Two weeks into 2018, I once again find myself discussing an issue that I’ve been discussing for nearly four years now. I’m referring, of course, to a law known as “right-to-try.” Such laws, all based on a legislative template published by the libertarian Goldwater Institute, purport to allow terminally ill patients to bypass the FDA and access experimental drugs that have passed only phase I testing. As anyone with a basic knowledge of clinical trials knows, this is an incredibly low bar for safety, and phase I trials are not even designed to show efficacy. When the right-to-try movement made its first big splash on the national scene back in 2014, which was when several states beginning with Colorado passed the first right-to-try laws, both Jann Bellamy and I pointed out how these laws, seemingly inspired by the movie Dallas Buyers Club, were an illusion, a sham, a misguided and actively patient-hostile “solution” (why will be explained below) to a problem that right-to-try advocates greatly exaggerated in order to promote these laws. Indeed, in 2014 some libertarian advocates even latched on to the fear of Ebola as a scare tactic to advocate for right-to-try, while others (like Nick Gillespie and Ron Bailey) accused the FDA of killing millions through slow approval of new drugs. I kid you not. Basically, right-to-try advocates succeeded in portraying opposition to right-to-try as callous and betraying a lack of compassion for terminally ill patients as well as an assault on freedom itself, all mixed, of course, with a heaping helping of anti-government rhetoric directed at the FDA. Basically, the reason so many states passed these laws so quickly was through a combination of ignorance among the general public of how drugs are approved and a campaign to demonize opponents, such that opposition to right-to-try was perceived among politicians as akin to opposition to mom, apple pie, and the American flag.
Eventually, as these laws metastasized, passing in more and more states (38 as of October!), advocates promoted a federal version of the law. The first attempt, the Compassionate Freedom of Choice Act, went nowhere in 2014. So did the second attempt in 2016. Of course, such a law could not have passed then because it almost certainly would have been vetoed by the previous President, but the point is that it didn’t even get out of committee both times. Then came President Donald Trump and a push for deregulation. Let’s just say that the environment in Washington had…changed. For one thing, Vice President Mike Pence is a supporter of right-to-try. In any event, The Trickett Wendler Right to Try Act was reintroduced in 2017. When even in a Republican Senate the bill appeared to be going nowhere, its sponsor, Senator Ron Johnson, threatened to hold the renewal of the bill authorizing the FDA to collect user fees from companies seeking FDA approval for their drugs hostage if right-to-try language was not added to it. Ultimately, to mollify him, Senate leadership agreed to hold a vote on Sen. Johnson’s bill, and, as almost always happens when such a bill comes up for a vote, it passed easily.
That was the situation in August, when last I wrote about right-to-try. To be honest, I was surprised that the House hadn’t passed the bill and President Trump hadn’t signed it into law yet. Unfortunately, earlier this week I learned that one last push is being made to pass the bill. Before I discuss that, let’s take a look at why right-to-try laws are so problematic and harmful to patients.
The problem with right-to-try (state version)
As I mentioned before, the push to pass right-to-try legislation at the state level is basically a product of forces that want very much to weaken the FDA’s power to approve and regulate drugs, with each law following rather closely, with minor variations, the legislative template originally published by a libertarian think tank, the Goldwater Institute. Such legislation includes several major shared features. First is 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, some with some room for interpretation.
One of the most problematic passages, if not the most problematic passage, is the one where the term “investigational drug, biologic product, or device” is defined:
“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 [sic] and remains under investigation in a United States food and drug administration-approved clinical trial.
Every right-to-try bill or law I’ve ever read uses the above definition or relatively minor variations. Anyone who knows anything about drug development knows 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. It is utterly impossible for such a small clinical trial to determine the safety of a drug. 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,” the intent also being to find the best dose to use in subsequent Phase II and Phase III trials. 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.
Right-to-try laws are also profoundly unjust, as nearly all of them limit who can access experimental drugs by wealth. The reason is that all of right-to-try laws have a provision that says that health insurance companies do not have to pay for such treatment and nearly all of them also say that the company providing the experimental therapeutic under right-to-try can charge the patient for it. A terminally ill patient could easily go bankrupt before he dies, 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. In at least one state I know of, the right-to-try law allows a drug company to go after a deceased patient’s estate to collect. It goes beyond that, though. If a patient uses a right-to-try drug and suffers complications, many of these laws essentially state that the insurance company doesn’t have to pay for care resulting from that complication, and most such laws state that patients undergoing right-to-try therapies lose their coverage for hospice.
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, a libertarian paradise!
Right-to-try laws also limit what patients can do in the event of malpractice or negligence. All of them broadly immunize physicians advising or administering right-to-try medications or using right-to-try devices against malpractice suits or actions against their medical license by the state medical board related to their participation in right-to-try. All of them also immunize 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.
I frequently refer to state right-to-try laws placebo laws because they basically do nothing but make advocates and legislators feel as though they did something good for terminally ill patients. After all, the FDA controls drug approval, and its power overrides state law. For that reason, few would be the drug companies willing to risk their FDA approval by providing experimental drugs to patients without the FDA’s permission. Of course, the Goldwater Institute is not run by idiots. Its leadership knows this. The purpose of state-level right-to-try laws was never really to help terminally ill patients. It was to put pressure on lawmakers to pass a federal right-to-try law as a first big step towards weakening the FDA.
H.R. 878: Right to Try Act of 2017
H.R. 878: Right to Try Act of 2017 is simpler than most state-level laws and is currently very similar to the bill passed by the Senate in August (S. 204: Trickett Wendler Right to Try Act of 2017). It has two main provisions. First:
Notwithstanding the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.), the Controlled Substances Act (21 U.S.C. 801 et seq.), and any other provision of Federal law, the Federal Government shall not take any action to prohibit or restrict—
(1)the production, manufacture, distribution, prescribing, or dispensing of an experimental drug, biological product, or device that—
(A)is intended to treat a patient who has been diagnosed with a terminal illness; and
(B)is authorized by, and in accordance with, State law; and
(2)the possession or use of an experimental drug, biological product, or device—
(A)that is described in subparagraphs (A) and (B) of paragraph (1); and
(B)for which the patient has received a certification from a physician, who is in good standing with the physician’s certifying organization or board, that the patient has exhausted, or otherwise does not meet qualifying criteria to receive, any other available treatment options.
In essence, this part of the law would basically tell FDA and other regulatory agencies not to interfere with the use of experimental drugs by terminally ill patients under state right-to-try laws. That’s no surprise, although the language does seem a bit broader than I would have expected—but, as they say, I am not a lawyer. For purposes of this bill, experimental drugs are defined the same way as in state right-to-try laws, any drug that’s passed phase I clinical trials.
Now here’s the truly pernicious, stupid part of the bill:
(b)No liability or use of outcomes
(1)No liability. Notwithstanding any other provision of law, no liability shall lie against a producer, manufacturer, distributor, prescriber, dispenser, possessor, or user of an experimental drug, biological product, or device for the production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that is in compliance, with subsection (a).
(2)No use of outcomes. Notwithstanding any other provision of law, the outcome of any production, manufacture, distribution, prescribing, dispensing, possession, or use of an experimental drug, biological product, or device that was done in compliance with subsection (a) shall not be used by a Federal agency reviewing the experimental drug, biological product, or device to delay or otherwise adversely impact review or approval of such experimental drug, biological product, or device.
The part about liability is self-explanatory. It basically immunizes manufacturers, distributers, doctors, and patients against federal liability for using and possessing experimental drugs, just as state right-to-try laws immunize them against state liability. No surprise there.
The real surprise is the part barring the FDA and other regulatory agencies from using reported outcomes from patients using experimental drugs under right-to-try. That means that if a patient uses an experimental drug under right-to-try and suffers a serious adverse reaction, the FDA cannot consider that reaction in its deliberations over approval of the drug. This clause is obviously intended to address the concern of drug and device manufacturers that if they provide an experimental therapeutic to a patient under right-to-try and the patient suffers complications due to the treatment, the approval of its product might well be jeopardized. This, of course, is not an unreasonable concern on the part of manufacturers, given that it can cost as much as $1 billion to bring a drug or device to market, and by the time the product has passed phase I clinical trials a great deal of that cost has already been invested in development. However, this clause goes way, way too far. Basically, it means that even if a patient death is clearly due to use of an experimental drug under right-to-try, that death cannot be considered by the FDA in deciding whether to approve the drug.
Think of it this way. Let’s say dozens of patients die from using an experimental drug under right-to-try. This bill, if passed, would bar the FDA from even considering those deaths during its deliberations regarding whether to approve the drug for marketing or not. This is not a good thing for patients. It is profoundly anti-patient. Basically, the Trickett Wendler Right to Try Act of 2017 would not help terminally patients. It would endanger them. Existing Expanded Access (sometimes also called Compassionate Use) programs by the FDA are, as I pointed out above, no longer so onerous and requests under them are almost always approved. Right-to-try laws only strip away patient protections without providing any potentially useful new rights to terminally ill patients.
As I like to do whenever I write about right-to-try, here I will refer readers to the excellent bullet point summary of the problems with right-to-try published by the New York University School of Medicine Working Group on Compassionate Use and Pre-Approval Process.
The Koch brothers make a last push to pass right-to-try
About a week ago, I saw this Tweet:
— Alison Bateman-House (@ABatemanHouse) January 8, 2018
Koch brothers-backed groups are launching a campaign urging Congress to pass legislation allowing terminally ill patients to request access to experimental drugs the Food and Drug Administration (FDA) hasn’t approved.
Nearly 40 states have this law, known as “Right to Try,” already on their books. But Freedom Partners, in partnership with Americans for Prosperity — two groups funded in part by billionaire brothers Charles and David Koch — say federal legislation is needed to assuage patient fears that the federal government will override state laws.
The new push, launched Monday, consists of a lobbying effort, 30- and six-second digital ads, a social media effort and more.
On Twitter, we can see Americans for Prosperity is pushing the message and the ads:
— AFP (@AFPhq) January 14, 2018
Here’s the main ad being used by Americans for Prosperity and Freedom Partners to promote right-to-try:
Congress is on the cusp of delivering real hope to millions of Americans who are desperately seeking potentially life-saving treatments that are just out of their reach. Support #RightToTry. https://t.co/1TEg2G6kyj pic.twitter.com/2tNK2ifmgq
— Freedom Partners (@FreedomPartners) January 12, 2018
The ad is nauseating in the extreme, full of the usual exaggerated and misleading talking points and appeals to emotion commonly used by right-to-try advocates. So is the propaganda appearing on the Freedom Partners website. Indeed, its arguments are disingenuous and misleading in the extreme:
Though the FDA boasts of granting over 99% of expanded access requests it receives, it only received 1,757 requests for expanded access in total last year, minuscule in comparison to the 596,000 Americans who died of cancer in 2015, the 155,000 who died of chronic lower respiratory diseases, or the 111,000 who died of Alzheimer’s. This number is troubling in light of the nearly 26,000 patients receiving experimental treatments in France in 2016 under a similar program, meaning nearly fifteen times as many patients receiving experimental treatments in a country one-fifth the size. Underlying this disparity is the burden placed on patients by the FDA, discouraging them from even submitting a formal application.
In an article for The Goldwater Institute, Carla Mann Woods, formerly a medical device industry executive, and now a board member of the Alfred E. Mann Institute for Biomedical Engineering at the University of Southern California, put it this way: “In this era of both scientific revolution and information where anyone can find anything on the Internet, ask yourself this: Can you actually believe that only 1,200 dying Americans want to live badly enough to find a legitimately applicable, unapproved therapy and ask to get it?”
No one is arguing that we shouldn’t do better in expanding access to experimental drugs. However, comparing compassionate use approvals to the total number of patients dying of cancer is a false metric given that the vast majority of terminally ill patients wouldn’t be likely to qualify for most experimental drugs anyway, either based on disease type, burden, or comorbid conditions. As for the example of France, I can’t help but note the the French National Agency for Medicines and Health Safety report cited. I was puzzled at first, as I saw little reference to what Freedom Partners was talking about, but it would appear that it was talking about a Temporary Authorization for Use (TAU):
A Temporary Authorisation for Use is an exceptional, special procedure which, since 1994, has given numerous patients, for whom there is no available alternative treatment, access to medicines that do not have a MA in France. They may be named-patient Temporary Authorisations for Use (TAUn), i.e. granted for a specific named patient, or concern a group of patients (cohort Temporary Authorisation for Use, TAUc).
Since 2012, ANSM has been developing a new policy aimed at expanding the use of cohort TAUs in order to foster fair, closely monitored access to innovative treatments for patients whose treatment options have been exhausted.
In fact, this is a false and deceptive comparison. Access to unlicensed drugs in France under a TAU is a very different beast compared to access to unlicensed drugs through right-to-try in that the French government still has to approve the use of unlicensed medicines. In France, a drug requires a marketing authorization (MA) and price and reimbursement agreements. Indeed:
The French early access programme is one of the few European compassionate-use programmes to allow cohorts of patients. In fact, two types of ATU status exist. The first one, known as nominative ATU, is available on a named-patient basis under the responsibility of the prescribing physician. The second one, cohort ATU, is intended to apply to a group of patients and is established at the request of the pharmaceutical company for specific indications , Hospital pharmacies are exclusively in charge of supplying ATUs to in- or outpatients. As with other drugs, hospital pharmacies purchase ATUs by directly negotiating with manufacturers. Pharmaceutical companies have the freedom to determine ATU pricing. The National Health Insurance (NHI) is responsible for the cost associated with these treatments. For outpatients, NHI fully reimburses ATU expenditures to hospitals on the presentation of bills. For ATUs delivered to hospitalized patients, additional funding, known as ‘MIGAC’ (Missions d’intérêt Général et d’Aide à la Contractualisation), is available to hospitals on top of the diagnosis-related group (DRG) funding. Several blockbusters have been available in France through the ATU programme prior to getting an MA. Examples include: bevacizumab (Avastin®), erlotinib (Tarceva®), lenalidomide (Revlimid®), ranibizumab (Fucentis®) and sorafenib (Nexavar®).
If granted, the programme guarantees patient access before MA and also during the time of agreement on reimbursement and price.
The contrast between the French early access program and right-to-try could not be more clear. TAU is not a right-to-try law. In the French program, government regulatory agencies are heavily involved. (Indeed, in the very report referenced by Freedom Partners, it points out that there must be good evidence that the drug is likely to work before a TAU will be issued and details how the government must monitor usage.) In contrast, under right-to-try, the FDA is explicitly cut out of the decision-making process and can’t even consider results seen in patients using right-to-try in determining whether to approve an experimental drug. In the French program, the government pays for the experimental drug. Under right-to-try, the patient is completely on his or her own. You get the idea. The Freedom Partners’ propaganda is so deceptive as to be virtually a lie. In fact, the existence of the French TAU program puts the lie to the claim that right-to-try is needed to expand access to experimental drugs. The French have done it without sacrificing regulatory oversight through a right-to-try law. We could too if we so desired.
In retrospect, the involvement of the Koch brothers makes a lot of sense. I had always suspected that there had to be much more behind the right-to-try effort than just the Goldwater Institute, which, while influential, is not nearly large enough to have mounted such an effort in so many states over such a short period of time on its own. I can’t help but remember back when right-to-try passed almost in secret in Michigan, the Goldwater Institute was able to fly in patient advocates from all over the country. It was a suitably impressive effort. The involvement of the Koch brothers reinforces more than ever my conclusion that right-to-try is not (and never was) about helping terminally ill patients. It’s always been about weakening the FDA’s ability to regulate drugs.
An excellent editorial by Steven Joffe and Holly Fernandez Lynch in the latest New England Journal of Medicine makes this very point, the first time I’ve seen it so explicitly argued in a large mainstream medical journal. Although they think that the potential harm to patients and clinical trials may be overstated by opponents, they recognize the real purpose of right-to-try as the “foot-in-the-door” to further deregulation that would weaken the FDA’s health mission:
Nevertheless, its passage would remain important. Indeed, the serious consideration the legislation is being given reflects a broader effort to weaken medical product regulation. The Goldwater Institute has launched a campaign in the name of free speech to allow manufacturers to share information with physicians and others about off-label uses of approved drugs, which has resulted in at least one state law to that effect. The FDA has traditionally tightly regulated this practice, but recent federal court cases have threatened its authority in the name of protecting truthful commercial speech. The FDA’s new commissioner, Scott Gottlieb, appears poised to move the agency toward a more permissive stance on off-label communication.
If a federal right-to-try bill becomes law, the long-standing principle that broad access to medical products should await evidence of safety and efficacy will contend with the principle that patients with life-threatening diseases should have unfettered access to agents that have passed a bare minimum of safety testing. This logic could ultimately extend to patients with serious chronic illnesses and, conceptually at least, to all patients who find their approved treatment options unsatisfactory.
This is what I’ve been arguing for nearly four years now, that right-to-try is only part of a broader push to weaken the FDA and, if passed, that the next step would be to push to make right-to-try apply to more than just terminally ill patients. Ultimately, the push would be to make it apply to everyone. It’s good to see this argument explicitly stated in the pages of a journal as highly read and respected as the NEJM.
Until now, the likelihood of passing right-to-try in the House was considered rather low. Indeed, in October, FDA Commissioner Scott Gottlieb testified and requested changes to the bill, noting, “If enacted without changes, sponsors and other persons providing eligible investigational drugs to eligible patients under the specified conditions of the bill would not be subject to a number of sections of the FD&C Act and FDA regulations related to clinical trials, premarket approval, and labeling. The current language in S. 204 may therefore preclude FDA from taking enforcement actions based on those provisions.” He also stated, “The perception is that this legislation will pressure companies to supply more expanded access drugs but that remains to be seen,” noting in his written testimony:
It is important to note that access to investigational products requires the active cooperation of the treating physician, industry, and FDA in order to be successful. The most common obstacle to access to the investigational product is the willingness or ability of companies to provide it. Neither FDA nor physicians or patients can compel a company to make a product available – and companies may decline requests for a variety of reasons. For example, they may have produced only a limited quantity of the product (companies ramp up manufacturing after marketing approval), have minimal resources to administer expanded access requests, or have concerns that granting requests for expanded access may exacerbate the challenge of recruiting clinical trial participants – and delay product development.
In other words, the FDA could oversee more expanded access requests, but companies are reluctant to take part.
There’s still hope of stopping right-to-try, however. One hopeful sign is that Senator Greg Walden, Chairman of the House Energy and Commerce Committee, is opposed to the bill, and his is the committee that has to vote to send the bill to the floor for a vote. Unfortunately, he is under great pressure from the Koch-backed Freedom Partners, Vice President Mike Pence, and the House leadership to send the bill to the floor for a vote. Another is that the version passed by the House would have to be basically identical to the version passed by the Senate last year to avoid a conference committee and two new votes, one in the House and one in the Senate. If the House version is changed sufficiently, which is not unlikely, then those votes will have to occur, and there will be a chance to block the bill again. It’s not clear how much time there is. With a potential government shutdown looming on Friday if a budget isn’t passed, I’m optimistic that no floor vote will happen on right-to-try this week, but that doesn’t mean that it won’t come up soon after that.
One of the clearest problems that let right-to-try become the behemoth that it is now is the lack of resistance to it. I’ve complained loudly about how none of the major medical organizations expressed opposition early on, probably because they didn’t want to be painted as the bad guys. Indeed, the American Society of Clinical Oncology, to its shame, said nothing official about right-to-try until its statement of opposition last April, three years after the first laws were passing. More of that will be required, and it will be important to let legislators know that there is actual opposition to this bill among the public by contacting our Representatives.
Right-to-try is a cruel sham by the Goldwater Institute using terminally ill patients as cannon fodder in its interminable war against government regulation. Here is where it needs to be stopped, because if it isn’t it will only be the first step, or, as Joffe and Fernandez Lynch put it:
Are we prepared to abandon the FDA’s gatekeeping role in favor of unfettered patient autonomy and market forces, risking precisely the problems that prompted Congress to grant the FDA its present authority? The agency has made substantial progress in balancing the needs of desperate patients and the principle that all patients deserve evidence that the benefits of medical products justify their risks. We upset that balance, and diminish the FDA’s public health mission, at our peril.
It can’t be stated too often. The goal of right-to-try is not to help terminally ill patients. It’s to diminish and weaken the FDA.