From Non-believer to Believer: A Conversation on the Journey from Skeptic to Proponent of Oncology Real-World Evidence

00:00:00: You are listening to an ADIS Journal podcast.

00:00:12: Hello and welcome to the third and final part of this podcast series on practical approaches to understanding real-world evidence, published by Oncology and Therapy.

00:00:21: My name is Adam Brufsky and I am a professor of medicine at the University of Pittsburgh and co-director of the cancer therapeutics program at the UPMC Hillman Cancer Center in Pittsburgh.

00:00:32: Today, I am joined by Dr.

00:00:34: Ray Lu for a discussion of our own personal journeys toward recognizing the value of real world evidence and its application to clinical practice.

00:00:42: Thanks so much, Adam.

00:00:43: I'm excited to contribute to this important topic.

00:00:46: As Adam mentioned, my name is Ray Lu and I'm the director of research for hematology oncology at Kaiser Permanente Northern California.

00:00:53: I'm also an assistant clinical professor at UCSF and practicing oncologist at Kaiser San Francisco Medical Center.

00:01:00: So, in the first two parts, we gave an overview of the relative strengths and limitations of randomized clinical trials and real-world studies, as well as a few of the methods and statistical approaches that are commonly used in these real-world studies.

00:01:13: Now, in this podcast, we will take a more personal approach and discuss how we evolved from being skeptics of real-world evidence to proponents of the modern, rigorous studies that are more common today.

00:01:28: I think it's important to recognize that most clinicians practicing today did not study real-world evidence as part of their formal training.

00:01:36: So it makes sense that there will be some uncertainty and doubt regarding this new data source.

00:01:41: And real-world studies, as we think of them today, are undoubtedly new.

00:01:45: Current trends indicate a growing interest in real-world studies, and even if you don't embrace their findings, it is important to be aware of the data they are generating.

00:01:52: Our goal today is to share a few events that let us to be more comfortable with real-world evidence.

00:01:58: Adam, can you tell us a bit about your first exposure to real-world studies?

00:02:02: Sure, Ray.

00:02:03: My initial interest in real-world evidence stemmed from a desire to know more about clinical outcomes and treating patterns for patients with her to positive metastatic breast cancer that were underrepresented in randomized clinical trials at the time.

00:02:16: These included patients who were elderly, from racially diverse groups, and those with central nervous system atastasis.

00:02:24: I had the opportunity to get involved with an early multi-center observational study called REGISTER that featured a large enough sample size to investigate some of these subgroups.

00:02:34: Our findings demonstrated effectiveness of hereditary directed therapies in all of these populations studied.

00:02:42: Very interesting.

00:02:43: So how does experience change your thinking on the value of these types of studies?

00:02:47: In several ways.

00:02:49: Our findings were largely consistent with the randomized clinical trials but also revealed some important cardiac safety data for elderly patients, as well as disparities in outcomes for black patients and white patients.

00:03:01: Secondly, we thought carefully about the limitations of the study design and took steps to mitigate selection bias using multivariate analysis, which aimed to adjust differences in baseline demographics and disease characteristics between the treatment groups.

00:03:15: So these studies generated new clinical data of interest to me.

00:03:19: Furthermore, I gained familiarity with the design, statistical methods, and interpretation of real-world data.

00:03:26: Ray, can you share your introductory experience with real-world studies?

00:03:30: For me, it was reading a paper about ten years ago that got me thinking about patient representation in clinical studies.

00:03:36: Gomez and Collies compared patients in Northern California who were diagnosed in NCI-designated cancer centers, with those diagnosed in other hospitals and clinics.

00:03:45: What they found was evidence that patients from NCI cancer centers differed from patients from the other centers on a variety of characteristics.

00:03:53: Since most clinical trials are conducted at major cancer centers, if we enforce the idea that we might be missing some patient groups if we limit ourselves to evidence generated by RCTs, real-world evidence can help fill in those gaps.

00:04:06: I view any reliable source of information that can help me offer the best possible care to the patients I see in clinic as a worthwhile pursuit.

00:04:14: It has taken some time, but I think you and I have come to a place where looking at real-world studies can support our treatment decision-making processes as a complement to randomized clinical trial-derived evidence.

00:04:26: What do you think are some of the barriers to acceptance of studies based on real-world evidence?

00:04:31: I think that a critical factor is simply lack of time.

00:04:34: Busy practitioners have so many competing responsibilities that delving into a new data source can seem daunting.

00:04:40: And while observational studies have been around for centuries, what we consider modern real-world studies are only a few years old.

00:04:47: Awareness and acceptance.

00:04:48: take time.

00:04:50: I agree, Ray.

00:04:51: For clinicians to commit to the challenge of integrating real-world evidence into their practice, it must be perceived as an effort worth making.

00:04:59: To that end, I think it would be useful to provide a couple of practical examples that demonstrate how real-world findings can support care delivery in the clinic.

00:05:09: Say, for instance, that you have a patient with breast cancer who has an ECOG performance status score of three.

00:05:15: As you know, RCT eligibility criteria often limit enrollment of patients with ECOC scores above two.

00:05:21: You may not have clear guidance for these particular patients.

00:05:25: To further understand the relationship between ECOC performance status and clinical outcomes, my colleagues and I conducted a retrospective study which analyzed the data from over twenty-one thousand electronic health records available from a large integrated health system.

00:05:38: The results of our study, which analyzed patients with ECOC scores zero to four with emergency department visits, hospitalizations and mortality, suggested that patients with scores greater than two could be at much greater risk for six-month mortality than patients with scores zero or one.

00:05:54: This information may be useful in the treatment decision-making conversations that you have with your patient.

00:06:00: That is a nice example of a gap in the literature that has been filled with real-world data.

00:06:05: Studies like these may be a useful resource for clinicians by providing insights into the challenges associated with the treatment of some patients that are not typically found in randomized controlled trials.

00:06:15: Continuing on the theme of underrepresented groups, I think real-world publications in the HER-II negative metastatic breast cancer space have a great deal of value for clinicians who are treating patients that are often not enrolled in randomized clinical trials.

00:06:30: One example might be a patient with homicide-propositive HER-II negative metastatic breast cancer who also has congestive heart failure.

00:06:37: Even though cardiovascular comorbidity is prevalent in patients with breast cancer, About half of breast cancer randomized clinical trials to date have excluded these patients, so data on clinical outcomes for them are limited.

00:06:50: Fortunately, large multi-center, retrospective databases can be used to investigate the effectiveness of available treatments in this population.

00:06:58: For example, my colleagues and I conducted a real-world study on the effectiveness of a standard of care treatment for patients with hormone receptor positive for two negative metastatic breast cancer and certain cardiovascular diseases.

00:07:09: The evidence we generated may help clinicians be more confident in treatment selection for such patients.

00:07:17: Great example, Adam.

00:07:18: And I think we should be clear that the findings from the studies we've discussed today are in no way meant to supersede recommendations from randomized clinical trials.

00:07:26: They are simply another source of information to support decision making in everyday clinical practice.

00:07:32: That is indeed an important point and an appropriate conclusion to this podcast and to this report series.

00:07:41: to learnings from randomized clinical trials, and can help support care that is both optimal and equitable.

00:07:47: My thanks to Ray for joining me today.

00:07:50: I also want to thank our other co-hosts, Chris and Winston, as well as the oncology and therapy journal for hosting this series.

00:07:58: We hope that the topics covered have been useful, whether you're a real-world evidence veteran or just beginning your journey.

00:08:05: We urge you to continue to watch this space for innovations.

00:08:08: that will move evidence-based medicine forward and approve outcomes for patients.

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