Not too long ago, I expressed alarm at a series of bills that were popping up like so much kudzu in various state legislatures, namely “right to try” bills. Both Jann Bellamy and I warned that these bills gave a false illusion of hope to patients with terminal illnesses. Basically, these laws claim to grant the “right” of patients with terminal illnesses to access promising experimental medicines that have not yet been approved by the FDA. Indeed, these investigational drugs need merely to have passed phase I trials, and these “right to try” laws would allow them to be used in pretty much any human with a terminal illness who can persuade a pharmaceutical company to let them have such drugs. Of course, as I pointed out, such laws are based on a false premise, namely that there are lots of promising drugs out there that could save lots of lives of terminally ill patients, if only the hidebound FDA would get out of the way and let the people try them. The problem (besides the false assumption behind such laws) is that they are all state laws, and the FDA and federal law still trump state laws with respect to drug approval.
Apparently, advocates of “right to try” laws have gotten around to trying to take care of that little obstacle, too. I’m referring to a federal law under consideration in the House of Representatives and championed by the usual suspects, including the Alliance for Natural Health USA, a “health freedom” group that has yet to see a pro-quackery bill it doesn’t like.
In any case, at the time I originally learned about this bill, HR 4475, which was introduced by Rep. Morgan Griffith (R-VA) and entitled “The Compassionate Freedom of Choice Act of 2014,” its text hadn’t yet been published to the Congressional website. I did learn that the bill has been floating around for a while in various forms (for instance, former Representative Ron Paul (R-TX) apparently introduced it.) Now its text has been published, as Guy Chapman has noted. He calls it a “quack’s charter,” and he’s only off by a bit. The bill doesn’t go quite as far as he believes, but the bill is still plenty bad, man. If enacted, HR 4475 would amend the Food, Drug, and Cosmetic Act by inserting after section 561 (21 U.S.C. 360bbb) the text of HR 4475. This section of the Food, Drug, and Cosmetic Act is entitled “Expanded Access to Unapproved Therapies and Diagnostics,” and it’s the section of the act that regulates exactly that. The interesting thing is that this particular section of existing law is the framework under which the whole system of single patient INDs (also known as “compassionate use exemptions”) is already based. As I’ve described before, single patients can receive promising unapproved drugs under what’s known as a single patient IND, which has to be approved by the Institutional Review Board and the FDA and allows single patients to receive unapproved drugs. You can (and many have) argued that the single patient IND process is too cumbersome and restrictive, but HR 4475 seeks to (mostly) nuke this requirement. You’ll see what I mean in a minute.
First, the law states that:
Nothing in this Act or section 351 of the Public Health Service Act prevents or restricts, and the Food and Drug Administration shall not implement or enforce any provision of law preventing or restricting, the manufacture, importation, distribution, or sale of an investigational drug or device intended for use by a terminally ill patient in accordance with subsection (b).
Guy Chapman went a bit beyond what the law would actually permit in his analysis, I’m afraid. HR 4475 clearly does not authorize the use of quackery like Hoxsey therapy, Gerson therapy, or anything else like that in terminally ill patients, although I suppose it is theoretically possible that advocates could get an IND for one of these quackeries and then carry out a phase I clinical trial, after which the quackery would fall under the definition of an investigational drug or device according to HR 4475. (In this, perhaps the Gonzalez protocol would qualify, given that it’s undergone two clinical trials, the last of which was disastrously negative, but it was a clinical trial.) HR 4475 does, however, basically allow unfettered access by “terminally ill” patients to any “investigational” drug or device, which is defined as a drug or device that “(1) has not yet been approved, licensed, or cleared for commercial distribution under section 505, 510(k), or 515 of this Act or section 351 of the Public Health Service Act, and cannot otherwise be lawfully marketed in the United States; and (2) is or has been the subject of one or more clinical trials.” In other words, it’s very much like one of those “right to try” laws that are such a horrible idea but nonetheless are popping up like kudzu in state legislatures.
Again, however, the difference is that “right to try” laws in states would have little or no effect, because the FDA would still rule supreme over drug approval, and federal law trumps state law. HR 4475 would in essence codify “right to try” in the federal law under which the FDA works, which would do many orders of magnitude more harm to cancer patients and terminally ill patients. Basically, this law would allow any “terminally ill” patient access to any investigational drug with an IND that’s gone through at least phase I trials. I’ve explained before in great detail why that’s such a horrible idea, but it’s worth briefly repeating the following point. Most investigational drugs that make it past phase I trials still end up failing. The chances for doing harm far exceed any chance for benefit. Drugs with seemingly miraculous activity against cancer, like Gleevec, that show up in phase I clinical trials are exceedingly rare. Indeed, HR 4475 says nothing about whether the clinical trials the investigational drug or device being to be used in terminally ill patients has undergone even need to show promise or not. Under HR 4475, a drug that completely failed in phase I clinical trials by showing unacceptable toxicity (for example) could be distributed to a terminally ill patient as long as the patient is told that the drug failed phase I clinical trials.
Next up in HR 4475, there’s this:
- (b) Patient Requirements.–In order for an investigational drug or device to be intended for use in accordance with this subsection, such drug or device must be intended for use by a patient who has–
- (1) been diagnosed with a terminal illness by a licensed physician;
- (2) been informed by a licensed physician that no drug or device that is lawfully marketed in the United States is likely to cure the illness; and
- (3) executed a written informed consent document that states–
- A) the known and potential risks and benefits of such drug or device; and
- B) any indications of the illness for which a drug or device is lawfully marketed, or for which treatment is otherwise available, in the United States.
- c) Prohibition on Requiring the Disclosure, Collection, and Reporting of Certain Information by Food and Drug Administration.–
- (1) In general.–The Commissioner of Food and Drugs may not require the disclosure, collection, or reporting of–
- (A) any information related to the delivery, administration, or use of an investigational drug or device pursuant to this section; or
- (B) any information related to the clinical outcomes experienced by a terminally ill patient supplied an investigational drug or device pursuant to this section.
- (2) Exception.–Nothing in this subsection prevents the sponsor of a clinical trial from voluntarily disclosing, collecting, or reporting information to the Food and Drug Administration.
One notes that “terminal illness” is not defined. I could go all Orac-style snarky on you and point out that life itself is a terminal illness (one that’s sexually transmitted, as well). We all die eventually. On the other hand, there are other diseases that are arguably terminal that can take a long time to kill. Even metastatic breast cancer is now potentially survivable for several years, even longer if it’s an indolent type with a low volume of metastatic tumor. Where do you draw the line in defining “terminal”? Normally, for purposes of laws, “terminal illness” is defined according to a certain estimated prognosis for life expectancy, be it six months, a year, or whatever. Even Abraham’s law did that. My guess is that this is to allow the widest number and variety of people with “terminal” illnesses access to unapproved treatments as possible. All you have to do is to find a doctor to say you’re terminal and there are no approved drugs or devices that can save you, and you’re good to go! Really? Any licensed physician, regardless of specialty? Moreover, under these circumstances, as described in this bill, “informed consent” is a joke, a cruel parody of real informed consent. In clinical trials, even in single patient INDs, the informed consent process is lengthy and detailed. In any event, the bill reads as though it were written specifically for Stanislaw Burzynski, as it would allow someone like him to abuse the IND process without even the threat of the FDA bothering him.
Now here’s the kicker. One of the criticisms of “right to try” laws is that drug and device companies won’t want to allow patients to have access to their investigational drugs or devices because adverse outcomes might affect their application for approval to the FDA. HR 4475 has that covered:
- (c) Prohibition on Requiring the Disclosure, Collection, and Reporting of Certain Information by Food and Drug Administration.–
- (1) In general.–The Commissioner of Food and Drugs may not require the disclosure, collection, or reporting of—
- (A) any information related to the delivery, administration, or use of an investigational drug or device pursuant to this section; or
- (B) any information related to the clinical outcomes experienced by a terminally ill patient supplied an investigational drug or device pursuant to this section.
- (2) Exception.–Nothing in this subsection prevents the sponsor of a clinical trial from voluntarily disclosing, collecting, or reporting information to the Food and Drug Administration.
In other words, the drug and device companies who allow “terminally ill” patients to use unapproved drugs and devices don’t even have to collect data on the outcomes patients who take their unapproved drugs or use their unapproved devices under this law, and, if they choose to do so, don’t have to report those outcomes to the FDA. It’s all voluntary. It’s hard to imagine a provision more irresponsible than this. Add to the parody of “informed consent” in this law is the fact that the law basically makes any reporting of patient response or adverse events completely voluntary. Basically, if you’re a terminally ill patient, this law strips away all the copious protections for human subjects in research that the law currently provides. You’re completely on your own, and the drug company is not responsible for anything, so much so that the law even ends with this provision:
Except in the case of gross negligence or willful misconduct, any person who manufactures, imports, distributes, prescribes, dispenses, or administers an investigational drug or device in accordance with section 561A shall not be liable in any action under Federal or State law for any loss, damage, or injury arising out of, relating to, or resulting from–
- the design, development, clinical testing and investigation, manufacturing, labeling, distribution, sale, purchase, donation, dispensing, prescription, administration, or use of the drug or device; or
- the safety or effectiveness of the drug or device.
In other words, if something goes wrong, the terminally ill patient or his surviving relatives can’t even sue, unless there’s obvious gross negligence or willful misconduct, whatever that is, even if there turns out to be an obvious defect in the design of the drug or device. In other words – terminally ill patients, you’re completely on your own. Masquerading as a “health freedom” law that will let terminally ill patients have access to experimental drugs under a process less difficult than currently existing IND procedures, HR 4475 is a stealth assault on the very heart of clinical trial ethics. Remember, one of the main principles of the Common Rule and other statements of principles regarding human research subject protection is that vulnerable groups need more, not less protection. Those particularly vulnerable groups are traditionally defined as children, prisoners, and students, the former of whom rely on parents to exercise judgment and the latter two of whom are subject to potential coercion. I would argue that terminally ill patients are a particularly vulnerable population in that they are desperate and prone to grasp at anything represented as having a chance of saving their lives. If anything, they need more, not less, protection.
Basically, HR 4475 is a solution in search of a problem. It’s based on the assumption that there are just oodles and oodles of new investigational drugs out there that could save the lives of lots and lots of terminally ill patients, if only the government would get out of the way and let the people have access to them. This is libertarian magical thinking at its most pernicious; there’s no compelling evidence for this assumption and plenty of evidence against it. (And, no, my characterization of this assumption underlying HR 4475 is not a straw man.) Even if you view the IND process as being in dire need of liberalization, it’s still a “solution” that won’t fix the process but will, in essence, destroy the process. It’s also clearly one of a number of attempts by the health freedom movement to get a “foot in the door.” If successful, then similar arguments will be made to expand the “right to try” principle and decrease regulation on investigational agents for larger and larger populations. Although HR 4475 is clearly not explicitly designed to aid quacks who peddle treatments like Gerson therapy or the Gonzalez protocol, it would be a godsend to someone like Burzynski, and it could potentially be a boon to unethical drug and device companies, who would be free to peddle their investigational drugs and devices, both promising and even those that failed, to that most vulnerable of patient populations, patients with no hope of survival. Health freedom, indeed. Apparently “health freedom” means the freedom of pharmaceutical companies to provide treatments whose efficacy is unknown and that are unlikely to make a significant difference in outcome (or even might be toxic) without actually having to learn anything from the exercise.