This is it. This is likely the climax, and I fear that the outcome will not be good.

I’m referring to the plan for the House of Representatives to vote on the Senate version of a federal “right-to-try” bill, which I learned about from STAT News late last week:

The House is set to take up a controversial “right-to-try” bill next week — and if it passes, the Food and Drug Administration will have to work harder to protect patients than it would if a different version of the legislation were advancing, Commissioner Scott Gottlieb told STAT in an interview.

Gottlieb’s comments, made at FDA headquarters on Thursday, indicate that one of President Trump’s top lieutenants believes Congress is moving forward with a bill that contains less of his agency’s input than an alternative version of the bill — a more recent, updated bill that passed the House in March but ultimately stalled in the Senate

Broadly, right-to-try legislation aims to give terminally ill patients a different pathway to access experimental treatments that are not FDA approved.

Regular readers might be familiar with the saga of right-to-try, which Jann Bellamy and I have written about many times before. However, given that the last time I visited this saga was in January, when right-to-try supporters, with the help of Vice President Mike Pence and the Koch Brothers’ Americans for Prosperity and Freedom Partners, were making a final push to pass a federal right-to-try law, it’s still worth going through the history of how we got to this point, where Congress is on the verge of passing a bill that, if passed, would strip important patient protections from terminally ill patients. It’s a saga that goes back four years. We will look at the actual bill being considered in the House, so that I can explain why it’s actually the worse possible option, but first a little history.

How right-to-try got here

As I pointed out what seems to me to be so long ago, 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.

Another aspect of these bills is, as Jann Bellamy and I have described many times, how, compared to existing expanded access programs, 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!

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 to make access to experimental therapeutics easier for terminally ill patients. Indeed, not surprisingly, 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 state 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: The 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 Prescription Drug User Fee Act (PDUFA), 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, the Trickett Wendler Right to Try Act of 2017. This is the bill that is coming up for a vote next week. Oddly enough, it’s not the most recent version of the bill.

The Trickett Wendler Right to Try Act

So let’s discuss the bill again, S. 204, the Trickett Wendler Right to Try Act of 2017 (or, if you want the full version of the name, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017). The bill was championed by Sen. Ron Johnson (R-WI), who has been flogging it for at least two years and managed to get a vote on the bill by threatening to hold the renewal of the bill funding the FDA hostage unless right-to-try provisions were attached to it. Had that happened, that would have been a disaster, because it would have “baked” right-to-try into the very founding legislation that funds the FDA through user fees. Ultimately, Sen. Johnson appears to have been placated by a promise to put right-to-try to a vote. Predictably, the bill passed unanimously last August.

When the bill went over to the House, there was less enthusiasm for it, at least as written. Indeed, Sen. Greg Walden, Chairman of the House Energy and Commerce Committee, was opposed to the bill as written, and his was the committee that had to vote to send the bill to the floor for a vote. Unfortunately, then as now, Rep. Walden was 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. Rep. Walden managed to improve the bill considerably by actually consulting with the FDA, although, as I’ll briefly relate, even the new House version that was passed (H.R. 5247) wasn’t that great. It just wasn’t as awful as S. 204.

And, make no mistake, S.204 is awful. Let’s take a look at some of the provisions. As with all the state right-to-try laws, it defines an “eligible investigational drug” for right-to-try as a drug that has passed phase I testing, has not been approved by the FDA but has a pending application for approval, and is undergoing further clinical trials. Now here’s where things get patient-hostile:

(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.

So, 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 decides that the use of these outcomes is critical to determining the safety of the drug or the applicant wants them used. Not the FDA official charged with overseeing the approval of the drug. Not even the FDA Commissioner. The Secretary of HHS. How often do you think that the HHS Secretary will step in and insist on the use of right-to-try outcomes for the approval of a drug? I’d be willing to bet that the answer would be: Not very often—or even basically never.

It is fortunate, then, that there is an additional provision that allows the HHS Secretary to delegate this authority. This provision, however, is less than it appears:

(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.

This is somewhat better, in that the HHS Secretary can delegate this decision to the FDA Commissioner or the director of the specific agency within the FDA charged with premarket review of the drug. Even so, notice the language. Rather than what the default should be (that all outcome data should be considered when examining a drug for FDA approval), this law would force 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.

Then, of course, there are provisions regarding liability:

(b) No Liability.—

(1) ALLEGED ACTS OR OMISSIONS.—With respect to any alleged act or omission with respect to an eligible investigational drug provided to an eligible patient pursuant to section 561B of the Federal Food, Drug, and Cosmetic Act and in compliance with such section, no liability in a cause of action shall lie against—

(A) a sponsor or manufacturer; or

(B) a prescriber, dispenser, or other individual entity (other than a sponsor or manufacturer), unless the relevant conduct constitutes reckless or willful misconduct, gross negligence, or an intentional tort under any applicable State law.

I find it rather fascinating (and telling) that there is 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, S. 204 leaves doctors out to twist in the wind but still protects manufacturers.

There are also provisions in S. 204 that require the FDA to publish right-to-try usage to its website. That is probably the least objectionable part of the bill.

To the House and back

When S. 204 went over to the House, it ultimately became H.R. 5247, and, thanks to Rep. Walden’s committee working with the FDA, there were a number of improvements. For example:

(ii) The requirements described in this clause are the requirements under subsection (b) or (c) of section 561, including—

(I) the reporting of safety information, from clinical trials or any other source, as required by section 312.32 of title 21, Code of Federal Regulations (or any successor regulations);

(II) ensuring that the informed consent requirements of part 50 of title 21, Code of the Federal Regulations (or any successor regulations) are met; and

(III) ensuring that review by an institutional review board is obtained in a manner consistent with the requirements of part 56 of title 21, Code of the Federal Regulations (or any successor regulations).

This seems to be requiring informed consent through standard federal regulations. However, there is a caveat, as noted by Holly Fernandez Lynch, whose Tweetstorm is worth revisiting:

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.

I won’t go into much more detail about the House version that passed, because that’s not the version being voted on this week. Basically, the House version that passed is a significant improvement over the version that passed the Senate and will be voted on the House as is this week. However, it was still pretty bad. Of course, leave it to Congress to pick the worst of the two bills out there.

The final push

Make no mistake. There are powerful forces pushing for this vote. In the normal course of Congressional activity, what would happen next is that there would be a conference committee to reconcile the House and Senate versions of the bill that have passed, and then the reconciled bill would be voted on again by the House and the Senate. This is not what is happening. Here’s what is happening and why.

Originally, the House version that passed was going to the Senate for consideration. At that time, Sen. Charles Schumer blocked consideration of that bill:

The announcement on Thursday that it will take up the Senate’s bill comes as congressional momentum had appeared to grind to a halt the past two months, leaving the path forward on the measure unclear.

Senate Democrats last year didn’t object to the bill Johnson introduced with Sen. Joe Donnelly (D-Ind.), which also sidesteps the FDA.

But since the opposition from House Democrats, Senate Minority Leader Charles Schumer (D-N.Y.) has voiced concerns about taking the FDA out of the equation and objected to a request to bring the House bill up by unanimous consent.

House Democrats voiced concerns about patient safety that were echoed by some advocacy groups.

At the time, this move appeared to doom right-to-try. Unfortunately, as I said before, powerful forces are backing right-to-try, including the Koch brothers and Vice President Mike Pence. I fear that opponents to right-to-try might have shot themselves in the foot by blocking the Senate from considering the House version, which, while bad, is not as bad as the Senate version. (At least the House version leaves open the possibility of IRBs being involved in right-to-try cases.) As a result, the only option that right-to-try supporters had left was to try to get the House to pass the even more awful Senate version essentially as is, and they used various parliamentary rules to make it happen. Basically, the fix appears to be in, as Richard Plotkin notes:

It appears the Senate understood that H.R. 5247 shouldn’t be brought up for a vote, which resulted in the current effort to have the House approve S. 204. It is not disputed that S. 204 was passed by the Senate in response to Sen. Ron Johnson (R-Wisc.) putting a hold on Prescription Drug User Fee Act (PDUFA).

Because of this, there was no real opportunity for the Senate to consider S. 204 on the merits. In other words, S. 204 does not have the support of the Senate and was approved based on the unconscionable “wheeling and dealing” by Johnson.

Add to that pressure from Vice President Pence, President Trump, and the Koch brothers, and this is going to be damned difficult to stop. Indeed, I fear that FDA Commissioner Scott Gottlieb appears to have given up completely, as these recent Tweets show:

Here’s a reminder of what Gottlieb said that STAT News interview:

Gottlieb said his agency will have to work harder to protect patients than it would have had to under the structure set up in the alternative bill, which was spearheaded in large part by Energy and Commerce Committee Chairman Greg Walden of Oregon. The bill the House will vote on next week, from Sen. Ron Johnson (R-Wis.), didn’t include as much of the FDA’s input and could open the pathway to more patients.

“In terms of making sure that it balances [access to experimental drugs] against appropriate patient protections, I think the Walden bill gives us less work to do,” Gottlieb said. “With the Johnson bill, we’d have to do a little bit more … in guidance and perhaps in regulation to achieve some of those goals, and I think those are the goals that Congress wants us to achieve.”

He said the newer Walden bill “baked in more of the technical assistance we provided.”

And his walkback:

In a subsequent interview Thursday afternoon, Gottlieb added that he is supportive of the Johnson bill, and said he had not realized the House was set to vote on that bill when he spoke with STAT earlier in the day.

“We can implement the Johnson bill in a way that achieves what Chairman Walden set out to do,” Gottlieb said.

“We felt that there were certain aspects of the [Johnson] legislation 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 both the letter and the spirit of this law,” he added.

Is that whistling I hear at the gate of the graveyard? Sadly, it sounds that Gottlieb has resigned himself to this awful bill passing.

The real purpose of right-to-try

In the end, right-to-try has almost nothing to do with actually helping terminally ill patients access promising experimental therapeutics that might save their lives. It never has been. In actuality, right-to-try is a first step in weakening the FDA, with the ultimate goal of reducing it to a pre-thalidomide, pre-Kefauver-Harris Amendment, which required the FDA to assure not just drug safety but efficacy as well.

If right-to-try passes this week (and if it passes President Trump will sign it into law), 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. Right-to-try is just the beginning.

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. Patient advocates are going to keep fighting right up to the vote, and I urge SBM readers to contact their Representatives. Never say die, and it isn’t over until the fat lady sings. However, I fear that we will find out the effects. I also fear that the next steps will be to loosen regulations against promoting off-label drug use, expanding the definition of who’s eligible for right-to-try, and otherwise dismantling patient protections in the name of “deregulation.”



Posted by David Gorski

Dr. Gorski's full information can be found here, along with information for patients. David H. Gorski, MD, PhD, FACS is a surgical oncologist at the Barbara Ann Karmanos Cancer Institute specializing in breast cancer surgery, where he also serves as the American College of Surgeons Committee on Cancer Liaison Physician as well as an Associate Professor of Surgery and member of the faculty of the Graduate Program in Cancer Biology at Wayne State University. If you are a potential patient and found this page through a Google search, please check out Dr. Gorski's biographical information, disclaimers regarding his writings, and notice to patients here.