Expanding Access to Clinical Trials: What Oncologists and Payers Need to Know

In this episode of Breaking Down Health Care, John Hennessy, MBA, and Michael Kolodziej, MD, explore the evolving landscape of oncology clinical trials, discussing the challenges of patient enrollment, the impact of pharmaceutical-sponsored research, barriers posed by inclusion and exclusion criteria, and the role of clinical pathways and payers in facilitating trial access.

John Hennessy, MBA: Hi, I'm John Hennessey. I'm a principal with Valuate Health Consultancy, and I'm with Mike Kolodziej, my partner in our series Breaking Down Health Care. Today we're going to talk about a topic that's important to cancer patients and to cancer professionals across the board, and that's clinical trials. Clinical trials are hopefully a part of what we do in oncology. Mike, you've been doing this for a long time and clinical trials have evolved a whole bunch. Talk about your experience with clinical trials and how that changed during your career.

Michael Kolodziej, MD: Every oncologist who goes through training is ingrained with the idea that having your patients receive care on a clinical trial is something you should strive for, that enrollment in a clinical trial should be the best available care for the patient. And then there's the altruistic societal benefits of contributing to the medical knowledge base and advancing the science of oncology. Every oncologist who goes through an academic program believes that clinical trials are a good thing. And then there's the reality of getting out there as a newly minted, fully trained, board-certified oncologist and how challenging it can be to do clinical trials.

That challenge is not just for the community oncologists; it's also for academic oncologists, depending on what institution they're at. Part of the reason for that is, as you pointed out, clinical trials have evolved over time. Way back when I was a fellow and then on the faculty of an academic medical center that wasn't the first-rate academic medical center, we participated in National Cancer Institute (NCI) cooperative group trials. There were these big multi-institutional organizations, like the Eastern Cooperative Oncology Group, the Southwestern Oncology Group (SWOG), the National Surgical Adjuvant Breast and Bowel Project (NSABP)—these big NCI-funded groups of multiple institutions that took on really big trials that were answering really big questions, and those trials were available to member institutions. Each group had its own trials, but often there were what are called intergroup trials, so they all participated together.

When we think about things like how to find out that a particular adjuvant chemotherapy regimen in breast cancer was worth doing, those big trials all came from the cooperative group. That's the way it was done—until it wasn't. At the University of Oklahoma, where I worked, we were part of the Southwest Oncology Group. We had access to all the SWOG trials. We also had relationships with a lot of the community oncology practices that could put patients on those trials through the mother institution.

But things changed, and they changed largely because of the rising importance of pharmaceutical companies in performing oncology research. Coincidentally, as they assumed prominence in this space, the cooperative group fell in prominence. The rules of the game changed because they could decide where they were going to have the trial open and what institutions could put patients on trial. You couldn't just say, "I want my patient in that trial," because if you were practicing in a place where the trial was not available, your patient was not eligible unless they were willing to travel to another institution.

In addition, those big cooperative group trials were often large, randomized clinical trials—the pinnacle of medical evidence, the best kind of trials: arm A versus arm B, randomized, double blind, controlled, etc. But that's not what most of the pharmaceutical trials were. They were different because their goal was US Food and Drug Administration (FDA) action—it was approval of a drug. Often, we had these phase 2 trials; on a good day, they were randomized phase 2 trials. It became a little bit harder, especially in the community, to get access to the best novel therapies. We are still living in that challenging space today.

It is true that if you're in the US Oncology Network, which has a very sophisticated research arm, then you do have access to many of the clinical trials. But if you're out there on your own, forget it. You're not going to have access to the trials. You just can't do it. I think a lot of oncologists would love to put more patients on trial if they had access to the kind of trials that would benefit their patients, but they just plain don't.

Hennessy: One of the things that I remember from back in the last millennium was that it wasn't uncommon to put 30 or 40 people onto an adjuvant breast trial through one of the cooperative groups. Now we see a lot more inclusion and exclusion criteria that make it very difficult to put even 5 people from a practice on a trial. Is that part of what makes these clinical trials more challenging than it used to be? Is that a good thing, bad thing, or just a thing?

Dr Kolodziej: It's absolutely part of the problem. It's clear that inclusion and exclusion criteria are designed to get as pure a cohort of patients as possible, where comorbidity might not cloud the interpretation of the study. Again, remember, we're talking about biopharmaceutical company-sponsored research, where the goal is positive FDA action. You don't want a lot of noise.

The second thing is that a lot of the trials are biomarker driven, which means you have to be able to measure the biomarker, and your patient has to have it. A lot of these biomarkers are not very commonly seen in the community. When I was in practice and even after I left practice, people would say, "Only 2% to 3% of cancer patients go on a cancer clinical trial." That's true, but it's not because the oncologist didn't want to do it. It's just hard for the community oncologist to get patients on the trial because they're older, they're sicker, they don't have the biomarkers, or the trial is not open at your site. We need to confront the challenge of meeting the community where they are in terms of the kind of patients they take care of and then overcoming the challenge of the burden that we place on patients when they go on clinical trials, which is not insubstantial.

Hennessy: I think it's sometimes forgotten that we're asking patients to do a lot, and we're asking practices to do a lot as well. But that transactional sludge involved in some of these trials eliminates a subgroup of patients.

Let's talk a little bit about inclusion and exclusion criteria and the challenge of taking these clinical trial data and seeing the patient in front of you who maybe would not have met those criteria. How do you translate what that narrow science element is to the patient in front of you at any particular point in time?

Dr Kolodziej: Oncologists do this all the time. When the therapy is an FDA-approved therapy and there's a trial to figure out, perhaps, which one is superior, the oncologist will interpret the patient's situation and make their best clinical judgment if they can't put the patient on a trial. There's nothing you can do about it. You can't put the patient on a trial. It's a lot harder when it's a novel therapy that you can't otherwise get. If you're fortunate to have a patient with the wherewithal and the financial means, it's not unusual for a community oncologist to send their patients to a major academic medical center to be enrolled in that trial.

However, talk about burdens for the patient. Historically, the demands in terms of how often you need to get CT scans or where you need to get CT scans, what kind of labs you need, and extra visits in between treatment were so onerous for patients that it was really hard. Even if you thought there was something really good for your patient down there at Sloan Kettering, it was not so easy. We haven't even talked about whether insurance will pay for it. That's actually gotten a little bit better. We've gotten better in terms of making it possible for patients to go on.

The other thing—and I always look for silver linings from the COVID era—is we really started to talk meaningfully about using telehealth to accomplish a remote monitoring of patients so that they didn't have to drive back and forth just to do what you and I are doing: have a nice little chat to determine performance status. We're not there yet, but at least we're having meaningful discussion about how that kind of stuff can facilitate patient engagement and enrollment.

Hennessy: We talk a lot about clinical pathways. One of the things that I always appreciated about the pathways we worked on at US Oncology was that clinical trials were essentially on pathway. Do you think that pathways and that model of care, or having order sets or things that highlight the opportunity for a clinical trial, are helping improve awareness and enrollment in trials? Or is it counterbalanced by these really tough inclusion and exclusion criteria?

Dr Kolodziej: I would say that if you're in a large network like US Oncology, they help because it reminds you. In the most sophisticated pathways programs, not only do they tell you a research trial is available, but they also tell you which research trial is available. That's perfect. But I would say in the world at large, especially, for example, in payer-sponsored pathways programs, I don't think it does much at all.

A lot of that is because, as we've discussed, not every trial is open everywhere. I remember so many times in my career where there was a biomarker-driven trial, I really wanted my patient to receive that therapy, but I had to send them somewhere to get it. For old patients, sick with cancer, that's not particularly appealing to them. We need to overcome that.

Hennessy: A quick note there about payers—you’ve had the unique experience of being a practicing oncologist and on the payer side as well. Do payers embrace clinical trials?

I remember a very small study by the Fred Hutchinson Cancer Center showing that it was maybe economically better for patients to be on a clinical trial than fourth-line, I don't know what I'm going to do, but I'm going to do something.

Have payers embraced this, or are they still struggling with the value of a clinical trial in the context of oncology care?

Dr Kolodziej: They haven't embraced it enough, in my opinion. First, let's be clear that Medicare, Medicaid, and commercial health plans are required to pay for the usual costs associated with clinical trials. There should not be an insurance impediment to enrollment in a clinical trial. The problem is what the government and insurance companies define as clinical trials is very precise. It has to be a government-sponsored trial or a trial that's registered with the FDA and the NCI, meaning a trial that's could potentially lead to regulatory action. An every day, run-of-the-mill trial doesn't meet those criteria, does not qualify.

That aside, clinical trials are great for payers. The reason clinical trials are great for payers is because therapies are so expensive, so you get that off your ledger. You don't have to worry about the cost of drugs.

How do we know this is true? We know that the oncology care model promoted enrollment on a clinical trial because they figured out that it was good to take that off the government's books. Several oncology care model participants have published that when they had a patient on trial, that patient always did great. They always outperformed the target price. Why? Because you remove more than half of the total cost of care for the patient by putting them on a sponsored clinical trial. So, the answer is yes. For whatever reason, payers haven't embraced that as much as I think they ought to.

Hennessy: Thanks for tuning into this segment of Breaking Down Health Care. If you like what we're talking about or you want us to talk about some other stuff, send a note to Mike and I through the program. Look forward to seeing you again in a few weeks.