FDA Dual Track Legislation Advances

S&P Global: Four Republican lawmakers have authored new legislation to permit drugs for critically ill patients to enter the market before completing late-stage trials, saying the bill was necessary because the U.S. Food and Drug Administration’s regulatory process was too slow and burdensome.

The bill would create a time-limited conditional approval pathway in the U.S. similar to a system that has long been used by European regulators.

…The conditional approval would be valid for one year and could be renewed annually for up to five years….Companies would be required to meet certain obligations, like completing clinical investigations to provide full demonstration of safety and effectiveness and other studies.

…Companies could seek full U.S. approval at any time. The FDA would be required to let manufacturers include in their applications the real-world evidence they collected during the conditional approval period.

The lawmakers want the FDA to be able to grant the limited marketing authorization to new drugs that have successfully completed phase 1 and 2 trials, with the idea that companies could generate revenue to help fund their phase 3 studies.

They emphasized their legislation is targeted especially at small biopharmaceutical companies that may struggle to cover the costs of late-stage trials.

Under the dual-track approval system, companies would be able to sell pharmaceuticals earlier but would be required to track outcomes so greater real world information would be developed in the FDA process. The result is a more dynamic approval process better suited to modern medicine. The idea is due to the excellent Bartley J. Madden (note my bias).

Madden and Nobel-prize winner Vernon Smith explained the dual-track idea, noting:

Today’s world of accelerating medical advancements is ushering in an age of personalized medicine in which patients’ unique genetic makeup and biomarkers will increasingly lead to customized therapies in which samples are inherently small. This calls for a fast-learning, adaptable FTCM environment for generating new data. In sharp contrast, the status quo FDA environment provides a yes/no approval decision based on statistical tests for an average patient, i.e., a one-size-fits-all drug approval process.

A similar process has been adopted in Japan for regenerative medicine.


Of course, what this dual-track system connotes is that the life of a critically-ill patient is worth less than the life of a patient who is not critically-ill. It probably is worth less. What concerns me is that taking greater risk with critically-ill patients will likely result in more negative outcomes, resulting in a slower approval of drugs not faster. Is that a risk worth taking? Now, it's possible that negative outcomes with critically-ill patients won't slow the approval process, that regulators (drug companies, doctors, and patients) will accept the sacrifice of critically-ill patients no different than the sacrifice of lab rats.

"Your life is worth so much to me that I won't let you try this treatment. Please understand that your suffering and death are giving future generations confidence that the proper forms were followed."

+1. Prohibiting a terminally ill person from even trying to save their life is such a noble humanitarian goal. I’ll never understand people with rayward’s position. Hard to think of a more obviously idiotic and harmful idea than opposing the right to try. “Sorry, that drug is too dangerous. We care too much about you not to just let you die.” Christ, what a moronic thought.

Very different than the sacrifice of lab rats. The rats are not allowed to choose.

This idea is dangerous, would give many patients false hope and further drive up already high and climbing U health care spending. Drug companies have been working behind the scenes to advance this policy for years.

Worst of all, this is legislation is completely unnecessary. FDA already runs a program to grant waivers for patients to access drugs before approval when an effective therapy hasn't already been approved. The agency has approved nearly every request submitted under this program to date: https://www.fda.gov/news-events/public-health-focus/expanded-access


That's what I was wondering when I read Alex's post: I thought the FDA already had such a program. How does this new one differ from the existing one?

It's a good idea overall, although one can see that it has some downside: desperate, vulnerable patients and families and doctors being pressured by say Purdue Pharma to use their products.

It clearly allows pharma companies to use the power of the market to earn money from offering drugs for sale, while being able to use the results in lieu of expensive clinical testing, which cut into a company's bottom line.

And the current process adds risk to that same company bottom line - testing on patients who are paying the full price of the medicine ensures the pharma company is able to make money even if it turns out that a particular drug is ineffective, or has bad side effects.

Kind of a win win for everyone. The sick patients, the drug companies and accelerating drug testing. Can't have that now can we???

This is a truly excellent result. Madden authored the book Free To Choose Medicine: Better Drugs Sooner at Lower Cost, which can bought on Amazon.

More information about him can be found on the Free To Choose Medicine web site at http://freetochoosemedicine.com/?page_id=13473

Would you want a seriously ill loved one to face the prospect of needing to decide whether to take an experimental drug without even the informed consent required for clinical trials?

Considering that clinical trials likely are not allowed to charge for the medicine being tested, this sounds like a huge step forward in harnessing the power of the market. Why should a drug company's clinical trials be for free for patients when there are potentially huge markets waiting for any medicine that could possibly help them.

The "market" is the millionaire patients who are terminally ill?

Or Medicare/Medicaid patients with government paying the bills?

Are you arguing private insurers, mostly employers, should hike premiums to pay for these drugs?


TANSTAAFL indeed. The current system of clinical testing is an expense to a company's bottom line. Opening up testing to paying customers will reduce the cost of clinical trials, and if the past is any guide, the pharma companies will undoubtedly use the money to keep the U.S. the world's leading pharmaceutical market.

"They emphasized their legislation is targeted especially at small biopharmaceutical companies that may struggle to cover the costs of late-stage trials."

This is an absolute joke of a statement. If the drug is promising, money is always available for late stage trials. More often than not, big pharma companies who keep constant watch on this will help fund the trials and may in the end acquire the company. As I also noted in a subsequent post, FDA already has a regulation in place to allow companies to recover costs for investigational new drugs through the Treatment IND regs which also allow expanded access.

Pharma already is the #1 or #2 industry for ROI. The returns are there.

If the barrier you're trying to address is to allow payment for product that don't work or are unsafe, there's already a legal way to harness the market. It's called dietary supplements.

You mean *getting* to decide. And yes, I would prefer that my dying loved one have that opportunity.

Not if you actually cared about them. This is being pushed, like the Right to Try Act, by people whose sole goal is to get any possible government involvement out of the way, not by any desire to improve patient care. Most clinicians dont really want these laws since we have to sit with the patients and families when things dont go well. You guys dont care about the many patients who will die, or die sooner or die badly, because you might be able to find that one pt who lived a few months longer AND these was no govt involvement.

That said we probably do owe a debt of gratitude to people who pushed for sooner approvals as drugs are getting out sooner and if you want to try a drug that is any stage of research, not just in clinical trials you can now get it quickly through the EA program, where it will be monitored for safety.


Get the government out of forcing people to resign themselves to death instead of try experimental drugs? Absolutely. I guess I just don’t care enough about patients to prioritize their acceptance of death over the possibility of some reprieve.

How are some people so reflexively technocratic that they think it’s better for a person to just *die* than “risk” a treatment without the full federal government stamp of approval. Great epitaph for a loved one: At least they died with FDA approval.

Similarly to adding another lifeboat to the Titanic, one doesn't want to denigrate steps in the right direction, but really, isn't this just politicians fiddling around with their previous mistake? If the politicians really wanted to fix it, they would make the FDA advisory rather than mandatory.
Patients who were looking for the blessing of government on the drugs they take could heed the FDA's pronouncements; those who wanted to go their own way or follow the advice of private testing companies (that would inevitably spring up in this environment of freedom), could do that too.
"What? No one pointing a gun at you and telling you what drugs you can take?" Yeah.

...step back and view the big-picture of Americans and their government establishhment.

How is it that congressmen & FDA bureaucrats have arbitrary life&death legal authority over what chemicals Americans may use for medical treatment ??

There is absolutely no basis in the US Constitution for such a situation to exist. And Congress/FDA have a very poor record in executing this extra-legal economic intervention.

That it now indeed does exist and is blindly applauded by many ... is a much larger problem for Americans' well-being than any narrow focus on individual medical chemicals.

Little noticed in the article:

"Most products fail."

This is about money. Do the company's propose to give away their drugs for free as part of the trial?

Or, will we be paying for failed products?

Will this encourage more failures, as there is no check. Will companies which could have paid for trials, now not do them or do abbreviated trials with human guinea pigs.

As they say, incentives matter.

I like the way this is presented as something novel when in fact companies have had the ability to do this for many years under FDA's Treatment IND regulations. Companies could also sell drugs granted a Treatment IND to recover costs, they could not profit from such sales as the drugs were deemed investigational.

In the early 1990s I was part of the Public Health Service working group that came up with guidelines for the parallel track release of investigational HIV drugs when there were no good treatment options for the disease. One of the things we struggled with was how to preserve the clinical trial process as well as monitoring for adverse drug reactions. Even the AIDS activists who sat on this work group did not want to compromise the ongoing clinical trials as they wanted drugs with proven efficacy and known safety profiles.

While it might be fun for economists and libertarians to think this is their idea, it really isn't. The pharma industry had discussions about such an approach at least a decade before such literature started appearing.

This approach will not be the panacea that folks think. Companies seldom produce enough drug product beyond that need in the clinical trial. Even if it were happen, what type of safety surveillance will be required? Will informed consent be required? Will the ongoing clinical trials be compromised? What will the pharma company's liability be if new serious adverse reactions appear?

Most practicing MDs have little understanding of the clinical trial process and don't even manage their patients all that well with currently approved drugs. How many patients even read the inserts that come with their medicines (they surely don't read the full prescribing information that is easily sourced from the dailymed website at the National Library of Medicine.

This is and has always been a dumb idea in search of a virtually non-existent problem.

Clearly, you are missing the point of such proposals - this allows companies to harness the power of the market to ensure they can sell an even broader range of products than those currently offered.

The market should decide what treatments are best for people facing death - and there is no reason that the pharma companies cannot do their best to ensure this fear is handled through commercial, not regulatory, transactions.

Just imagine the burden on so many people during the AIDS crisis of the 80s - there was no reason that drug companies should not have been able to offer any product for sale to people facing a death sentence. Pharma companies have never been motivated by a sense of pure charity, and opening up the market will increase the range of products being sold.

Do you not understand the concept of product liability??? Companies use FDA approval as a defense against lawsuits and are usually successful. The only way your approach works is for required "informed" consent from the patient and a waiver of all liability. As I said, patients and most MDs are ill equipped to make decisions on experimental drugs.

You clearly know nothing about drug discovery and development. I was in on the original discussions to expand access of experimental AIDS therapies. The scheme we came up with worked, access to treatment was there, and drugs were also quickly approved.

Product liability can also be restricted by lawmakers - and it would certainly be to the benefit of a pharma company to be able to escape lawsuits when providing not yet approved medications.

People are not ill equipped when it comes to the desire to purchase anything that offers even a glimmer of hope to those facing death.

I know that if there is legislation that increases access to untested drugs and increases pharma company earnings, there will be a constant drumbeat to let the power of the market function, and increase the amount of drugs that can be sold.

In the late 1970s and early 1980s a lot of people were trying amygdalin (Laetrile) for treating various cancers. Clinics in Mexico were selling the treatment. It didn't work. Do you really want to go down this path again??

If the FDA were to get out of the way, Laetrile would be legally available in 20 states or so, thus keeping patients at home.

And maybe if Laetrile was finally broadly available, there would be no question about its efficacy after a decade or two of selling it to anyone feeling their life would be extended by buying it.

And there is no question that there remain advocates of Laetrile who would be pleased to sell that product again.

If someone who’s terminally ill takes a drug and it doesn’t work, they die. If they don’t take it... they still die. What exactly is the benefit of the former? Explain to me why even a 0.0001% of surviving is worse than a 0%? Is it just the idea of something without a government imprimatur working that upsets you? God forbid a regulatory body not be perennially vindicated.

The replies to this comment include these lines: "If the FDA were to get out of the way, Laetrile would be legally available in 20 states or so"

"If someone who’s terminally ill takes a drug and it doesn’t work, they die. If they don’t take it... they still die. What exactly is the benefit of the former?"

The advocates for unfettered sales to desperate patients miss the big picture, namely the opportunity cost of the sales efforts. That's where the economic inefficiency and waste is produced.

It's analogous to one of the important hidden costs of crime: if I steal your TV set, seemingly all that's happened is a redistribution of assets. But in addition to the issues of justice or fairness, there's also the opportunity cost: I should be working at doing something productive rather than working at stealing somebody's TV. Criminals are spending effort doing socially useless activities.

And the same for the crooks and charlatans who manufacture and sell laetrile and other quack cures. It's the medical market's equivalent of Keynes' workers digging holes and filling them in again: wasted activity, a misallocation of human resources where people are making laetrile or snake oil instead of ... anything that would be remotely useful, even flipping burgers at a fast food restaurant.

It would be lead to better outcomes if each patient were required to spend $20000 on Powerball tickets.

Are there life-saving treatments being held up by bureaucrats? Real breakthroughs in pharmacology are actually quite uncommon. What was the last big game changing drug?
It might be interesting to compare the number of people not getting treated due to regulatory hurdles with the number not getting treated due to the cost of approved pharmaceuticals.

OMFG! I just read the piece by Vernon Smith. No one who is involved in medicine would actually believe what is being proposed will cut the costs of pharmaceuticals. This is ideologically driven it is unbelievable.



It seems, at best, this is a duplicate program (Republicans have, and I fully supported this, passed proposals to speed up drugs for terminal patients and the FDA has invented it's own programs), and at worse, it may contain loopholes that Pharma companies can exploit.

And that's really the danger isn't it? I can't really say what my issue with the bill is, but I am absolutely certain lawyers at Pharma companies will come up with something. The question is, is the benefits worth it. I have a hard time believing they are.

Take a look at Hatch-Waxman. Or the Orphan Drug Act. Whenever one of these bills comes along companies, and the government for that matter, abuses it. The benefits of Hatch Waxman outweighed the loopholes. Orphan drug act is more mixed.

One possible loophole: Company says drug A will cure rare disease B. Due to this bill, it can bring the drug straight to market with little testing, right? But the companies real intention was to sell the drug for disease C, which isn't particularly rare or life threatening.

So it goes through the motions of this bill for B but in reality encourages doctors to treat patients with C.

And sure, maybe there are safeguards. But that's the point, it is literally impossible to design a bill, particularly a pharma bill, without having some loophole of some kind, especially when it is written by lobbyists, which, and I know this from working in the industry, they all are. The congressmen don't write a word. It is literally their job to write the bill in such a way to disguise the stuff they want in the bill to get it past Congress and journalists. And if a congressman asks about it, the lobbyist throws back intelligent sounding nonsense to make the person seem like an idiot. Granted the lobbyist knows more, but they have an agenda.

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