The moment I have feared ever since Republicans took control of all three branches of Congress last fall has come one step closer to reality. Actually, it’s merely one of many. occurrences that I have feared, given that Donald Trump has been our President for over six months. Although you won’t find much in the news about it, yesterday the Senate easily passed a federal version of so-called “right-to-try.” Senator Ron Johnson, who threatened to hold up Senate business unless a right-to-try rider was approved for the bill funding the FDA for the next seven years, was ecstatic:
— Senator Ron Johnson (@SenRonJohnson) August 3, 2017
As was Christina Sandefur of the Goldwater Institute, the libertarian think tank who concocted the idea of using right-to-try as a means of enlisting terminally ill patients as sympathetic pawns in its never-ending war on government regulation in general and the ability of the FDA to protect patients from unsafe and ineffective drugs:
— Christina Sandefur (@cmsandefur) August 3, 2017
Basically, all that has to happen in September, when Congress reconvenes, is for the House to pass this law. One the one hand, I’m relieved that it’s just the standalone law that passed and that right-to-try wasn’t attached to the bill that allows the FDA to collect user fees from companies seeking FDA approval for their drugs and devices, but that doesn’t make the bill any less dangerous to patients. I will also grant that, as you will see, the bill as passed is not as bad as the original version of the bill (S. 204: Trickett Wendler Right to Try Act of 2017), but it still has the potential to do a lot of mischief, endanger a lot of patients, and empower a lot of scammers. To understand why, though, you need to understand what right-to-try is.
Right-to-try: A cruel sham that politicians can’t oppose
I’ve written many times before over the last three years about how “right-to-try” laws have swept the states. When last I wrote about right-to-try, 37 states had passed such laws over the course of a mere three years, and I observed at the time that it wouldn’t surprise me in the least if most or all of the remaining states were to pass such laws within the next year or two. Basically, the idea behind these laws is that the FDA is killing patients (I’m only exaggerating slightly) through its slow drug approval, overcaution, and bureaucratic inertia, or at least letting them die because life-saving drugs are being held up. So the idea, hatched by the Goldwater Institute was that terminally ill patients should have the “right-to-try” experimental drugs not yet approved by the FDA because they have nothing more to lose. Of course, it’s not true that they have nothing more to lose, but I’ll discuss that more later. Basically, right-to-try laws purport to allow the terminally ill “one last shot” by letting them access experimental therapeutics outside of FDA-sanctioned clinical trials. However, these laws operate under a number of false assumptions, not the least of which is the caricature of the FDA as being slow, inefficient, and unwilling to bend, as you will see. They also strip away a number of protections for patients, as you will also see.
Who could argue with that, right? That is, of course, the issue. These laws sound very pro-patient, but they are in reality a Trojan horse designed to weaken the regulatory power of the FDA. They are a cruel sham, an illusion. As I’ve said from the beginning, Dallas Buyers Club might have been a good movie (I actually was disappointed in it when I actually saw it), but it’s a horrible basis for public policy on drug regulation. Indeed, right-to-try is a triumph of marketing that allowed anyone who perceived how it degrades patient protections, sells false hope, and harms the clinical trial process to no one’s benefit as heartless monsters who have no empathy for dying patients and value science over people. Indeed, this is exactly the sort of rhetoric one sees aimed at opponents on Twitter:
Amen to that! Thank you 4 your tireless efforts Christina. Ignore those like healthy @gorskon who thinks we all should die 4 science & FDA
— B Hanson (@SCPioneer) August 4, 2017
Holding back innovation is bad for patients? The same dying patients in search of better options, often when there are none. Why the angst?
— Stefanie C (@CowleyStef) August 4, 2017
Basically, if you speak out for patients and against right-to-try, you will be painted as cold and indifferent to the suffering of terminally ill patients. For me, nothing could be further from the truth. Either that, or you’ll be painted as being in the pocket of big pharma. All of this propaganda had a very chilling effect on criticism. I realize it’s an unscientific sample, but I know of no one involved in, for instance, cancer clinical trials at academic medical centers who supports right-to-try. Yet, whenever right-to-try bills were introduced in various states, the silence from medical professional organizations, universities, cancer centers, and the like was deafening. When right-to-try came to Michigan, almost no one testified against it, and the Goldwater Institute was free fly in a parade of families of patients with terminal illnesses who were convinced that right-to-try would give their loved ones a shot at life. The same sort of thing happened in the Senate over S.204:
But more liberal lawmakers faced significant lobbying, featuring heartbreaking stories of young children or newlyweds facing shortened lives. Meanwhile, the most powerful opposition, the drug industry and doctors’ groups, kept their disagreement very low-profile. Their soft voices gave lawmakers little political protection for a “no” vote.
“There’s no doubt about it — there are a lot of patients out there that think this is the answer to their prayers. … They certainly believed that, and they pushed their members of Congress to support a bill that in many cases the members of Congress thought was not a good idea,” said Zuckerman.
PhRMA’s low-profile on right-to-try hurt detractors from the outset. The industry group never took a formal position on the state right-to-try laws or earlier federal proposals. But it consistently reiterated its concerns about any approach to experimental medicines that sought to bypass the FDA and the clinical trial process. Of the major drug makers, only Merck formally came out against the earlier Johnson bill.
“It’s huge,” NYU’s Bateman-House said of PhRMA’s reluctance to take a stronger public stance. “When I speak with legislators, they say, ‘Well if it’s that bad, why isn’t pharma speaking against it?’”
The same could be said of the American Society of Clinical Oncology (ASCO), which spent the last three years taking no position on right-to-try until three months ago, by which time it was too little, too late. It’s not for nothing that I once remarked sardonically that opposing right-to-try is perceived the same way as opposing mom, apple pie, and the American flag—or worse, wanting to kill mom, defile apple pie, and shred the American flag. Again, I exaggerate, but not by much.
By drafting terminally ill patients into its war with the FDA, the Goldwater Institute could basically falsely equate criticism of right-to-try with attacks on dying patients. It was a cynical and very likely intentional strategy, and it worked brilliantly to silence groups that could have been the most effective opposition to right-to-try until it was too late. But what’s wrong with right-to-try anyway? To answer that, I’ll briefly reiterate the problems with state right-to-try laws and then to discuss the problem with the federal right-to-try bill as passed.
The problem with state right-to-try laws
All the state right-to-try laws hew pretty tightly to an approved model legislation template originally developed by the Goldwater Institute. Given that, all state right-to-try laws share several major features. The first was the requirement that the disease the patient has be terminal, usually defined as having a life expectancy of less than six months, although the model legislation is more vague, requiring an “advanced disease,” defined as “progressive disease or medical or surgical condition that entails significant functional impairment, that is not considered by a treating physician to be reversible even with administration of current federal drug administration approved and available treatments, and that, without life-sustaining procedures, will soon result in death.” Various states define this condition in somewhat different ways, but you get the idea. In fact, the federal legislation uses a definition more like the latter than the former.
One of the most problematic passages, if not the most problematic passage, in all right-to-try laws, including the federal one passed by the Senate, is the definition of “investigational drug, biologic product, or device”:
“Investigational drug, biological product, or device” means a drug, biological product, or device that has successfully completed phase 1 of a clinical trial but has not yet been approved for general use by the United States food and drug administration and remains under investigation in a United States food and drug administration-approved clinical trial.
Every right-to-try bill or law I’ve read uses minor variations of the above definition. Anyone who knows anything about drug development shudders when reading passages like that. The reason is that having completed a phase 1 trial is a dangerously low bar to clear to allow more widespread use of a drug. Basically phase 1 trials are small trials, usually consisting of less than 30 subjects, that look for major toxicities and adverse events. That is not enough to determine safety, nor is it intended to. Phase I trials are designed primarily to identify major side effects and to use a process known as dose escalation to determine what is commonly referred to as the “maximum tolerated dose.” It is utterly impossible for such a small clinical trial to determine the safety of a drug. Phase II and Phase III trials are needed to confirm safety. Think of phase I trials as a screening test looking for the most obvious toxicities, with phase II and III studies confirming them. Indeed, even phase III trials can’t always adequately demonstrate that a drug is safe; it’s not uncommon for less common adverse effects not to show up until post-marketing surveillance, when much larger numbers of patients receive the drug. Moreover, only 5% of all cancer drugs that enter clinical testing are ultimately approved for patient use. Among drugs tested in phase II trials, only 30% go on to phase 3. I like to point to the cautionary example of amonifide for treating breast cancer. The drug made it through phase I trials, but serious life-threatening hematologic toxicity emerged during phase II trials.
Another problem with right-to-try laws is that they are extremely inequitable. Basically, right-to-try laws limit who can access them by wealth. The reason is that all of them have a provision that says that health insurance companies do not have to pay for right-to-try treatments and most such laws allow drug companies to charge whatever they see fit for the experimental drug. Insurance companies can pay if they so desire, but what’s the likelihood of an insurance company paying for an experimental treatment?It goes beyond that, though. If a patient uses a right-to-try drug and suffers complications, these laws basically state that the insurance company doesn’t have to pay for care resulting from that complication, and all such laws state that patients undergoing right-to-try therapies lose their coverage for hospice while undergoing right-to-try treatment. Thus, a terminally ill patient could easily go bankrupt before he died paying for drugs accessed through right-to-try laws, and many couldn’t access experimental therapeutics through such laws in any event because they simply don’t have the money or the fundraising wherewithal to do so.
Right-to-try laws also limit what patients can do in the event of malpractice or negligence. All of them immunize physicians advising or administering right-to-try medications against malpractice suits or actions against their medical license by the state medical board for doing so. All of them contain provisions broadly immunizing companies providing experimental therapeutics under right-to-try from liability. All of them contain provisions stating that state employees can’t interfere with a patient seeking right-to-try, which could be interpreted to mean that a doctor at an academic medical center at a state university couldn’t counsel a patient not to seek right-to-try without running afoul of the law. As Jann notes, even if state authorities believe, for example, that an elderly person is being exploited for financial gain by a physician, presumably this provision would prohibit their acting.
Right-to-try laws are patient-hostile in other ways, too, as Jann Bellamy and I have described many times. The most egregious example of which is how they strip patient protections away from patients who access them. One way to see this is by comparing what happens when a patient accesses an experimental therapeutic under the FDA expanded access program to what happens when another patient accesses one under a right-to-try law. Under FDA expanded access, patients retain full protections under federal and state laws. They can sue for malpractice if there is any, and their care is still monitored by an institutional review board (IRB), with any adverse events recorded and considered by the FDA. Moreover, the FDA approves nearly all such requests (99%). In contrast, under right-to-try, there is no IRB oversight. It’s all between the company and the patient.
Finally, I not infrequently call state right-to-try laws placebo legislation because such laws basically does nothing while making everyone feel better. That’s because the federal government, not the states, controls drug approval. Basically, the state can say that patients have a “right-to-try,” but only the federal government can actually guarantee such a “right.” It’s actually fortunate that state-level right-to-try laws are placebo laws, because if they actually did what’s in their text they would be profoundly harmful to patients.
The problem with the version of “right-to-try” passed by the Senate
In marked contrast to state-level laws, any federal right-to-try bill that becomes law would not be placebo legislation. It would be harmful, and the Trickett Wendler Right to Try Act of 2017, although amended to be less harmful than the original version, is still a danger to patients. I described in detail what was in the original version of this bill in previous posts; so I won’t dwell too much on it. The key points of the original bill were:
- No interference by the federal government with state right-to-try laws.
- No liability for either drug companies providing right-to-try or doctors recommending right-to-try
- No use of outcomes from patients accessing right-to-try in FDA consideration of drug approval.
So let’s look at S.204 as passed by the Senate. It’s still bad, but not as bad because there are amendments that mitigate some of the worst aspects of the original. Unfortunately, it still uses an overly broad definition of who can access right-to-try. Basically, anyone with a serious illness as defined by the FDA is eligible. The bill also retains the dangerously nonsensical provision that any drug that’s passed phase I trials and is still in active development can be accessed through right-to-try.
One thing the new “right-to-try” does is to change the provision in the original version that forbade the FDA from considering outcomes observed in patients accessing a drug by right-to-try in its deliberations over whether to approve the drug or not:
(1) IN GENERAL.—Notwithstanding any other provision of this Act, the Public Health Service Act, or any other provision of Federal law, the Secretary may not use a clinical outcome associated with the use of an eligible investigational drug pursuant to this section to delay or adversely affect the review or approval of such drug under section 505 of this Act or section 351 of the Public Health Service Act unless—
(A) the Secretary makes a determination, in accordance with paragraph (2), that use of such clinical outcome is critical to determining the safety of the eligible investigational drug; or
(B) the sponsor requests use of such outcomes.
The “Secretary” above is the Secretary of Health and Human Services, although the HHS Secretary can delegate the decision to the FDA Commissioner.
The new right-to-try also requires the FDA to post information regarding right-to-try on its website:
(1) IN GENERAL.—The manufacturer or sponsor of an eligible investigational drug shall submit to the Secretary an annual summary of any use of such drug under this section. The summary shall include the number of doses supplied, the number of patients treated, the uses for which the drug was made available, and any known serious adverse events. The Secretary shall specify by regulation the dead line of submission of such annual summary and may amend section 312.33 of title 21, Code of Federal Regulations (or any successor regulations) to require the submission of such annual summary in conjunction with the annual report for an applicable investigational new drug application for such drug.
(2) POSTING OF INFORMATION.—The Secretary shall post an annual summary report of the use of this section on the internet website of the Food and Drug Administration, including the number of drugs for which clinical outcomes associated with the use of an eligible investigational drug pursuant to this section was—
(A) used in accordance with subsection (c)(1)(A);
(B) used accordance with subsection (c)(1)(B); and
(C) not used in the review of an application under section 505 of this Act or section 351 of the Public Health Service Act.
As you can see, this is better, but still problematic. Basically, the FDA Commissioner can decide on an individual basis whether or not to use right-to-try outcomes in considering the approval of a drug. I can see considerable potential for favoritism and abuse in this provision, in which favored companies can do what they like and not have to worry about whether right-to-try outcomes will count against them and less favored companies will have to worry. it is, however, good that at least there will be some transparency, as some information will have to be made publicly available.
The modified bill also softens the protections against lawsuits against manufacturers and doctors recommending right-to-try with an exception to immunity if “the relevant conduct constitutes reckless or willful misconduct, gross negligence, or an intentional tort under any applicable State law.” Now, I’m not a lawyer, but here’s one huge problem with this that I see. State right-to-try laws in general completely immunize manufacturers providing experimental therapeutics under the law and doctors recommending such therapeutics from any legal liability; so in those states there would be nothing patients could sue for, even in the case of “reckless or willful misconduct, gross negligence, or an intentional tort.” If there are any lawyers out there, feel free to correct me if I’m wrong, but it appears that only in states without right-to-try would this provision mean anything.
Now that S.204 has been passed by the Senate, it moves on to the House, where, unfortunately, it is highly likely to pass. Given the anti-regulatory mood of the current Congress, coupled with the successful branding of right-to-try opponents as either in the pocket of big pharma or indifferent to the suffering of the terminally ill, it will be very, very difficult to stop this bill. That doesn’t mean that we shouldn’t continue to try, but we should have no illusions. We are likely to see what happens if right-to-try becomes the law of the land at the federal level. While it’s true that this version is not quite as patient- and science-hostile as the original version, it is, unfortunately, plenty bad, man.
It’s also not as though we haven’t had a chance to see if right-to-try provides any of the benefits claimed for it. Unfortunately, thus far, right-to-try has been a miserable failure, despite three years for it to have proven its worth. I know. I’ve looked for “success stories,” and the Goldwater Institute has been unable to provide them.
Sandefur has, however, been able to provide the same old talking points about the FDA Expanded Access Program and about how slow the FDA allegedly is approving drugs. It actually turns out that the FDA is faster than its European counterparts approving drugs and that the expanded access program is nowhere near as onerous as ideologues like Sandefur like to paint it. Indeed, there is a nice FAQ maintained by the NYU Working Group on Compassionate Use and Pre-Approval Access that answers pretty much every talking point, and I’ve discussed these same talking points before. It’s basically a lot of misinformation promoted by ideologues.
Nor is this “success story” persuasive if you look into it more:
Now, as to Right to Try: when real-life examples of its early success are reported, Klugman’s response is to deny that they are true—and this is frankly bizarre. Dr. Delpassand has testified to Congress that within a year of his state’s enacting Right to Try, he successfully treated 78 terminally ill cancer patients using LU-177, a drug that had successfully completed its three phases of the FDA-approved clinical trials and has been available in European countries for years, but has still not received final FDA approval for sale. I should know, since I’m his lawyer: Dr. Delpassand had administered a successful FDA-approved clinical trial for LU-177 therapy for five years, but was then told by the FDA that he could not add more patients to the trial. Right to Try enabled him to continue administering LU-177 to patients suffering from neuroendocrine cancer after the FDA blocked the trial’s expansion. His patients were exceedingly grateful. One said that without Right to Try, he “would have had to go on disability to make trips to Switzerland.” Another said he “would have traveled to Switzerland for this same treatment and follow-up appointments every three months,” but thanks to Right to Try and Dr. Delplassand, he was able to stay in the United States and spend the time with his wife and kids. “This law,” he told me, “has been a life saver!”
I discussed the example of Dr. Delpassand and his company Excel Diagnostics in detail before, as well as how Dr. Delpassand is a cheerleader for the Goldwater Institute who’s done promotional videos for right-to-try before. Basically, the treatment being promoted by Dr. Delpassand for neuroendocrine tumors has promise. It even was found in a phase III trial published earlier this year to produce a significant increase in progression-free survival for midgut neuroendocrine tumors. However, as I described in depth, there was something fishy about the story. He claimed to be administering his radionuclide treatment under Texas’s right-to-try law, but he was charging patients and the Texas right-to-try law, as I was so pointedly reminded when I discussed the issue, doesn’t allow manufacturers to charge for their experimental therapeutic.
Basically, reading between the lines in Sandefur’s article, I now think I know what happened, and it’s not exactly what is being claimed. What it sounds like to me from Sandefur’s carefully worded account, plus what I’ve looked up before, is that, after having reached his accrual target for his clinical trial, Dr. Delpassand wanted to add additional patients to it even though the trial was closed. The FDA balked at this request—and understandably so. The reason was almost certainly that adding patients to a clinical trial after it’s closed is, in essence, changing the design of the trial post-hoc. It would also have increased the time necessary to analyze the trial. So Dr. Delpassant appears to have used the right-to-try law to get what he wanted. As I documented before from a patient webpage, he also appeared to be charging patients close to $40,000 for the treatment, although it is unclear whether he charged for his radionuclide or not or whether he followed the Stanislaw Burzynski method and charged large sums of money for everything else but the drug and thus made money that way.
I mention the Houston Cancer Quack Stanislaw Burzynski on purpose, because, before Dr. Delpassand, he was the only “investigator” I had heard of who had actually used right-to-try to bypass the FDA and continue to administer his antineoplastons. I fear his is the business model that right-to-try will enable, complete with exploitation of patients on a greater-than-Burzynski scale.
“This bill is inherently deceptive,” Alison Bateman-House, a medical ethicist at New York University who led the charge against Johnson’s bills, wrote in an email. “What [patients] have a right to (and did long before this bill) is to ask drug companies for permission to use their experimental drugs outside of clinical trials. If the drug company says no, both before and after this legislation, that’s the final word: neither the FDA nor the courts have to power to make companies provide access to their experimental drugs-in-development.”
It’s very much understandable why so many terminally ill patients and their families have embraced right-to-try, even though it is basically the distillation of Goldwater Institute libertarian ethos in which you can have “choice” and “one last chance” if you have money or are able to acquire it and are totally on your own if you don’t or if you are unfortunate enough to suffer an all-too-predictable and likely complication from an experimental therapeutic. So-called “right-to-try” is a cruel sham that holds out the false hope of survival to terminally ill patients and their families. In return, all they have to give up is patient protections and agree to pay to be guinea pigs to test a drug company’s product. The product of an ideology that uses the terminally ill as shields to hide the ideological motives behind the law, which are to hobble the FDA, right-to-try is a terrible idea. It’s bad for patients, but it just passed the Senate and could well become the law of the land when the House reconvenes in September if it isn’t stopped. In the end, it is not cold, cruel, or indifferent to oppose right-to-try. It is not anti-patient. Quite the opposite, in fact. It is as pro-patient as you can get to try to stop this cruel sham that preys on the desperation of dying patients in order to enlist them in a crusade to neuter the very agency that is responsible for protecting them from quacks and charlatans like Stanislaw Burzynski.