Bioethics Clinical trials Medicine Politics

As I predicted, the exploitation of desperate patients using right-to-try begins

I warned you. I’ve been warning you for four years. Now that a federal right-to-try law has passed, the profiteering has begun. Let patients beware!

Well, that didn’t take long.

When last I wrote about the cruel sham and scam known as “right-to-try” concocted by the quackery-friendly for-profit hospital chain the Cancer Treatment Centers of America and foisted on gullible legislators by the libertarian propaganda group disguised as a think tank, the Goldwater Institute, it had just passed Congress thanks to a last minute push by Vice President Mike Pence, President Donald Trump, and, of course, the Koch brothers, I warned about how the unscrupulous could use it to profit off of desperate terminally ill patients. Basically, it legalized at the federal level the practice model of cancer quack Stanislaw Burzynski, whose antineoplastons had passed phase I testing (which, as incredibly low a bar as it is, is required by right-to-try) and is still in phase 2 clinical trials (also a requirement of right-to-try). Also, as you recall, Burzynski built his fortune charging enormous “management fees” for treatment that could run into the hundreds of thousands of dollars. It’s a scam he’s been doing for forty years now, and, unbelievably, is still getting away with.

To be honest, I really didn’t think that I’d be writing about right-to-try again so soon. I really didn’t. After all, it’s been less than two weeks. However, something happened that I warned about, and it happened even faster than I could have imagined in my worst fears. I’ll just lay two headlines on you. The first one is from STAT News by Adam Feuerstein, Here come the right-to-try profiteers. The FDA is powerless to stop them. The second is from Bloomberg News by Michelle Cortez, The ‘Right to Try’ Could Cost Dying Patients a Fortune. Both articles are about BrainStorm Cell Therapeutics, a small biotech company developing a therapy for the deadly neurological condition amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease), a uniformly fatal degenerative neurological disease that tends to strike people over 50.

Before I get to what BrainStorm is doing, first let’s briefly review right-to-try. Basically, it was a scheme dreamed up by a Cancer Treatment Centers of America executive back in 2013. CTCA, if you recall, is a for-profit chain of cancer centers whose business model is to combine quackery (e.g., naturopathic oncology) with real medicine that is also known to inflate its outcome figures through cherry picked data. This executive took the idea to the libertarian propagandists at the right wing bill mill known as the Goldwater Institute, which came up with the very salable name “right-to-try” and wrote some model legislation. That task done, the Goldwater Institute proceeded to promote this model legislation, beginning in Colorado, where it passed in 2014. Since then, right-to-try laws have been spreading like kudzu to the point where 40 states now have them.

State-level right-to-try laws all have several features in common, based on the Goldwater Institute legislative template. First, as I mention above, the idea is to allow terminally ill patients the “right to try” experimental therapeutics. The experimental drug must have (1) passed through phase I trials and (2) still be in clinical trials for FDA approval. Although Goldwater Institute flacks have made the claim on numerous occasions that this guarantees that the experimental therapeutics are “safe,” but that claim is utter nonsense to anyone who knows anything about how clinical trials work. Phase I trials, after all, usually involve less than 30 people and are designed to determine the maximal tolerated dose and to screen new drugs for toxicity and adverse reactions too severe to justify continued testing. Right-to-try laws purport to allow terminally ill patients (defined somewhat differently, depending upon the state and the law) to obtain experimental drug right from the company making it. The company may agree to the request or refuse it. Most right-to-try laws allow the company to charge for the drug. These laws also protect doctors, companies, pharmacies, and anyone else involved in a right-to-try transaction from any sort of liability related to it, as well as explicitly exempting insurance companies from paying for such treatments. (Indeed, the language of some laws, as I’ve discussed before, could be interpreted as allowing insurance companies to refuse to pay for treatment related to complications related to a right-to-try drug.) Basically, “right-to-try” has been more properly called “right-to-ask” because the law doesn’t obligate companies to actually supply the drug. Worse, these laws basically leave patients entirely on their own, potentially paying huge sums of money for unproven medications because, of course, there is no requirement that companies provide the drug for free.

The key problem, with right-to-try laws was that they addressed a problem that didn’t exist and addressed it badly. After all, the FDA already has expanded access programs that approve something like 98% of requests without stripping protections from patients, such as oversight by an institutional review board (IRB). Of course, the key problem with state right-to-try laws from the perspective of the Goldwater Institute was that the FDA still controls drug approval. In other words, federal law overrides state law, and most companies would be very loathe to cross the FDA by letting patients have their experimental drugs outside of the auspices of a clinical trial whose purpose is to produce evidence of efficacy and safety that can be used as part of an application for drug approval.

Enter federal right-to-try, which was passed last month and signed into law. Basically, this law has the same sorts of provisions as state laws (phase I trials, no liability, patients can be made to pay) plus some federal-specific aspects. The worst of these provisions is this. The FDA Commissioner cannot use outcomes from right-to-try drug use in his consideration of whether to approve a new drug for market unless the sponsor (drug company) requests it or the Secretary of Health and Human Services determines that such outcomes are “critical to determining the safety of the eligible investigational drug.” In this case the HHS Secretary must justify this decision in writing. The HHS Secretary can also delegate this decision no lower than to the director of the relevant agency in the FDA in charge of approving the drug under consideration. Anyone want to guess how willing the HHS Secretary will be to do this very often?

I speculated that quacks would love this law, but cautioned some of the zealous opponents of right-to-try that few quacks would be able to take advantage of it because few are the quacks whose treatments have passed phase I clinical trial testing. In this, Burzynski is an exception. On the other hand, that doesn’t mean that the potential for abuse doesn’t exist:

A small biotechnology company may be the first to offer dying patients unproven drugs under a new U.S. law called Right to Try that deregulated access to such experimental treatments.

But it won’t be for free: Brainstorm Cell Therapeutics Inc. would charge for a therapy it is developing for the deadly condition known as Lou Gehrig’s disease. While details are still being worked out, the company’s chief executive officer pointed to the price of bespoke cell therapies used to treat cancer that cost more than $300,000.

“Companies cannot be NGOs,” the nongovernmental organizations that help provide care to impoverished countries, Brainstorm CEO Chaim Lebovits said in a phone interview. “We have to have an incentive.”

If it decides to proceed, Brainstorm — a company with no drug on the market yet and no revenue — would introduce a profit motive into an effort many expected to be altruistic, adding more controversy to an already contentious debate. Small drugmakers where much of the innovation in medicine originates can’t afford to provide their compounds for free, and terminally ill patients with no other options may be eager to pay for access. There would be little protection for patients already grappling with a tumultuous time in their lives, adding financial risk to the known medical gamble.

But what is BrainStorm’s treatment? The company calls it NurOwn®. I have to admit that looking over the company’s website I immediately had my doubts about it. It reeks of dubious stem cell treatments, quackery even. Check out the page on this treatment and see if you don’t share my concerns. Basically, BrainStorm uses mesenchymal stem cells (MSCs). I note that two of the clinics that the FDA has cracked down on for their practices advertise MSCs. Indeed, Stemedica, the company that took advantage of the family of Gordie Howe to promote a stem cell-based treatment for stroke, also claims it was using MSCs to treat stroke. To be fair, just because quack stem cell clinics claim to be using MSCs to treat all manner of diseases doesn’t mean that BrainStorm isn’t on to something, but I must admit that I find the scientific justification for its ALS treatment to be rather spotty:

Where others leave off with MSCs, BrainStorm begins. Our patented NurOwn® technology takes MSCs and, by growing them in proprietary conditions, converts them into biological factories secreting a variety of neurotrophic factors (NTFs). NTFs are growth factors known to support the survival of neurons in a variety of conditions, and in animal models of many neurodegenerative diseases.

The NurOwn® technology was developed in the laboratories of Professor Dani Offen and the late Professor Eldad Melamed, at Tel Aviv University, and has been the subject of many publications. Our NTF-secreting MSCs (or, MSC-NTF cells) are designed specifically to treat neurodegenerative diseases by allowing us to deliver several NTFs at or close to the site of injury.

There’s a list of publications, but none of the links actually go to publications on the main page. It took multiple clicks to get to many of the publications. For instance, there is a phase I trial that shows a single dose of MSCs was safe. There’s also a phase 1/2a clinical trial carried out at Hadassah Medical Center in Jerusalem that suggests an effect on two measures of ALS progression at a marginally statistically significant level that are probably transient. Is there something there? Maybe. Even though the scientific justification seems to be a bit of handwaving, with genetically engineered MSCs basically making a bunch of growth factors for neurons seemingly without a lot of careful targeting based on the pathophysiology of ALS, maybe it’s worth doing phase III clinical trials on. However, one thing I will say for sure is that it is not worth paying for before phase III trials show it to be efficacious and safe, with a clinically meaningful effect in ALS patients. Fierce Biotech notes that there is also a phase 2 trial that “found limited evidence of efficacy, with placebo matching NurOwn on measures of lung function and ALS progression.” Basically, the phase 2 trial NurOwn was unable to slow the progression of ALS compared to placebo, leading the company to start doing a responder analysis to try to find a signal indicating efficacy.

To me the existing evidence of efficacy for NurOwn is barely enough to justify continuing with a phase III trial, but apparently BrainStorm disagrees.

Or BrainStorm is looking for money wherever it can get it to continue to fund its product development:

Brainstorm, listed in the U.S. and run from New York and Israel, is trying to address the tension head-on. After requests for access to Brainstorm’s NurOwn experimental drug came pouring in following the passage of Right to Try, the company held conference calls with patients and investors to talk through details.

Only doctors who participated in the drug’s clinical trials would be included in the Right to Try program under consideration at Brainstorm, CEO Lebovits said. It would be a semicommercial enterprise with modest profits that wouldn’t exploit patients’ desperation, he said. The company, which had operating costs of $5 million last year, would work to obtain funding from foundations or other charitable organizations to help pay for at least one financially strapped patient for every two who are able to pay for it, he said.

Lebovitz says this venture wouldn’t exploit patients’ desperation, but how does he know that? I don’t know about you, but to me the very fact that his company will be selling an unproven treatment to patients with a terminal illness based on a marginally promising phase 2 trial indicates that the company will be exploiting desperate patients. This is even more true given that the treatment could carry a similar cost to recently approved cell therapies known as CAR-Ts, which are tailored for each patient by isolating the patient’s T cells and genetically engineered to produce chimeric antigen receptors, or CARs, in a similar but more complex way than how BrainStorm engineers NurOwn from the stem cells isolated from each patient. The cost of CAR-T treatment? Roughly between $375,000 and $475,000. So what we’re talking about here is the possibility that terminally ill patients with ALS could be paying the cost of a house for a treatment that hasn’t even been shown to be effective in anything resembling a convincing manner yet.

Yes, it’s nice that BrainStorm will try to obtain foundation funding to pay for around a third of the patients requesting its treatment under right-to-try, but that’s not nearly enough. In fairness, I also note that there is a provision in the new federal right-to-try law that limits what companies can charge to “direct” costs only. But what does that mean? Who is going to audit BrainStorm’s books to make sure that only direct costs are charged to patients. I can’t help but point out that the BrainStem CEO himself said that the intent is to make a “modest profit.”

Proponents of right-to-try, like Sen. Ron Johnson, who sponsored the bill that is now law, claimed that it wouldn’t permit this, but who’s going to stop BrainStem? The FDA? There’s no real mechanism for enforcement of the provision in right-to-try that supposedly bans companies from charging more than “direct costs,” and I highly doubt that the FDA will want to be too aggressive here. Why? Do you remember what happened when FDA Commissioner Dr. Scott Gottlieb expressed support and a willingness of FDA to work with right-to-try to protect patients seeking drugs under the new mechanism? Let’s recap.

It didn’t go well—for Dr. Gottlieb.

Basically, the law’s primary sponsor, Sen. Ron Johnson, slapped Dr. Gottlieb down so hard that that he’ll be digging himself out for a long, long time. The beatdown came in the form of a letter that made the intent of right-to-try very, very clear:

As I made clear to my colleagues in the Senate and the House before each body voted on S. 204, this legislation is fundamentally about empowering patients to make decisions in cooperation with their doctors and the developers of potentially life-saving therapies. This law intends to diminish the FDA’s power over people’s lives, not increase it.

Poor Dr. Gottlieb. He thought that right-to-try was about expanding access to promising therapeutic agents and not about emasculating the FDA. Well, Sen. Johnson sure set him straight, and because Sen. Johnson set Dr. Gottlieb straight I highly doubt that Dr. Gottlieb will be too enthusiastic about being too aggressive going after companies like BrainStorm looking to profit (whether “modestly” or otherwise) from right-to-try.

BrainStorm is just the pioneer. It’s the first company out of the gate, testing the limits of right-to-try. Given the fiercely anti-regulatory nature of the Trump administration and Congress, it is very likely that BrainStorm will get away with doing whatever it wishes selling its unproven stem cell treatment for ALS under right-to-try. If it does, you can count on a lot of biotech startups and other pharmaceutical companies emulating BrainStorm and getting away with it. Trust me, quack stem cell companies that have done phase I trials on their quackery are chomping at the bit to follow BrainStorm’s example.

Never mind how many patients go bankrupt or suffer grave harms pursuing an experimental therapy that is incredibly unlikely to prolong their lives.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

26 replies on “As I predicted, the exploitation of desperate patients using right-to-try begins”

Crap. Don’t you hate being right sometimes? Your quote from Sen Johnson shows he got it slightly wrong himself, the law is to empower providers of unproven therapies to help patients decide to part with a lot of cash. I see this going very badly for a long time before something (hopefully) is done to fix it.

Now I haven’t really studied these right-to-try laws in-depth, but am I correct in my assessment that apart from the phase I trial requirement, there are no real provisions whatsoever to protect patients from being exploited at their own risk? Not even a cap on what these companies may charge desperate patients for the privilege of being a guinea pig? And what about accountability after the fact? Do these companies even have an obligation to document and publish the outcome of treatments they administer under these laws? (Not that this kind of anecdotal evidence actually proves much, but it is still better than nothing to help other patients make up their mind about entering such a treatment program or not.)
I fully agree with JDK: you seem to have been spot on in all your criticism and your overall conclusion that this is a cruel sham. I’m really feeling sorry for you Americans for this horrendously ill-advised addition to the expensive mess that constitutes your system of healthcare, even though your actual doctors are among the best in the world…

You are correct. The patient is on their own for due diligence and caveat emptor. If the treatment goes bad, the pharmaceutical company, the patient’s physician, their hospital NO ONE can be sued for malpractice, even if there’s actually malpractice.

You know, I think that provision might actually be the law’s actual undoing. Trial lawyers might try to get that declared unconstitutional because it denies patients access to the courts when alleging actual malpractice on the part of their physician. I’d be curious to know what Dorit thinks about that likelihood since IANAL.

Not only is the company not required to document or publish the outcomes, but the FDA is not allowed to consider any negative outcomes without specific permission (I think the head of HHS).

So if this thing kills half the patients before they figure out who not to give it to, that can’t automatically be used against them when they try to file for approval.

It is actively dangerous.

Incorrect. The version of Right to Try that was signed into Federal law included the same cost-recovery restriction that is in place for FDA-authorized Expanded Access. 21 CFR 312.8(d)1. Cost recovery for group access programs is limited to the direct aggregate cost of manufacturing, delivery, and program administration that is born by the sponsor. No profit margin is permitted in the U.S. it’s been this way for 30 years and was clarified and streamlined in 2009. It has nothing to do with Right to Try, despite popular misconceptions. What’s intriguing is the prospect of Brainstorm’s 300k charge. Either they don’t completely understand the restriction, or they intend to ignore it, OR they intend to establish a tiered pricing program by which some patients pay more than others based on a means test. The sliding scale approach was part of a business model my partners and I inquired to FDA and never received a clear answer.

The problem is practical. There’s no way for the FDA to verify costs before a RTT patient receives a drug. The FDA had been explicitly cute out of the process.

You know, when I logged on this morning for my daily dose of Insolence, and saw today’s headline, the FIRST thing to pop out of my mouth was, “Well. That didn’t take very long.” Then I read the first sentence of Orac’s post.

Sadly, that’s the only thing I’ll be laughing about today. Oh, man. I was afraid of this. I was so afraid of this.

People are going to die, and it’s going to take something horrific like what happened in 1937, or in the 60’s, for the public to wake up and demand this monstrosity be repealed. Worse, the country is facing so many other problems this one will sit on the back burner awhile.

No, RTT won’t do much; it is a grand sideshow, which may be the best or the worst thing about it depending on how you feel about legitimate, FDA-authorized Expanded Access. The Brainstorm case has nothing to do with Right To Try. Everything presented here is possible under the provisions we have had for the last 30 years….except for the curious price of $300k, which sounds too high. I break that down in a previous post on this thread.

RTT eliminates IRB oversight for RTT patients and explicitly cuts the FDA out of the process. That’s quite different from expanded access.

A microscopically small bit of good news from this is that Burzynski’s bottom line could suffer from now-legal competition from companies previously hesitant to adopt his model of quackery. Then again, as you note, he’s been doing this for 40 years, so he might be able to leverage his experience to jump out front by offering something dubious other than his “piss cure”.

Burzynski sold his home at 20 E RIVERCREST DRIVE, HOUSTON on June 4th for 3.75 Million. He did buy at the top of the market before the crash so he lost almost 40% Plus 100 grand a year in property taxes and 30 grand a year in HOA Fees. Whether this is significant as to the competition or just an old hustler getting ready to die I don’t know nor care. It would be interesting to see if he were diagnosed with one of the various cancers he claims to treat if he himself would subject himself to the horrid side effects of “antineoplastins”.

Sadly I’m sure he didn’t sell it to give refunds to his marks.

I can’t help but wonder if he’s getting ready to move to Mexico given his new partnership with a Tijuana clinic.

While I agree with you that desperate people are being preyed upon, you miss the elephant in the room, namely that our entire health care system is designed first and foremost to make a profit, the only health care system in the developed world so designed. While there are many many doctors and other health care personnel devoted first to their patients’ best, it is NOT just the for-profit insurance companies and the pharmaceutical companies that do their best to MAXIMIZE incomes. Recent studies have shown that medical charges for various procedures have increased over the past years at rates far in excess of inflation. Studies have found that some doctors who own their own labs and radiology equipment order more tests and charge more than other doctors. And, unfortunately, additional research has found that many medical interventions and drugs are based on biased studies, cherry picking data, or simply grandfathered in. However, this should call for greater oversight and transparency of the scientific process; not rejecting it for unscientific complementary and alternative medicines.

Given that our health care system is designed to make money, it should be no surprise that many within it will market whatever will increase their bottom line!

There are so many things that need to be done. Even if our hospitals and medical establishments stop offering CAM, desperate people will seek it out. We need to improve education in our schools of scientific method/thinking and logic. We need to adopt a non-profit single-payer health care system. It won’t by itself stop individuals from exploiting vulnerable people; but will remove the most costly and unnecessary part, that is, the huge administrative waste and hurdles in our system. Then it will be easier to deal with other problems using data, e.g. overuse, underuse, etc.

@ Orac,

Please continue to keep us informed of which doctors get rich and infamous pursuing their experimental therapy through the right-to-try law.

It’s a heavy burden that is likely to affect consumer confidence in the American healthcare system.

Any bets on how long before these anti-regulation loons manage to get Kefauver–Harris repealed? This is essentially a limited removal of the protections of that law as they would have applied to treatments for terminally ill patients. Repealing Kefauver–Harris is the next logical step: doing so would remove the FDA’s power to regulate pharmaceuticals for safety and effectiveness. It will practically emasculate the FDA as far as drugs are concerned, which I think is the game plan for the Goldwater Institute and its libertarian compatriots. Hopefully we don’t get another thalidomide, or worse, another elixir sulfanilamide, before people remember what the laws were for.

Is it wrong of me to hope that everyone at the Goldwater institute is currently eating a big bowl of Honey Smacks they bought a month ago?

That would be wrong. And it wouldn’t teach them anything.

I think JustaTech is referring to that recent news of some batches of Honey Smacks being contaminated with salmonella:

This is the FDA’s watch, and if the FDA is abolished in the name of libertarian ideals, the way it seems that the Goldwater Institute wishes, there will be nothing but the free market to protect the consumer from something like this. Fat lot of good the free market does you if you’re the unfortunate bloke who got the salmonella-contaminated cereal.

Does the right-to-try law weaken the Hippocratic Oath?

In a sense, isn’t the FDA a watchdog organization intended to support and maintain the “spirit” of the Hippocratic Oath?

No. The FDA’s mission has nothing to do with the Hippocratic Oath. The duty of the FDA is to ensure the purity of food, drugs, and cosmetics. In the case of medications, to ensure safety and efficacy of medications that come to market.

Well, doesn’t assuring the safety and efficacy of medications that come to market assist doctors with “do no harm”?

It appears there’s not much wax left on your candle, Panacea. 🙂

No, it doesn’t, you disingenuous hack. You’re comparing apples and oranges.

Doctors have to do their due diligence in diagnosing patients, and determining a treatment plan. All medications have risks, and the FDA can only ensure those risks are well known and identified, while keeping the most dangerous drugs that do little or do nothing off the market. The physician still has to know what he’s doing, and there’s a risk vs benefits calculation that the physician makes in consultation with the patient.

The FDA does not “assist” doctors with that, and it’s not a watchdog agency. It is a regulatory agency that’s been defanged by anti-science nut jobs in government.

My big worry was that scum like Burzinsky would take this bill and use it as a shield against paying any penalty for operating his ridiculously high priced pee clinic. I thought that ethical medical establishments were not supposed to charge patients for being in a clinical trial ? So now they can ? or was that just a guideline ?

I think that the main providers of treatments under right-to-die-broke, I’m sorry, I mean right-to-try, will be the quacks. It will be easy money for them, much more than they made under the old system.
More legitimate companies may not want to risk their public image if things go wrong with any of their treatments, although both groups can say, “He was going to die anyway, so you can’t claim that our product killed him.”
On the other hand, watch for the eventual storm of anecdotes when unhappy survivors wake up and realize they’ve been conned.

I think there is a big difference between quackery and the scenarios laid out above.

Quackery is known to be ineffective. Any therapy that may be hypothesized to work (whether it’s based on basic science, on animal studies, on a compelling collection of clinical case studies, etc.) has a possibility — however small of actually being effective.

No treatment works 100% of the time, no treatment is 100% safe. The FDA is in the business, based on scientific evidence, to find that a particular treatment’s benefits outweigh the risks for some populations. But that’s really an arbitrary and subjective call. While making this call is 100% necessary for policy making and the development of a standard of care, individuals can, rationally, make different choices.

A treatment coming out of phase I going into phase II may have a 0.5% chance of ever making it through phase III and eventual FDA approval (I don’t know the overall numbers, but I suspect I’m not far off). And it may be very expensive. But as long as an individual knows the odds are stacked against him (or her) and has the means to pursue the slim chance, why prevent him (or her)? We’re not talking about public funds or shared funds and I have read nothing that suggests fraud.

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