A group of cancer researchers is trying to conducting randomized trials aimed at maximizing the value of oncology treatment regimens.
The group, called the Value in Cancer Care Consortium, is headed by Allen Lichter, former CEO of the American Society of Clinical Oncology.
The new consortium plans to ask research questions that fall into three categories:
Can a lower dose or a different administration schedule produce similar results as the dose on the FDA label?
Can a less expensive drug be used insetead of a more expensive drug?
Should patients be on drugs continuously as long as they’re experiencing a response?
“We have the resources to organize our board and the scientific committee to begin to engage sites and to sign sites up as study participants, to begin to write the first protocols and to get them IRB-approved, and to build a small staff,” Lichter said. “And so that we are fully prepared now to move forward with the organization. What we do not have in hand right now are the funds to actually do the studies. And we need to begin to share with the world that we are duly constituted and ready to do this type of work.”
Lichter, chair of the consortium, spoke with Paul Goldberg, editor and publisher of The Cancer Letter.
Paul Goldberg: I understand you’re focusing your attention on drug pricing. What will you be doing?
Allen Lichter: Well, that’s actually not accurate.
I like to be corrected.
AL: I mean, drug pricing is an important issue. But the focus of this effort is not on drug pricing. The focus is on asking whether we can add value to cancer care by optimizing the dose and scheduling of current drugs, or at times substituting a less expensive drug for a more expensive drug, but getting the same outcome for our patients. So we’re really focusing on value. The price issue is a real issue, but that is something that others are tackling.
Who is involved?
AL: The group was started with collaborations between Mark Ratain from the University of Chicago, Len Saltz from Memorial Sloan Kettering, and Larry Baker from the University of Michigan. I attended a meeting recently at ASCO, where this group presented the concept of an organization like this, and presented some of the early results from a pilot study about dosing the prostate cancer drug abiraterone. And I was attracted to their work. They asked me if I would chair the board of directors of this organization, knowing that I had some time on my hands in my retirement, and I said that I would.
I guess I’m backing into it, but what’s the name of the organization?
AL: It’s the Value in Cancer Care Consortium, and we call it Vi3C.
Oh, cool. What kind of questions will you be asking?
AL: I would say they fall into three main areas at the moment. One, again, is looking at the dose and scheduling of current cancer drugs. It is unlikely for most drugs that the first time through the FDA approval process, the dose and scheduling has been perfectly optimized.
Abiraterone is an interesting example of that, where the drug is better absorbed with food and yet the FDA trials and the label say the drug should be taken on an empty stomach.
So, it becomes fairly natural to begin to explore whether for certain cancer drugs, under the appropriate circumstances, where we could test whether a different way of administering, a different dose or a different schedule would optimize value, that is maintain the outcome while reducing the amount of drug the patient is required to take.
The second group of studies is the study of substitution: whether a less expensive drug can do the same job as a more expensive drug.
I think an interesting example of studies like that come from the field of ophthalmology, where in both macular degeneration and edema secondary to retinal vein occlusion, a dose of bevacizumab at $50 produces the same results as a dose of more expensive drugs in the range of $2,000.
And the ophthalmologists have carefully done these studies and shown convincingly that this less expensive agent can be substituted. And we think there are situations in oncology that deserve attention along those lines.
And finally, there are situations where we must ask questions about the duration of therapy.
For many drugs, we understand about starting them. We don’t know that much about when to stop them.
Should patients be on drugs continuously as long as they’re experiencing a response? In some of the newer targeted therapies or immunotherapies, is the result achieved after a few months of therapy, and the therapy can be stopped or at least interrupted? So those are examples of the types of studies we will be paying attention to.
How will you select agents that you would test?
AL: I think the approach that we have taken is to form a scientific advisory committee. We were delighted when Ian Tannock [of Princess Margaret Cancer Centre] and Gabe Hortobagyi [of MD Anderson Cancer Center] said that they would co-chair this group.
They are meeting for the first time at ASCO to begin organizing, and we’ve asked them to take a look at the landscape to suggest a series of studies that they feel are both scientifically important and relate to this question of value.
We on the board will work with the scientific advisory committee to rank order these studies, and we’ll start from the top and start to work our way through them. So, it’s not clear yet, since the committee hasn’t met, what they’re going to recommend to us, but we’re very anxious to hear their thoughts.
Are we talking about pilot studies, or are we talking about definitive studies? Are these going to be superiority trials or non-inferiority trials? Or are you trying to ask questions to intrigue prescribing physicians and maybe not even answer them definitively?
AL: Yes, well, that is one of the key questions. Obviously, there’s a whole field in literature and science to non-inferiority studies, depending on how close you want your definition of non-inferiority to be.
The size of the trials can get impressively large. We probably do not have the resources to do studies of thousands of patients, and are going to be asking some important questions about how equivalent these two arms need to be, how tight must the error bar be around them if clinicians were going to say the two therapies are clinically identical enough to be substituted.
And the answers to those questions are not known right now. We have to begin to explore that.
And we think, Paul, that they’re context-related as well. That is, the clinically relevant answer for one drug in one set of circumstances may be quite different than the clinically relevant answer for another set of drugs and another circumstance.
So, this is new space that we’re going to be exploring as we design the statistical sections of these studies.
Is price going to be an end point?
AL: No. Although, obviously, if the duration of therapy is reduced, the total cost of the therapy begins to come down.
If a less expensive drug is substituted, the price begins to come down, or if a drug that is being given at a dose of 100 can be used at a dose of 50, the cost comes down. But that is really an offshoot, if you will, of what we’re trying to do, in terms of showing that we can add to the value of cancer therapy, not by passing a new law or needing importation of drugs from overseas, or changing the entire way the drug distribution system works in this country.
We can have an immediate effect on the value of cancer care by just using drugs more wisely.
Well, there’s this paper that you referred to in JAMA, the Avastin paper. I see that this was funded by [National Eye Institute]. Has NCI expressed interest in such studies?
AL: We have not spoken to the NCI. We will be talking to them.
And it would be wonderful if the NCI wanted to participate in this. I don’t know whether they will or not. But I think the National Eye Institute has set a wonderful example of saying that some of these questions about drug equivalence and sparing patients and the healthcare system unnecessary costs are scientifically meaningful questions.
How will you get the results disseminated?
AL: You know, the standard way of doing this, of course, is to present your findings both at meetings and in journals, the ASCO meeting being one of the prime examples of where we hope the results of our studies can be put forward.
We won’t be able to go into physician offices and detail them about these studies. But we hope that much like the ophthalmologists have experienced, that as these results become more widely known, tactics patterns will change. They certainly have in ophthalmology.
And we hope that if our studies show that there’s a higher value way of using the therapy, that clinicians will use it.
What about funding? Do you have any funding and who would be giving you money? Is it the foundations or is it the pharma companies? Would pharma companies give you money to check and test the value of their drugs and of their competitors’ drugs?
AL: Well we were hoping The Cancer Letter would underwrite most of this …
We will. We will be happy to direct at least $1,000 worth… No, actually, strike that. We can’t, because then we won’t be able to cover you.
AL: All right, let’s start over.
No, let’s keep it.
AL: So, we were pleased to have the opportunity to apply for a grant from the Arnold Foundation in Texas to provide funds to set up the infrastructure for the Vi3C organization and we were pleased to have that grant funded.
We have been, along with everybody else, concerned about the ever-increasing cost of care and the financial toxicity that we find our patients facing. This is something that can produce results in a fairly rapid fashion.
So, we have the resources to organize our board and the scientific committee to begin to engage sites and to sign sites up as study participants, to begin to write the first protocols and to get them IRB-approved, and to build a small staff.
And so that we are fully prepared now to move forward with the organization. What we do not have in hand right now are the funds to actually do the studies. And we need to begin to share with the world that we are duly constituted and ready to do this type of work.
If you look at this abiraterone study of 72 patients that was presented at the ASCO GU meeting earlier this year, equivalent results were seen with a 75 percent reduction in dose just by taking the drug with food versus fasting.
This is a drug that costs several thousand dollars a month and is well over a billion dollars in sales worldwide and potentially increasing over time. So, the potential increase in value is enormous for the investment of a relatively small amount of money in doing the study. So we hope that we can attract interested organizations to help us with the resources to get the studies actually done.
So, you’re probably thinking insurers, right? And foundations.
AL: Well, you know, we would hope that, and have been in contact with the foundations of some of the major health insurance companies, and they’ve expressed some interest. But most major corporations in this country self-fund their health care costs.
We hope that individual organizations or business associations who are interested in health might be interested in this. And, of course, as evidenced by the Arnold Foundation, we hope that other foundations might be interested in this. If a prostate cancer foundation wanted us to do a more definitive study of a prostate cancer drug, or if a lung cancer organization was going to help us with a lung cancer study, we think these types of things would be wonderful.
What would the costs be of studies?
AL: You know, we haven’t finalized that yet, but one could estimate that per case, the fully loaded cost of a study could be in the $10,000-$15,000 per patient range, to help support the infrastructure of the group, all the data collection and statistical analysis, the regulatory reporting and to reimburse the sites for their cost.
So, the ophthalmology study that was recently published was 350 patients, and we’ve been, at least in a very back of the envelope way, thinking about studies that going to be somewhere in the 300-400 patient range.
So, you’re talking about, on the low end, a $3 million cost to do the study and maybe at the high end $6 million.
That’s not a lot of money, as major clinical research goes, and the potential benefit from that modest investment could be 100 times what was put into it.
Yeah, system-wide but per funder it could be… actually it could still be worth it, if you’re a GM.
AL: Yeah, I think that just on the front end, if you had an expensive drug and were doing a trial where half the patients received a much smaller dose, interestingly enough, they’re savings during the cost of the trial, because the patients are not consuming and having to pay for as much drug.
So, we don’t know that that savings will fund the trial, but this is a unique opportunity where actually the study itself contains savings built in.
Oh my, so that would actually be the reason for somebody to fund it.
AL: I think there are a lot of reasons for them to fund it.
But this is not a study where the control arm is X and the experimental arm is something that costs five times X. This is actually in many respects just the opposite.
I also point out that there’s a tremendous importance for doing these studies for the practicing community itself. As we get into more and more the value based purchasing and payment systems, when we get into risk sharing and such, it is imperative upon practices to learn how to reduce costs in a fairly continuous fashion.
And studies like this that can show how you can treat patients at lower costs with the same or potentially even better results become not only beneficial for the patients, but beneficial for practices as they negotiate these new payment models.
This is something that just is starting to be recognized right now. This is connected to the issue of real world evidence? Do you even need to run prospective trials? Could you perhaps glean this information from datasets that are already in existence?
AL: We don’t think so. Most physicians will use drugs very much along the lines of the labeled dose of the drug. Dose reductions and modifications are done depending on clinical symptoms.
But it is unlikely that, spontaneously, a large group of physicians would begin to start therapy for patients at a very different dose than the labeled dose. Somebody’s gonna have to show the evidence. As a physician, I’d want to know that if I said to my patient, “We’re gonna treat you with half the dose, but I have data to show that it’s just as effective,” I would need that.
If I were a patient, I’d want to know that I can safely take this lower dose and not sacrifice any of the benefits. So, I don’t think this will come simply spontaneously from analyzing real world data.
So, nobody is collecting that; therefore you need to go forward prospectively.
AL: Well, CancerLinQ is an example of a database that is, in fact, collecting drug utilization, drug dose and outcome data and could make observations along these lines. But as I say, I don’t think a natural experiment is occurring right now. We have to prime the pump with these types of studies.
Well, sounds like people should be flagging you down at ASCO and asking you how they can help.
AL: We would love to talk to people who are interested in seeing this work move forward. We think it’s very important.
As I say, Paul, we have been, along with everybody else, concerned about the ever-increasing cost of care and the financial toxicity that we find our patients facing. And doing something about it has been difficult. There have been lots of policy discussions, but relatively little concrete action.
And this is something that can produce results in a fairly rapid fashion, and in a meaningful fashion, without having to do anything but the clinical science that oncologists have been engaged in for decades. And we’re excited about the possibility.
Well, thank you very much.
