Back in the beforetime (i.e., before 2020, when COVID-19 changed everything), a frequent topic for me (and Jann Bellamy) dating back a decade was the push for “right-to-try” laws. The very first time that I wrote about “right-to-try,” I compared the idea to the movie Dallas Buyers’ Club, noting that it might make material for a great movie but that it was terrible for patients and terrible policy. (More detail on why a little later.) I also noted how, with the support of the “free market” Goldwater Institute, right-to-try laws started metastasizing to various states, including my own. Ultimately, these laws passed in state after state after state. As long as they stayed at the state level, however, right-to-try laws were largely performative and ceremonial, given that the federal government, through the Food & Drug Administration (FDA), regulates drug approval, not the states. Basically, these state laws gave the illusion that something was being done, when, in fact, at the federal level nothing changed.
The endgame of the Goldwater Institute, which provided the template legislation to be customized to work for each individual state, was never the passing dozens of state right-to-try laws, of course. Those laws were merely the first step. They were designed to pressure Congress to pass a federal right-to-try law by amassing political support and then allowing advocates to use the argument that state laws weren’t enough because the FDA was in charge of drug approval and regulation. Various pushes to pass a federal right-to-try law were made in 2014 and in 2016. None of these efforts went anywhere until after Donald Trump became President in 2017. Even after Trump became President, it took nearly a year and a half for the Goldwater Institute and other right-wing “free market” think tanks to finally push a federal right-to-try bill over the finish line, spearheaded by Senator Ron Johnson (R-Wisconsin), who has been a not-infrequent topic of this blog going back years due to his desire to “deregulate” medicine and, more recently during the pandemic, his having become a raging antivax and anti-public health loon who likes to host “roundtables” featuring the worst COVID-19 cranks and antivaxxers. Ultimately, Congress passed a federal “right-to-try” bill, President Donald Trump signed the bill into law in 2018.
Given that it’s been five years since I last wrote about right-to-try. So why am I writing about it now? Simple. In his acceptance speech to the Republican National Convention last Thursday, former President Donald Trump bragged about right-to-try, as though it were one of his signature accomplishments while in office. Let’s take a look at what he said in his 92-minute speech:
Right to Try, Right to Try is a big deal. We’ve got Right to Try. They were trying to get that for 52 years. Somebody’s terminally ill. And hopefully there’s nobody in this audience, but it does happen, a lot. They’re terminally ill and they can’t use our new space-age drugs and other things that we are way ahead with. We have the greatest doctors in the world. The greatest laboratories in the world, and you can’t do it. They’ve been trying to get that approved for 52 years, wasn’t that easy. The insurance companies didn’t want to do it. They didn’t want the risk. The labs didn’t want to do it because if it didn’t work, people are pretty far down the line toward death. They didn’t want to do it. The doctors didn’t want to have it on their record.
So I got everybody into an office — 52 years, they tried. Sounds simple, but it’s not. And I got them to agree that somebody that needs it will, instead of going to Asia or Europe or some place, or if you have no money, going home and dying — just die — we got them to sign an agreement. They agreed to it, where they’re not going to sue anybody. They can get all of this stuff. They’re going to get it really fast, and what’s happened is we’re saving thousands and thousands of lives. It’s incredible. Right to Try. It’s … great feeling.
This moment led me to wonder what the actual results of “right-to-try” have been; that is, after I got done facepalming at the rest of the nonsense surrounding Trump’s claim that right-to-try was “saving thousands of lives.” One bit of nonsense is that “we’ve” been fighting for right-to-try for 52 years. I have no idea where Trump got that figure from, because in reality right-to-try emerged around 2013-2014, which is when I first took notice and started writing about it. I suppose that he might have been referring to various programs to make access to experimental therapeutics easier that do date back to the late 1970s, although even current expanded access programs that exist in the US were largely a product of activism on behalf of AIDS patients during the AIDS epidemic in the 1980s. Ironically, one of the earliest examples of expanded access was for medical cannabis for glaucoma in 1976, which spawned a lawsuit (Randall v. U.S.), the ruling in which provided the legal basis for 1978 expanded access program for medical cannabis for glaucoma and then later in the 1980s for experimental AIDS therapeutics.
Regardless of all of Trump’s usual obfuscation and wholesale making stuff up, I thought it worthwhile to revisit right-to-try, given how long it’s been since I’ve written about it. Is it really “saving thousands of lives”? (Spoiler alert: The answer is no.) This should not be surprising given how poor the results were in 2019, a year after the law passed and just before the COVID-19 pandemic changed everything. First of all, what is “right-to-try”? I’ve called it a cruel sham, and Jann Bellamy has called it an illusion, but why do we characterize the law this way?
Right to try
Ostensibly, “right-to-try” laws were named because they supposedly grant terminally ill patients the “right to try”; i.e., access to experimental therapeutics. On the surface, this idea sounds benign enough. After all, what kind of heartless bastard could possibly oppose granting desperate, dying people a “chance,” a “right to try” anything that might save them. However, those of us who know drug development immediately saw the problem with the concept, and, as always, the devil is in the details. In this case, as I will explain, the details involved not only regulatory misconceptions, a deceptive view of what phase 1 clinical trials test for, and an excessively optimistic idea of the likelihood that an individual patient might benefit from gaining access to an experimental therapeutic, but various practical issues, such as who pays for the medication. (Hint: Given that “right-to-try” is a highly “free market” and libertarian concept, it isn’t the government or the pharmaceutical companies.) That doesn’t even consider that these laws, including the federal law, were the end result of a quack-friendly chain of cancer centers, Cancer Treatment Centers of America (CTCA), and the rabidly anti-regulation Goldwater Institute, to which CTCA had reached out to propose the idea. (As an aside, CTCA was acquired by the City of Hope Cancer Center in 2022 and CTCA facilities have since been rebranded under the parent name. That might be a topic for a future post.)
The biggest problem from a scientific and patient safety standpoint with “right-to-try” was (and is) that, according to these laws, drugs to be “tried” need only have passed phase 1 trials for them to be made available to patients. Let me just emphasize now, as I’ve emphasized in every post I’ve ever written about right-to-try, phase 1 trials do not demonstrate efficacy. They are only designed to test for safety and toxicity, determine the maximum tolerated dose, and provide an estimate for the dose to use in the actual randomized clinical trials designed to determine if the drug works for the intended indication. Think of phase 1 trials as a screening test looking for the most obvious toxicities, with phase II and III studies confirming them. Indeed, even phase 3 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 2 trials, only 30% go on to phase 3.
The concept of “right to try” bills was immediately highly popular, because if you don’t know a lot about medicine and how clinical trials work it sounds like a good idea. What could be the possible harm, after all? Indeed, it’s not for nothing that nearly every time I write about right-to-try, I remark sardonically that opposing right-to-try is perceived by most people the same way as opposing mom, apple pie, and the American flag—or worse, the same way as wanting to kill mom, actually defile apple pie à la American Pie, and shred the American flag. I exaggerate, but not by much.
The federal “right-to-try law” is officially known as the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017. Its main provisions include:
- Terminally ill patients (as defined by state law in right-to-try states) have the right to bypass the FDA and obtain experimental drugs from the company making them. The FDA is not involved in this decision, nor is there institutional review board (IRB, ethics board) oversight. Basically, critical protections provided by the FDA to patients in clinical trials are not in effect in right-to-try.
- Drugs eligible for right-to-try need only have passed phase 1 clinical trials, have an IND application with the FDA, and be in phase 2 clinical testing. As I’ve discussed more times than I can remember, this provision is insanity. Right-to-try advocates (like the Goldwater Institute) have frequently claimed that this assures that the drug to be “tried” is safe, which is nonsense. Phase 1 trials usually only enroll less than 30 patients, and are designed primarily to screen out drugs with toxicities too severe to justify continued testing in phase 2 trials.
- Doctors prescribing right-to-try drug treatment, pharmacists dispensing the drugs, and companies providing right-to-try drugs are shielded from liability. While fear of liability is not an unreasonable concern regarding experimental therapeutics, in my not-so-humble opinion, the blanket protection from liability goes too far in this law, seemingly shielding doctors from all liability, not just liability related to adverse events and outcomes from the experimental therapeutic.
- 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?
Worst of all, I’d like to emphasize again, right-to-try is entirely unnecessary, given that expanded access programs in the FDA approve >99% of applications to use experimental drugs outside of clinical trials and do so without stripping away scientific and ethical oversight the way that right-to-try does.
Now let’s compare the above to the requirements of the FDA’s Expanded Access Program as of 2018, right before right-to-try was signed into law:
Sometimes called “compassionate use”, expanded access is a potential pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.
Expanded access may be appropriate when all the following apply:
- Patient has a serious or immediately life-threatening disease or condition.
- There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
- Patient enrollment in a clinical trial is not possible.
- Potential patient benefit justifies the potential risks of treatment.
- Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.
Investigational drugs, biologics or medical devices have not yet been approved or cleared by FDA and FDA has not found these products to be safe and effective for their specific use. Furthermore, the investigational medical product may, or may not, be effective in the treatment of the condition, and use of the product may cause unexpected serious side effects.
Basically, right-to-try is expanded access without FDA or IRB oversight. It allows any doctor, quack or not, to determine whether the potential benefits of an experimental therapeutic (be it drug or device) justifies the risk of treatment, based on just phase 1 clinical testing, which does not establish safety or efficacy. (Indeed, there is a reason why cancer quack Stanislaw Burzynski tried to use right-to-try to sell his quackery and that COVID-19 quacks did the same.) Again, remember. Phase 1 testing generally enrolls at most a few dozen patients, often fewer, to test for the most obvious toxicities and to find a dose to use for phase 2 clinical trials. You cannot say that potential patient benefits outweigh the risks based solely on phase 1 clinical trial results. At best, you can say that the drug is not dangerously toxic. Again, the very purpose of right-to-try was to eliminate FDA oversight over an expanded access-like program that lacks even rudimentary patient protections. That is a feature, not a bug, of the law, as right-to-try was always intended as a major step in neutering the FDA’s regulatory authority. Another feature of the law is that it has no mechanism to pay for “right-to-try” experimental therapeutics, which means that the patient and patient’s family are on the hook for the often massive expense of “trying” experimental therapeutics, consistent with the libertarian, “free market,” antiregulatory origin of the law.
But has right-to-try done what Donald Trump claimed in his acceptance speech? I think you know the answer to that.
Right-to-try in practice
The last time I wrote about right-to-try in 2019, I tried to evaluate how it had actually functioned, basing my post on a STAT+ News article by Ed Silverman critically examining the effect of the law during its first year, from which I’ll briefly quote:
Despite the hubbub over the “right-to-try” law, a recent survey found that nearly half of drug makers indicated they would require regulators to review a decision to provide an experimental treatment to a person with a life-threatening disease.
Specifically, 13 of 29 drug companies indicated they want a relevant regulatory authority to review requests that are granted to such people. Of these, six specified they would ask the Food and Drug Administration to conduct a review and five stated they require a research ethics committee or institutional review board, according to a report from the Government Accountability Office.
The results show many drug makers still prefer to follow the mandate in the FDA expanded access program, which was created to provide a route for people with serious or life-threatening illnesses to request experimental treatments from the pharmaceutical industry. The program requires a physician to submit a request to a drug company, and for the FDA to sign off on providing a medicine.
Silverman noted that this is in contrast to right-to-try, which does not require a drugmaker to receive endorsement from the FDA before making an experimental drug available to a patient, also noting another key part of the propaganda that had gotten right-to-try passed, namely that the FDA is too slow to approve new drugs and that its expanded access program is too cumbersome. Of course, as I had discussed multiple times before (and continue to do now), it might have been true at one time that the expanded access program was too cumbersome for the average patient, but in recent years the FDA had made great strides in streamlining the program. I had also noted that the FDA approval process is not slow, given what needs to be done. Indeed, at the time right-to-try was made law, as fast or faster than the systems in most industrialized countries, including the EU. In any case, in 2019 STAT News noted that during the first year of right-to-try only two patients had gained access to experimental therapeutics using the law.
The first patient was a man with glioblastoma, and it was noted that, even though he had invoked right-to-try, the company still involved the FDA and an IRB:
A close look at the details of this “first” right to try case shows both the FDA and UC Irvine’s IRB were involved. So why did ERC-USA choose the right to try pathway over the expanded access program? UC Irvine’s IRB states that the institution follows the statutory requirements of California’s right to try law, which mandates more stringent reporting and informed consent requirements than the federal law.
ERC-USA notified the FDA that it planned to treat a patient under the Right to Try Act. The company received an acknowledgement from the FDA in July 2018—nearly six months before the patient started receiving treatment in late November. Right to try proponents have asserted that the FDA’s expanded access program contains unnecessary bureaucratic steps that discourage patients from seeking experimental therapies in the first place. But ERC-USA likely chose to involve the FDA and UC Irvine its IRB to ensure that any provision of an experimental agent to a patient outside of a clinical trial wouldn’t interfere with the product’s clinical development and to confirm that the patient was aware of possible risks and benefits.
The second case involved a patient with amyotrophic lateral sclerosis (a.k.a. Lou Gehrig’s disease), a fatal progressive degenerative disease of the nervous system, and the company offering right-to-try, Brainstorm, sounded very much like a quack stem cell company that had, in essence, turned right-to-try into its business model, as I discussed when I characterized right-to-try being all about the Benjamins and neutering the FDA.
So what’s happened since 2019? Suffice to say that Donald Trump’s claim that right-to-try is saving the lives of “thousands” of patients is utterly divorced from reality. As a number of news sources have pointed out, for instance, Politico:
However, the Right to Try pathway was only used for four drugs last year. In fiscal 2023, the FDA received nearly 2,300 compassionate use requests and allowed most to proceed.
In actuality, 99% of expanded access requests had been granted by the FDA in the year prior to the passage of “right-to-try.” Politico also reported that only four applications were received in 2023, but the article is behind one of the more persistent paywalls that I’ve ever seen; so I couldn’t get into the full details. The most recent FDA report on right-to-try reveals, however, that between 2018 and 2022, there were only 12 drugs for which right-to-try was invoked, and, yes, in 2023 only four. In other words, only roughly three orders of magnitude less than what Trump claimed, and it is very likely that most uses did not save the life of the patients involved.
In other words, five years after its passage, right-to-try has been a spectacular failure. It does not do what its proponents claimed that it would do. It provides no advantage or benefit above and beyond what the FDA expanded access program provides in terms of letting seriously or terminally ill patients access promising investigational drugs not yet approved by the FDA. It is a sham, and a cruel one, as I’ve argued all along. The only “good” it might do is for unscrupulous companies that want to use it as a profit center or facilitate its use as a profit center. It is thus indeed fortunate that right-to-try has been such an abject failure thus far, as it could have been harming thousands of patients but thus far has not.
Unfortunately, should Trump be elected President again, the same forces that pushed for right-to-try want to “improve” it:
The slow uptake has led some of the law’s biggest proponents to call on Trump to expand upon the program in his first 100 days if he’s elected in November, likely reopening the debate into the FDA’s role in the oversight of access to experimental treatments. Right to Try supporters want Trump to encourage drug manufacturers to participate through incentives and benefits, and Trump’s campaign said he is open to changes to the law.
And Representative Andy Biggs (R-Arizona):
The lawmaker wants Trump to expand the law in his first 100 days if he wins reelection — an idea the Trump campaign said the former president is open to.
“We protect and give some immunities and benefits to pharmaceutical companies,” Biggs said. “We could have provided more of an incentive to pharmaceutical companies to provide these drugs and biologics to people who need them.”
This sounds like a recipe for the federal government to pay or otherwise incentivize pharmaceutical and device manufacturers to bypass the FDA and sell their wares directly to patients, as long as the patient is ill enough.
If Trump is elected again, you can bet that right-to-try will be expanded, patient protections further eroded, and pharmaceutical companies incentivized to use it to bypass the clinical trial process used by the FDA to approve drugs, all as just part of a much broader agenda to destroy the “administrative state.” That’s because right-to-try was never about helping desperate terminally ill patients. Rather, it’s always been a wedge whose tip is those very patients being jammed into the FDA regulatory apparatus in order to open it up to the radical “free market” and all its attendant quackery.