Editor’s note: Dr. Hudis hosts the ASCO in Action Podcast, which focuses on policy and practice issues affecting providers and patients. An excerpt of a recent episode is shared below; it has been edited for length and clarity. Listen to the full podcast online or through iTunes or Google Play.
I am really pleased to have with us ASCO's Chief Medical Officer and Senior Vice President Richard L. Schilsky, MD, FACP, FASCO, FSCT, for a conversation focusing on right-to-try policies. To take you behind the curtain of how we put these shows together, this episode was recorded a couple of weeks ago. After we recorded it, federal right-to-try legislation was enacted, making right-to-try the law of the land. ASCO remains very concerned about the impact of this law and we are going to continue to educate our members about what it means for oncologists and their patients. [Editor’s note: The transcript has been edited slightly where appropriate to clarify that federal right-to-try legislation was enacted and is no longer pending.]
CH: It might be useful to define for our audience two terms. One is right-to-try, and the other is something that immediately gets mixed in with this discussion, expanded access. What are they and what is the difference between those two approaches?
RS: Both are programs that aim to provide patients with serious medical illness access to investigational drugs that have the potential to benefit them. The fundamental difference between the two is the involvement of the U.S. Food and Drug Administration (FDA) to provide regulatory oversight in the process. The expanded access program, which has been in place at the FDA for many years, is a mechanism by which doctors and patients can submit a proposal to FDA requesting the use of an investigational new drug for a patient who has a serious medical illness and no good therapy options. The right-to-try legislation that has been passed in many states and now at the federal level has taken the view that the FDA is something of an obstacle to patients obtaining access to investigational drugs and seeks to provide patients with the opportunity to request access to those drugs without the intermediary step of the FDA review. That's the fundamental difference between the two programs.
It's important to point out that right-to-try is a catchy phrase. It's a bit of a misnomer because it doesn't actually provide patients with the right to try anything. It provides patients with the right to ask for a drug, and the key gatekeeper in the entire process is the pharmaceutical company that is the manufacturer of the drug. The drug companies are not required to make their drugs available under either program, and none of the [state or federal] right-to-try legislation requires that they do so. In many cases, the drug companies have made a decision not to make their drugs available at this point in the drug's development.
CH: Right-to-try has become a somewhat emotional issue in the general public. What is driving this loud public debate about right-to-try?
RS: It's pretty straightforward: You or a family member or loved one has a serious, life-threatening illness, no established therapies, a high risk of dying from that illness, you want to explore every option, and if there is a drug out there that has undergone some level of clinical testing and has shown some promise in treating your particular medical condition, it makes sense that people might want to try that drug. I think it's important to keep in mind that most of the right-to-try laws [including the recent federal law] permit the request for the drug to be made for any drug that has completed phase I clinical trials.
We have to remember a few things about a drug at that point in its development. After phase I, we know something about its acute toxicities. We know relatively little about what its chronic or delayed toxicities might be. We know something about a reasonable dose that should be studied further, but we don't necessarily know what the optimal dose is for any given person. We usually know very little about how the drug performs in patients who didn't qualify for the phase I clinical trial, such as patients who might have varying degrees of organ dysfunction, like a very sick individual might have. And typically, we know very little about the drug's efficacy because it hasn't yet undergone the formal efficacy testing in the later stages of drug development. There is a quite a bit of risk associated with accessing a drug after just the phase I trials have been completed.
The other thing that's important to point out is that because these drugs, by the nature of the program, are investigational, the patient's doctor is unlikely to have had any experience in using the drug unless they participated in a clinical trial of the drug. For many of the drugs that might be accessed under right-to-try, the typical doctor has essentially no clinical experience, might not even know the dose, might not know anything about the side-effect profile or how to manage those side effects.
Families, loved ones, and patients will say those risks are trivial compared to the hope that the drug will be transformative for them. Statistically, we know that the chances of that are, sadly, pretty low, but not zero, and I think that's probably part of the emotional drive here as well.
Let's remember that even where we have a lot of good data on the success rate for new cancer drugs that enter clinical development, the chances of a drug making it from phase I through to phase III and then on to the market is 10% or less. Most of the drugs never turn out to have real clinical benefit. The chances that an individual who has a serious, immediately life-threatening illness will have a truly clinically meaningful benefit from that drug are exceptionally small.
I think that it's very hard to argue the emotional drive for these therapies with objective data and logic, the paradigm of clinical development, and rational expectations. But I think it's important that patients understand (as when they undertake any therapy) the potential benefits, and that has to be weighed against the potential risks.
CH: This is a partnership, in the end. The patient can't actually get and administer most of these drugs without the cooperation of their clinician. How does it obligate the clinician who cares for that patient? If your judgment as a clinician is that no targeted therapy, for example, is appropriate at this time, but the patient is, in a sense, demanding one, what happens in the physician-patient relationship? Is there any legal responsibility for the doctor to work as an agent for a patient who wants a specific therapy?
RS: [The prior state and recent federal] right-to-try laws generally do not obligate the physician to comply in working with the patient to obtain access to a drug. They also offer, in most of the laws, substantial protections for physicians so that they're not liable for bad outcomes that could occur in a setting where the drug is administered and doesn't work. Most of the laws protect clinicians from disciplinary actions regarding licensure, protect them from loss of Medicare certification, and have other provisions in place so that the physician is actually protected against liability.
It's important to note that most of the right-to-try laws, while they include protections for physicians, don't include important protections for patients. Most notably, patients are at risk for paying for the cost of the drugs, they may be at risk for paying for the cost of the medical care associated with administering the drugs. The laws don't include any provisions that require insurance companies to reimburse the cost of that care, so patients have some financial liability under the right-to-try programs. That doesn't exist with the FDA expanded access program, where there are limits on the costs that can be passed on to patients.
ASCO strongly supports patient access to investigational drugs, but ASCO's position begins with participation in clinical trials as the best way to provide access to investigational drugs to patients.
CH: In everyday discourse we hear complaints that the FDA and ASCO are too strict in terms of getting new drugs into market, followed almost within seconds by complaints that we're too loose and we're letting lots of drugs in that have minimal effect and are expensive. This argument in the political arena informs some of the discussion for the lay audience and our patients. ASCO has put a stake in the ground that strengthening the expanded access program is a preferable way to go. Can we talk about some of the specific steps that have been taken to try to improve the existing expanded access program?
RS: FDA has taken great steps toward simplifying the process by which one can submit an application to the agency to receive the drug. It's important to remember that, when submitting to the FDA, there are several things that have to be included: a short clinical protocol that describes the unmet medical need of the patient, the rationale for treating with the drug that's being requested, the dose that is intended to be administered, and how the patient is going to be monitored for side effects during the treatment. It's also necessary to obtain Institutional Review Board approval to administer that drug to the patient. Most importantly, you have to submit to the FDA documentation from the sponsoring pharmaceutical company that they're willing to make the drug available. As I said earlier, it all starts with getting that permission and documentation from the sponsoring pharmaceutical company. The FDA has made a real effort to streamline this process, to reduce the required form to a single page, to limit the time required to complete the form, and to simplify the associated documents that are necessary. While it's still not quite as easy as one might like, it's far easier than it used to be.
The good news is that the FDA approves more than 99% of the requests that it receives, typically within a matter of days, and can actually approve a request for expanded access or compassionate use within hours if it's a true medical emergency. The FDA is not the obstacle in patients obtaining investigational drugs.
Listen to the full podcast online or through iTunes or Google Play. Read the ASCO in Action Brief: Right-to-Try and Expanded Access to Investigational Drugs, a comprehensive explanation of right-to-try legislation. The brief includes resources to facilitate physician-patient conversations on accessing investigational treatments outside of clinical trials, including Cancer.Net, ASCO’s patient information website, the Reagan-Udall Expanded Access Navigator, and an FAQ document.