Food and Drug Administration building.

Food and Drug Administration building.

Since 2014, 33 states have passed so-called “right to try” laws. These laws purport to give patients with a terminal illness access to “potentially lifesaving” drugs, biologics and medical devices that have not yet been approved by the FDA, but without all the regulatory protections required by the FDA’s “compassionate use” program, even though the FDA grants almost all requests. Promoted by patient advocacy groups and the libertarian Goldwater Institute, and aided by plenty of heart-wrenching anecdotes, right to try bills have sailed through state legislatures.

Notably missing from the cheerleading section have been medical ethicists (also here), physicians and physician organizations, and the drug industry itself, as well as David Gorksi here at Science-Based Medicine (plus me, once) and our good friend Orac over at Respectful Insolence. (See full list at the end of this post.) Critics find the claims that “potentially lifesaving” drugs will actually benefit terminal patients overblown, the risks underappreciated, and the procedures for obtaining unapproved drugs inadequate to protect patients from adverse consequences, both medical and financial.

The controversy to this point has operated pretty much in the theoretical arena, given that right to try laws have two huge stumbling blocks which prevent drug companies from wanting to participate:

  1. They are almost certainly unconstitutional as an attempt to bypass federal regulation, and,
  2. nothing protects drug, device or biologics manufacturers from getting into hot water with the FDA for side-stepping the approval process or liability for damages caused by their products.

All that will change if a new Senate Bill or its House counterpart removing federal obstacles to the full implementation of state right to try laws passes and is signed into law by President Trump. (An almost certainty if it gets to his desk, given his antipathy to the FDA.) Unfortunately, even then we may not know who was right about right to try laws and their “potentially lifesaving” consequences. That is because, per the pending bills:

  • Their implementation will be carried out completely shielded from any regulatory oversight;
  • Results are barred from use to improve outcomes for other patients; and
  • Complaints for even the most egregious malfeasance will never see the light of day.

State “right to try” laws

The Goldwater Institute’s model act has served as a template for state right to try laws. (These laws cover drugs, medical devices and biologics, but for simplicity’s sake from now on we’ll just say “drug.”) Although states sometimes amend the model act’s recommended language, state right to try laws typically have the following provisions (excluding liability issues, which we’ll get to in a minute):

  • The drug must have successfully completed Phase I clinical trials and still be involved in the FDA’s clinical trial process. As we know, Phase I is designed to assess toxicity and dosing but not safety or effectiveness. And any evidence of either safety or effectiveness which appears at this point may not hold up in later phases of the process.
  • To access the drug, the patient must have a “terminal illness,” defined broadly as “an advanced stage of a disease with an unfavorable prognosis and no known cure.” (Not all states use this term; California requires that the patient have an “immediately life-threatening disease or condition,” meaning, “a stage of disease in which there is a reasonable likelihood that death will occur within a matter of months.”)
  • The patient, in consultation with “a physician” (no matter the physician’s lack of expertise in treating cancer or other terminal illnesses, or, for that matter, never having a previous relationship with the patient at all) has “considered” all other FDA-approved treatment options.
  • The patient has a prescription “or recommendation” for the drug and has given informed consent (or it has been given for him if he is a minor or mentally incapacitated).
  • The drug’s manufacturer can, but is not required to, make the drug available and can choose whether to charge the patient.
  • Insurance companies can, but don’t have to, cover the cost of the drug itself. (Unless they’re forced to, I think it’s safe to assume insurers are not going to pay.)
  • The state medical board is prohibited from acting against a healthcare provider “based solely on” the recommendation, prescription or treatment with the investigational drug.” “Based solely on” is not further defined.
  • Any “official, employee, or agent of the State” is prohibited from blocking or attempting to block patient access to a drug, no matter what the circumstances. Thus, 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.
  • Written informed consent is required, including acknowledgement that current treatments are not likely to prolong the patient’s life, a description of the best and worst outcomes (including worse symptoms and a hastened death) of using the investigational drug, acknowledgment that insurance is not obligated to pay for any of this and that it may jeopardize the patient’s eligibility for hospice. The patient must understand that he, or his estate, is liable for all expenses consequent to treatment, which can be substantial.

Of course, this guarantee that the patient will be knowledgeable about the consequences is illusory if the knowledge isn’t there. As David Gorski pointed out, Phase I trials leave much to be discovered about the drug under investigation:

Phase I trials can be as few as 20 patients. That is not enough to determine safety, nor is it intended to. Phase I trials are designed primarily to identify major side effects and to use a process known as dose escalation to determine what is commonly referred to as the “maximum tolerated dose.” It is utterly impossible for such a small clinical trial to determine the safety of a drug. . . . Phase II and Phase III trials are needed to confirm safety. That’s why the premature diffusion of unapproved drugs has the potential to increase morbidity from adverse events and even hasten death. One example is amonifide for treating breast cancer. The drug made it through phase I trials, but serious life-threatening hematologic toxicity emerged during phase II trials. . . . Indeed, even phase III trials can’t always adequately demonstrate that a drug is safe; it’s not uncommon for less common adverse effects not to show up until post-marketing surveillance, when much larger numbers of patients receive the drug. Moreover, only 5% of all cancer drugs that enter clinical testing are ultimately approved for patient use [because they meet the FDA’s standards for safety and efficacy]. Among drugs tested in phase II trials, only 30% go on to phase III.

In other words, investigational drugs get out of Phase I with high odds that they aren’t safe and don’t work. As a former pharmacology professor who has worked in drug development both for the FDA and industry said:

Right-to-try” legislation“makes sense for people who don’t understand the complexities of the drug development process. As a rare Republican working at the FDA and a generally politically conservative person, I am all for more freedom and less government intervention — but not when it comes to drug approval. The truth is, I am not quite ready to entrust the general public (or, for that matter, a senator with no scientific or clinical background) to circumvent the FDA through “right-to-try” and to make independent recommendations regarding clinical pharmacology, pharmacogenomics, biomarkers, and long-term drug safety.

Big Pharma has its doubts as well:

“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,” said Sascha Haverfield, vice president of scientific and regulatory affairs for the Pharmaceutical Research and Manufacturers of America. He suggested that medical providers, the pharmaceutical industry and FDA should seek ways to improve access to clinical trials.

Despite the hyperbole about potentially lifesaving drugs, there is no actual evidence that right to try has benefitted a single soul. As Orac noted, the Goldwater Institute is claiming that a Texas physician is defying the FDA and bravely offering treatments via Texas’s right to try law, but they offer no evidence that this has been successful. (In fact, Orac discovered that one of this physician’s patients has died of cancer after a GoFundMe plea to pay for her treatments, to the tune of $38,000, but the details of whether this was through right to try are murky.)

Greenlighting “right to try” implementation

Part of the reason proponents’ claims regarding the putative benefits of right to try laws remain untested is that that drug companies are reluctant to provide experimental treatments outside clinical trials. They fear liability for injuries to patients and that adverse events will affect the likelihood that their drugs will be approved in the simultaneously ongoing FDA approval process.

These fears will be allayed, and any constitutional impediments to implementation resolved, if the recently introduced Senate Bill 204 or House of Representatives Bill 878 become law. Both prohibit the federal government from taking any action “to prohibit or restrict” the use of drugs (or devices or biologics) “intended to treat a patient who has been diagnosed with a terminal illness” (which has the same meaning as in state law; again, not all states use that term) and “is authorized by, and in accordance with state law.” The bills repeat the states’ requirement that the drug must have successfully passed Phase I clinical trials and still be in the FDA’s drug-approval pipeline.

They also require that the patient have:

received a certification from a physician, who is in good standing with the physician’s certifying organization or board, that the patient has exhausted, or does not meet qualifying criteria to receive, any other available treatment options.

These provisions will do away with any threats of the FDA’s acting against a drug company for stepping outside the rules and obviate any constitutional issues. But the last one also appears to encourage even more futile treatments than the state right to try laws. According to the model act, the patient and his physician need only have agreed that available treatments “are unlikely to prolong the patient’s life.” These bills seem to require that patients exhaust marginally beneficial treatments (“any other available treatment options”) before accessing investigational drugs.

For all the supposed concern about helping some terminal patients access “potentially lifesaving” treatments via unapproved drugs, these bills remain oddly unconcerned about other, equally terminal patients whose lives may depend on approved drugs. Any useful information that might come out of treatment with an investigational drug accessed via right to try can’t be considered by the FDA in determining whether to approve the drug:

the outcome of any production . . . dispensing, possessing or use of an experimental drug . . . shall not be used by a Federal agency reviewing the experimental drug . . . to delay or otherwise adversely impact review or approval . . .

Of course, who’s keeping track anyway? S. 204 and H.R. 878 do not require any record keeping or reporting of results. To my knowledge, the only state requiring reporting of results, including adverse events, to the authorities is California. An example of why this is a reckless waste of potentially valuable information occurred just yesterday in the news that Juno Therapeutics had pulled the plug on a once-promising treatment for a rare form of leukemia due to five deaths in clinical trials. Deaths of patients who access treatment via right to try are either unrecorded or, if known, cannot be used in assessing whether the treatment should be approved.

The Goldwater Institute’s model act does not relieve physicians and drug companies from liability for negligence. The model act does provide that the right to try law will not create a private right of action as long as the physician or company “is complying in good faith with the terms of this act and has exercised reasonable care.” In other words, while the usual state tort laws permitting suits for negligence (including malpractice) are not affected, the right to try law in and of itself does not create a new cause of action for damages arising out of treatment with an investigational drug. Even if a particular state didn’t adopt the model act’s language and doesn’t mention liability at all, we can safely assume that the state’s usual tort laws apply and the patient could sue for damages for negligence.

S. 204 and H.R. 878 would override state tort law by absolving drug companies and physicians of all liability, not only for negligence, but for gross negligence as well, as long as they act in accordance with the state right to try law and the physician certifies that the patient has exhausted or doesn’t meet the qualifying criteria for other treatment options.

Given that none other than Dr. Stanislaw Burzynski has helped himself to the benefits of his state’s right to try law, we should all be concerned.

A bill with the same language was considered in the last Congress but was stopped by Sen. Harry Reid. Sen. Reid is gone now and Republicans have their knives out for “abusive” federal regulation, aided and abetted by a president who openly disdains the FDA and its “slow and burdensome” approval process getting in the way of “miracles.” Right to try laws have a better chance than ever to be transformed from (as David Gorski rightly called them) feel-good placebo legislation into a libertarian purgative for the FDA. Unfortunately, terminally ill patients, not Congress, the president, or the state legislatures, will suffer the side effects.


Other “Right to Try” posts

Posted by Jann Bellamy

Jann J. Bellamy is a Florida attorney and lives in Tallahassee. She is one of the founders and Board members of the Society for Science-Based Medicine (SfSBM) dedicated to providing accurate information about CAM and advocating for state and federal laws that incorporate a science-based standard for all health care practitioners. She tracks state and federal bills that would allow pseudoscience in health care for the SfSBM website.  Her posts are archived here.