1. DiGiulio, Sarah

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For some patients with life-threatening conditions for which all approved therapies and treatments have failed, investigational drugs might be sought out. If those patients cannot access that drug through a clinical trial, two pathways exist that can make those medications available: Expanded Access and Right to Try.

Holly Fernandez Lync... - Click to enlarge in new windowHolly Fernandez Lynch, JD. Holly Fernandez Lynch, JD

The former is a process that has been around for decades that involves both the FDA and the company who makes the drug weighing in on the decision about whether or not the drug will be made available to the patient. The latter is the result of a new 2018 federal law that takes the FDA out of the equation.


In a recent commentary article, Holly Fernandez Lynch, JD, MBE, and her coauthors argue the case for why the Expanded Access pathway is preferable (J Clin Oncol 2019; doi: 10.1200/JCO.19.01741). Fernandez Lynch is the John Russell Dickson, MD Presidential Assistant Professor of Medical Ethics and Assistant Faculty Director of Online Education, both in the Department of Medical Ethics and Health Policy at the Perelman School of Medicine at University of Pennsylvania.


"I want oncologists to be aware of the different pathways-and that Right to Try isn't the only pathway," she told Oncology Times. "There was a really effective pathway that was already in existence [when Right to Try was legalized]."


1 What is important to know about "Right to Try" versus "Expanded Access" pathways?

"Expanded Access is a long-standing pathway. It's been around for several decades. And its key feature is that you have to get FDA sign-off to get the investigational product. A doctor and patient decide together that an investigational product might be beneficial. If the patient is unable to enroll in a clinical trial, then they go to the drug company and say, 'we'd like to access this product outside of your trial. Are you willing to provide it?'


"The company can say yes or no. And they might have lots of good reasons for saying no. They might not have the resources to provide the drug outside a trial; they might not want to distract from their clinical development pathway, because getting the product approved is the best way to help the most patients; or they might just think the patient is not a good candidate for the product.


"But if the company says yes, the next step under Expanded Access is to ask the FDA for permission to use the investigational product outside of a trial. FDA is then looking at various eligibility criteria. Does the patient have a serious or life-threatening condition? Are the risks and benefits reasonable? Has the patient exhausted approved alternatives? Will Expanded Access interfere with ongoing clinical trials?


"The big difference with Right to Try is that you don't have to go to the FDA at all. With [this] you go to the company, and if they say yes, you're good to go. The product has to be past phase I for Right to Try, which is different from Expanded Access. And it has to still be in active clinical development. But there's not an independent entity standing in to say you can only have this product if the risk and benefits are reasonable for you, that's not one of the legal requirements. FDA isn't making that judgment, and IRB approval isn't required either. That's another difference from Expanded Access.


"The most important thing to note is that Right to Try cuts FDA out of the process. Proponents of the law say that's a good thing; 'FDA is standing in the way.' But it turns out that FDA says yes to almost 100 percent of Expanded Access requests. So, they're really not a barrier.


"Also, in about 10 percent of the cases in which FDA authorizes Expanded Access, they offer additional information to minimize risk. For example, they might say-'yes, you can use this product, but you should make sure the patient is aware of this safety concern or you should change the dose.' They might have information the physician and even the company don't have. So cutting FDA out when they weren't the barrier and when they were offering helpful information is really problematic. And that's exactly what Right to Try does."


2 Does FDA's involvement in the Expanded Access pathway delay getting patients drug access?

"No, it really doesn't. There was a period of time where the FDA process was more burdensome; but over the past decade, FDA has really streamlined things. For example, the form physicians need to fill out is now supposed to take only 45 minutes. [And FDA] can turn emergency requests around in 24 hours and most other requests are handled in just a few days.


"There's also a new pilot program specific to oncology, called Project Facilitate, where physicians are assigned a liaison from FDA who walks you through the process, helps you contact the company, and really tries to make it easy."


3 As a next step, what would you like to see happen?

"The purpose of our article was to help physicians and oncologists understand their options. If a patient comes in and says I'm interested in Right to Try, we think the first response should be 'Let me tell you about Expanded Access.' It will likely still help you access the drug you're interested in, but it's more protective of you as the patient and it's more protective of patients in general.


"One of the concerns around Right to Try is safety reporting. Under Expanded Access, you have similar reporting requirements to what you would have for a clinical trial. But for Right to Try, companies just have to make an annual safety report to FDA of aggregated data: how many doses they provided, for what indications, and any adverse events that they know about. So it doesn't have to be nearly as robust. That's bad for the patients who are taking the product-and it's also bad for future patients because there might be bad things that are happening that we're not getting data about.


"So while I think Expanded Access is the preferable pathway, in the rare instance that there's a company that says we'll only provide the product through Right to Try, then the physician can still add protections back in that resemble Expanded Access. They can commit to doing intensive safety follow-up even though it's not a requirement of the Right to Try law. They can reach out to FDA to make sure they have all the information they need to use the product as safely as possible, again even though that's not a requirement of the law. They can ask their IRB to weigh in. They can do all of these things voluntarily as a matter of their professional duties in the care of patients."