Ellen V. Sigal, PhD
Why wouldn’t you support a patient with a terminal illness the “right to try” any therapy that may save his or her life? The answer to this question—one engulfed in a political debate in Congress—seems simple. It is not. [Editor’s Note: On March 21, 2018, the House of Representatives approved a right-to-try bill that would give patients with terminal illnesses a right to try unproven experimental drugs without government oversight. The bill now moves to the Senate for approval.]
I firmly believe that someone with a late-stage terminal illness should have the chance to try an experimental therapy. I have seen many tragedies caused by disease. I have witnessed countless patients losing their battle with cancer while desperately trying to find treatment, including the loss of my own family members and friends.
As much as we all want to help these patients have access to effective therapy, the “right to try” as a political stance is not the answer, nor is the attempt to circumvent the authority of the U.S. Food and Drug Administration (FDA) to protect patients.
Safeguarding Patients’ Health and Preventing False Hope
The idea of “right to try” has been discussed a lot recently, culminating in President Trump’s call to action for Congress to pass a federal right-to-try bill in his State of the Union speech this past January. I strongly believe that steps should be taken to allow patients to gain access to clinical trials and continue to ensure our regulatory system is expediting therapies in a safe and efficient manner. We can always be doing more to save patients’ lives. But we must be honest in this debate. We must not give patients false hope through a flawed legislative proposal. We must ensure that patient safety is still a top priority.
The right-to-try legislation proposed by Congress seeks to grant all terminally ill patients access to experimental therapies once approved alternatives have failed and is a way to remove the FDA’s oversight authority by bypassing the expanded compassionate use access process.
Proponents of the legislation claim the current compassionate use program the FDA has in place, which authorizes more than 99.4% of requests, is too slow. It is important to note the current process has been streamlined, so that the FDA is reviewing most requests within 24 hours, and it takes patients less than an hour to fill out the application. The problem is not the FDA, and it is imperative that the agency not be removed from the review process of patients receiving any type of therapy, even an experimental one. The unfortunate truth of the proposed legislation is that it effectively provides zero protections for patients and will not actually result in greater access to experimental therapies.
Addressing Barriers to Clinical Trial Enrollment
Great strides have been made in patient access to experimental therapies compared to where we were 5 or 10 years ago; however, much more needs to be done for the sake of patients with cancer. As we contemplate a new piece of federal legislation, such as the right-to-try bill, it is imperative that we first examine the reason why patients want greater access to experimental therapies. By doing so, we will discover it is because patients are unable to obtain access through clinical trial enrollment. To make right-to-try legislation beneficial to patients, there are significant issues we must address.
First, we must ensure that any legislation includes informed consent provisions about the risks involved. Current right-to-try laws allow patients to request therapies from companies that have passed a phase I trial with the FDA. However, it needs to be clear that during a phase I trial, only a small group of patients receive the therapy; the treatment is tested in carefully controlled conditions designed to find and detail obvious toxicities; and the trial is meant to identify a tolerable range of potentially effective doses before the drug advances to a larger phase II trial. The extent that a patient can give informed consent based upon such little clinical information is limited.
Second, almost 90% of new drugs never make it to market because they are ultimately found to be too dangerous for patients or shown to be ineffective. Not to mention that during the phase I trial, there are no reliable data whether a therapy works, and toxicities can be discovered in later phases of trials. By including an informed consent process that is well defined and supported by adequate clinical data in the final piece of legislation, there could be a stronger guarantee to patients that they can sufficiently judge the experimental therapy and weigh the potential risks and benefits as well as the magnitude of their decision.
We must also clarify the limits of right to try that extend beyond this legislation to clinical practice. This includes the responsibility of advocacy organizations, professional societies, and, most important, oncologists, who need to better communicate the risks of and access to experimental therapies with patients as they guide them through what are stressful and confusing treatment decisions.
Expanding Access to Experimental Therapies
Under today’s laws, patients have the right to request an experimental therapy from a drug sponsor through the expanded access pathway, but the company is under no obligation to provide the therapy. The proposed federal legislation is not providing a new “right”—the patient will still be able to submit a request to the drug sponsor, and the sponsor can still deny it.
Contrary to what some politicians would have us believe, much has already been done and continues to be done to address the many issues surrounding patient access to treatments, particularly access to experimental therapies for patients who have exhausted all other options.
“The Breakthrough Therapy designation is deemed one of the most revolutionary initiatives in drug development in recent history, with more than 80 therapies already approved.”— Ellen V. Sigal, PhD
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My organization, Friends of Cancer Research (Friends), has worked with ASCO to address the problem of clinical trial enrollment. Our work primarily focused on expanding eligibility criteria and removing the barriers standing in the way of patients from participating in clinical trials. Through our joint project, which resulted in a comprehensive examination of eligibility criteria for cancer clinical trials, we identified five areas that were most likely to restrict a patient from enrolling in a clinical trial and the least likely to affect the safety of the participants: minimum age requirements for trial enrollment, HIV/AIDS status, brain metastases, organ dysfunction, and prior and concurrent malignancies.1 Although expanding clinical trial enrollment will not solve all the problems facing patients seeking experimental therapies, it is important to acknowledge the extensive work being done to expand access to patients.
Another issue is to make sure our regulatory system is best equipped to rapidly and safely evaluate and approve new therapies. This is also something that Friends took a big step toward 5 years ago when we created the “Breakthrough Therapy designation” to expedite the development and review of new drugs. We worked with members of Congress and leadership at the FDA to enact the Food and Drug Administration Safety and Innovation Act, which provided the Breakthrough Therapy designation, and it was signed into law in 2012.2 This designation has not only changed the way the FDA approves life-saving therapies for patients, but how industry develops treatments for patients who so desperately need them. This designation is deemed one of the most revolutionary initiatives in drug development in recent history, with more than 80 therapies already approved.3
Additionally, in 2017, the FDA instituted a tool called the Expanded Access Navigator (http://navigator.reaganudall.org) to raise awareness among doctors, patients, and families regarding the compassionate use of experimental therapies. This tool is currently being piloted in oncology with the goal of increasing accessibility of information to patients and providers.
It should also be pointed out that although 38 states currently have their own right-to-try laws in place, there are no published data showing these laws have actually led to patients accessing experimental therapies.
A Path Forward
Everyone can agree that terminally ill patients should have access to promising experimental therapies when all other available options have been exhausted. A federal right-to-try bill could be a path forward in achieving that goal, but it must not be harmful to patients by exposing them to lethal side effects or removing oversight by the FDA—an agency whose mission is to protect public health from the process. In its current form, the proposed legislation does nothing for patients other than provide false hope by allowing them to request a drug with no evidence of efficacy they may never receive and—should they receive it—may do more harm than good.
There are still critical adjustments to be made to right-to-try legislation. However, with significant changes, patients with life-threatening diseases and no other options could be given greater access to the information they need to decide whether they should pursue an experimental therapy or not. ■
Editor's Note: On Tuesday, March 13, the House of Representatives (H.R.) voted against passage of H.R. 5247, legislation that if approved would have allowed seriously ill patients to get investigational therapies once approved therapies have failed, and without receiving permission from the US. Food and Drug Administration (FDA). This vote was taken under a House procedure called “suspension of the rules” which is typically used to pass non-controversial bills. Votes under suspension require a two-thirds majority. The final vote, 259 representatives in favor of the legislation and 140 representatives against, failed to reach the required majority.
DISCLOSURE: Dr. Sigal reported no conflicts of interest.
Dr. Sigal is Chair and Founder of Friends of Cancer Research.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
1. Kim ES, Bruinooge SS, Roberts S, et al: Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. J Clin Oncol 35:3737-3744, 2017.
2. U.S. Food and Drug Administration: Fact Sheet: Breakthrough Therapies. Available at https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed February 23, 2018.
3. U.S. Food and Drug Administration: Frequently Asked Questions: Breakthrough Therapies. Available at https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed February 23, 2018.