When I wrote a week ago about the sham that is “right-to-try”, one criticism (among many) that I made of these misguided, profoundly patient-unfriendly laws was that I have as yet been unable to find a single example of a patient who has managed to obtain access to an experimental therapeutic through such a law, much less been helped by it. So-called “right-to-try” laws, of course, claim to provide a mechanism by which patients with terminal illnesses can obtain access to experimental therapeutics not yet approved by the FDA but still in clinical trials. They are, as I’ve pointed out, a cruel sham, placebo legislation that makes lawmakers feel as though they’ve done something good but do nothing of substance for patients while providing them with false hope. The federal government through the FDA controls drug approval, which means that states can’t compel a drug company to provide a drug to a patient, and most drug companies would not want to risk jeopardizing approval of their drug, which is what could happen if they grant access to an investigational drug under right-to-try and the patient suffers an adverse event. After all, the success rate for drugs that have passed phase 1 (which is all that right-to-try requires) in phase 3 trials is only on the order of 9-12%, meaning that that’s the most optimistic probability that such drugs would benefit a patient. In reality, it’s almost certainly much, much lower.

Basically, the whole right-to-try movement is built on a delusion, namely that there are scads and scads of cures out there that are only being kept from the people by the cautious bureaucracy of the FDA. If the people could just get the FDA out of the way—or so the delusions go—cures would flow to the people. Add to that the libertarian delusion of the Goldwater Institute, upon whose model legislation nearly all of these bills and laws are based, that the free market will take care of safety issues, and it’s possible to see the long game being played, a strategy designed to drastically weaken the FDA’s control over drug approval. Then add to that the way that right-to-try legislation strips virtually every protection away from patients in clinical trials. For instance, no IRB oversight is required in right-to-try. There is nothing in the laws that provide for paying for the experimental therapy being used. Indeed, not only do insurance companies not have to pay for right-to-try, but they don’t have to pay for any care that results from complications resulting from right-to-try. If a patient chooses right-to-try and it goes wrong, he’s completely on his own.

All of this brings me to a story I saw after I wrote last week’s post. The story is about an unfortunate man named Bob Bardone who last summer got one of the worst pieces of news a human being can get. He found out that he had amyotrophic lateral sclerosis (ALS), and it was estimated that he probably had about two or three years to live. His story is, as is the case for most ALS patients, heartbreaking. ALS, as many of you know, is a relentlessly degenerative neurologic disease in which the patient gradually loses motor control. Ultimately, patients lose the ability to walk, to move, to speak, and, ultimately, to breathe. Indeed, if there is a disease that I fear more than cancer, it’s something like ALS, which produces a nightmarish, unstoppable deterioration. There’s currently only one drug approved for ALS that I’m aware of, riluzole, but it only adds at best months to life expectancy. If ever there were a disease that needs new treatments, it’s ALS.

As you might recall, Missouri was one of the first states to pass right-to-try legislation. As such, and because of his past connection to the state, Mr. Bardone and his wife decided to move back there in order to be closer to family and, not coincidentally, to try to take advantage of right-to-try:

The move to St. Louis happened to bring them hope. They learned Missouri had become the third state to enact “right to try” legislation, which went into effect in August and allows terminally ill patients to try promising drugs yet to be approved by the FDA.

The family had been closely following news about a drug, GM604. Its maker reported that it significantly slowed the progression of ALS in 12 patients over 12 weeks with no dangerous side effects, though some scientists question the findings. The drugmaker, Genervon Biopharmaceuticals, is seeking fast-track approval from the FDA to sell the drug before spending years studying it in larger numbers.

“My dad had hope for the first time since diagnosed with ALS when he found out Missouri was a right-to-try state,” Connors said. “He thought that because he was moving back to Missouri, that he could try this drug.”

Bardone’s neurologist tried to get more information about the drug, and the family made emotional requests to the company. Genervon, however, refused to provide it.

After months of trying, the family is disappointed and frustrated, and Bob Bardone’s health is worsening.

“Can you imagine the hope we felt?” Connors said. “This entire process puts the most emotional time in our lives on even a more emotional roller coaster.”

The article further notes:

But right-to-try laws may be meaningless because companies can refuse to provide their experimental drugs. They may only create a false sense of hope among desperate families.

“It gives people a false impression that somehow because it’s a state law, it mandates this, but really it just gets everyone up in arms,” said Dr. John DiPersio, the deputy director of the Barnes-Jewish Hospital Siteman Cancer Center. “All it’s doing is causing commotion and confusion.”

This is, of course, exactly what I’ve been saying about these laws for over a year now. They are placebo legislation. They do absolutely nothing to help a man like Bob Bardone, but they do give patients like him false hope, only to cruelly take it away.

I can anticipate right now one objection. Why did Genervon Biopharmaceuticals refuse to give Mr. Bardone access to the drug? There are quite a few reasons why companies might not want to do this. This story, for instance, reports that Genervon has been overwhelmed by requests for its drug from ALS patients. Therefore, it chose to concentrate on getting fast track approval from the FDA, which “would give immediate access to all ALS patients, require doctors to prescribe and monitor patients’ progress, allow us to continue gathering data … and the cost would be supported by health insurance.” This is, of course, a perfectly reasonable justification, particularly given that if a patient had an adverse reaction to its, something that is more likely if the drug is given outside of the controlled setting of a clinical trial, it could delay or even scuttle approval of the drug by the FDA. Also, some companies are small venture companies with inadequate resources to dedicate to fulfilling right-to-try requests. Indeed, some of these smaller companies might just barely have raised enough capital to make enough of the drug to do the clinical trials necessary to gain FDA approval. These are, of course, exactly the sorts of companies that we want to encourage, not impede, because they aren’t the big pharma behemoths and they tend to be more imaginative and daring.

The Goldwater Institute’s response to these problems with right-to-try shows just how clueless or disingenuous it is. Basically its flacks argue that the FDA should assure companies that outcomes of patients who receive drugs for compassionate use will not negatively affect a drug’s approval. Seriously? That response basically indicates to me that the Goldwater Institute knows that right-to-try is a sham and has no power over the FDA, given that it’s reduced to suggesting that the FDA do something that it knows the FDA cannot do legally or ethically. Besides, the FDA already has a compassionate use program that rarely turns down a request. Also, as I’ve described, even the problem with how onerous the forms are for a physician to fill out is being dealt with. As this story notes, most applications are dealt with in four days, and the FDA has drafted a new form for such requests that, when finalized, should take a physician 45 minutes or less to complete.

There’s an excellent summary of the problems with right-to-try laws that was published on Friday on the Health Affairs Blog that I missed before but won’t now. It’s by David Farber, Preeya Noronha Pinto, Arthur Caplan, and Alison Bateman-House. They are quite blunt, noting that, contrary to the name given these laws, they provide no new rights to patients. They also point out that these laws have created an expectation that terminally ill patients will be able to quickly access life-saving experimental drugs by being exempted from FDA oversight but that that expectation is “quite simply, false.” They also point out that legally:

If RTT laws are understood as actually providing a right to direct access to an investigational product without FDA approval or oversight, they would be “preempted” by federal law, meaning the federal laws are so powerful as to effectively nullify their state RTT counterparts. Indeed, several federal courts have already concluded that FDA’s comprehensive regulatory regime governing the manufacturing, approval, labeling, and distribution of drug products preempts state laws designed to legislate in this area. If challenged in court, we anticipate RTT laws will be similarly treated.

And:

It is only a matter of time before courts nullify RTT laws. In the meantime, these laws offer vulnerable patients misplaced hope and do not attempt to minimize the serious health and safety risks inherent in treatment with unproven treatments. State legislatures still evaluating the merits of RTT laws should think twice. Patients facing terminal illnesses have enough issues to navigate without being given false hope through legislation that is ethically, legally, and clinically flawed.

I don’t know if it’s definitely a matter of time before the courts nullify right-to-try laws, but that would seem to be a likely outcome. Of course, as I’ve discussed before, the purpose of right-to-try laws is not what is ostensibly claimed. Rather, it’s a long game in which—or so it is thought—the buildup of pressure through the states will force the FDA to loosen its grip on drug approval. Some of the more “open” libertarians will even argue for the neutering or even outright abolition of the FDA, claiming that the free market will take care of drug safety and efficacy.

I do find one thing hopeful. Over a year ago, when the very first of these laws were wending their way through state legislatures, few, if any, medical groups spoke out against them or openly opposed them. Indeed, as I described in my very own state, when our right-to-try bill came before the legislature, none of the major medical societies or cancer centers openly opposed it, and I was definitely discouraged from doing so. Again, as I’ve said so many times before, opposing right-to-try can easily be painted to be akin to opposing mom, apple pie, and the American flag and having a propensity to drop kick puppies through flaming goal posts. Never mind that right-to-try laws are profoundly anti-patient laws.

That time seems to be coming to an end. After a year, people are starting to realize that, regarding right-to-try, the emperor has no clothes. The story about Bob Bardone is one indication. I don’t recall seeing such a skeptical story about right-to-try in a long time, if ever, complete with a human interest story that demonstrates quite effectively what a sham these laws are. Then there’s this story about the right-to-try law introduced into the California legislature:

The California bills have drawn opposition from the California Medical Association and from groups representing nurses and oncologists. A group representing pharmaceutical manufacturers has sent a letter warning against skirting the FDA’s established channels.

“We have serious concerns with any approach to make investigational medicines available that seeks to bypass the oversight of the Food and Drug Administration and clinical trial process, which is not in the best interest of patients and public health,” a letter from Pharmaceutical Research and Manufacturers of America says.

And:

The California Medical Association states that they have significant patient safety concerns with allowing access to unproven drugs outside of the FDA’s clinical trials and compassionate use programs. They further argue that offering unapproved therapies without credible scientific rationale or controlled monitoring could lead to not only endangering terminally ill patients further but potentially exploiting their hopes and circumstances. The Association of Northern California Oncologists cite the difficulty of identifying a terminally-ill patient, the danger a “right to try” policy outside the context of a clinical trial would present to adult clinical trial enrollment and the lack of an informed consent process to protect patients seeking investigational drugs as reasons for establishing their oppose position on the bill. The California Nurses Association/National Nurses United (CNA) maintain that this bill does nothing to address the real barriers to “compassionate use” revealed in a recent article in the NEJM entitled Practical, Legal, and Ethical Issues in Expanded Access to Investigational Drugs, specifically stating that nothing in this legislation impacts the availability of drugs to terminally ill patients unless the manufacturer of the drugs allow it to be used in advance of FDA approval. The CNA goes on to state instead of taking on the cost of drugs and challenging drug manufacturers that charge excessive prices for all drugs sold in California, this bill reinforces the status quo for investigational drug costs.

These are all good points. However, it’s probably too little, too late, given that the CMA refused to take a stand on this legislation initially. Indeed, there remain editorials trotting out the same Goldwater Institute talking points. Contrary to these dubious arguments, right-to-try laws sell terminally ill patients and legislators a bill of goods. They promise access to life-saving experimental drugs while leaving vulnerable, desperate patients open to false hope, lack of the oversight that patients in clinical trials receive, huge medical bills, and loss of medical coverage for any complications that might result from trying unproven drugs. People seem to be finally waking up to the sham that is right-to-try, but too late.

 

 

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.