From the Archive: How Genentech Designs Inclusive Clinical Trials to Reach More Patients
Shalini Mohan, MD, Head of Health Equity & Inclusive Research, US Medical Affairs at Genentech, spoke last year about how the organization’s approach to inclusive research is changing the way they approach trials.
How is Genentech rethinking its approach to ensure adequate representation?
We’ve now conducted several clinical trials in US Medical Affairs that demonstrate you can include specific populations of patients across disease areas. In three trials – EMPACTA, CHIMES and ELEVATUM – we specifically focused on some of these underrepresented populations. Those trials have run efficiently, and have enrolled faster and ahead of schedule. We've heard feedback from patients and their providers that they appreciated the opportunity to be able to participate.
In the EMPACTA COVID-19 pneumonia clinical trial, we collaborated with physicians at hospitals with diverse populations after real-world data suggested that minority and rural patients were being disproportionately affected by COVID-19. In the CHIMES multiple sclerosis trial, we utilized stipends, on-demand transportation to and from the site and created culturally competent education materials. And in the ELEVATUM diabetic macular edema (DME) trial, we utilized stipends and on-demand transportation to and from the site, and expanded the inclusion criteria to not exclude more severe types of DME.
How are you supporting patients to participate in trials?
We have a number of patient support programs and aim to address potential patient financial toxicity of clinical trial participation across our studies.
Identifying and implementing services offered really begins with having transparent conversations with the providers and institutions that care for these patients, because that helps us to learn what’s feasible. One example is using PayPal to reimburse, because it’s a logistical possibility that several vendors provide. But to have a PayPal account, you need a credit card and to have a credit card, you need credit, and some patients don’t have that. By digging into these potential “enablers of participation,” we can learn what is really feasible. We’re open to iterating; we are not a “set it and forget it” company.
"Identifying and implementing services offered really begins with having transparent conversations with the providers and institutions that care for these patients, because that helps us to learn what’s feasible."
Can you tell us about the process to broaden the inclusion criteria of the ELEVATUM study?
The first step was to understand what the impact would be of adjusting the inclusion criteria.
In ELEVATUM, we were trying specifically to enroll Black, Hispanic-American, and Native American patients. We need to understand what their disease burden is at a granular level and disease severity matters in that case. Expanding the criteria allowed us then to enable their participation. The previous criteria also may have been why we didn’t achieve our goal of enrolling these patients in our pivotal trials. It all comes back to the patients you’re trying to get in the study, and if expanding the I/E still ensures safe participation for the patients.
And if there is a potential safety concern about expanding the criteria to include patients with more severe disease, it may be that we have to try to find patients earlier in disease. That requires asking: “What does that look like from a patient journey perspective? What clinics are managing those patients? How do we get them to a retinal specialist to confirm diagnosis?”
Can you speak about the CATORI study, and how that’s been crafted to reach Native American and Native Alaskan populations?
That study is one I’m most proud of. Over the last 18 months or so we have built relationships with the community to understand their needs to design a meaningful study. Our approach began with an acknowledgement that we as an industry have historically done a poor job of reaching this patient population, and that they carry a disproportionate disease burden.
We were very successful in enrolling Native American patients in our COVID trial because we were able to include a site adjacent to Navajo Nation where some patients were being referred to for hospitalization. The patients who we enrolled were grateful for the opportunity to have participated in a trial and their participation also challenged the myth that they would not be interested in clinical research and lacked trust in the system. In order to be able to ensure representation of these patient populations in future studies we need to understand how and where they receive their care and the barriers they face. That’s where CATORI comes in as a non-interventional study that focuses on patient-level barriers so we can learn how to better reach these patients and develop relevant clinical trials that will ultimately be more representative.
"Our priority is to understand the barriers and co-create solutions that address barriers that hinder underserved populations from participating in clinical trials or accessing innovative therapies."
What have you learned from the study so far?
One thing we learned was the impact of how they receive their healthcare. Indian Health Services (IHS) is responsible for providing medical services to members of federally recognized Native American Tribes and Alaska Native people but it’s not insurance and due to chronic underfunding primarily focuses on general health services rather than preventive or specialty services. Patients who require screening services or advanced care at locations outside IHS often have to use the purchased/referred care (PRC) program which is limited and challenging to use for patients as there is no guarantee of care offered or costs covered.
We built relationships with several Indigenous physicians with the intent of better understanding how we could design trials that effectively reach this patient population knowing those hurdles. Their feedback, and tribal feedback on how to respect tribal sovereignty, has helped us to learn more about creating a study that is meant for this population. That’s been evidenced by the level of engagement we’ve seen and the interest in participating.
How does Genentech approach its diversity, equity and inclusion strategy?
Our Chief Diversity Office established three pillars: “Fostering Belonging,” “Advancing Inclusive Research,” and “Transforming Society.” Those pillars provide a framework for the whole organization to understand how their individual functions relate to our efforts in diversity, equity and inclusion. It can be challenging to implement diversity and equity from a business perspective, but being very clear in where we want to go is helpful in defining specific outcomes for teams.
How does your work connect to those pillars?
Within medical affairs, my team is bringing to life that second pillar of “Advancing Inclusive Research.” Our priority is to understand the barriers and co-create solutions that address barriers that hinder underserved populations from participating in clinical trials or accessing innovative therapies. We aim for the evidence that we generate in US Medical Affairs to be representative of the patients that get the disease, whether that’s through prospective clinical trials, investigator-initiated studies, or real-world evidence generation. Clinical trials and evidence generation with representative patient populations is a starting place to advance health equity because we can translate learnings to inform how we can meet our triple aim goals and enhance personalized health care.
What are the metrics that are being developed to ensure that diversity, inclusion and equity are built into the activities that you're doing?
For trials, we're looking at what the demographic and patient characteristic distribution of a trial looks like, and whether that's consistent with the real-world population. We're still working through other ways to measure other activities for designing more inclusive trials, such as reviewing the types of institutions and providers that we work with. We've established a patient advisory council to review clinical trial protocols from different lenses. Some of these patients may live in rural areas or underserved urban areas. They’ll raise questions like, “It’s fine that this assessment takes place every three weeks. But did you know that I’ll have to take a half-day off work every time?”
Those concerns help us to brainstorm how we can get those assessments done, such as finding a local entity to partner with. Even just the fact that study teams are going through that cycle is a way to measure if the system is working. The more amendments that arise in patient support services or study execution means that we’re constantly evaluating if everything is on track.
Externally, how are factors like FDA guidelines on diversity changing your work?
The FDA has issued multiple guidance documents that focus on inclusion of diverse patient populations and statements of FDA’s position and expectations moving forward. The expectation will be that sponsors of medical products develop and submit a Race and Ethnicity Diversity Plan to the agency early in development and with the aim of clinical trial populations matching the prevalence of disease in the real-world setting.
The rationale is intuitive but the challenge is in logistic execution; understanding what those barriers are to participation and in having policies and processes advance for us to be able to enable participation of those patients. Sometimes it’s not as simple as us saying, “We want to get those patients in a study.” It’s choosing the right clinical trial sites where they receive care, designing trials that are feasible for these sites to conduct, ensuring inclusion/exclusion criteria do not inadvertently exclude a portion of the population, and including patient services such as transportation and childcare reimbursement to enable participation. We need to rethink how we approach clinical research, in order to make sure we are reaching the goal of having trial populations mirror real-world populations.
