The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is the organization that will perform the critical task of postmarketing surveillance for biosimilars and their reference biologics. Started in 2015, the BBCIC is a nonprofit, scientific public service initiative, which partners with multiple stakeholders to accomplish its mission. In the first post of our two-part interview with Cate Lockhart, PharmD, PhD, we explore how the organization is moving beyond start-up mode and towards providing real-world evidence on the efficacy and safety of biosimilars.
BR&R: Cate, what experiences or interests brought you to the BBCIC?
CATE LOCKHART, PHARMD, PHD: I was working in a small biotech company in Seattle. I was the health economics department. As is often the case in small biotech companies, it was a department of one.
I came into this role at the BBCIC in January 2018. Prior to that I’d been working on a part-time consultant basis with my predecessor, Bernadette Eichelberger, who was the architect of this organization. I had been working with her for a year and one-half or so, and to some extent, I learned about the inner workings of the BBCIC before I jumped into this role.
But what was really attractive to me was that it bridges a lot of areas of research, reflecting a lot of my experience in pharmaceutics, health economics, and pharmacy. This was, in so many ways, the perfect job for me because it really does marry all of those elements.
WHAT MAKES THE BBCIC TICK?
BR&R: Can you give us a little bit of a background on the collective intelligence methodology that underlies BBCIC.
LOCKHART: Sure. One of the unique elements of the BBCIC is our governance structure and the framework under which we operate. It’s a consortium, which means we bring together multiple stakeholders from a variety of perspectives. We have organizations who are manufacturers, we have managed care organizations, we have payers, we have some other nonprofit and some patient-engagement organizations. All of whom come to the table together for the common goal of conducting this research into the safety and effectiveness of biosimilars and their reference biologics.
Part of the logic behind that is, first, it helps to reduce some of the bias or perceived bias inherent in some research. Our work is not beholden to any one company, because all of the resources are pooled. In fact, some of our participating organizations are direct competitors, all sitting at the same table. That helps increase the credibility of the research.
Second, it gives us the opportunity to draw on the very broad expertise of our participants to hopefully make the research questions and the results that come out of our work relevant to as broad an audience as possible.
Third, it maintains a very high level of transparency. We operate under a charter. We have a board of managing directors. We also have a planning board or steering committee. Each of our participating organizations has a seat on the planning board. We have a science committee to help drive the scientific direction. We have a communications committee, and then we have our research teams. Each of these roles is clearly delineated in our charter, which is a publicly available document. We don’t operate in a black box.
BR&R: The BBCIC’s process is based on an existing program—the FDA’s Sentinel program.
LOCKHART: That’s a good point. The BBCIC is not part of the Sentinel program, but we leverage the infrastructure that was developed for Sentinel. The FDA spent a lot of time and money developing their common data model and coordinating its data partners to display and report their data in a specific way, so we’re leveraging that. There was no need to reinvent the wheel.
One key difference, in my opinion, is although our capabilities are very similar to Sentinel’s, our mission is a bit different. For one thing, we really are focused on biosimilars and their reference biologics. In that way, it fills a gap that FDA simply doesn’t have the bandwidth to address.
The research that BBCIC does is proactive. The FDA tends to be reactive, investigating potential safety signals once they occur. That is, they may receive a signal through their safety reporting system, at which time they can activate Sentinel and investigate the safety signal further. Their primary purview is response to safety.
On the other hand, BBCIC is proactively looking at safety and effectiveness in a real-world setting. That differentiates us to some extent from the other existing organizations that are doing this sort of large-scale, multi-stakeholder, multi-data source, observational research.
CAN WE CAPTURE SIGNALS OF WANING EFFECTIVENESS?
BR&R: Monitoring biosimilars’ efficacy or effectiveness seems to be extremely important, particularly with all of the discussions that we’ve heard about lot-to-lot variations and the potential for manufacturing changes. This also applies to the reference biologics.
Can you provide an example, if you can, of how the process might actually identify efficacy changes or maybe decreasing potency?
LOCKHART: We’re going into this under the assumption that there will be no discernible difference, because that’s what we believe. These products have gone through the FDA review process, and we trust the FDA reviewers and their process.
Effectiveness is a challenging outcome to measure when you’re analyzing administrative claims alone. So to get a better picture, we may be interested in looking at different types of data sources. Part of our work is to understand those gaps in data to measure effectiveness and identify other data sources that can help fill in the picture.
Because of the scale of our data “network,” for lack of a better word, we can more easily identify rare events. We expect the safety signals or signs of effectiveness changes to be [hiding] in the data, so you need to have a very broad, diverse network of data to identify those signals. With BBCIC, we have that breadth of administrative claims data to help answer some of those questions.
BR&R: When using an administrative data set, can we somehow identify switching as a marker for waning effectiveness? Hypothetically, if patients with rheumatoid arthritis who were receiving a biosimilar for etanercept began switching more frequently over time to a biosimilar or reference biologic for adalimumab, for instance, could that potentially hint at decreasing effectiveness? I’m guessing that one would need a tremendous amount of data collected from the various participating institutions to validate that sort of trend.
LOCKHART: It’s true. Switching is an interesting topic, and we’ve devoted a fair bit of time to it. When you’re starting to do observational research with administrative claims, adding switching into the mix introduces some difficulties in analysis.
You’re right—you do need a lot of data in order to really evaluate any switching trends, and you need enough longitudinal data in order to evaluate any outcomes. When a patient switches from one biologic to a non-biologic, from one biologic to another with a different mechanism of action, or between a biosimilar and reference product, you need to have data covering sufficient time of exposure in order to identify an emerging signal. We’re looking into some of those questions today.
It’s hard to answer the question of why a patient switched therapies. It could be a clearly administrative reason: A certain payer made a drug formulary change and suddenly covers only the biosimilar and not the reference product. That’s easier to identify. In some diseases, like rheumatoid arthritis, patients are on a pretty circuitous trajectory anyway, and they do a lot of switching. It’s hard to tease out what outcomes are a result of a switch versus a result of the underlying disease. Those are some of the difficult questions that we have to wrap our heads around.
We’re also looking into some methodological questions and developing some best practices for how to examine switching, because it does introduce quite a bit of complexity. That said, the European experience has yielded a richer field of data because of their longer utilization of biosimilars. Their studies have not shown, in the literature I’ve seen, any differences in safety or efficacy based upon switching. But again, teasing out the nuances is challenging with any data source.
Part 2 and the conclusion of our interview with Dr. Lockhart will be published in an upcoming post.
