I hadn’t expected to write about this topic again so soon, but then I didn’t expect a major newspaper to have written such a boneheaded editorial about it. In a way, I hate to write this post, because USA TODAY did great things once. There, Liz Szabo wrote the single best science-based report on cancer quack Stanislaw Burzynski. Still, even usually reliable news outlets make mistakes, and in this case the editorial board of USA TODAY made a huge one when it published an editorial entitled FDA vs. right to try: Our view. Seriously, if there’s a case to be made for right-to-try laws, this editorial sure doesn’t make it. Heck, I have a hard time telling whether whoever wrote this actually bothered to read the various right-to-try laws, so off-base are the arguments used.
If you don’t know what I’m talking about, now’s as good a time as any to review the various aspects of “right-to-try” laws in the form of some old posts of mine and one by Jann Bellamy:
- The illusions of right-to-try laws by Jann Bellamy
- Dallas Buyers Club-inspired “right to try” laws: Good movies don’t make good policy
- The cruel sham of “right to try” comes to Michigan
Now, on to the USA TODAY article. It starts out with a comparison that seems reasonable on the surface but is really comparing apples and oranges. I’m referring, of course, to the recent moves on the part of health officials in the US and Africa to try unapproved drugs to treat Ebola virus disease, citing this discussion by the WHO regarding the ethics of using unapproved treatments for Ebola. On the surface, comparing this to the sorts of patients who would be eligible for right-to-try laws seems like an appropriate comparison, but it’s not. First, there’s a big difference between Ebola virus disease and the sorts of diseases that will drive patients to seek experimental drugs under right-to-try. Ebola virus disease is not a terminal illness. As I’ve discussed before, nearly 50% of people infected with it, if they receive modern medical care, will survive. Indeed, it is for this very reason that I’m not entirely convinced that using the experimental drug ZMapp, the experimental drug consisting of three different monoclonal antibodies against proteins of the Ebola virus, is wise given a benefit-to-risk ratio that is virtually completely unknown. After all, it hasn’t even passed phase 1 trials yet, which, ironically, means that it wouldn’t be eligible for use under right-to-try, even in states where right-to-try has passed, Colorado, Missouri, and Louisiana. Also, ironically, this tells us that the FDA has broad power to grant compassionate use exemptions even more liberal than right-to-try, which more than bolsters the argument that if any reform to the compassionate use exemption/single patient IND process needs to happen at the federal level.
Another factor to be considered is that Ebola is an infectious disease that is rapidly fatal (as in days, not weeks or months), and Africa is in the middle of the largest Ebola outbreak in history. Certainly these are mitigating factors, particularly given that the sorts of drugs that would be used in right-to-try would be highly unlikely to save a life, because by the very definition of right-to-try, only patients with a terminal illness qualify. In a rapidly fatal infectious disease, the equation is different, with a higher likelihood of making a difference than in truly terminal illnesses. Again, even so, it’s not clear to me that releasing ZMapp to the two Americans was a good idea. Both got better, but we still have no idea if it was due to the ZMapp or if they were among the 45% or so who survive.
The USA TODAY editorial then regurgitates the same old talking points that right-to-try advocates have been pushing for ages:
The process for getting experimental drugs is so daunting that fewer than 1,000 people sought and got federal approval to take such drugs last year.
Food and Drug Administration rules require patients to clear a series of hurdles. First, they and their doctors must find a company to provide its drug. Many drug makers — worried that a patient’s death will spur a lawsuit or harm their chances for final FDA approval — refuse.
Even then, patients still need a hospital review board to sign off, a contract between the hospital and the drug maker, and FDA approval. The FDA application process, according to its own estimates, can take up to 100 hours.
Now, the bureaucratic absurdity is generating a backlash.
Colorado, Louisiana and Missouri recently approved “right to try” laws, which seek to simplify the process. The Michigan Senate passed a bill last Wednesday; in Arizona, an initiative will appear on the November ballot.
These carefully crafted measures allow patients and their doctors to go directly to a pharmaceutical company to seek access to drugs, but only those that have cleared the first phase of clinical trials and remain in development. The laws protect drug makers from lawsuits. And, pointedly, they seek to cut out the FDA, which now has final say.
First, as has been pointed out before, the FDA approves the vast majority of compassionate use exemptions. Granted, the paperwork burden can be excessive. In particular, it’s truly off-base to include the hospital review board signing of as part of the “bureaucratic absurdity” regarding compassionate use exemptions. Either that was an oversight, or the person writing the USA TODAY editorial is utterly clueless about clinical trials and drug approval. That “hospital review board” is called an institutional review board (IRB), and its task is to protect the rights of human subjects in research. If there’s one thing you don’t want to tinker with too much, it’s IRB approval. Similarly, in this argument we see the same wishful thinking and fantasy that are always at the heart of arguments by “right to try” advocates, who seem to think that there are all manner of drugs out there that can save the lives of patients with terminal cancer or diseases like amyotropic lateral sclerosis. As I’ve pointed out multiple times, the vast majority of drugs won’t make it through clinical trials to be approved because they won’t demonstrate efficacy and/or adequate safety to be approved. so the chances of prolonging life significantly taking unapproved drugs. The chances for causing harm are therefore much greater than that the drug will help. Just as bad, testing drugs like this outside of clinical trials, unless the drug being tested is the rarest of the rare “miracle” drug, is unlikely to provide usable information about efficacy, although such use can provide information about adverse effects.
USA TODAY is right about one thing. These bills are “carefully crafted,” but not to do what USA TODAY thinks. They’re usually portrayed as being a spontaneous movement among patients and patient advocates. To some extent that’s true, as right-to-try has roots in AIDS activism. There’s a reason why some of its advocates refer to it as the “Dallas Buyers Club law.” Several years ago, the Abigail Alliance promoted similar laws, efforts that resulted in a US Supreme Court ruling that patients do not have a Constitutional right to unapproved drugs. However, this latest round of right-to-try activism has the fingerprints of the libertarian Goldwater Institute all over it. Indeed, the Goldwater Institute is flying its flacks to states considering these laws. (I know it did so in Michigan last month.) If you look at the text of the right-to-try laws already passed and right-to-try bills under consideration, you will see that they are almost identical to the Goldwater Institute’s model legislation.
The intent of the Goldwater Institute can be gleaned in its policy paper, Everyone Deserves the Right to Try: Empowering the Terminally Ill to Take Control of their Treatment. Particularly obvious is the part where the Goldwater Institute bemoans the expansion of FDA authority in the 1960s by the Kefauver-Harris Amendments that required that the FDA not just to demonstrate safety but efficacy as well. This expansion of FDA power was in reaction to the thalidomide debacle, leading the Goldwater Institute to make the rather bizarre (OK, very bizarre) argument that because the issue with thalidomide was a safety problem, not an efficacy problem and because thalidomide was never approved in the US (mainly due to the FDA, let’s not forget), the expansion of FDA power in response to the thalidomide debacle was “unwarranted”? As I discussed before, the report itself is also loaded with emotionally charged language about the FDA and terminally ill patients and a whole boatload of highly dubious statements. Every experimental drug is apparently “potentially life-saving,” at least the ones that made it through phase I trials, which apparently is enough to be “deemed safe by the FDA” (at least if you are foolish enough to believe the Goldwater Institute’s talking points).
Reading the model legislation itself, one will see an extreme emphasis on protecting companies providing experimental drugs and physicians who recommend them from lawsuits. Moreover, it’s a very libertarian law. Patients are completely on their own. They have to pay for everything themselves, and that liability doesn’t end after they die. There’s a specific provision stating that the drug company can go after the patient’s estate. There’s another provision that states that “the patient’s health plan or third party administrator and provider are not obligated to pay for any care or treatments consequent to the use of the investigational drug, biological product, or device,” the exception being if it’s in the contract that the health plan pay. In other words, if a patient uses an experimental drug under right-to-try and suffers a serious complication, the patient’s health insurance plan doesn’t have to pay for the medical expenses necessary to take care of that complication.
So what does this mean? Basically, it means that only the rich will be able to take advantage of the provisions of right-to-try; that is, assuming that the laws aren’t struck down as unconstitutional. Of course, what the Goldwater Institute is counting on is the same thing that’s happening in states that have legalized marijuana for recreational use: That the federal government (in this case, the FDA) will decide that it’s too much trouble to enforce the law. While it’s true that there are inequities in the clinical trial system, these tend to be based more on geography and difficulty traveling to medical centers offering clinical trials. For right-to-try, it’s a pure, free market paradise, where companies can charge as much as they want for drugs that have only passed phase I clinical trials. I could see unscrupulous pharmaceutical companies resurrecting drugs that have passed phase I but went no further, opening phase II trials to which they don’t plan on accruing very many patients. Step 3: Profit.
To get an idea of what I mean about the libertarian bent of these laws, take a look at what Christina Sandefur of the Goldwater Institute says after being challenged with an observation that what right-to-try is all about is not helping terminally ill patients but rather letting those who can afford it (i.e., the rich) have unfettered access to experimental drugs:
— Christina Sandefur (@cmsandefur) August 13, 2014
Note the false dichotomy and how she ignores the likelihood that right-to-try laws will harm far more people than they are likely to help.
Bioethicist Art Caplan hammers the financial inequity in his response, FDA is not the main problem. There, he identifies this key problem with right-to-try laws, namely that they leave patients completely on their own far more than even the most lurid nightmares about our current clinical trial system promulgated by the Goldwater Institute to portray it as the worst injustice to patients known to humans. That’s the dirty little secret of “right-to-try.” What disappoints me about Caplan’s response, is that that’s the only aspect of these bills he concentrates on. Nothing about the dangers. Nothing about the exaggerations of the potential benefits and minimization of the risks. I realize he only had around 500 words, if that, but I’m not sure that financial issues were the ones to focus on, although I do give him props for this:
Right-to-try laws are basically “right to beg” laws. Begging is not what the dying and desperately ill should be asked to do. Legislators should stop enacting feel-good laws and show they care by finding the money to pay for experimental drugs and the travel and expenses involved in getting to them.
ADDENDUM: Looking at it again, I just noticed something about the Goldwater Institute model legislation. Remember how I was puzzled about how the Michigan right-to-try legislation had changed its wording about the disease to which it applies from “terminal illness” to “advanced illness”? Take a look at the model legislation. What does it say? Yep. “Advanced illness.” Now I know why the Senate bill in Michigan was changed. It was changed to match the new Goldwater Institute template. Does anyone wonder why this might be? I don’t. Clearly, this change in wording opens the way for such laws to apply to more than just terminal illness. Unfortunately, it was also passed by the Senate last week. True, the Michigan version states that “advanced illness” means the same thing as “terminal illness” for purposes of the bill, but that would be easy to change, and the Goldwater Institute template says no such thing now.
Does anyone still doubt that the intention of these laws is to open up right-to-try to everyone and thereby gut the FDA’s authority, bringing us back to the libertarian paradise of the days before the FDA, when wandering snake oil salesman wandered from town to town, selling their nostrums? We’re told that we don’t need the FDA because the “market” will protect us. Remember how well that worked out last time.