who are serious about LE... GET OUT OF THE US.

Here's your real gamble.

Will the US change course before budgetary collapse?

If you don't think it will, its time to bail. For many reasons, not just LE.

Do you like getting groceries? Do you like eating? Do you have any idea what kind of taxes will be imposed on you if we don't get this under control and fast?

Do you want your healthcare rationed?

Now, I may be wrong here in my 3 options, and if you can think of a way that TPTB will slime their way out as they usually do, please, bring those thoughts forward. We need to know about them so we can plan accordingly.

For now, I'll stay in Canada. Its a good option for this.

If you need a place to stay Reason, I got a spare bed. The winters won't be so bad if we have LE :)

Posted by: Mark Borbely at April 17th, 2018 11:46 AM

Scott,

I hope. But I don't think there's going to be tons of feverish anticipation judging by all the comments and articles related to it. Especially now that we live in a world where everything is politicized heavily, especially when it comes to the 'haves' and 'have nots'. That said, I have a feeling that we're more likely to see multiple indications for something like senescent cell removal (within current regulatory boundaries... like osteoarthritis for instance) and maybe some off label use. At least before there's a sweeping change in regulation. I hope I'm wrong and that i won't have to partake in medical tourism eventually, but we'll see.

Posted by: Ham at April 17th, 2018 12:13 PM

Mark,

I feel like a lot of what you're discussing would be mitigated even if we only got moderate healthspan improvement, much like the mainstream loves to tout. It would accomplish the goal of driving down medical costs, while not actually extending lifespan... which should make the 'bioethicists' of the world rejoice. After all, you can't play god or live too long. Of course, it would suck for those of us that actually want LE, but whatever happens, happens. Still, who knows what the cost of a drug that extends even healthspan would be, especially in the US. I'm not one of the people up in arms about the rich, but I am curious to say the least.

That said, unfortunately it's not really so simple for most people to just get out of the US. Especially those who are still working, or with relatively young families. I'm in that boat for instance. There's no way I could convince my wife to just up and move to Canada or the UK unless I happened to find a job paying at least triple what I'm making now, which is highly unlikely. She wouldn't want to leave her family or friends, which I understand. I personally don't have much keeping me here, but it is what it is.

While life can change in an instant, and it's hard to project so far out, right now I think my (and many others, I wager) personal best bet would be to wait another ~25-30 years (I'll be 32 this year), then go work on obtaining permanent residency in Canada, or St. Martin or elsewhere in the Caribbean... because I sincerely do not believe anything in the US is going to change anytime soon unless it HAS to. And like you mentioned, TPTB sleeze their way out of everything. The politicians are corrupt, and go out of their way to spite and undercut the other party any chance they can, and a large amount of people vote against their own best interests whether they know it or not. It sucks.

Posted by: Ham at April 17th, 2018 1:39 PM

@Ham those bioethicists can get screwed. They are a threat and have no right to tell other people how long they can live.

Posted by: Scott e at April 17th, 2018 1:45 PM

Scott,

I agree. But they don't seem to. I mean read that article that was posted here the other day from the national post. It said something along the lines of "ethicists are starting to ask how much life is enough?", before going into a politicized rambling about the evil white tech CEO 'haves' and the 'have nots'. I'll be damned if someone else is telling me how long to live though.

Posted by: Ham at April 17th, 2018 2:23 PM

I could not said any of this better myself. Abolish the FDA and we will see considerable progress on the healthcare front.

Posted by: Nathan at April 17th, 2018 2:41 PM

I'm affraid I'm the dissenting voice here. I'm not in favour of dismantling the FDA and similar agencies everywhere, only to reform them. I'm not a libertarian, I don't think liberty is the most important thing in the world, nor that it must be guaranteed above all. And thus all the above reasoning crumbles away. We simply have different axioms, and probably will never convince the other camp.

Posted by: Antonio at April 17th, 2018 3:12 PM

I agree with Antonio on the FDA. I don't want to dismantle, but I want massive reform. There's a place for rigorous testing, but it shouldn't cost what it does or take as long as it does either.

Posted by: Ham at April 17th, 2018 3:24 PM

I hope things may improve. (a) In fact no one real rej bio therapy has enter process of registration. So we may only guess how long such a process will be. (b) New threapies based on cell or gene engineering like immunotherapy or CRISPR gene therapy was approved in less than 5 years from emerging. You can argue that they for very severe pathologies for wich approval is simpler, hovewer many ageing pathologies are very severe, like cancer, neurodegenerating , stroke , fibrosis, arthritis and so on. (c) SENS therapies are designed to be metabolically inert -- because they just eliminate the key damage, they do not need to interfere with metabolism, so it is much easier than usual to avoid side effecs and interactions with other therapies, which means they are easier to develop and test -- and much safer. This also gives hope that approval may be simpler.

Posted by: Ariel at April 17th, 2018 4:10 PM

@Ham,

I hear you brother, and I understand. It isn't easy at all. I had to do something similar at the age of 43. It wasn't another country, but it may as well have been. Lived in Ontario all my life, economics forced me out to Alberta. Family, friends all back in Ontario. I get to see them once a year if I'm lucky, but it was a matter of survival.

Isn't that what we are all trying to do? Survive? I'm 47 now, and I think I have a pretty good chance of making it to LEV. Even if I don't make it to LEV, at least my quality of life should be improved. That alone is enough to fight for. So, I made sacrifices. They paid off, in SPADES. So now, I'm paying down debt, and socking away cash for a multi-pronged future. We don't know how this is going to wind up. I DO know HOW I want it to wind up, and that's why we're here, we want to push for the world we want.

At 31, you still can pull it off. Even if you have kids. Japan would be ideal if you could make it. The EU second, Canada 3rd.

Oh and side note, don't worry about the bio-ethics people. I've been following aging tech for almost 20 years now. The change in attitude is MASSIVE and the momentum is there.

Once you show its possible, the doors are going to be blown off this. We are starting to see scientists, companies and individuals really coming forward and pushing this.

-Peter Diamandis cellularity These guys are getting serious money. The are dead on serious about making 100 the new 60.

-Jim Mellon This guy is a powerhouse. He is building a pharma company with the help of the people who brought us Lipitor and Viagra. He's working with AgeX, Aubrey, In-Silico and Sinclair. in fact, I'd be looking for news REAL soon on the next leg of Juvenescence.

-All the SENS spinouts, Ichor, Oisin, Lysoclear etc... and soon an AGE breaker? BRING IT ON.

Remember, ignore the healthspan vs lifespan quagmire. If your healthy, you don't die. Its all PR spin. Until we get that first crack in the armor.

Ham, let me turn that frown upside down. When has ethics ever won over profit? Look at the planet, if we do make it to LEV, we're going to have a lot of work ahead of us cleaning this place up. We actively hunt children in schools like animals to keep the NRA and gun makers flush with cash.

If American society is willing to do that, do you think they will put down the I.V. drip holding a genomic cure for aging because of "Ethics"?

I hate greed, but we may as well make it work for us.

Posted by: Mark Borbely at April 17th, 2018 5:40 PM

@Mark Borbely
>Government agencies will not change unless they absolutely HAVE to.
And I would say they will resist the change well after they have been dragged and goaded. And when they start transforming it will be a half-ass effort and a lot of leap service. C'est la vie...

Posted by: cuberat at April 17th, 2018 5:58 PM

@Mark Borbely
>...We could all right now be on Rapalogs and Metformin...
Rapamicine has quite nasty side effects. Metformin, on the other hand...you can easily get a prescription if you take a candy before you blood is drown, and it is given almost automatically by the doctors.

>2) I like to call option 2 "Putting Grandma in the woodchipper". Forced death of the elderly when they become too sick/expensive to deal with. I doubt we will see this to be honest. It's been tried in the UK and it really backfired. Cost Theresa May her shot at a majority. Again, you might see this in the US, but try this in Canada or the EU. Not going to happen

No way it can happen in US. Unless it is done in a really opaque way like price discrimination and such. The same powers of the bad press that slow down adoption of new therapies will slow down any initiatives to deny medical coverage for the elderly.

@Ham At April
>I feel like a lot of what you're discussing would be mitigated even if we only got moderate healthspan improvement, much like the mainstream loves to tout. It would accomplish the goal of driving down medical costs, while not actually extending lifespan...
If you improve health, you automatically increase the lifespan. Depending on the therapies you might get to square-ish life expectancy curves. But we don't die of age itself. We die because of some sickness...

Posted by: cuberat at April 17th, 2018 6:13 PM

Arial
>In fact no one real rej bio therapy has enter process of registration. So we may only guess how long such a process will be.

Mark Borbely
>Once you show its possible, the doors are going to be blown off this. We are starting to see scientists, companies and individuals really coming forward and pushing this.

Here is the key. The first therapy that gives more than marginal result will take the world by storm. Especially it improves the skin and makes you look youthful or at least not such an old fart... All the celebrities will go on medical tourism. Then the politicians, and then the all minor celebrities and youtube stars. There will be a few high-profile failures and horror stories. And there will be pro and anti-regulation swings.

Unfortunately, there will be a decade of fraudulent promises mixed with the real thing.
The cheaper treatments will for sure be used in off-shore clinics. The more expensive ones will be delayed, though.

Posted by: cuberat at April 17th, 2018 6:22 PM

@Mark Borbely
>Remember, ignore the healthspan vs lifespan quagmire. If your healthy, you don't die. Its all PR spin. Until we get that first crack in the armor.

I cannot agree more. If the investors can pour insane amount of money in some stupid ICOs or continue waste money on uber then some for sure has a pile of cash waiting for the first result, the first crack. But it has to show results. And then nothing will able to stop the deluge. It will be backed by the mix most powerful emotions and instincts: greed, self preservation, fear to miss out, desire to be sexual attractive, etc. All this backed by pools of investors money ...

But we need the first proven treatment to work. And not a treatment that consists of fasting and exercise coupled with a few food supplements and vitamins . But rather a one-off treatment that has noticeable effects...

P.S.
sorry for spamming the thread

Posted by: cuberat at April 17th, 2018 6:33 PM

I think the genetic approach to LE is the way to go in achieving LEV. We have a great start with the new CRISPR technologies. They will provide the path to LEV, in my opinion.

Posted by: Biotechy at April 19th, 2018 5:12 AM

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