Gilbert Benavidez is a Policy Analyst with Boston University’s School of Public Health. He tweets at @GBinsolidarity. Research for this piece was supported by the Laura and John Arnold Foundation.
‘Right-to-try’ legislation recently passed in the House after having previously passed in the Senate. The bills will now move on to a conference committee. If you haven’t been following the bills, this explainer will bring you up to speed.
What is the ‘right-to-try’?
Roughly speaking, the concept of ‘right-to-try’ is to increase access of terminally ill patients to experimental drugs or medical products. The legislative manifestation of this goal on the Federal stage has been toward the establishment of a means by which terminally ill patients could access experimental drugs (those that have passed Phase I of the Food and Drug Administration (FDA) clinical drug trial process) without getting FDA approval.
The patient’s rights movement behind right-to-try is made up of multiple organizations, led largely by the Goldwater Institute, an Arizona-based conservative think tank. The Goldwater institute has spearheaded successful efforts to get state level legislation passed in 38 states. The right-to-try is also supported by the President.
But, over 75 patient groups oppose the legislation, saying that it creates “false hope” and “…would cause serious harm to the most vulnerable patients.” Former FDA commissioners are also pushing back against the bill. For ease of exposition, I will use the term ‘triers’ for participants in this movement.
What’s the landscape now?
Currently, to access experimental treatments, patients can either enroll in clinical trials or seek ‘compassionate use’ exceptions from the FDA. Triers see the FDA requirements for compassionate use as red tape and that they seek to circumvent. Those requirements are:
- The patient and a licensed physician are both willing to participate.
- The patient’s physician determines that there is no comparable or satisfactory therapy available to diagnose, monitor, or treat the patient’s disease or condition.
- The probable risk to the person from the experimental treatment is not greater than the probable risk from the disease or condition.
- The FDA determines that there is sufficient evidence of the safety and effectiveness of the experimental treatment to support its use in the particular circumstance.
- The FDA determines that providing the treatment will not interfere with the initiation, conduct, or completion of clinical investigations to support marketing approval.
- The sponsor (generally the company developing the investigational product for commercial use) or the clinical investigator (or the patient’s physician in the case of a single patient expanded access request) submits a treatment plan that is consistent with the FDA’s statute and applicable regulations.
- The patient is otherwise unable to obtain the treatment or to participate in a clinical trial.
Research by Jarow et al. shows that from 2005-2014, over 1000 compassionate use applications were received per year by the FDA’s Center for Drug Evaluation and Research. All but 0.3% of them were approved. In October 2017 the FDA made the process even easier. Now, use of the drug can go forward with approval from merely one Institutional Review Board (IRB) member at the prescribing physician’s facility, as opposed to approval from the entire IRB.
What are the bills about?
The House and Senate each passed their own, relatively similar, versions of the bill. Both bills would provide a pathway for patients to use experimental drugs outside of clinical trials and without going through the FDA compassionate use process. However, drug manufacturers, sponsors of clinical trials, prescribers, or hospitals could still deny use of experimental drugs. For simplicity, I’ll be focusing on the Senate bill for the remainder of this post, which passed in August of last year.
Originally introduced in January 2017 by Wisconsin Senator Ron Johnson, the bill is intended to “authorize the use of unapproved medical products by patients diagnosed with a terminal illness in accordance with State law…”
Two provisions of the bill are intended to get buy-in from drug manufactures and clinical trial sponsors. One is “Use of Clinical Outcomes,” which states that adverse outcomes (harmful side effects, death, etc.) cannot be used to delay or adversely affect the review or approval of drugs. Moreover, sponsors of clinical drug trials (almost always drug companies themselves) can request that the FDA use the clinical outcomes of triers in the review or approval of the drug. It is not clear in the bill text if such a request must be approved.
The second is the “No liability” provision, which states that patients and their families must waive their right to sue sponsors of clinical drug trials, manufacturers, and/or prescribers. Patients and families are unable to sue if, for example, the drug kills the patient more quickly or more cruelly than the underlying disease would have.
What’s controversial about the bill?
There are many controversies, including undermining of the FDA and providing false hope to patients. I will discuss the three that most concern me.
1. Patient safety. Clinical drug trials are overseen by the FDA and consist of four phases (three phases before the drug is released to market, and, in some cases, a fourth post-market phase, which is not always honored). If something terrible happens, trials in the first three phases can be shut down by the FDA. Under the legislation, triers use of an experimental medication would fall outside of FDA purview. As noted above, the Senate bill text states that adverse clinical outcomes cannot “delay or adversely affect the review or approval” of the drug in question. If something goes awry during compassionate use, the trial would not necessarily be stopped.
2. Patient rights. As noted above, in the current Senate bill text, liability of sponsors, manufacturers, and prescribers is waived. Patients and their families effectively waive their right to sue for damages, unless there is evidence of fraud, misrepresentation, or willful misconduct. As Resnik and Parasidis noted in 2013 in the Journal of Medical Ethics,
The US federal research regulations prohibit informed consent, whether written or oral, from including provisions in which human subjects (or their representatives) waive or appear to waive legal rights.
The bill text here is antithetical to these regulations. The assumed retort is that compassionate use provides drugs to ‘patients’ not research subjects. That is, we are talking about treatment, not research. That leads directly to my last concern.
3. Patient/research subject confusion. As noted above, the bill states that sponsors of clinical trials can request that the FDA use the triers’ clinical outcomes in the drug review and approval process. This further blurs the line between patient and research subject, akin to the ‘therapeutic illusion.’ As Annas writes, the therapeutic illusion occurs when
research, designed to test a hypothesis for society, is confused with treatment, administered in the best interests of individual patients.
The goal of research is generalizable knowledge through experimentation. Research subjects are not patients, though some of them mistakenly believe they are — that the research is being done for their own therapeutic benefit.
The right-to-try bill seems to conflate patients and subjects in the following way. Presumably people administered drugs on a compassionate basis are patients. After all, they are not enrolled in a clinical trial and the point is to let them try a new agent in the hopes it will improve their health. But if their outcomes are used by clinical drug trial sponsors in research, as allowed by the bill, the patients become (or are a lot like) research subjects. But, they are not protected by an IRB or U.S. federal research regulations.
What are the prospects for the bill reaching the President’s desk?
The bill must now go to a conference committee, where members of the House and Senate will hash out what the final version will look like. Given the similarities of the two bills, I imagine the final bill will be on the President’s desk soon where it will be promptly signed into law. My guess is the concerns expressed above, and others, will remain.
