Last year, I did several posts on what I consider to be a profoundly misguided and potentially harmful type of law known as "right-to-try." Beginning about a year and a half ago, promoted by the libertarian think tank known as the Goldwater Institute, right-to-try laws began popping up in state legislatures. I wrote about how these laws are far more likely to do harm than good, and that is a position that I maintain today. The idea behind these laws is to give terminally ill patients access to experimental drugs—in some cases drugs that have only passed phase I testing—that might help them. It's an understandable, albeit flawed argument. After all, it's perfectly understandable why terminally ill patients would fight for drugs that give them hope, and it's just as understandable why politicians and the public would see such a goal as a good thing. In practice, as I will explain again in the context of this update, such laws are far more likely to harm patients than help them. Indeed, as you will see, in the year since the first wave of right-to-try laws have passed, not a single patient that I can find has obtained access to experimental drugs under a right-to-try law, much less been helped by them.

Unfortunately, given how effectively "right to try" has been sold on grounds of providing terminally ill patients hope and as a matter of personal freedom, it's clear that this wave is not going to abate. Since Colorado passed the very first right-to-try law almost exactly a year ago today, a total of 17 more states now have passed passed similar legislation, the most recent being Tennessee, and 22 others have introduced legislation. It's a good bet that right-to-try will pass in all of those states, because, as I've explained many times before and in many interviews, if you don't understand clinical trial ethics and science, opposing the concept of right-to-try comes across like opposing Mom, apple pie, and the American flag, and leaves opponents open to false—but seemingly convincing—charges of callousness towards the terminally ill on the order of enjoying drop kicking puppies through flaming goalposts.

The con game that is "right-to-try" metastasizes

As I've pointed out many times before, opposing right-to-try is actually pro-patient, because these right-to-try laws that are passing all follow an explicit template written by the Goldwater Institute, and that template is very much a sham. For one thing, states do not control drug approval; the federal government through the FDA does. Consequently, state-level right to try laws, while giving the appearance of giving access to experimental drugs to patients, do nothing to actually achieve that goal. Worse, even if a patient were to get an experimental drug through right-to-try, these laws very much reflect the think tank that created them in that they leave the patient basically on his own. He can be charged the full cost of the investigational drug, which means that the only people who might be able to take advantage of these laws are those who are already rich or who are very good at fundraising. Worse, these laws explicitly indemnify drug companies and physicians from any liability arising from adverse outcomes, which means that even if a physician committed malpractice in advising or administering right-to-try drugs he probably couldn't be sued. Moreover, such laws explicitly bar state employees from blocking or attempting to block an eligible patient's access to an investigational drug or treatment. Even though there is a clause that says "counseling, advice, or a recommendation consistent with medical standards of care from a licensed health care provider is not a violation of this section," where does "advice" end and "blocking" begin? Certainly as a physician in what is now a right-to-try state whose law has identical language, I wonder.

Even worse still, many of these laws, such as the one in Michigan, are written such that if a patient suffers a complication from a right-to-try drug or treatment his insurance company can argue that it doesn't have to pay for the resulting care to treat that complication. Indeed, Colorado's law requires that informed consent for right-to-try must explicitly make clear that, "the patient's health insurer and provider are not obligated to pay for any care or treatments consequent to the use of the investigational drug, biologic product, or device" and that "in-home health care may be denied." Elsewhere, the Colorado right-to-try law states:

An insurer may deny coverage to an eligible patient from the time the eligible patient begins use of the investigational drug, biologic product, or device through a period not to exceed six months from the time the investigational drug, biologic product, or device is no longer used by the patient; except that coverage may not be denied for a preexisting condition and for coverage of benefits which commenced prior to the time the eligible patient begins use of such drug, biologic product, or device.

In other words, if you access an experimental treatment under right-to-try, and you suffer a complication from the investigational treatment, you could well be out of luck getting your insurance company to pay for the medical and/or surgical treatment necessary to treat that complication. If your insurance company so decides, you'll be on the hook for everything subsequent to that treatment. Indeed, to me the language in some of these bills implies that insurance companies can deny coverage for any new problems that come up after the patient starts using experimental therapy, whether caused by that therapy or not. These issues have largely been ignored in the news coverage of these laws, but the oncology community is finally waking up to them, as demonstrated by a recent article in HemeOnc Today in an article entitled "Expansion of 'Right to Try' legislation raises ethical, safety concerns":

"There are a lot of issues not addressed in the bill that make the feasibility more challenging," W. Thomas Purcell, MD, MBA, associate director for clinical services at the University of Colorado Cancer Center and executive medical director of oncology services at University of Colorado Hospital, told HemOnc Today . "If the drug is made available, who is going to administer it? Who is going to pay for any side effects related to the treatment? Are insurance companies going to cover any treatment-related complications? There are a lot of practical things that come into play with the introduction of the law, although the law doesn't address any of those things."

Actually, although he raises the same concerns I've been raising for over a year now, Dr. Purcell is about as wrong as wrong can be about one thing. The problem is not that the laws don't address these things. It's that the laws do address these things rather explicitly. Dr. Purcell seems blind to how these laws address these things, which is in a way likely to be highly detrimental to patients. In fact, I wonder if Dr. Purcell has even read his own state's law! It says right there in black and white that insurance companies don't have to pay for care or complications related to such drugs! That means that either the patient does, or we taxpayers do when patients suffering such complications are forced to go on Medicaid because they can no longer afford their medical care.

Another example of someone echoing what I've said many times appears here:

"People do not actually read the bills," Alison Bateman-House, PhD, MPH, MA, Rudin postdoctoral fellow in the division of medical ethics at New York University Langone Medical Center, told HemOnc Today . "They think 'Right to Try' sounds fantastic and allows access to treat terminally ill patients. How could you not support that? For the most part, the response that we've seen is that these laws don't do much, aside from giving people hope."

Dr. Bateman-House is also partially wrong. The problem is not that people don't read the bills. It's that people don't understand the anti-patient implications of the bills in terms of insurance coverage, eliminating the right to sue, and the like; don't understand clinical trials; and don't understand that it is the federal government, not state governments, who control drug approval and access to experimental drugs. Indeed, when I'm in a cynical mood, I wonder if Goldwater Institute flacks do understand all these things but don't care because they're playing a long game designed to weaken the FDA in the name of an ideology that, against all evidence to the contrary, preaches that the free market can assure drug safety and efficacy better than any government agency. Indeed, this intent can be seen in one version of the Goldwater Institute template (and in the Michigan right-to-try law), which changed the term "terminal illness" to "advanced illness," without really changing the definition. I would not be surprised if, a few years from now, after the majority of states have passed right-to-try, there is a push to open up "right-to-try" to serious medical conditions that are not terminal on the basis of "fairness" and "compassion." It's coming. Mark my words.

Finally, there are the issues of safety and false hope. As I've said before, as hard as it is to believe, there are things worse than suffering a terminal illness; for instance, suffering a terminal illness and then bankrupting yourself before you die or suffering a terminal illness and then suffering a major complication of an experimental treatment that you have to pay for, thus bankrupting yourself before you die. Now, consider this. The only requirement for an investigational drug or treatment to be made available under right-to-try is that it has to have passed phase I testing and still be in clinical trials (i.e., phase II or III studies). Again, as I've described before, this is an incredibly low bar for safety, given that most phase I trials include less than 30 patients and are meant mainly as screening trials to identify the worst side effects and an appropriate dose to use in phase II trials. Yet, as I described before, the Goldwater Institute blatantly describes drugs that have passed phase I testing as having had their safety adequately established. It's a lie.

Indeed, as is pointed out in the HemeOnc Today article, the risk for toxicity is actually higher in patients who would exercise right-to-try because by definition such patients have to be ineligible for a clinical trial. Remember, clinical trials are designed to minimize risks and maximize potential benefits because it is an ethical imperative in human experimentation, codified in the Common Rule and the Helsinki Declaration. One way they do that is to design the inclusion and exclusion criteria to achieve that end. Moreover, there have been cases where the use of an experimental therapy has become popular based on public pressure related to early evidence.

An excellent example of just what I've been warning about for a long time shows up in the HemeOnc Today article citing Dr. Yoram T. Unguru, a pediatric oncologist at the Herman and Walter Samuelson Children's Hospital at Sinai Hospital in Baltimore and bioethicist at The Johns Hopkins Berman Institute of Bioethics:

In multiple cases, access to an experimental therapy has been expedited due to an early benefit observed in early studies that was not substantiated in subsequent research, Unguru said. One example was the use of autologous bone marrow transplantation in women with metastatic breast cancer, based on preliminary data published in 1995 in the Journal of Clinical Oncology . "This completely backfired," Unguru said. "In addition to being poorly designed, the study raises serious ethical concerns and, ultimately, people did much worse, including some who even died. This is why we go through the laborious, lengthy and, at times, seemingly maddening trial phases." Although physicians and drug companies are required to report data attained from patients treated through the FDA's compassionate use program, Right to Try laws do not carry such stipulations.

And, as Colin Begg, PhD, chairman and attending biostatistician in the department of epidemiology and biostatistics at Memorial Sloan Kettering Cancer Center, adds, echoing (again) things I've been warning about for over a year:

Eliminating the FDA from the equation may have many significant consequences. "There is good reason we have the FDA," Begg said. "The rigorous testing with scientific methods of drugs that come through the pipeline is absolutely essential. Without it, the market would be flooded with drugs that do not work. You would have a cupboard full of drugs that you would want to try, and you would have no idea which one to try because there would be no reliable evidence about the efficacy of any one of them." Right-to-try laws may create a precedence for additional changes to drug R&D. "If we go down this road, there might be a loosening of the standards of drug approval in the first place, and that would be bad for public health," Begg said. "This movement may ultimately lead to situations where … drugs, in general, would no longer have to go through such rigorous testing to see if they work."

Unfortunately, what Dr. Unguru and Begg apparently fail to realize is that the libertarian Goldwater Institute cares little or nothing about the difficult balancing of patient rights versus patient safety and societal good that our current clinical trial system tries to maintain, with varying degrees of success depending on the specific situation. An argument, for example, that right-to-try might make it more difficult to recruit patients to clinical trials holds exactly zero water with the Goldwater Institute and most other supporters of right-to-try. Indeed, associated as it is with the "health freedom" movement, the goals of the Goldwater Institute's right-to-try push appear to align quite nicely with the goal of some libertarians to eliminate most of the FDA's authority because of an ideology, which views any government intrusion into the free market with a jaundiced eye and even believes that the unfettered free market will take care of sorting out safety and efficacy of drugs. We all know how that worked out before the passage of the original act creating the FDA in 1906 and the Kefauver Harris Amendment of 1962 that introduced the requirement that drug manufacturers demonstrate efficacy as well as safety to the FDA before a drug is approved.

Those of us who take care of breast cancer patients remember Dr. Unguru's cautionary tale from the 1990s. Indeed, the clinical trial publication that fueled the demand for high dose chemotherapy with bone marrow transplant for advanced breast cancer was ultimately retracted. The bandwagon effect is a powerful force affecting politics and even prominent researchers and physicians before the evidence is adequate to recommend a treatment. If this can happen with a treatment as incredibly toxic and risky as bone marrow ablation with high dose chemotherapy followed by stem cell rescue, imagine how easily it can happen with less spectacular examples.

Over a year ago, when the states on the vanguard of the right-to-try movement were first seeing such legislation introduced, I learned the hard way just how willing the movement was to paint its opponents as those proverbial puppy-kicking, American flag burning, cold-hearted "scientists." Indeed, back then almost the only people I saw routinely speaking out against right-to-try were noted bioethicist Arthur Caplan and little ol' me, an insignificant blogger. When right-to-try was introduced into my own state's legislature, my interaction with my state representative, who politely thanked me for pointing out the many problems with right to try, but made it clear through his response that he was likely going to vote for it anyway, showed that, from a political standpoint at least, ethics- and science-based medicine were not likely to prevail in Michigan or anywhere else over the emotional appeal of "doing something" to help terminally ill patients. It didn't matter whether that "something" will actually do what it promises or not. Later, I met with an advocate of the biotech industry who testified against the bill. He described a scene in which he was the lone expert testifying against right-to-try versus a flack from the Goldwater Institute and patients with terminal illnesses and their families, the latter of whom all glared at him as though he were personally going to execute them or their ill family member. I learned that no one associated with a major cancer center was willing to publicly oppose right-to-try, even though they uniformly thought it was a horrible idea. If I had found out about the hearing in time to have made the trip to Lansing—as I recall, it occurred with little notice and on one of my operating room days—I honestly don't know if I would have had the wherewithal to do so myself, given the pushback I had received from my previous posts on the matter.

As I said, right-to-try is a con game perpetrated on desperate patients, offering them false hope but instead delivering nothing of value that can't be obtained under FDA compassionate use programs, as is pointed out by the opinion piece written by Dr. Jeffrey M. Peppercorn, a medical oncologist specializing in breast cancer at Massachusetts General Hospital, in a point-counterpoint forum included after the HemeOnc Today article that asks: Do the changes to the FDA's compassionate use program eliminate the need for 'Right to Try' laws? Dr. Peppercorn takes the "yes" position:

However, the question is not whether promotion of access to promising drugs for patients with terminal disease is justified, but how this can best be accomplished. The same imperative that drives Right to Try laws underlies the FDA's compassionate use program. The primary difference is that access to experimental drugs through compassionate use programs is regulated in the interest of both the patient and society. Physicians must seek FDA approval before a manufacturer provides the unproven drug, and the rationale for use of the drug, absence of alternatives, informed consent and review by an independent institutional review board must be documented. In addition, toxicities and outcomes after administration must be reported. This process promotes responsible practice of evidence-based medicine — even as the evidence evolves — and provides a chance for monitoring, both of the specific intervention and of the use of experimental therapy more generally. Although the process can be burdensome, the FDA has recently streamlined the application to allow for completion in less than 45 minutes and still allows for rapid approval of emergency access by phone when this is clinically justified.

Exactly.

The key difference between right-to-try and FDA compassionate use programs is that right-to-try strips pretty much all protections from patients who would use it; requires them to pay for the drug and any care related to the drug; prevents them from suing manufacturers and doctors if something goes wrong; prevents the state from taking action against the licenses of providers who give patients bad advice recommending right-to-try; tells insurance companies that, not only do they not have to pay for the investigational agent or device, but they don't have to pay for any complications arising from use of the investigational agent or device; and makes doctors and other health care providers working for right-to-try states leery of advising too strongly against right-to-try, lest they be prosecuted for "blocking" access to experimental drugs. FDA compassionate use programs, in marked contrast, require review and oversight by an institutional review board (IRB). The other difference was that, although 99.5% of compassionate use/expanded access requests are approved by the FDA, the process was onerous. As Dr. Peppercorn points out, that is rapidly changing, arguably eliminating the "need" for right-to-try. Yet right-to-try marches on, because the reason for right-to-try is not as represented by the Goldwater Institute. Rather, it's to weaken and ultimately neuter the FDA.

Other pernicious effects of right-to-try

Patients come first, and must always come first, which is why my key objection to right-to-try remains (and will always remain) that it is bad for patients. However, the HemeOnc Today article also points out other problems with the legislation. One is that it presents a major dilemma to industry. Now, I realize that few people are particularly sympathetic to industry, and even we "pharma shills" (at least that's what right-to-try proponents and those supporting alternative medicine, groups that not-infrequently overlap, call us) recognize that pharma is nowhere near innocent in provoking that reaction. Now that right-to-try laws are metastasizing throughout the US, oncologists are finally taking notice of the alarms that we few have been sounding:

The fact that manufacturers are not liable if a drug obtained through Right to Try fails or causes significant harm may allow pharmaceutical companies to benefit from such legislation, Unguru said. "The way the laws are written, pharmaceutical companies are under no commitment to release these drugs, but should patients be able to access them, there is almost no consequence in the event of a bad outcome," Unguru said. "Bypassing the current regulatory system means that some drugs that may not be safe or ready for widespread use essentially get a 'free pass.' Some pharmaceutical companies might see such laws as a way to test their drugs in a way they typically would not be able to without being held accountable." This would pose significant safety issues to society. "It is hard to argue that individual patients who are dying and want access to a drug should not get it," Begg said. "But the concern I have is that the ability of drug companies to market drugs that have not been properly tested is not in the interest of the public."

The Texas State Senate and House have passed versions of a Goldwater Institute-inspired right-to-try law. The only difference in the two bills is that the House version would allow manufacturers to provide experimental drugs to patients at cost, whereas the Senate version would require that companies that provide such drugs donate them. Assuming the two versions are reconciled and passed and the governor signs the bill, say goodbye to any chance of shutting down Stanislaw Burzynski, as the law would explicitly bar the Texas Medical Board from pursuing its current action against Burzynski's medical license, given that he could claim his antineoplastons have passed phase I clinical trials and are in phase II, which makes them eligible for right-to-try. Even if the Senate version prevails, Burzynski's business model of providing his unproven antineoplastons for free but charging big bucks for "case management" fees would remain intact.

Most drug companies are not as unethical as Burzynski, however, which is why most do not support right-to-try and the Pharmaceutical Research and Manufacturers of America (PhRMA) is not supportive, as described in the HemeOnc Today article. Pharmaceutical companies remember incidents like this:

In the past, public pressure has forced pharmaceutical companies to grant access under compassionate use. Last year, Chimerix denied Josh Hardy — a then 7-year-old boy who developed an adenovirus infection after undergoing a bone marrow transplant for rhabdoid tumor of the kidney — access to the experimental antiviral drug brincidofovir (CMX001). After a social media firestorm — which included death threats to the company's leadership — Chimerix commenced an open-label phase 3 trial so Hardy could enroll and receive treatment. "This became publicized, and everyone assumed that if Josh Hardy got brincidofovir he would survive," Bateman-House said. "He did get brincidofovir, and he did survive. Thomas Duncan, the man who died of Ebola in Texas, got the same drug and died. Chimerix is a small drug company and brincidofovir is its only drug in development, and its stock took a nosedive after Duncan's death. If it were not for the fact that phase 3 trials were already close to completion, this could have killed the company. If Josh Hardy had died, that could have killed the company."

In other words:

"It can go either way — you're damned if you do and you're damned if you don't," Unguru said. "If you release the drug and it does badly, then you're going to get bad press. If you don't release it, then you risk being vilified."

And if the company charges for the drug and things go badly, it will be doubly vilified, even though small pharmaceutical companies often have just enough venture capital to make enough of the drug to do the clinical trials necessary for approval, and releasing drug jeopardizes its ability to do those trials.

Physicians are also put in a bind when a patient has exhausted everything and wants to pursue right-to-try. End-of-life discussions are very difficult to begin with, because, as I've pointed out before, no physician wants to be hope's executioner. Yet, sometimes that is our job, and the best we can offer is palliation. Given that right-to-try theoretically requires less effort than an expanded access exception, there will be enormous pressure on physicians to accede to the wishes of a terminally ill patient to pursue right-to-try even if the physician thinks it won't work. The option of right-to-try might thus actually provide a physician with an option to avoid the hard discussion that end-of-life care entails and just facilitate the patient's getting the drug. As Dr. Charles F. Levenback, professor in the department of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center, puts it:

"I've heard ethicists say physicians may go in the direction of compassionate use to avoid the difficult conversation about mortality and the limits of what we can provide," Levenback said. "All of compassionate use is predicated on the physician's responsibility to be candid about the purpose of treatment — palliative vs. curative — and setting the patient's expectations correctly."

Correct. However, some doctors are better at doing this than others.

The track record of right-to-try thus far

Given that it's now been a year, or nearly so, since the first batch of states passed their right-to-try initiatives, I asked a simple question: Has a terminally ill patient obtained an investigational agent through right-to-try yet? Note that I didn't even ask whether a single terminally ill patient has benefitted from right-to-try, because that's much more difficult to ascertain. Doing extensive Google searches, I could not find a single example, although I did come up with a lot of examples of patients expressing hope that such laws would get them access to investigational drugs (like this one). My next thought was that, if anyone would know of a case in which a terminally ill patient has been granted access to an experimental drug under right-to-try, it would be the Goldwater Institute. Fortunately, I came across this conversation on Twitter:

.@cmsandefur Except that #RightToTry laws don't really do that. False promise. — David Gorski (@gorskon) May 6, 2015

The question was put to Ms. Sandefur:

.@cmsandefur Has anyone anywhere gotten experimental drug under #RightToTry? It's been a year now since Colorado. I know of no case. — David Gorski (@gorskon) May 6, 2015

Her response:

@gorskon these laws are just now going into effect,& it takes time to acclimate to overhaul of status quo. Offer to have a real convo stands — Christina Sandefur (@cmsandefur) May 6, 2015

Which resulted in:

@gorskon Again,I welcome thoughtful,substantive discussion, but I'm not interested in unproductive back-and-forth. You know where to find us — Christina Sandefur (@cmsandefur) May 6, 2015

What's irritating about this exchange is that this clearly was was an attempt to engage Ms. Sandefur in a "thoughtful convo"—or, at least, as thoughtful a conversation as you can have on Twitter. In any case, I think it reasonable to assume that, if there were a patient in Colorado—or anywhere else, for that matter—who has successfully obtained an experimental drug under right-to-try, Sandefur would know about it and would not have hesitated to provide links to relevant news stories. She did not. Instead she chose to dodge the question and make excuses. Similarly, Kurt Altman, national policy adviser and general counsel for Goldwater Institute, mentioned no patients who had yet benefited from right-to-try in his "counterpoint" to Dr. Peppercorn's opinion piece. I know he would have if such a patient existed. Certainly, if I were writing in favor of right-to-try, I would use the examples of such patients if they existed.

Right-to-try laws: Bad for patients

I have little doubt that some version of right-to-try will likely pass in every state in which it has been introduced, which means we could be looking at up to 40 states, possibly more, with such laws by next year. It must be emphasized that the vast majority of legislators proposing such bills and passing them into laws and the patients lobbying for right-to-try do so with the best intentions, believing such laws will help terminally ill patients. These patients, according to mistaken popular belief, have nothing left to lose when in fact they do, even though it might not seem that way. In the idealistic desire to help the terminally ill, supporters of right-to-try either don't pay attention to or downplay the significant negative aspects of these bills, which permit the loss of insurance coverage, stripping of IRB protections that patients receiving such medications through expanded access programs, the economic injustice in which only the rich or those capable of raising large sums of money could benefit if the drug company was unwilling to provide the investigational drug for free, and the potential additional risk of harm that can come from using experimental drugs outside the rigorous design and protections of clinical trials. Most people are similarly unaware that granting less controlled access to such medications is far more likely to cause an individual patient harm than good. Moreover, liberalization of expanded access programs to vastly decrease the burden of paperwork and effort on the part of physicians and patient has already been placed in draft guidelines, rendering right-to-try unnecessary.

So why are right-to-try laws so popular? In an editorial last year published in JAMA Internal Medicine entitled "The Strange Allure of State "Right-to-Try" Laws", Patricia Zettler and Henry Greely ask the same question, noting that a recommendation from a physician is no substitute for the evidence of safety and effectiveness that comes from later-phase clinical trials:

So what is the point of these laws? A skeptic might point out that opposing experimental treatments for dying people is unpopular. Patients have publicized—and gained public support for—their efforts to obtain experimental treatments through social media. Lawmakers have little to lose politically by supporting these laws. Companies, seeing their ineffectiveness, have no powerful reasons to oppose them. And libertarians can celebrate an attack on big government. The problem is that all these efforts are unlikely to actually help the patients with life-threatening diseases. Indeed, these laws may be harmful if they draw attention and resources away from efforts to develop effective treatments, engender confusion about the FDA pathway for compassionate use of medications, or create false hopes for terminally ill patients.

All of which right-to-try laws do, and worse.

There will always be a conflict between personal freedom and protecting patients, as well as ensuring maximal societal good. We see this in opposition to school vaccine mandates, support for cancer quackery and dubious stem cell clinics, and, of course, right-to-try. Unfortunately right-to-try laws represent dangerous placebo legislation. They only give the illusion of doing something given that the FDA, not the states, controls drug approval. The reason for their existence is not so much to help patients, but as part of a long game to build a groundswell of support for policies that would ultimately hobble the FDA's ability to oversee the efficacy and safety of drugs. These laws are bad for patients, bad for doctors, bad for drug development, and bad for science. That's why going through the states is the wrong way to attack this problem. If we as a society believe that terminally ill patients should have easier access to investigational drugs, then reforming how the FDA handles compassionate use exemptions, not a patchwork of state laws with no teeth, is how it should be done.