DIY Gene Therapy

by on January 24, 2017 at 6:03 am in Economics, Law, Medicine, Uncategorized | Permalink

As I noted in yesterday’s post, Will Trump Appoint a Great FDA Commissioner?, personalized medicine is a challenge to the FDA. Technology Review has an excellent piece on an extreme version of personalized medicine, DIY gene therapy:

Hanley, 60, is the founder of a one-man company called Butterfly Sciences, also in Davis. After encountering little interest from investors for his ideas about using DNA injections to help strengthen AIDS patients, he determined that he should be the first to try it. “I wanted to prove it, I wanted to do it for myself, and I wanted to make progress,” says Hanley.

Most gene therapy involves high-tech, multimillion-dollar experiments carried out by large teams at top medical centers, with an eye to correcting rare illnesses like hemophilia. But Hanley showed that gene therapy can be also carried out on the cheap in the same setting as liposuction or a nose job, and might one day be easily accessed by anyone.

…Hanley opted instead for a simpler method called electroporation. In this procedure, circular rings of DNA, called plasmids, are passed into cells using an electrical current. Once inside, they don’t become a permanent part of person’s chromosomes. Instead, they float inside the nucleus. And if a gene is coded into the plasmid, it will start to manufacture proteins. The effect of plasmids is temporary, lasting weeks to a few months.

Hanley’s method is painful and doesn’t last long but it’s remarkable that it can be done at all.

At least one additional person who underwent self-administered gene therapy is a U.S. biotech executive who did not want his experience publicly known because he is dealing with the U.S. Food and Drug Administration on other matters.

Hanley says he did not secure the approval of the FDA before carrying out his experiment either. The agency requires companies to seek an authorization called an investigational new drug application, or IND, before administering any novel drug or gene therapy to people. “They said ‘You need an IND’ and I said, ‘No, I don’t,’” recalls Hanley, who traded e-mails with officials at the federal agency. He argued that self-experiments should be exempt, in part because they don’t pose any risk to the public.

Hat tip: Samir Varma.

1 priior_test2 January 24, 2017 at 6:33 am

Truly, time to free laetrile from its FDA shackles. After all, it has seemingly been used to treat cancer since 1845 ( https://en.wikipedia.org/wiki/Amygdalin#History_of_laetrile ), and has the sort of proven track record that the Bartley J. Madden Chair in Economics at the Mercatus Center is unlikely to disparage. At least when it comes the evil overreach of the FDA, that is.

Really, everyone with one foot in that invisible graveyard should have the right to buy laetrile, whenever and wherever they want. Particularly is they are informed patients, paying for the privilege to use something with the following side effects – ‘The side effects of laetrile treatment are the symptoms of cyanide poisoning. These symptoms include: nausea and vomiting, headache, dizziness, cherry red skin color, liver damage, abnormally low blood pressure, droopy upper eyelid, trouble walking due to damaged nerves, fever, mental confusion, coma, and death.’

2 dan1111 January 24, 2017 at 7:15 am

Modern, FDA-approved chemotherapy treatment is likewise the application of poison to your body. Literally every single one of those side effects is also a side affect of approved chemotherapy treatments.

3 prior_test2 January 24, 2017 at 7:26 am

Yes, it is. Except that a certain amount of efficacy, proven with clinical trial, is assumed to exist. But in a world where alternative facts are seemingly in the ascendant, clearly laetrile is just as good as any other poison.

4 Veobaum January 24, 2017 at 7:32 am

But what does that have to do with rights of self-experimentation and discovery?

5 dan1111 January 24, 2017 at 7:54 am

How much can people be trusted to make their own informed decisions about their care and what risks to take, as opposed to the government making the decision for them?

How high should the bar be for “evidence of efficacy” for treatment of a terminal condition that may have no known, approved curative treatment?

What would the effect of less FDA regulation be on the overall evidence gathering and drug development process?

These are serious questions which Alex’s position raises, but you aren’t interested in the issues, only in beating this blog’s authors with whatever stick happens to be nearby. In this case it was “ha ha ha, don’t you know that non-approved drugs are dangerous, you moron?” A point which was totally irrelevant since all approved cancer treatment is also dangerous.

6 Veobaum January 24, 2017 at 7:58 am

Exactly.

7 anon January 24, 2017 at 10:05 am

Or, in a situation I am familiar with, is this actually a rational criticism “from the wrong person?”

How exactly do you stop hustlers from selling DIY gene therapy kits by mail, as they once did laetrile?

How is random experimentation by random dudes not “the public?”

8 dan1111 January 24, 2017 at 10:24 am

@anon, a cost-benefit analysis is needed. The problem with this debate is that the costs of low regulation are highly visible, while the costs of high regulation are invisible. This weighs the debate heavily in one direction.

Yes, hustlers selling fraudulent medicine are a problem. So are harmful side effects from inadequately tested drugs. But what about the harm caused by drugs not being developed because the costs are too high in the current regulatory environment? If regulations reduce the number of life-saving treatments being developed, then patients die as a result. But they aren’t visible like a patient who dies from a drug side effect.

9 anon January 24, 2017 at 10:31 am

The fundimental problem is that we can’t tell if this “invisible graveyard” we are supposed to imagine is big or small, or even if some are indulging in a “fantasy graveyard.”

Picking up on the argument below, that “every other similar agency in every other country makes those tradeoffs non-optimally.”

Doe foes of “regulation” recognize all the “missing graveyards?”

The lives saved by food and drug regulation? Or for that matter, motorcycle helmets?

10 Ray Lopez January 24, 2017 at 11:29 am

@dan1111 – right on, brother right on. Anybody who knows anything about cancer knows that cancer cells are like “fungus” in that they are very fragile, being a form of incomplete and less than robust DNA, and the theory behind chemotherapy (both chemical and radiation) is to blast the body site having cancer, which will kill all cells, but the cancer cells, being more fragile, will die faster than the normal cells.

11 Avens January 24, 2017 at 7:24 am

Please stop posting on this blog. You’re worse than my sil from whom every utterance is identity-boosting self-indulgent contrarianism.

If it were just genuine argumentation for the sake of discussion, it would be fine. But yours is a transparent, stereotypical personality quirk that we all recognize. Please heckle somewhere else.

12 Veobaum January 24, 2017 at 7:32 am

+1

13 prior_test2 January 24, 2017 at 7:42 am

‘If it were just genuine argumentation for the sake of discussion’

The point about laetrile in connection with the Bartley J. Madden Chair in Economics at the Mercatus Center continuing attacks on the FDA has been going on for years. Actually, it took years for the Bartley J. Madden Chair in Economics at the Mercatus Center to even acknowledge that there might be at least another reason, behind his pure desire to improve the health of humanity, why he posts on such subjects.

Unfortunately, if I were to post more details, only a select few would be likely to read them, if the experience of the past five years or so is to be used as a guide.

‘But yours is a transparent, stereotypical personality quirk that we all recognize’

Guilt – I used to work at GMU PR dept. a couple of decades ago. And much like pointing out a fully understandable reason for Prof. Tabarrok to post like he does on this subject, I also pointed out what a PR fantasy the founding story of MRU was, with its tale of youtube, a $4 app, and two GMU professors.

But maybe you can read about Bartley J. Madden on your own, without anyone needing to provide excerpts, links, affiliations, etc.

True, it is hard to please everyone – instead of link and text laden posts like in previous years, the last few weeks have been an attempt (not always successful, of course) to be a bit less digressive, as per another commenter’s suggestion.

Of course, the mockery of the GMU econ dept. goes way back in time within GMU, so you do have that right – it can be a really hard habit to break, it seems.

14 dan1111 January 24, 2017 at 8:02 am

“Unfortunately, if I were to post more details, only a select few would be likely to read them, if the experience of the past five years or so is to be used as a guide.”

I’m a bit confused by this logic. Because you still seem to be posting comments. A lot of them.

No one is paying attention, so you need to make your comments as banal and substanceless as possible, but it is still important to post the comments themselves?

15 dan1111 January 24, 2017 at 8:04 am

BTW, looked up Bartley J Madden just for kicks.

He’s a former investment manager who now promotes limited government and free market ideas. Gasp!

16 prior_test_translator January 24, 2017 at 8:30 am

I believe Bartley J Madden is spreading propaganda through this blog. I don’t like that.

17 Ray Lopez January 24, 2017 at 11:33 am

@Avens – Stop blogging? You directing this offensive comment to who? AlexT or prior_test2? Both of them have a right to speak and both of them make, on occasion, good points. Even AlexT, with his bogus first generation simplistic anti-IP arguments (which I’ve heard so often before, but if you’re not skilled in the art they seemingly make sense, in the same way communism makes sense to a peasant farmer).

18 prior_test_translator January 24, 2017 at 8:31 am

I disagree with this post because the FDA is a good thing and protects us from dangerous medical treatments.

19 NatashaRostova January 24, 2017 at 10:28 am

This is such a horrible meme argument.

>The FDA is not working as intended, there are numerous cases where onerous processes are preventing high tech innovation and rapid prototyping etc.
> hehe… but have you ever considered this random example from the past where [example drug] people thought was useful was actually not useful and dangerous? Boy, you must feel pretty stupid right now for not knowing about this link to [example drug]. Looks like the FDA is actually totally great and there is no nuance to anything ever 8)

20 Alan January 24, 2017 at 6:59 am

That list sounds like the end of so many drug commercials these days.

21 rayward January 24, 2017 at 7:04 am

Tabarrok doesn’t believe in the wisdom of crowds, preferring instead the individual’s wants and desires. I’ve been involved in a project to develop a wireless capnography device that would monitor vital signs. It’s part of the “remote monitoring” technology that has received lots of attention (and investment) over the past few years. The economic incentives for such devices include Medicare rules adopted several years ago that punished hospitals (by denying reimbursement) for patients readmitted within a short time; by monitoring (remotely) discharged patients, readmissions would be cut. What’s held back widespread development and use of remote monitoring are two factors: first, the how do you make money from it factor (i.e., who would pay and how much would they pay), and second, the WTF factor. This comment is about the WTF factor. The idea of 24/7 health care is appealing to lots of people, presumably including people such as Tabarrok who prefer a highly individual approach to medicine rather than the wisdom of crowds approach that has been the custom. If everyone has a remote monitor, who will monitor the monitors? That’s the WTF factor. And it’s the response I get from physicians. It’s one thing to monitor patients confined to a hospital, but quite another to monitor everyone, at home, at work, at the gym, on the road. Monitoring every individual, like finding highly individual therapies for every individual, is fine in theory but not so fine in practice. Economics is like that too.

22 dan1111 January 24, 2017 at 7:19 am

What do you mean by the “wisdom of crowds” approach to healthcare? How did you reach the conclusion that Alex would support remote 24/7 monitoring? I don’t get this at all.

23 Lurker January 24, 2017 at 7:29 am

‘Who will monitor the monitors?’

Isn’t that what Watson is for?

I am no expert, but it does seem there is a lot of opportunity for automating health care services. A disruption of the intermediary, like Apple did with the recording industry. Certainly that is the sort of thing they are looking at as the next big growth opportunity.

Also, wouldn’t having this sort of information available to the individual on their “wrist watch’ (so to speak) encourage people to be more proactive in their own health maintenance?

24 Chip January 24, 2017 at 9:32 am

Isn’t the wisdom of crowds determined by allowing individual wants and needs to play out?

How do you get the former without allowing the latter to occur?

25 Just Another Right Wing Economist January 24, 2017 at 7:23 am

As if FDA is the problem lool, the problem is the science. I know libertarians are a bit stubborn, but you are a professor, you are supposed to see a bit beyond your own mood affiliation… There are some very good reasons for FDA to do what they do, of course, they are far from perfect, but c’ mon….

26 prior_test2 January 24, 2017 at 7:44 am

If you are just another right wing economist, I’m sure that the motivation of the Bartley J. Madden Chair in Economics at the Mercatus Center should be fairly obvious. It is not about the science.

27 prior_test_translator January 24, 2017 at 8:32 am

Conspiracy!

28 DavidPtr January 24, 2017 at 10:47 am

Sometimes, there really aren’t good reasons. There is no good reason for a company producing a generic medication, for example, to go through a three year, multi-million dollar effectiveness trial for a drug that has already been proven to be safe and effective. All the company should have to do is prove that it can produce the drug to appropriate purity.

29 AlanG January 24, 2017 at 8:29 am

I can well remember back to the dawning of the biotechnology era (I started my career in drug regulatory affairs right around the time of the first approvals of human growth hormone and alpha-interferon). I well remember everyone saying that these products were intrinsically safer because they are HUMAN proteins and won’t pose the same toxicity issues as xenobiotic drugs. Well here we are 35 years later and the number of adverse events from biotechnology products is no smaller than those identified for their chemical counterparts. In some cases the rare adverse events are much worse (just listen to one of the many television advertisements where the litany of side effects is recited). Now maybe plasmid DNA electroporation is safe, maybe it works, but the only way to know this is to do the clinical research. We have informed consent, institutional review boards, and FDA review of INDs for a very good reason: patient protection.

I didn’t post this yesterday on the FDA commisioner discussion but I always find it instructive when these debates come up to look at the history of antineoplaston research (https://en.wikipedia.org/wiki/Burzynski_Clinic) The investigator argued that this was a natural cure for cancer and INDs were not needed. Treatment didn’t work and a lot of sham science was reported out. Now the libertarians may not like the FDA but in the absence of somebody who has no vested interest and will review and adjudicate the data, how do you make an informed decision??

As has been pointed out laetrile was thought to be a wonderful drug and folks were traveling to Mexico to get it from a clinic down there. Didn’t work and was toxic. Caveat emptor. I have worked with he FDA for over 30 years and have seen the agency evolve over time. Decisions are science based and one can have confidence in the reviews. Can the same be said of the work done at Butterfly Sciences?

30 dan1111 January 24, 2017 at 8:52 am

“We have informed consent, institutional review boards, and FDA review of INDs for a very good reason: patient protection.”

This is a common, but question-begging response. Does the current drug regulation do an optimal job of “patient protection”, especially balancing the costs of avoiding harmful drugs with the costs of not making potentially beneficial drugs that lessen the harm of disease available? Alex and some others argue that it does not. Maybe they are incorrect, but their points can’t be rebutted with a simple appeal to “patient protection”.

Lack of federal regulation, or a lower bar for approval, would probably increase cases of quacks selling ineffective or dangerous drugs (like the examples you cite). However, it may also make beneficial drugs available more quickly and quicken the cycle of innovation in medical research. What is the right balance between these two effects? One of the main problems here is that one side of the equation (harm caused by bad drugs) is highly visible, while lost benefit from drugs that are not approved or not developed is invisible.

“Now the libertarians may not like the FDA but in the absence of somebody who has no vested interest and will review and adjudicate the data, how do you make an informed decision?”

Let’s leave aside the libertarian “true believer” argument on whether the FDA should exist. Even if one thinks the government is necessary as an impartial actor, that doesn’t imply the current setup is optimal. The FDA could still exist with a lower bar for drug approval. Or the FDA could provide evidence reviews on an advisory basis, to inform doctors and patients without being the gatekeeper telling them what they are allowed to do. There are many options between the status quo and the extreme of no regulation at all.

31 AlanG January 24, 2017 at 9:38 am

@dan1111- FDA, doctors and patients all have to weight the benefits and risks of the drugs the approve (FDA), prescribe (MDs) and take (patients). The entire clinical trial process is designed to optimally find out 1) whether the drug works and 2) how safe it is to take according to the approved indication. No drug is entirely safe and some drugs work better for some patients. This is a fact of life. I always began talks by stressing, “the right drug, in the right dose, at the right time.” As I and others said yesterday, the FDA is not the problem. If there is an outstanding drug with good clinical data, it is approved quickly. I know of no case where a good drug was not approved or not developed as per you statement in the first point.

You seem to think doctors will make informed decisions if there is just an evidence review. Do you think they would even read this information? How many doctors are even familiar with the full prescribing information that is available today (https://dailymed.nlm.nih.gov/dailymed/index.cfm)? Do they have a reasoned base discussion with patients about any prescribed therapy? Certainly not in my experience and many of my colleagues. If you think an alternative scenario to current FDA oversight is valid by all means pose it and let us see what the up and down sides are. Point out some good drugs that are languishing because of the current regulatory regime.

32 David R. Henderson January 24, 2017 at 9:57 am

AlanG didn’t really answer dan1111’s point. AlanG has correctly pointed out the tradeoffs. But he hasn’t shown that the FDA makes those tradeoffs optimally. To make that case, AlanG would have to show that every other similar agency in every other country makes those tradeoffs non-optimally.

33 anon January 24, 2017 at 10:09 am

That was a bit of a tell. Since you dislike government in general you will distrust the FDA and fly by the seat of your pants.

I am thankful this is a far from mainstream position.

34 dan1111 January 24, 2017 at 10:11 am

You are no longer allowed to fly by the seat of your pants more than two feet high outdoors, because it’s federally regulated airspace.

35 AlanG January 24, 2017 at 3:04 pm

@David R. Henderson – To better amplify the point and address the issue you raise, the three major regulatory regions Japan, US, and Europe (European Medicines Agency) have worked along side industry through the International Conference on Harmonization (ICH http://www.ich.org/home.html ) to harmonize regulatory requirements throughout the regions. There are other countries who have joined in full or via observer status to take advantage of this work. Plenary sessions are regularly held and there are numerous work groups. Ultimately, each regulatory agency is responsible for its own decision regarding product approval. Now you and others might argue that this is not optimal and maybe that is the case. Even if you wanted FDA to accept such decisions, there is no guarantee that there would be a reciprocal acceptance of an FDA approval by Japan or Europe. Japan has always argued that special sub-trials need to be done to address unique issues in the Japanese population and some would say this is just silly. The point is that over 2/3 of new drugs get a first approval in the US relative to other major regulatory regions. I know FDA regularly published this information.

Drugs with clear clinical endpoints have straight forward trials and the regulatory submissions are easy to evaluate. However, for many other drugs things are less clear and as I’ve noted this is one of the very big hurdles in developing an effective Alzherimer’s drug. FDA has used expedited reviews and issued approvals for oncology drugs with requirements for further testing. There are some oncology drugs that can provide a cure (mostly the blood and blood related cancers) but for solid tumors that’s not the case. In such cases remission is usually looked at. FDA tolerates a much greater adverse safety profile for oncology drugs and requires much more assurance of safety for drugs and vaccines given to health people. The vaccine case is particularly illuminating as many of these are given to infants and young children. Clinical trials tend to be very large so that rare adverse reactions can be uncovered with statistical accuracy (1 in 10,000 rare event requires a trial size of 30,000). I think we parents are well served by caution in this area.

I hope that addresses things, let me know if it doesn’t and I’ll try again.

36 dan1111 January 24, 2017 at 10:09 am

Is the situation where it takes 10 years and a couple of billion dollars to bring a drug to market really optimal? I just can’t believe that. It’s not just the FDA review once evidence is in place, it’s the whole process of gathering “good clinical data” and all the requirements around that (which have grown much more onerous in recent years).

One idea would be to have less of a hard line between research and clinical practice. I’m allowed to subject myself to quite a lot of risk within the special context of a clinical trial, if I sign on the line. Why not broaden the contexts in which people can choose to consent to increased risk and using something that doesn’t have a full evidence base, in the name of science? These days data about routine care can be collected very easily from clinical systems and analysed, to provide an evidence base that improves on an ongoing basis.

37 Axa January 24, 2017 at 10:47 am

This discussion is bit like Marxism. Alex is like Marx telling the workers how shitty their life is and how they must revolt and take control. However, the oppressed workers (gene scientists) say “no problem we’re fine” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330248/

38 dan1111 January 24, 2017 at 11:56 am

A couple of researchers, but presumably not all, are fine with it. Anyway, the system should be optimised for the benefit of patients, not researchers.

39 Mark Thorson January 24, 2017 at 8:24 pm

Were travelling to Mexico? They’re still going! Laetrile and more!

http://cancercontrolsociety.org/forms/trip/bus_tours.html

If you’re a dentist or a nurse, you can get continuing education credits just for taking the tour of Tijuana clinics! Muy bueno!

40 rayward January 24, 2017 at 8:48 am

Does medical technology add more years of good health or just add more health care spending late in life? Here is a good summary by the always impressive Austin Frakt: https://www.nytimes.com/2017/01/23/upshot/blame-technology-not-longer-life-spans-for-health-spending-increases.html?action=click&contentCollection=upshot&region=rank&module=package&version=highlights&contentPlacement=2&pgtype=sectionfront

41 Axa January 24, 2017 at 9:31 am

It’s a nice inspirational history, it should be on Buzzfeed.

In more practical concerns, if I show up an invoice of this guy to my medical insurer, will they reimburse the expenses? FDA approval and insurer coverage are not the same. Alex tells a story where the FDA is the only obstacle between a new procedure/drug and patients. This is an economics blog, perhaps it’s time to look at why insurers cover some procedures not approved by the FDA and refuse to cover some FDA approved drugs.

42 AlanG January 24, 2017 at 9:42 am

Some drugs are not covered because of formulary decisions by the insurer. They believe that alternatives exist that are as good as the drug that is denied coverage. They also have tiered co-pays where you pay more for a drug that is not their preferred one. they also might require you to utilize a less expensive drug regimen to see it it works before allowing use of an expensive biotech drug (methotrexate therapy for psoriatic arthrits before going onto the Enbrel). all of those are economic decisions by the insurer to control costs. Otherwise your premium would be much higher.

43 Axa January 24, 2017 at 10:24 am

The specific topic is “personalized medicine”. A curious case is the Oncotype DX test with no FDA approval but it’s covered by most health insurers. This test started to be applied by 2010 and only until 2015 clinical utility studies came up. The studies show the test works, but proving it took years. http://www.breastcancer.org/symptoms/testing/types/oncotype_dx

It would be interesting if some journalist told the whole story of this personalized medicine application. This test helps to decide if chemotherapy is needed or not to treat breast cancer by assessing the “aggressiveness” of it. This specific cases shows that FDA approval is tangential to the advance of personalized medicine.

44 AlanG January 24, 2017 at 2:46 pm

There are a lot of tests that are not covered by FDA’s medical device regulations. These are largely tests carried out in certified labs under the Clinical Laboratory Improvement Act (CLIA). There might be some aspects of a particular test that might be regulated by FDA but it depends on the nature of the test. A lot of the older chromosomal genetic testing has never been regulated by FDA. I suspect the one you refer to falls into that category.

45 Thanatos Savehn January 24, 2017 at 12:38 pm

Some cancer sufferers are starting to experiment with Coley’s toxins in an effort to trigger a massive response while they wait for the FDA to decide what to do about immunotherapy. If they can aggregate and analyze their results and find something positive and reproducible they might outrun and so undermine the bureaucrats.

46 AlanG January 24, 2017 at 2:47 pm

Hope they have better luck than all the researchers who have spent upwards of 100 years looking at this treatment.

47 Thanatos Savehn January 24, 2017 at 6:06 pm

They just need the kind of luck Barry Marshall had.

Along those lines, what do you make of the hints suggesting that Alzheimer’s etiology has an infectious component? And, when will Pharma throw in the towel on the small molecule business model?

48 Jeffery Mewtamer January 24, 2017 at 2:11 pm

I don’t think a complete lack of regulation would be a good idea, and I’m not convinced the problem of drug approval has an optimal solution, but I’m not convinced the FDA does a substantially better job than its foreign counterparts.

That said, an approval process that takes 10 years and costs billions of USD on top of costs inherent to drug development sounds downright ridiculous.

Some things I wonder though:
Since the fall of the soviet union:
How many drugs have been approved in another developed nation but have been rejected by the FDA?
Of these, how many have been linked with above average incidence of serious or life threatening side effects?
How many drugs approved in another developed nation have not undergone FDA evaluation?
Of these, how many have been linked with above average incidence of severe or life-threatening side-effects?
How do the FDA’s foreign counterparts compare in a similar analysis?

If other developed nations are approving large number of drugs the FDA rejects with little or no increase in incidence of severe or life-thretening side effects, I would think that strong evidence that the FDA might be turning out too many flase negative for drug safety, and if foreign nations are approving lots of drugs whose makers aren’t even pursuing FDA approval, I’d think that strong evidence that the procedure itself might be acting as a substantial barrier to entry. Of course, if foreign countries are approving lots of drugs that seem to be doing as much harm as the diseases they’re supposed to treat, that’s an indication the foreign country might be too lax in it’s approval process.

Admittedly, I’m not pharmacist and my medical training is limited to a college first-aid class I took in 2014 and I let my first-aid certs expire, but based on my limited knowledge, I’m leaning towards thinking the FDA either rejects too many drugs or has made their approval process prohibitively long and expensive and I’ve heard little to suggest it’s foreign counterparts, at least in the developed world, have a significantly bad record of approving bad drugs.

49 AlanG January 24, 2017 at 3:12 pm

“That said, an approval process that takes 10 years and costs billions of USD on top of costs inherent to drug development sounds downright ridiculous.”

I’ll not deal with the cost of drug development, the Tufts Center of the Study of Drug Development has done that cost analysis and they have provided information on their methodology. However, it’s not the approval process that takes 10 years, but the total time from discovery to approval. As I noted in a post above, development time is highly contingent on the indication being studied and what the data requirements might be. The better the surrogate end points, the quicker the development time. Consider the early days of HIV when a lot of the basic biology was still being worked out. the first approvals were for antivirals that had been around for a long time as possible oncology drugs. Then when the biology of the virus was worked out alternative drugs were synthesized and studied. New gene technologies permitted the use of viral load as a marker. Most of the newer class of HIV therapies were developed quickly and the regulatory time at FDA was usually shorter than six months.

50 qetzal January 24, 2017 at 9:25 pm

For those who think FDA regulations are too stringent, consider that 90% of all drug candidates that go into clinical testing end up failing. Even more shocking (IMO), almost 40% of drugs the get to Phase III testing still fail. In other words, even after a drug has shown preliminary evidence of efficacy in Phase II, there’s still almost an even chance that it will ultimately prove to have insufficient efficacy and/or safety. If we eliminated the requirement for Phase III testing, then half (at least) of all approved drugs would be ineffective and/or unsafe. If we eliminated the requirement for even preliminary efficacy in Phase II, as some would advocate, we could expect something like 80% of all drugs to be ineffective/unsafe.

Those statistics should also give pause to people who advocate for so-called real-world testing and approval. If a drug company, motivate by profit, can’t reliably determine if a drug works based on a highly controlled Phase II clinical trial, why should we think that uncontrolled, highly variable data consisting essentially of hundreds of individual n=1 trials would do better?

That’s not to say that I’m convinced FDA’s approach is optimal. But I don’t believe there are any easy or obvious fixes.

Lastly, coming back to the question of DIY gene therapy, I don’t object in principal to Hanley wanting to do gene therapy on himself, using plasmids and electroporation. I think he’s being foolish, and I can essentially guarantee that it won’t work. Literally billions of dollars have been devoted to that idea, and so far, it’s never worked. (I say that as someone who helped spend some of those billions while working at a gene therapy company that ultimately failed.) But if he wants to try it anyway, that’s his choice as far as I’m concerned.

Where I think this gets tricky is, where did he get the DNA? Where did he get the electroporation equipment? Did he make it all himself, or did he buy it from someone else? Should companies be allowed to sell DNA and electroporation equipment for people to use on themselves, with no regulations or oversight? Personally, I’d argue no. I tentatively believe there is a net societal benefit to having regulations and approval requirements in this arena.

51 Abelard Lindsey January 25, 2017 at 12:04 pm

One problem with FDA regulation that has yet to be mentioned here is that the FDA does not consider aging itself to be treatable medical condition. So, even if a therapy is effective at treating aging, the FDA will not approve it. I suspect this antiquated policy is due to nothing more than bureaucratic inertia. As such, DIY medicine is necessary for the development of effective anti-aging medicine and, no, there is no net societal benefit to having restrictions on the sale of DNA and laboratory apparatus to private individuals. I think people should have the freedom to experiment on themselves, as long as they are willing to live with the risks, and should have the commensurate freedom to purchase the instrumentation and supplies necessary for such self-experimentation.

If the FDA is too rooted in its bureaucratic culture to consider aging to be a curable condition, then its mandate to regulate bio-medicine as it relates to aging should be curtailed and a new government agency created, if necessary, to monitor the efficacy of anti-aging therapies.

52 qetzal January 25, 2017 at 10:47 pm

I think you’re wrong about FDA and ageing. See, e.g. http://www.newsweek.com/2015/12/25/diabetes-drug-could-be-anti-aging-miracle-404370.html. Also, in the US, the legal definition of a drug includes “articles (other than food) intended to affect the structure or any function of the body of man or other animals ]FD&C Act, sec. 201(g)(1)].”

Hard to see how something that slows ageing or reduces age-related effects on the body wouldn’t fall under that definition.

53 Abelard Lindsey January 27, 2017 at 12:33 pm

It was something like 5 years ago that some spokesperson from the FDA reiterated the position that the FDA did not consider aging to be a disease and, therefor, would not even consider approval for anti-aging therapies even if they worked. Perhaps attitudes have changed since that time. My point is that if the FDA refuses to consider aging to be a disease, then it needs to be either reformed or abolished and replaced by a new agency that will consider aging a disease. In any case, such antiquated attitudes towards aging are no longer appropriate.

I would like to see fast track development and approval for anti-aging medicine like SENS in a manner similar to that ot the approval of the HIV/AIDS therapies. If Thiel manages to convince trump to appoint Jim O’neill as FDA chairman, I think we’ll get such fast track approach to curing aging.

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