Given how disproportionately Boston Medical Center’s patients were impacted by the novel coronavirus (COVID-19), the hospital is ensuring it plays a central role in advancing COVID-19 science and treatment. Since cases began to surge in Boston, BMC has been involved in 19 studies, with approximately 70 percent focused on COVID-19 treatment and the remainder centered on other areas such as data collection and testing.
The Office of Development at BMC recently sat down with Infectious Disease Physician and Director of the Infectious Disease Clinical Trials Unit Nina Lin, MD, and Chief of Rheumatology Tuhina Neogi, MD, PhD, to learn more about their research efforts and to better understand the significance it bears for diverse patient populations at BMC and beyond.
First and foremost, why is diversity in research so crucial and how can BMC contribute to that?
Nina Lin, MD: BMC is in a unique space to recruit minority patients who have historically been underrepresented in research clinical trials. Engaging in our patient population can fill an important data gap in the field. One example is with HIV research. Current first line therapy for HIV infection, integrase inhibitors, seems to be having some unexpected side effects such as weight gain and metabolic disorders. Observational data seems to suggest this is mostly happening in African American and Hispanic women—who are completely underrepresented in all the clinical trials. So pharmaceutical companies went back to look at their clinical trial data and there was no signal for such side effects [because African American and Hispanic women weren’t represented in the research]. We can help pharmaceutical companies and clinicians really understand the gap between what’s happening in real life and what has been shown in earlier clinical trials.
How is diversity in research contributing to health equity?
Tuhina Neogi, MD, PhD: Clinical trials are an important part of health equity. Why shouldn’t our patients have the opportunity for promising therapies? And a very important part of BMC’s mission in research is showing that we can do this research ethically and in partnership with patients. We need to engage our communities so they can feel fully engaged as partners in helping to direct the research that’s needed for their communities. In many regards, research that involves our patients will be directly contributing to the understanding of health disparities and how systemic inequities contribute to adverse health outcomes.
With regard to COVID-19 research, why is it so important to include BMC’s patient population in clinical trials?
TN: COVID-19 is disproportionately affecting those who are vulnerable, and that is who BMC serves. Not only that, but they are having more severe outcomes from COVID-19. If we don’t offer trials to the people who are hardest hit and most affected by this disease, then it is a huge miss.
NL: Without their representation, clinical trials wouldn’t be applicable to the entire patient population in the US and they may not be applicable to inner city populations like we are treating at BMC because these individuals may present [symptoms] and respond [to interventions] differently to the white male population classically studied in trials. It’s really critical we get the message across to have mandatory inclusion of these populations.
What was it like bringing COVID clinical trials to BMC in the beginning? What were some challenges you had to overcome?
NL: While other patients and other hospitals were initially offered the experimental drugs, [sponsors] were passing over BMC and a special population who is at exceptionally high risk for COVID-19—people who are essential workers, people with lower socioeconomic status, people who are living in a crowded environment and people who were in homeless shelters. It took a lot of advocacy, networking and phone calls to bring these studies to BMC. I spent a lot of time in the evenings and off hours, behind the scenes calling past colleagues who are now in senior positions at pharmaceutical companies running these trials, to try to [bring] these treatment options and studies [to BMC]. I had to emphasize they could not ignore our important special populations and, ultimately, they agreed and offered us to be sites for some of these studies.
TN: It was a huge help having the support of BMC’s Chief Medical Officer Ravin Davidoff, MB, BCh, and President and CEO Kate Walsh. They were extremely hands on. They signed a letter acknowledging they were supporting our efforts [in pursuing these trials for BMC], and acknowledged we had teams in place from BMC’s Clinical Trials Office and the Institutional Review Board so that we could be up and running very quickly. It was all hands on deck.
What is the overall purpose of the studies you are leading?
TN: We are studying biologics [drugs that target the inflammation process in the immune system] and the general theme is that people who have COVID-19 pneumonia are having trouble with their breathing due to inflammation, reflected by some elevated markers of inflammation.
Some people have mild symptoms because their immune system is successful in combatting the infection. For others, as the body fights off the virus, the immune system goes into overdrive and they get hyperinflammation. The molecules that are part of that inflammation are known as cytokines. And those cytokines can end up doing the damage that causes worsening of the breathing and can result in the need for intubation. So these biologics are targeting certain aspects of that inflammatory cascade to try to mitigate the damage hyperinflammation can inflict when the immune system is working in overdrive.
Can you tell me a bit about the trials you have been working on?
TN: The study I’m running is a Novartis trial of a biologic that targets a cytokine called interleukin-1 beta (IL-1ß). The drug is called canakinumab and it targets a cytokine that is thought to be important in the hyperinflammation of COVID-19. The trial is focused on people who had COVID-19 pneumonia with hypoxia and elevated inflammatory markers.
NL: The initial study I ran is called the BACC Bay Tocilizumab Study. Similar to Tuhina’s study, it is an inhibitor of a cytokine, known as IL-6. It had been used for many years by rheumatologists for treatment of rheumatoid arthritis. The study recruited people who needed oxygen with signs of early inflammation. The thought was, if we give this medication, we would stop some of that out-of-control inflammation that is damaging the lung and other end organs that are associated with people who are acutely and severely ill with COVID infection. That study finished enrollment across several Massachusetts sites, including BMC, [Brigham and Women’s Hospital] and [Massachusetts General Hospital]. The primary study teams are now analyzing the data.
The other study I was able to bring to BMC was the Gilead-sponsored remdesivir study, an antiviral agent we are now giving to COVID-infected patients using an Emergency Access Program (EAP) [which is defined by the FDA as “a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available.”] This is different from the studies we’ve talked about so far because those are treating the inflammatory response to COVID and this one is an antiviral to kill off the virus. However, [not long after we opened for enrollment], preliminary data from Gilead across international sites [showed the drug was effective] and it led the FDA to approve [it] for the EAP. Through a lot of advocacy, we were able to get the medication for our patients as part of the EAP, although we were ultimately invited too late to contribute to the randomized clinical trial.
The third study I’m leading now is called the REMDACTA study, sponsored by Roche. It is similar to the first COVID study I ran but it’s [tocilizumab] in combination with remdesivir, with the rationale that treatment with an antiviral together with an anti-inflammatory agent may both decrease viral burden as well as the toxic cytokine storm. When the data came out for remdesivir treatment alone, it showed marginal effect on people who are close to being intubated with high level of oxygen requirement, but not late in disease with full respiratory failure. The rationale for the combination is that we could improve outcomes by both treating the virus and blunting the subsequent inflammation.
I’m also a co-investigator and helping infectious disease physicians run COVID studies. There is an exciting Regeneron study which will study an investigational medication, an antibody that targets the viral spike protein that binds to the host cell. It has a broader inclusion criteria so we hope to enroll more quickly than the other studies, many of which have very strict eligibility criteria bases as they are hypothesized to only benefit patients in particular COVID disease stages
What is one success that stands out to you so far?
TN: Our patient population is quite unique for the COVID trial I’m running. We were the fifth-highest recruiting site for the US and for a time, we were in the top third. Then because Massachusetts as a whole was very successful with its public health measures, our numbers went down. Despite that and the fact that we got into the trials late, we were still the fifth highest recruiting site in the country and 80 percent of our participants were non-English speaking. That’s just an incredible statistic and not heard of in typical clinical trials. We had our informed consent form and study information translated into a number of different languages—in total, we enrolled people who spoke four or five different languages in addition to English.
