Two gastroenterologists spoke with Becker's to discuss research challenges, advice for early-career physicians and more.
The physicians participated in a study published in The New England Journal of Medicine, showing the potential oral microbiome therapy SER-109 could have to fight recurrent C. diff.
Paul Feuerstadt, MD, is a practicing gastroenterologist at the PACT-Gastroenterology Center in Hamden, Conn. Louis Korman, MD, is co-director of Chevy Chase Clinical Research at Capital Digestive Care in Silver Spring, Md.
Question: How is research conducted in your independent GI practices, and how does it differ from the academic setting?
Dr. Paul Feuerstadt: Research in our practice is similar to the academic setting in how studies are conducted and structured, since everyone involved in the study follows the same protocol. What private practices offer are a group of patients that are sometimes more reflective of real-world practice. Within private practice settings, the opportunity to participate in clinical trials usually involves somewhat less bureaucracy and a more focused approach. We only participate in a handful of selected trials that fit with the expertise of the providers in our practice.
Dr. Louis Korman: There have been some of us at Capital Digestive Care and its prior incarnations who have been doing research for the past 30 years in some capacity. We've probably done hundreds of studies on different diseases like inflammatory bowel disease, chronic constipation, gastroparesis and many others. It differs from academic research in that academic settings have a general infrastructure that supports research throughout the organization. The benefit of being in a community setting is that you have a wide range of patients that you are seeing every day, but it's also challenging because you may not have the support that the research infrastructure provides.
Q: What gave you the idea to consider SER-109 as a treatment option and what inspired you to conduct this study?
PF: SER-109 is an exciting product that is a targeted narrow-spectrum therapeutic for the microbiota. It specifically addresses one of the deficiencies in the microbiota that we see in patients who get multiple recurrences of C. difficile infection. Given this logical treatment, it was exciting to have the opportunity to participate in this clinical trial and offer this to our patients. This study, along with the phase 3 study for RBX-2660 and the phase 2 studies for CP101 and VE303, all of which are microbiota-based live biotherapeutics focused on the reduction of recurrence of C. difficile infection when used in addition to a standard of care antimicrobial, fit nicely into our patient population since our offices are a tertiary/quaternary care center for patients with multiple recurrences of C. difficile infection. Many of these patients with chronic disease are looking for alternative options to what is currently available since they have usually failed those therapies. Given this, offering these clinical trials offers hope and a new treatment for these patients.
LK: We've been doing C. difficile studies for many years, and we've all been looking for an alternative to fecal transplants. We were involved in some initial trials, including looking at using this therapy for ulcerative colitis. It was important to support this study because the alternative way of treating people with recurring C. difficile, basically with fecal transplant, was very difficult and annoying. And those studies weren't even really funded because who is going to pay for a fecal transplant study? Our group was involved in other studies with Seres Therapeutics, and the opportunity to work with Dr. Feuerstadt and the other investigators was compelling.
Q: What was the most challenging part about working on this study?
PF: Clinical trials require a lot of attention to detail and this study was no different. The SER-109 study required that the diagnostic test for C. difficile be very specific to the study protocol. This led to very accurate diagnosis within the study, but patients did not always present from referring providers having had the specific tests that were required by the study. Many patients needed to be re-tested or were ineligible to participate in the trial because the test that was used to diagnose the patient was not the one required for study entry and the patient was already on an antimicrobial, rendering the patient ineligible for re-testing since the antimicrobial will frequently result in a false-positive test. Therefore, many patients who would have been good candidates could not participate due to the study design. With that consideration in mind, the study was very clean and identified a group of patients who truly had C. difficile infection.
LK: There are challenges with every study, but given the way that we previously treated C. diff with fecal transplants, those studies were much more difficult and there wasn't any funding to conduct them. Of course, finding participants is always a challenge. But other than that, the only other tricky thing was getting the timing right in terms of documenting C. difficile, making sure the patient was treated for a certain amount of time and that they received the active SER-109 drug within a certain number of days after they finished treatment.
Q: How do you think the findings from this study will affect the way the industry treats Clostridioides difficile?
PF: The SER-109 study was the first phase 3 clinical trial to publish their results in manuscript form considering a microbiota-based live biotherapeutic treatment. This is exciting because we believe the future of therapeutics for many diseases might involve this type of manipulation of the microbiota. In the case of C. difficile, we clearly understand the deficiency that SER-109 replaces. The therapy showed excellent results in clinical practice through the significant difference in rates of recurrence seen in the population with recurrent C. difficile infection, but also with the basic science considerations with the alterations of the microbiota presented within the study. It is awesome when form fits function in science and this translates to better outcomes for patients.
LK: It's going to change it completely because C. difficile is really common in people who've gotten antibiotics and who are older. What happens when you get C. difficile is that you kill the bacteria with antibiotics, but spores remain, so after a few days in certain people the spores germinate, and the C. diff comes back. It used to be that after a second recurrence, you would send the patient for a fecal transplant, which required getting the material and having the patient go through a full colonoscopy. At one point the FDA banned the use of fecal transplants and there was such an outcry because there was not really another effective treatment available. The FDA basically made an exception. With this therapy, what you're doing is replenishing the good bacteria, which helps to keep C. diff from colonizing. With the results we're seeing from this study, it looks very promising.
Q: What advice do you have for early-career physicians who want to do research and go into private practice?
PF: Getting involved in research is not for everyone. The best people to get involved in pharmaceutical trials are those providers who love the scientific process and who see specialized patient populations with that/those diseases. Offering the opportunity of new therapeutics for disease states is powerful as a provider and rewarding seeing new mechanisms of action and new approaches to treating diseases. The young practitioner who enjoyed conducting research in fellowship, who attends national conferences and keeps track of cutting-edge therapeutics within gastroenterology and who is highly motivated, can provide this wonderful service to their patients.
LK: One of the things Capital Digestive Care has done as it has grown is to create an organization called Chevy Chase Clinical Research that includes physician and physician assistant sub-investigators, as well as certified clinical research coordinators. It's great for our patients who need new options, and it helps make valuable contributions to the field of medicine. If you're an early-career physician, it would be good to make sure that the group you're considering joining has a support infrastructure and has a clear compensation model for physicians who want to research. So, it would be smart to research what kind of capabilities the practice has and what kind of commitment they have in terms of supporting research efforts.
Q: Are there any other studies in the pipeline from your GI practices?
PF: Our center participates in quite a few trials since many of our providers have sub-specialties that lend to having patients who would be interested in these newer treatment options. We participate in a wide array of trials considering various treatments of C. difficile infection, along with trials assessing products for the treatment of Crohn's disease, ulcerative colitis, eosinophilic esophagitis, celiac disease and many others. We also participate in trials considering technologies in endoscopy, such as capsule assessment of the colon. By contouring the studies for the patients that we see in our practice, we are able to provide these innovative treatments to our patients and offer opportunities for therapy that might not be available elsewhere.
LK: We're working on several different C. diff studies, and have studies on inflammatory bowel disease with several clinical trial sponsors. It's incredibly important for community practices to participate in studies and actively recruit younger physicians to do the research. It changes the character of the practice by bringing a certain level of scholarly activity that benefits the patients we serve and the field of gastroenterology and medicine as a whole.