I’ve been writing about the cruel sham known as “right-to-try” laws for nearly four years now, beginning when a libertarian think tank, the Goldwater Institute, started promoting its model legislation template. supposedly designed to allow terminally ill patients to have access to promising experimental drugs. I say “supposedly,” because none of the right-to-try laws thus passed in 38 states and counting so far will do anything to help terminally ill patients. Now, I learn, the federal right-to-try bill that I’ve written about multiple times is on the verge of a vote in the House of Representatives:
Energy and Commerce Committee leaders, along with key proponents of “Right to Try” legislation today announced an updated proposal will be considered by the House of Representatives on Tuesday. The bill, to be formally introduced tomorrow, will improve access to experimental treatments for patients with terminal diseases or conditions.
“This bill has been a long-time coming, but in striking the right balance for patients and their safety, the House is on track to deliver hopeful news for patients desperately seeking the right to try investigational treatments and therapies,” said Energy and Commerce Committee Chairman Greg Walden (R-OR) and Health Subcommittee Chairman Michael C. Burgess, M.D. (R-TX). “We encourage our colleagues on both sides of the aisle to support this important measure on Tuesday, and look forward to swift action by our Senate colleagues.”
Its sponsors claim that the revised bill will do the following:
- Create a new alternative pathway for patients who do not qualify for a clinical trial
- Establish a robust informed consent to access unapproved drugs
- Specify that any unapproved drug used in the new alternative pathway must have an active application and is not the subject of a clinical hold
- Include a sponsor and manufacturer notification to the FDA after they make an unapproved drug available to an eligible patient
- Guard patients from manufacturers purposefully misbranding or mislabeling drugs
- Provide liability protections for manufacturers, sponsors, physicians, clinical investigators, and hospitals that participate in the existing expanded access program and the new alternative pathway; unless there is reckless or willful misconduct, gross negligence, or an intentional tort
- Obligate sponsors and manufacturers to report adverse events to the FDA
- Provide certainty to manufacturers regarding how the FDA will use patient outcomes when evaluating new drug applications
Somehow, I very much doubt these claims. Let’s take a look. First, as always, here’s a little history. As I pointed out when a right-to-try bill was on the verge of passing in Colorado, when right-to-try came to my own state, and as these laws spread like kudzu all over the US, even coming back from the dead after a veto in California, the very concept behind right-to-try is designed not to help patients, but to give the appearance of helping terminally ill patients as it serves as the first step in cutting the FDA out of drug approval and regulation as much as possible. Consider: These laws, being state laws, have no teeth because drug approval is under federal jurisdiction. Sure, a state can say that patients have a right to experimental therapeutics, but unless the FDA agrees to say yes, no company with a drug in clinical trials for FDA approval is going to risk the wrath of the FDA by taking part in right-to-try. Basically, such laws are sold based on false hope and fear. Indeed, some libertarians even used the fear of Ebola as a tactic to promote such laws and accused the FDA of killing patients with bureaucratic inertia.
It’s much worse than that, however, because these laws are actively anti-patient, the claims of their supporters notwithstanding. the only requirements these laws have for testing of the drugs being “tried” are (1) that they have passed phase I clinical trials and (2) that they are still under development and undergoing further clinical trials. Anyone out there who is familiar with clinical trials knows that passing phase I is an incredibly low bar for safety. Phase I trials are “first in human” trials in which a small number of patients test the drug. Basically, the dose is escalated until unacceptable toxicity is encountered. The dose just below that is called the “maximum tolerated dose,” or MTD. The main purposes of phase I trials is thus to identify the highest dose that can be safely used and to identify the most severe adverse reactions and side effects. That’s it. Phase I trials are not designed to determine if a drug has any efficacy. Saying that a drug that’s passed phase I testing is safe, as I’ve heard many right-to-try advocates claim, is utter and complete bullshit. Phase I trials do not prove safety. They merely show that the drug is not too toxic to continue with efficacy testing.
Consistent with their libertarian origin, right-to-try laws also strip away many protections from patients. First, there is no requirement that companies provide the drugs for free or at a reduced price. Indeed, these laws explicitly state that insurance companies are under no obligation to pay, even though such a statement is unnecessary given that insurance companies don’t reimburse for experimental therapies. As a result, the only people who would potentially be able to access right-to-try are the rich or people who are very good at fundraising. A terminally ill person trying to access right-to-try can easily spend away his estate or even go bankrupt before dying. It’s even worse than that. The language in many of these laws can be interpreted to mean not just that insurance companies don’t have to pay for right-to-try but that they don’t have to pay for medical care as a result of complications suffered from using a drug under right-to-try.
These laws also immunize companies providing right-to-try drugs and physicians overseeing their administration from liability. 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.
Of course, the ideologues at the Goldwater Institute knew all along that state laws weren’t going to do anything. Indeed, they haven’t; basically right-to-try thus far has been a miserable failure, with almost no one accessing drugs through it. There’s a reason why I refer to right-to-try laws as “placebo” legislation. They give the appearance of doing something but really don’t do anything to address the issue of making experimental drugs more widely available to terminally ill patients. The idea, of course, was for these state laws to build momentum and pressure for Congress to act. The first iteration of federal laws was the Compassionate Freedom of Choice Act of 2014. It didn’t go anywhere, probably because it was too early. Another federal right-to-try bill was introduced in 2016, but it, too, went nowhere, likely stymied by electoral politics.
Then last year a federal right-to-try effort was undertaken again in the form of S. 204: Trickett Wendler Right to Try Act of 2017, introduced into the Senate by Ron Johnson (R-WI) and H.R. 878: Right to Try Act of 2017, introduced by Rep. Andy Biggs (R-AZ). An attempt was made to insert right-to-try language into the The Prescription Drug User Fee Act (PDUFA) is the law that allows the FDA to collect user fees from drug companies to fund the drug approval process, which was due to expire at the end of last September and needed to be renewed. To get a vote on right-to-try, Sen. Johnson held PDUFA hostage by threatening to obstruct it. Fortunately, this effort failed, but a version of right-to-try did ultimately pass the Senate. It’s been in the House ever since. Now it’s finally coming up for a vote after modification.
First, let’s look at the version I last saw, which is being promoted by the Koch brothers. It had two main provisions. First, it basically tells the FDA that it can neither interfere with a patient seeking experimental therapeutics under right-to-try nor with a company providing those therapeutics, nor with a physician prescribing those experimental therapeutics. Here is the truly stupid, pernicious part of the original 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.
You read that right. The last version of the bill banned the FDA 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.
So let’s look at the new version of the bill. It’s less horrendous in some ways, but in other ways it’s still the same ol’ same ol’. For example, it still requires only that a drug have passed phase I clinical trials and that (1) the drug still be in clinical trials or is the subject of an investigational new drug (IND) application; (2) is still under active development and production; and (3) has not had a clinical hold placed on it. Now here are the “improvements.” First, unlike the previous bill, this bill requires notification of the FDA that right-to-try is being invoked:
(3) NOTIFICATION.—The condition specified in this paragraph, with respect to an eligible investigational drug referred to in paragraph (1), is that the ponsor of such eligible investigational drug notifies the Secretary of the provision of such eligible investigational drug for use by an eligible patient pursuant to this section. Such notification shall be submitted within 7 business days of the provision of such eligible investigational drug as correspondence to the investigational new drug application described in subsection (a)(2).
That’s nice. The FDA can know that right-to-try is being offered, but it can’t do anything about it. There is also the same old provision about the use of clinical outcomes, but it’s not quite as bad as it was in the previous version:
(c) USE OF CLINICAL OUTCOMES.—
(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.
(2) LIMITATION.—If the Secretary makes a determination under paragraph (1)(A), the Secretary shall provide written notice of such determination to the sponsor, including a public health justification for such determination, and such notice shall be made part of the administrative record.
Such determination shall not be delegated below the director of the agency center that is charged with the premarket review of the eligible investigational drug.
So, basically, this new version says 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 director of the FDA center charged with the premarket review of drugs or the FDA Commissioner himself writes a notice justifying the use of these data or the applicant wants them used. Another improvement is that any physician administering right-to-try drugs must report adverse events to the company, which then is obligated to report them to the FDA. There’s also a carve-out from the freedom from liability of doctors who administer right-to-try such that this provision no longer applies to willful or “criminal misconduct, “reckless misconduct,” or “gross negligence relative to the applicable standard of care and practice with respect to the administration or dispensing of such investigational drug.” So, in fairness, this is an improvement, although one wonders why this carve-out from the immunity from liability for sponsors and manufacturers? Basically, this version leaves doctors out to twist in the wind but still protects manufacturers.
There are other apparent attempts to allay fears about patient protections. One is the requirement for informed consent according to federal regulations. However, as noted by Holly Fernandez Lynch, whose Tweetstorm is worth reading:
— HollyFernandezLynch (@HollyLynchez) March 11, 2018
She points out that those federal regulations explicitly state:”No informed consent, whether oral or written, may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.” This is a conflict that would probably require rewriting that section of federal regulations on informed consent. There is also now the requirement that an institutional review board (IRB) be involved in any right-to-try requests. I’m not sure how this would work, given that the bill would cut the FDA out of right-to-try requests. As Fernandez notes hopefully, perhaps IRBs charged with overseeing such requests would ask the FDA for guidance.
From my perspective, the bottom line is that this bill is only marginally less patient-hostile than the previous version. Yes, it’s good that some of the legal immunity has been lifted from physicians and investigators who might administer right-to-try medications. Yes, it’s good that, even though the FDA has been cut out of the decision process, an IRB is required. And, yes, it’s good that the FDA can, if it believes it necessary, consider clinical outcomes data in its drug approval decisions, although it’s not good that it will have to justify its doing so on a case-by-case basis. That requirement was clearly left in order to discourage the FDA from using clinical outcomes in its drug approval decision-making process.
There’s also a problem with the vagueness of who qualifies:
(a) DEFINITIONS.—For purposes of this section: ‘‘(1) The term ‘eligible patient’ means a patient—
(A) who has been diagnosed with an eligible illness;
(B) who has exhausted approved treatment options and is not eligible to participate in (for a reason such as the patient not meeting inclusion criteria) a clinical trial designed to evaluate an investigational drug for the treat- ment of such eligible illness with which the patient has been diagnosed, including one involving the eligible investigational drug, or for whom participation in such a clinical trial is not feasible (for a reason such as a lack of geographic proximity to the clinical trial)…
What does “not feasible” mean? Could it mean that the patient is unwilling to be randomized or just doesn’t like the requirements of a clinical trial? This is pretty vague.
There were two recent op-eds discussing the problems with right-to-try, one published by the American Society of Clinical Oncology (ASCO) by Ellen Sigal and one published in the New England Journal of Medicine by Steven Joffe and Holly Fernandez Lynch.
Sigal emphasizes how much has been done to provide expanded access through FDA programs to experimental therapeutics, and then observes:
Everyone can agree that terminally ill patients should have access to promising experimental therapies when all other available options have been exhausted. A federal right-to-try bill could be a path forward in achieving that goal, but it must not be harmful to patients by exposing them to lethal side effects or removing oversight by the FDA—an agency whose mission is to protect public health from the process. In its current form, the proposed legislation does nothing for patients other than provide false hope by allowing them to request a drug with no evidence of efficacy they may never receive and—should they receive it—may do more harm than good.
The same is true of the revised version. The requirement for an IRB is pretty toothless without direct FDA involvement. There are, for example, pretty lax IRBs for hire. Without the oversight of the FDA, this is not really an adequate patient protection. From my view, this bill is not a way forward. I also can’t help but point out yet again that the time to combat right-to-try was four years ago, when not a single state bill had passed. Now that 38 states have such laws and a regulation-averse administration and Congress are in power, it’s too late. This bill is almost certainly going to pass, and it will harm patients. ASCO said nothing back then, leaving a handful of academics and bloggers who dared to speak out to be subject to attacks by right-to-try advocates as cold, callous, and not caring about the terminally ill. As I’ve said many times before, the greatest propaganda coup of the Goldwater Institute was to use terminally ill patients as its weapons and shields in its battle to weaken the FDA. It worked spectacularly, to the point where opposition to right-to-try is perceived as being akin to being against mom, apple pie, and the American flag. No, it’s worse than that. It’s seen as being akin to being for puppy torture.
And here’s the real purpose of right-to-try, as described by Joffe and Lynch:
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.
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.
That’s exactly what right-to-try is about, going back to the days before the FDA. It’s not about helping terminally ill patients. It never has been. Right-to-try is just the first step, as well. You can bet that not long after right-to-try passes, the anti-regulation ideologues at the Goldwater Institute will start asking, “Why should right-to-try apply only to terminally ill patients? What about patients who are just seriously ill?” And so it will begin. It’s already begun on other fronts. For instance, the Goldwater Institute has launched a campaign in the name of “free speech” to allow manufacturers to share information with physicians about off-label uses of approved drugs. Elsewhere, the Foundation for Economic Education is promoting its Free to Choose Medicine plan, which would basically require only safety testing of drugs for them to be approved, thus moving us back to the pre-1962 situation.
That’s because right-to-try is only a little about helping patients. It’s far more about dismantling the FDA and giving drug and device manufacturers more freedom to market drugs and devices with much less testing. There is a better way.