Implementing Patient-Centered Outcomes in Cancer Trials

Today we are speaking with Dr. Ethan Basch, an oncologist who also does research on health services and drug regulatory policy at the University of North Carolina Comprehensive Cancer Center and the UNC School of Public Health. In a recent editorial in the New England Journal of Medicine, Dr. Basch wrote about a path toward including patient-reported outcomes, such as symptoms, in both labels for cancer drugs and in the published papers of trial outcomes. Dr. Basch is joining us to discuss his own experience with treating cancer patients, why patient-centered research is important, and why this type of information is frequently ignored.

-Interviewed by Anna Azvolinsky, PhD

Cancer Network: Dr. Basch, can you first tell us exactly what you mean by patient-centered outcomes and the types of information that you think should be included when clinical trials are presented and drug labels are written?

[[{"type":"media","view_mode":"media_crop","fid":"17965","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_1039409719031","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"1194","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"float: right;","title":"Ethan Basch, MD","typeof":"foaf:Image"}}]]Dr. Basch: This is a good question. The idea of patient-centered outcomes has really been evolving quite a bit over the past several years. For the most part, it refers to the outcomes of care that are considered meaningful to people, that are useful to them for making medical decisions. In the context of drug labeling or developing new drugs and other products, this idea means that when developing new ideas or other types of products, that we understand how the product affects people’s lives in ways that are actually meaningful to them. Not just outcomes that one could pick up by a blood test or by doing a CT scan, but the actual impact on a patient’s daily lives, the way that they feel, the way that they can conduct their activities and the way that they function.

Cancer Network: In your editorial, you mention that the labels for cancer drug hardly ever provide information on how the treatment ultimately impacts patients’ daily lives, as you just described. As I understand it, drugs for some noncancer indications do sometimes include this type of information on US drug labels? Why the difference with cancer drugs?

Dr. Basch: Yes, that’s right. It is surprising because in oncology, in cancer care, symptoms are so common. People have a lot of symptoms, a lot of difficulties in their daily lives related to the cancer itself and also related to the side effects of the drugs, but unfortunately it is very uncommon for this type of information to be seriously captured in studies that are testing new drugs, and it is exceedingly rare for this information to be well captured in the drug labels. By drug labels, I mean the information that is provided along with a drug to help consumers and clinicians understand how that drug works. If you look outside of cancer, it is a lot more common. About one-quarter of the drug labels outside of oncology, and much higher than that in particular areas, contain this kind of information.

For example, if you think about drugs for pain, analgesics, almost exclusively the most important outcomes that are measured come directly from patients. If you think about a headache medicine, you really have to understand how that medicine is affecting how people feel. So in this context, it is much more common to collect information directly from the patient. But if you go back to cancer care, where people are having a lot of symptoms related to advanced or metastatic cancer, and were interested to know what that product is going to do about their pain or fatigue, we really don’t collect that information. It is really hard to say why that discrepancy has occurred. I think a lot of it is just historical, some of it is cultural. If you go back not too far in oncology, the drugs were really not that effective, and we were really just focused on basic outcomes such as survival and unfortunately, we had to look at things like whether the CT scan or the blood test improved because we really did not have much more, and there was not a lot of hope that the drugs were going to make people feel better. But things have changed quite a bit in oncology, and oncology is starting to look quite a bit more like some of these other areas where patient-reported outcomes are more common. And this is because people are living a lot longer with their cancers. And people are on treatment for much longer. So in this new setting, the way that people feel is really important. If patients are living longer and or staying on chronic cancer therapy, it really is essential that we understand how they are feeling just as it is essential in some of these other areas outside of oncology where collection of this kind of information has been common for a much longer period of tinme.

Cancer Network: Can you describe your proposal to move to this patient-centered drug development?

Dr. Basch: Absolutely, I lay out in this piece several steps, six steps, that can be taken both by regulatory agencies such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in Europe, but also by drug companies to make development of drugs more patient-centered. The first step is really to have a discussion that is formalized early in the drug development process, where it is an expectation that the FDA reviewers and the representatives from the drug companies have an open discussion about how we will understand the impact of the product on the patient experience. Now, these kind of meetings are very common. They occur quite often in drug development, but during these meeting it is very uncommon that a patient-centered approach is discussed. So I am really advocating for it to be an expected component of these discussions that we try to understand what sorts of evaluations we will be doing to understand the impact of how patients feel and function.

I then move to the next step of actually developing those approaches in a way that is feasible for the drug company and acceptable methodologically for the regulatory agency. Again, this requires a back and forth and openness, both on the side of the regulators and the drug developers, and access to those who have methodological knowledge in this area. Next, I emphasize the importance of including questionnaires and tests for this kind of information in the various clinical trials that are being done, and then finally for the regulatory agency to emphasize including this information within the drug label-being very open to including this information so that people can really understand the properties of the product.

The end goal of these steps is that when a study or group of studies to develop a new product is complete, we will really have a good understanding of how people feel during that treatment, how it impacts the symptoms of the disease, and how the side effects affect people’s daily lives, and that this information will not only be published in scientific papers that come out of these studies, but that it be included in the drug label. The reason that this is important is that when I as a practicing oncologist sit down with patients or when a patient comes in to a doctor like me, having this information available will enable our discussion to focus on how the patient expects to feel during treatment, which I think is essential information. But, in order to get there, we really have to start almost at the beginning of the drug development process-as soon as we start to test products in humans-and this is what I call for, with some very specific and practical steps that can be taken.

Cancer Network: There are many stakeholders in this process. So, in your opinion, who has to make the first move toward this, and what are some of the major hurdles?

Dr. Basch: I do think that leadership is required in a number of different places. I think that this has to come from both the regulatory agencies and from the pharmaceutical companies, and also I think that organizations have to have a voice in this process, but honestly, my own feeling is that principal leadership has to come from the FDA. It has to come from the regulatory agency, because at the end of the day, the truth of how these things work is that when the FDA has an expectation, the drug companies will generally work hard to meet that expectation. Although many people in the drug companies do see this as being valuable, their priority is to develop products in a way that will get them to market, and in order to do that you have to meet the expectations of the regulators. It really has to start with regulators, with leadership at the FDA. I think a message has to be sent within the agency that if one does not understand the impact of a product in the way that a patient feels, then we really have an incomplete picture of the characteristics and properties of that product. It really makes it difficult to evaluate the value of both the efficacy and safety of that product if you don’t have this information at your disposal, and therefore that message has to come from leadership to the individual reviewers of the FDA, who are meeting day to day with drug developers, so that the reviewers will emphasize the importance of collecting this information.

I think the other piece is that the companies have to understand that there is a lot of value in understanding this information. When you understand how a patient feels, that provides important insight as to how your product is going to do once it is out on the market. If people have a lot of side effects or if they are not feeling much better with the drug, people will be less interested. If patients have a lot of side effects, they may not take the drug or refill the prescription. Clinicians may not be enthusiastic about prescribing the product and there are many examples of drugs where we picked the wrong dose. We picked a dose that was too high, it was not well tolerated and it went out on the market and people didn’t tolerate it well. By collecting this information early on, we can really understand the information. So I think that for the leadership in pharma to appreciate this and to send a message down to those on the clinical teams developing the products will also be very valuable.

I think the third stakeholder that people are talking more often about these days are actually the payers, the insurance companies. It turns out that the insurance companies are also very interested in this information because they want to know how people will feel when they are taking products. Although the payers traditionally have come into the picture later on in the process, after the product has already been developed, these days the payers are actually becoming involved earlier, and the drug companies are thinking about the informational needs earlier. So I think the third stakeholder here to think about are the payers, who I think really have to communicate to the pharmaceutical companies that this information needs to be collected, not late in the process (after a product is approved) but before the product is approved, so that the payers can really understand well how their patients will feel on these products. Just to recap, I really think that the most important voice here to get the process started is going to come from the regulatory agencies, from the FDA.

Cancer Network: Have there been any discussion or steps recently toward this more cancer patient-centered drug development by the FDA or any oncology associations?

Dr. Basch: There has been quite a bit of talk about patient-centeredness. The term has had much increased interest over the past couple of years. The FDA has had a couple of meetings, including public meetings to talk about patient-centered drug development and they are really very interested in it. There is a very sincere interest, I think, within the FDA, to be patient-centered. What I am talking about in this piece is a very practical step to getting one part of the process to be more patient-centered. There is a group within the FDA called SEALD, which is the Study Endpoints and Label Development team, that is very focused on integrating patient-related outcomes into drug labels. They developed a highly influential guidance document that was published several years ago, that outlines, for drug companies how to include patient-reported information in clinical trials, how to get that information into a labeling claim, a claim of efficacy or tolerability.

Recently, the FDA made a specific request to Congress for resources under PDUFA V, which is an allocation for support of various FDA activities, to provide them with funds for additional personal with expertise in this area. Very unfortunately, because of red tape, those funds have been held back from the FDA and I do mention in the piece the importance of figuring out a way to either release those resources or other resources to the FDA, so that they can make these very vital hires so that they can enable this sort of patient-centered approach to happen. So the FDA has actually been very interested in this and in oncology, specifically, at the leadership level, there has been quite a bit of talk about trying to be more patient-centered and bringing this information into labels. I really think the will is there, I think the commitment is there, and the understanding of the importance of this information is sincerely there. I think what is more complicated is implementation and that is really the impetus for me to write this piece-to assist in understanding some of the barriers that exist to actually accomplishing this very noble goal.  

Cancer Network: Thank you so much for joining us today, Dr. Basch.

Dr. Basch: My pleasure, thanks for having me.