Tony Hagen is senior managing editor for The Center for Biosimilars®.
Gary H. Lyman, MD, PhD, provides an expert overview on overcoming the challenges of discussing biosimilars with patients.
Communicating the essentials of biosimilars to patients requires background knowledge and the right approach. These lower-cost agents have the potential to save money and improve access to care, but this can be of no avail if patients don’t get the information they need the way they want it.
Gary H. Lyman, MD, MPH, is an oncologist, hematologist, and public health researcher who has long been an advocate for biosimilars and, indeed, has developed guidelines in support of using these biologics for the treatment of cancer. In a recent interview, he shared his insights on conducting the patient-provider conversation about biosimilars and how physicians can prepare themselves to succeed with this encounter.
Lyman is co-director of the Hutchinson Institute for Cancer Outcomes Research in Seattle, Washington; a full member of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center; and a professor of medicine and medical oncology at the University of Washington.
CfB: What’s missing from the patient-physician biosimilar conversation, and what are the essentials of communicating a patient’s biosimilar options successfully?
Lyman: I’m speaking primarily from an oncology perspective, but I’ve been involved with biosimilars from day 1. It’s important to focus on education and convince patients and providers about the enhanced regulatory process for molecular characterization, both structurally and functionally, of these agents. It’s far more sophisticated than it was 20 years ago when the first biologics were approved based largely on clinical comparative trial data. The FDA, and I’m in support of this, feels that there is sufficient depth of clinical data for demonstrating efficacy and safety once you fully characterize the molecule and its structural [and] functional characteristics and critical quality parameters. There are now dozens of these that the FDA is using to classify these biosimilars as highly similar to the originators.
Biosimilars get approved with data on pharmacokinetics, pharmacodynamics, and immunogenicity, and these trials are often done in patients with disease, but also in healthy volunteers, because at least in the oncology space, problems may not be as apparent in an immunocompromised patient who has been on chemotherapy or radiation therapy. Clinical comparative data are used to fill in any gaps of remaining uncertainty about the safety and efficacy of these agents to demonstrate that they are essentially the same as the originator molecules.
When talking with the patient, the challenge is to communicate a lot of this comfort with the regulatory process and the integration of biosimilars into treatment guidelines. ASCO has recently published an updated guideline in early stage breast cancer and [human epidermal growth factor receptor 2]–positive breast cancer that basically said the 5 approved trastuzumab biosimilars in the United States can be used equally or alternatively to the originator [Herceptin] without any concern about loss of efficacy and safety.
We have all that, and I communicate that to patients, along with my personal comfort with these biosimilars. But patients have many different levels of background and education, and the challenge is to communicate this information in a simple, nontechnical fashion. Many doctors don’t understand some of the terms, such as extrapolation and interchangeability. Even if the doctor has a science background, communicating biosimilar information to patients in any kind of depth is going to be a big challenge. We’ve encouraged professional organizations and health systems to develop targeted educational materials, such as pamphlets, that summarize these points in lay language.
It’s also important to make clear that no major safety issues have been raised with biosimilars. There has been no withdrawal of agents from the market. We really need to reassure patients that the experience to date tells us that these are safe and efficacious.
I do tell patients that biosimilars are approved with less clinical data than was used to approve the original agents, but those reference products were approved years ago when our technology was not nearly as good. Even so, there could be rare or delayed adverse events that emerge that you did not see in the limited clinical data used for biosimilar approval. I tell the patient, even if it seems unrelated to your treatment, let us know. We need to know if you’re having any unexpected symptoms or signs or concerns as time goes along.
Of course, the FDA is doing a lot of postmarketing surveillance of these agents. Each biosimilar is given a random 4-letter suffix that is used to track the performance of these products very closely. For Herceptin and the 5 approved biosimilars, you want to know which was given to the patient who developed a rash or some adverse event, and you can do that by being able to go back to the specific name and label given the biosimilar. But it’s traceable, and with the data capture, through patient-reported/physician-reported adverse events to the FDA, and just patients telling their doctor about problems, we hope that anything that’s slipped through inadvertently can be tracked and quickly pinned down if it has anything to do with the drug patients have received. Communicating all of this to the patient in a nontechnical fashion is a challenge.
One other issue is that biosimilars are biologic substances that cannot be reproduced exactly like a generic, and that’s one of the starting points I take with patients in communication. Biosimilars are not produced like generics in a test tube in the laboratory They’re produced in living systems like the originator biologic, and small differences will inevitably occur. And over time, there can be what we call drift in the structure and functional nature of these molecules.
Any small change in manufacturing, in the components that go into manufacturing these agents, could potentially change the molecular structure of these, although mostly this will not impact the functionality or the toxicity of these agents. You cannot assume that automatically, so the FDA mandates that changes in components or processes of the biosimilars and originator products be reported and evaluated to make sure no critical aspect of the molecule has been changed. I think everybody’s very much attuned to making sure that we track these molecules, these biologic substances, over time to make sure they’re the same as the original.
It’s very difficult in a 15-minute office visit to communicate this level of information, and even physicians are not necessarily always comfortable explaining this, so I think having this information in nontechnical language, written out, simple and short, and then allowing patients an opportunity to look it over and ask any questions that they come up with is a really critical part of our communication, rather than just throwing out a whole lot of jargon very quickly, which causes them to glaze over. They may not want to ask questions or they won’t know what to ask.
CfB: Do you find that the literature that you’re provided for this purpose is adequate, clear, and helps to ease patients’ concerns?
Lyman: We’ve developed some of our own, locally, and I know ASCO has, and I’m sure other professional organizations have done so, and they use outside observers, generally patient advocates or patients themselves to review it and validate the information or the conveyance of the information. I do think that, at least in many instances, due diligence has been done to make sure it’s comprehensive and understandable. That’s not to say it can’t be better.
I know that the Biosimilars Council and other organizations have worked on this as well. I think we all have the same goal: to make sure that patients fully understand about biosimilars and that they’re partners in this effort to improve access and reduce costs, but also to make sure safety and efficacy are maintained with these complex molecules. The information is available, but like anything else, it probably can continue to be improved over time—in particular, making sure that patients get their questions answered.
CfB: How are patients reacting? Are they throwing up their hands and saying, “Look, I just want to go with a brand drug. It’s so much easier”?
Lyman: It can be a problem. As I said, patients come in all shapes and sizes and backgrounds. It ranges between 2 extremes, one being they don’t want to know anything. “Just tell me what to do, doc. Tell me what to take and I’ll do it. I don’t want to know too much about it.” At the other end, I’ve had patients come in with a whole laundry list of questions because they were told they were going to get a new drug. They come in and say, “Oh, you know, I need to know all this stuff.” Most patients want to know or at least be told. You may have to quiz them or ask a couple of targeted questions to make sure they’re comprehending, or just to reinforce.
Most patients are in that middle ground. They’re going to trust you. The most common question I get is, “Would you give this to your wife or your mother?” and I’m generally able to say “Absolutely. These are perfectly safe and effective.” You can’t put that into the pamphlet, but for most patients, if they have any questions, they’re probably going to be of that nature rather than the technical ones. They do want to know they’re not being sold a bill of goods and being given a drug purely because it’s cheaper. I and my colleagues feel the same way. We don’t want to use biosimilars just because they’re less expensive.
CfB: Is there enough information out there to convince providers that biosimilars are safe and efficacious? Are you satisfied with the FDA’s decisions on biosimilars, outright?
Lyman: I am satisfied with the process, and the sophistication of the preclinical work that’s done is just light-years ahead of where things were when we approved Herceptin, Rituxan, Avastin, and many other original drugs. It’s just night and day, so that really reassures me. But given all that, I still am a strong believer in postmarketing surveillance, and the FDA has taken some recommendations from us and others to use big data for that. They‘ve engaged with CancerLinQ, the ASCO big data system. They’re working with Flatiron and other commercial big data suppliers.
I don’t think we can ever assume that because a study of 300 patients didn’t show some rare, serious, long-term adverse event, that it wouldn’t emerge when you have tens or thousands of patients taking this—often patients with more comorbidities than were included in the pivotal trials. As much as I’m comfortable with the process and the need to use biosimilars the way we’ve embraced them, it’s important not to let our guard down, and I think that’s reassuring to patients as well, to be able to tell them there are continuing efforts to monitor these agents very closely.
CfB: Should you be completely honest with patients and tell them whether they’re getting a biosimilar or an originator?
Lyman: I think you should. If you’re changing a patient from what they were getting, it’s absolutely crucial, because if you don’t, a nurse will tell them, or they’ll know from the bag, the prescription label, or the color of the medication. Or they’ll get a bill that mentions the drug that they’re taking. Trust is gold when it comes to communicating with patients. Otherwise they won’t be confident in your care.
Even when you’re starting a patient off on a biosimilar, it’s still worth the effort to explain, along with a brochure that details the process. And you should tell them that they can call any time if they have more questions, because you’re very comfortable that the treatments they are getting are as good as anything available for their disease. With only rare exceptions, you should be open and honest and tell the patient what they’re getting. If it’s a biosimilar, you can tell them that without spending an hour doing it.
CfB: What can doctors do if they feel they need more preparation for the conversation with patients about biosimilars?
Lyman: It’s 3 words: education, education, education. There are a lot of education materials out there, but it’s such a rapidly changing area. Many biosimilars have come along already, and we can expect more in 2021. Keeping up with that is not an easy task, just like all of medicine. We’re in a biologics revolution. Generally, with targeted small molecules or biologics, continuing education is just absolutely at the core of being an oncologist these days, and it’s true for biosimilars as well.
I’ve been privileged to chair an ASCO task force on biosimilars in educating oncologists on biosimilars, and we’re in the process of updating our original statement paper. I believe there’s a substantial segment of the professional community, including my oncology colleagues, who have not looked at the issue as deeply as I wish they had. And it’s understandable. The rate of change we are talking about here is not just biosimilars; it’s all of biologics itself—cancer, therapeutics, diagnostics, molecular testing, and so forth. I think we’re all kind of struggling with how do we attract that 50%, or maybe it’s even more, of oncologists who haven’t really dived in and fully educated themselves on biosimilars such that they can discuss them with comfort and reassurance to their patients.