Right-to-try: A bait and switch intended to weaken the FDA

On Wednesday afternoon, I happened to stop at the doctors’ lounge at my hospital to have lunch. There are lots of snacks there to supplement a sandwich, as well as coffee, soda, water, to go along with it. Unfortunately, there is also a TV there as well, and even more unfortunately, it was tuned to something I didn’t want to have to watch, namely the signing ceremony for the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017. It was quite nauseating to watch. President Donald Trump preened and made ridiculous claims for this right-to-try law like this:

Each year, thousands of terminally ill patients suffer while waiting for new and experimental drugs to receive final FDA approval. It takes a long time, and the time is coming down. While we were streamlining and doing a lot of streamlining, the current FDA approval process can take, as Scott just said, many years — many, many years. And for countless patients, time, it’s not what they have. They don’t have an abundance of time.

With the Right to Try law I’m signing today, patients with life-threatening illnesses will finally have access to experimental treatments that could improve or even cure their conditions. These are experimental treatments and products that have shown great promise, and we weren’t able to use them before. Now we can use them. And oftentimes they’re going to be very successful. It’s an incredible thing.

The Right to Try also offers new hope for those who either don’t qualify for clinical trials or who have exhausted all available treatment options. There were no options, but now you have hope. You really have hope.

As I’ve discussed many times before, the basic idea behind “right-to-try” is that the FDA is killing people (or letting people die) through its bureaucratic delays in approving drugs, lives that, if you believe right-to-try advocates, could be saved by cutting the FDA out of the decision between drug companies with experimental therapeutics and terminally ill patients who want to try them. It’s nonsense, of course. In actuality, the FDA is not unduly slow approving new drugs, in particular as compared to Europe, and, more importantly, there is an expanded access program that approves >99% of requests. True, the paperwork to access drugs through expanded access programs was once onerous, but the FDA has made great strides towards reducing that burden. Oddly enough, right-to-try advocates often mischaracterize an expanded access program in France as being a success story of right-to-try when it is not. (They also like to conflate cases of compassionate use or fast-track approval with right-to-try.) In other words, Trump’s speech is a total distortion of the true situation, as has been the case with so much that “right-to-try” proponents have said over the years that they have been promoting this law and the 40 or so state-level laws before it. As I have also discussed so many times before in the context of right-to-try going back to 2014, right-to-try provides no new right and no new access to experimental therapeutics that weren’t available before through FDA expanded/compassionate use programs. What it does do is to strip away important patient protections, leaving the most vulnerable, terminally ill patients, in essence on their own. It’s a bait and switch, the bait being the promise to help terminally ill patients, the switch being a major step in the process of dismantling the FDA.

Right-to-try: Never meant to help patients

I’ve been saying all along since 2014 that the goal of right-to-try laws was never to help terminally ill patients, but rather to weaken the FDA. Examined from a broader standpoint, right-to-try is nothing more than another weapon in the arsenal of right wing groups opposed on principle to government regulation, the target in this case being the FDA. Indeed, ditching the FDA has long been a fever dream goal in more ardent libertarian circles. Don’t believe me? Here’s one summary of libertarian arguments for dismantling the FDA. Basically, the arguments run the gamut from “opening the FDA up to competition” by “private inspection agencies.” Let’s just say I find this argument…unpersuasive. Libertarians will fall all over themselves to deny that such companies would have an inherent incentive to make getting their stamp of approval easy and more inexpensive (free market!), but their counterarguments tend to come down to strong laws against this (yeah, right) and “trust the free market.” As Aaron Brown put it:

You seem to think that eliminating the Food and Drug Administration is among the more radical libertarian positions. In fact, it’s one of the easiest. It’s very hard to imagine any libertarian supporting the FDA.

And:

Thus was born a hugely profitable and powerful combination of doctors, drug and medical device makers and regulators, which over the years has been a constant source of scandals. It delays innovation, drives up costs and—make no mistake—kills more people every year than mass shooters.

Although libertarians are a diverse group and value independent thinking, nearly all libertarians have to hate the theory of the FDA. A few of them might dispute the empirical evidence. I think fewer of them would dispute the historical record, because this kind of regulatory empire building and capture is very common and a major complaint of most libertarians.

Again, this libertarian trope about the FDA killing more people than it saves is utter bullshit, but it’s an article of faith among anti-regulation conservatives and libertarians.

Right-to-try strikes back against Scott Gottlieb

Whenever I point out that right-to-try is a tool, a step if you will, towards the ultimate dismantling of the FDA, inevitably someone will take umbrage and insist that, no, that’s not the purpose of right-to-try at all. They also accuse me of a lack of compassion, as though compassion for the terminally ill requires that I buy their arguments. Now that right-to-try is law, however, the mask is coming off. One of the architects of the federal right-to-try law that President Trump signed on Wednesday, Sen. Ron Johnson, rebuked FDA Commissioner Scott Gottlieb yesterday, setting him straight on the true purpose of right-to-try. I found this out in a STAT News article, ‘Right-to-try’ law intended to weaken the FDA, measure’s sponsor says in blunt remarks, which reported on a letter written by Sen. Johnson to Dr. Gottlieb in response to remarks that Gottlieb had made about right-to-try two weeks ago entitled Johnson to FDA: Agency Should Comply with Right to Try Law. First, he lays out the “offense” by Gottlieb that riled him up:

In a recent article about right to try, you appeared to suggest that the FDA would need to issue regulations to balance the law’s requirement against “patient protections.” The article quoted you as saying:

  • “In terms of making sure that it balances [access to experimental drugs] against appropriate patient protections . . . with [S. 204], we’d have to do a little bit more . . . in guidance and perhaps in regulation to achieve some of those goals.”
  • “We felt that there were certain aspects of [S. 204] that could be modified to build in additional patient protections, but if you weren’t able to do that legislatively, that there [was] a pathway by which you do that administratively and still remain consistent with the letter and the spirit of this law.”

You later tweeted: “I stand ready to implement [right to try] in a way that achieves Congress’ intent to promote access and protect patients; and build on #FDA’s longstanding commitment to these important goals.”

Silly Dr. Gottlieb. He actually thought that right-to-try was about expanding access to experimental therapies to terminally ill patients. Gottlieb, as I’ve discussed, was the “least bad” choice Trump could have made for FDA Commissioner. Sure, he’s all for “streamlining” drug approval processes (translation: making them easier and less rigorous), but he still exists within a continuum of “normal” among FDA Commissioners, albeit on the conservative end. He’s not a hyper-libertarian Peter Theil crony who thinks the free market will take care of drug safety, nor does he think that online rating systems, a “Yelp for drugs” if you will, would be effective at assuring drug safety. Gottlieb is, in contrast, the sort of FDA Commissioner that any Republican administration might have appointed. He actually believes in the mission of the FDA, as he showed when under his leadership the FDA started cracking down on quack stem cell clinics.

Because Gottlieb believes in the mission of the FDA, he understands how bad this new law is, how it will cut the FDA out of the process, leaving terminally ill patients unprotected by institutional review boards (IRBs)—or much of anything else, for that matter. So he tried to say how FDA would work to implement the law, including trying to do what the FDA is supposed to do and protect patients accessing right-to-try medications. It’s what any responsible FDA Commissioner would do.

Sen. Johnson wasted no time in setting Dr. Gottlieb straight on that score:

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.

I told you so. In the name of patient “empowerment” right-to-try is really about cutting the FDA out of the process of drug companies marketing their wares to desperate patients. Johnson makes that very explicitly clear in no uncertain terms:

It is designed to work within existing FDA regulations, definitions, and approval processes. It is not meant to grant FDA more power or enable the FDA to write new guidance, rules, or regulations that would limit the ability of an individual facing a life-threatening disease from accessing treatments. Under this law, the FDA’s oversight with respect to patient safety within a Phase I trial remains unchanged; the current thresholds for successful completion of such a trial phase remains unchanged.

That last bit about phase I trial requirements is a red herring. No one is claiming that right-to-try changes phase I clinical trial requirements. What right-to-try does do is something incredibly dangerous. It makes any drug that has passed phase I trials and has an active investigational new drug (IND) application and is in ongoing clinical trials eligible for right-to-try. As I’ve repeated more times than I can remember but still feel obligated to repeat any time I discuss right-to-try, it is deceptive as hell to call drugs that have passed phase I “safe,” as I’ve seen right-to-try advocates do more times than I can remember. Phase I trials generally only involve less than 30 patients and are not designed to verify drug safety. Rather, they are designed to detect the worst toxicities and make sure that the drug isn’t too toxic or hazardous to continue to test in phase II and III clinical trials. (There’s a big difference.) Phase I trials also do not demonstrate efficacy. They are not designed to do that, either. Basically, think of phase I trials as a screening test to make sure an experimental drug isn’t too dangerous and might have activity, enough to justify further clinical trials. Only around 10-15% of drugs that pass phase I go on to be approved by the FDA.

Ironically, Sen. Johnson is not entirely wrong in one thing that he asserts. It is true that right-to-try does not provide any new rights that patients didn’t already have before under expanded use programs. It also certainly doesn’t do anything to increase FDA power. After all, the bill’s primary sponsor just told Scott Gottlieb that that the very purpose of the bill was to weaken his agency and that he should, basically, stay out of right-to-try cases.

If that’s not clear enough, Johnson drives home the point. First, he wants as many patients as possible to be eligible for right-to-try:

S. 204, as originally introduced, applied to patients “with a terminal illness,” as defined by state law. I rejected the FDA’s proposed definition—“immediately life-threatening disease or condition”— because it would exclude patients with Duchenne muscular dystrophy, an illness that I explicitly intended to be covered by the legislation. As enacted, S. 204 defines terminal illness as “life-threatening disease or condition,” a definition that exists in current federal regulation. The FDA confirmed that this definition would include patients diagnosed with Duchenne muscular dystrophy.

Of course, state right-to-try laws generally define a “terminal illness” as one that is likely to cause death within six months, although the definition varies somewhat and some states don’t even necessarily require a “terminal” illness. Be that as it may, Sen. Johnson makes it very clear: Right-to-try should victimize apply to as many patients as possible.

Next up, don’t harsh me, bro, with any outcomes that might reflect badly on the experimental drug:

S. 204 requires that the Secretary of Health and Human Services may not use a clinical outcome associated with the use of an eligible investigational drug to delay or adversely affect the drug’s review or approval, unless use of that clinical outcome is critical to determining safety. This language is not intended to enable the FDA to expand the scope of existing safety determinations about investigational drugs.

No one ever said that it did, least of all Scott Gottlieb, at least as far as I can tell. As I’ve discussed multiple times, the language in the federal right-to-try law bends over backwards to make sure there are no consequences for companies agreeing to provide experimental medications to patients under the law. Indeed, the first version of Sen. Johnson’s right-to-try bill explicitly banned the FDA from using outcomes from patients using an experimental drug under right-to-try in its consideration. Seriously, I mean this. The original version of Sen. Johnson’s bill would have banned the FDA from even considering outcomes of patients who access right-to-try in its considerations over whether to approve a drug. At least the version that passed allows such consideration, although it requires jumping through some hoops. For example, the Secretary of Health and Human Services (or his designee, which can be the FDA Commissioner) must publicly justify using outcomes in this way. Basically, S. 204 as passed states that the FDA can’t use a clinical outcome or adverse event associated with the use of a right-to-try drug in its determination of licensure for sale unless the Secretary of Health and Human Services (or his designee) decides that the use of these outcomes is critical to determining the safety of the drug or the applicant wants them used. Rather than what the default should be (that all outcome data should be considered when examining a drug for FDA approval), this forces the HHS Secretary or a high level delegate to justify including right-to-try outcomes in the deliberations over whether the drug under consideration should receive FDA approval for marketing. In other words, the burden of proof is on the FDA, not the company seeking approval for its drug, as to why right-to-try outcomes should be included.

The FDA surrenders

Sadly, the FDA appears to have thrown in the towel, although I don’t know that there’s anything else it could have done:

In a separate email to staff Wednesday, Janet Woodcock, who directs the agency’s Center for Drug Evaluation and Research, told staff to direct any inquiries about the new law to drug companies.

“We believe that sponsors are in the best position to provide information on the development status of their products,” Woodcock wrote.

In other words, if Congress is going to cut the FDA out of right-to-try decisions and regulation, screw it all. Patients, don’t call us. Congress has eliminated our authority to deal with this. Call the company that makes the drug you’re interested. Congress cut us out; we can no longer interfere. You’re on your own.

Of course, that’s the entire idea behind right-to-try. I can’t even say that I blame Woodcock. What else is the FDA to do? After all, right-to-try isn’t even really a “right.” All it is is the right to ask companies making experimental drugs if they’ll let them try the drug. The companies are under no obligation to provide the drug and can basically charge whatever they want if they do decide to provide the drug.

Let’s take a trip back in time, back to 2014, back when right-to-try laws first started passing in state legislatures. Those state laws were (and continue to be) all based on a legislative template promulgated by the libertarian Goldwater Institute. This template had several elements in common:

  • Anyone with a terminal illness is eligible for right-to-try.
  • Any drug that’s passed phase I trials, has an IND, and is still under clinical trials is eligible for right-to-try.
  • There is no liability for doctors or companies participating in right-to-try.
  • Insurance doesn’t have to pay for right-to-try drugs. (This provision can also be reasonably interpreted as saying that insurance companies also don’t have to pay for the treatment of complications that occur because of the use of right-to-try drugs.)
  • Patients wanting right-to-try drugs are on their own when it comes to cost.
  • Drug companies don’t have to provide their experimental drug.

Yes, right-to-try is a libertarian wet dream. That’s not surprising, given its source. Again, right-to-try is a product of the Goldwater Institute, which tries to paint itself as a libertarian “think tank,” but has never been a true think tank. Rather, it has always been a far right-wing advocacy organization, so much so that before he died Barry Goldwater actually wanted his name removed from the group, but backed off because the Institute was dear to his brother. Unfortunately, the press treats the Goldwater Institute as a real think tank when it really isn’t. Rather, it’s part of the American Legislative Exchange Council (ALEC), a corporate-funded bill mill. That’s why, before there was right-to-try at the state level in 2014, there was a Goldwater Institute-written legislative template, a pre-written bill that could be (and was) modified as needed by states to fit into their existing regulatory framework. It’s why all state-level right-to-try laws contain the same elements listed above, including libertarian tropes like elimination of liability for companies and doctors participating in right-to-try, and provisions that basically leave terminally ill patients on their own if things go south. It’s why the Koch brothers’ threw their weight behind right-to-try and started lying about it, virtually guaranteeing that its Republican toadies, sycophants, and lackeys in Congress would find a way—any way—to pass something they could call “right-to-try.” That’s what happened.

Right-to-try: The Burzynski of “compassionate use”

It can’t be repeated too many times. Right-to-try has never been about helping terminally ill patients, at least not primarily. It’s always been about dismantling the FDA, neutering it, reducing its power to regulate drugs. As a side effect, it will also facilitate preying upon terminally ill patients by quacks. As I like to say, it’s legalized cancer quack Stanislaw Burzynski’s entire business model.Think about it. His antineoplastons have passed phase I trials. He’s maintained a plethora of phase II trials registered with the FDA that he’s been using as a marketing tool to bring patients to the Burzynski Clinic for 20 years. He charges huge fees to patients to be on his “clinical trials.” Thanks to right-to-try, after having beaten the Texas Medical Board for the umpteenth time, he now no longer has to worry about the FDA any more. He’s free to prey on patients via right-to-try to his black heart’s content. Janet Woodcock basically said so by instructing FDA staff to tell patients making right-to-try inquiries just to call the company making the drug they want. I can’t wait to see what quack stem cell clinics do under this law. Certainly, Burzynski started using the Texas right-to-try law almost as soon as it was passed.

Yes, the quackery potential behind right-to-try, I’m afraid, will be the subject of a future post, either here or at my not-so-super-secret other blog. In the meantime, I guess we’ll see what happens when the government abandons its responsibility to protect its citizens against drug companies. And don’t even get me started on the utter failure of medical professional organizations like the American Society of Clinical Oncology (ASCO) to speak out against state right-to-try bills. I was in contact with activists and legislators. They were begging professional medical organizations to give them ammunition against right-to-try bills and were met with silence, mainly because, as we opponents of right-to-try bills promoted by the Goldwater Institute found out, right to try is easy to demagogue. Its opponents are inevitably attacked as unsympathetic, uncaring, and wanting to prevent terminally ill patients from accessing their last chance at survival. In essence, opposition to right-to-try is painted as being akin to opposition to freedom and wanting to see terminally ill patients die horrible deaths. By the time ASCO actually spoke out last year, three years into the Goldwater Institute’s long game, it was way too little and way, way too late. More recently, ASCO issued a pretty close to useless FAQ for physicians to discuss right-to-try with their patients. ASCO failed. Big time.

Of course, it’s hard not to understand why ASCO, academic medical centers, and other medical organizations were reluctant to speak out. After all, the Goldwater Institute borrowed a page from the Burzynski playbook and used terminally ill patients as shields against criticism and weapons against critics. Criticizing right-to-try, no matter how dispassionately, let one be painted as attacking these patients. Burzynski knew about the compassion all of us have for terminally ill patients and how it would make critics reluctant to attack his quackery too harshly. The Goldwater Institute knows it too. This demagoguery has been very effective. After all, right-to-try is the law in 40 states and a federal version just became law this week.

We’ll see what happens next. Certainly, I will be watching. And reporting.