During our webinar “No One Left Behind: Addressing Clinical Trial Access and Issues Blocking Physician Participation,” there were so many questions that we decided to prepare this FAQ that consolidates thoughts from our presenters.
There was updated research presented during the webinar that showed the lack of diversity for both participant subgroups and investigators. If, for example, sponsors and CROs rely on the same sites for each trial, this may limit the opportunity for newer investigators. But at the same time, physicians and institutions providing health care to minority populations tend to be overworked and under-resourced. There is a practical question about their ability to participate in research.
For the patient population, barriers can range from language, literacy, economic factors (such as having medical insurance) and adequate transportation to travel to medical facilities. Among underprivileged populations, there may simply be no awareness of clinical trials. Without a general understanding of drug development, the very people who could benefit from participating in clinical trials may not even know to ask the question “are there are clinical trials that may help with my symptoms?” On the other side, there is also mistrust among certain populations whereby participants will be distrustful or fearful of clinical research.
COVID-19 has the potential to significantly alter clinical research. For one, clinical trials are now a global conversation, and the progress of COVID-19 trials is covered by mainstream media. People who wouldn’t have paid attention to clinical trials before are now aware of their purpose. This is a good thing in that it may result in more people asking whether there are clinical trials for their particular condition. At the same time, COVID-19 has exposed the disproportionate rate at which non-white people are more affected and are dying at a greater rate. Whether COVID-19 presents differently in ethnic populations or whether the populations most affected are living in conditions that heighten the chances for the virus to spread, much more analysis is needed.
Industry and government agencies need to work hand-in-hand to ensure that the participants of clinical trials align with the distribution of the population for the drug being tested. There needs to be a scientific justification for inclusion and diversity. The NIH, FDA and others have initiatives and programs to expand diversity, but more progress needs to be made. Greater transparency will create more incentives – the FDA is already moving in this direction with drug trial snapshot reports. However, there needs to be real incentives – or consequences – if trial populations aren’t representative. Grants and other funding sources could be linked to diversity requirements. It could be that the publication of a research study is contingent on the sponsor’s ability to demonstrate that it achieved a proportional representation of the population. There are steps that can be put in place that sponsor companies need to demonstrate in support of successful commercialization.
Yes, being a sponsor of choice means you are both ethical and caring. As a sponsor, you approach clinical research with more humility and prioritize patient safety. You have an open and helpful relationship with your sites, which includes adhering to agreed payment schedules. The outcome is more responsive, trust-based relationships. This approach is realistic and in the best interest of everyone involved in clinical research. There are sponsors already taking this approach, and we hope to see more.
Approaches, such as heat maps, can be helpful in identifying communities where there is a big sub-group of patients that could be a recruitment target for a particular clinical trial. Logically, it stands to reason that targeting a larger population increases the chances of meeting enrollment targets. But in reality, a larger population doesn’t necessarily translate into enrollment success. There are other considerations, such as the quality of the medical capabilities to serve a particular population, and also whether there are active investigators who can engage the community. Tools such as heat maps can help, but enrollment success will come down to the enthusiasm and capabilities of the investigators to drive interest and recruitment.
Real-world evidence (RWE) is playing a larger role. A lot of companies are looking at both RWE and observational data to identify patients by using information about demographics to attract the people in the sub-group. RWE should be able to play a role as long as access to medical records is adequate, which isn’t always the case. For example, in the US, electronic medical records are more geared towards billing, which makes it difficult to get useful clinical information from them.
This is certainly a dilemma because precision medicine increases the number of sites recruiting fewer participants. At the same time, the use of metrics and other factors focuses on sites with better track records and higher performance. These are counterbalancing trends. Precision medicine inevitably means you can’t reduce the number of sites and get more patients.
Patient advisory boards are one way. Another is speaking with subject-matter experts who can review and provide feedback. Talk with sites – engaging sites will give additional feedback. Sponsors can also set targets so that they are proactively addressing the need for diversity. For example, differences in metabolism by different ethnic populations could be the basis for a target.
For one, protocols can be written in more plain language. Soliciting input from patient or advisory boards to review draft protocols will provide a good perspective. Training is also a route to more understanding. Sites need to be trained properly. And that doesn’t mean training just once, it needs to be a continuous effort. It is also a good idea to make available a clear communication channel with sites, CROs and sponsors so that questions can be asked and answered right when they are needed.
Decentralized trials give us the chance to conduct trials wherever we can meet participants. This increases the chance to get more representation when you are not limited by physical boundaries or in-person visits. But it has the potential to marginalize communities that are less likely to have good access to modern technology. However, if you design decentralized trials specifically to address the challenges of diversity and technical obstacles, it can be empowering. Just applying a vanilla model of decentralized trials isn’t going to work.
This is a multi-pronged approach that includes education, more information and transparency. By engaging the local community, such as churches, community centers, etc., there is a chance to change the public perspective. There is also a need to educate and share more information with patients and their families. And HCPs also need more information about clinical research, so they can help debunk myths and refer more of their patients to relevant clinical trials. In general, greater transparency in clinical trials will go a long way to build confidence and trust in clinical research.
There is a need to actively campaign and raise attention in the media. Historically, public perception of clinical research and the pharma industry, in general, hasn’t been very good. Now, with COVID-19, there is a chance to change this perspective. So, we need to educate the public on why clinical trials need a mixed representation of participants and raise awareness with HCPs. There needs to be a comprehensive approach that mixes curricula with peer-review publications and public education.