As Lawmakers And FDA Consider Patient Diversity, What Can Sponsors Do?

By Ed Miseta, Chief Editor, Clinical Leader

Patient diversity is currently an important topic in clinical trials. The low percentage of patient participation in trials has long been a concern, but the even lower participation rates of women and other demographic groups is a bigger concern. Legislators and the FDA are now looking into ways to make trial participation more representative of the general population, but can sponsors and CROs be doing more?

For this roundtable article, I brought together representatives from three CROs to discuss what the industry can be doing to get greater patient diversity in clinical trials. The participants in this panel are:

• Dominic Clavell, senior director, site alliances, PAREXEL
• Gretchen Goller, senior director, patient access and retention services, PRA Health Sciences
• Terri O’Donnell, associate director, clinical operations, SynteractHCR
• Scott Iwasaki, executive director, project management at SynteractHCR

Ed Miseta: Low clinical participation rates for minorities have been a problem for years. Why does this problem still exist?

Gretchen Goller: There are multifaceted reasons why this problem exists. First, minority patients have not been a focus of the pharmaceutical industry. This occurs because the inclusion of minority patients has not been mandated by the FDA as they are for NIH trials. As a result, there is no initiative to change the homogenous group of patients that pharma has traditionally focused on because that would mean a more concentrated effort to diversify the tactics used to communicate, educate, and include patients of differing ethnicities. In addition, lack-of-trust issues and access to trial opportunities contribute to the problem.

Scott Iwasaki: I agree there are a variety of economic, social, and psychological reasons. Economically, participation in clinical trials may involve frequent and long clinic visits, which takes time away from the workplace and can result in the loss of income for those with more limited financial resources.

Access to clinical research centers may not be available for some minority groups that don’t have medical insurance and/or those who seek care at community centers where clinical studies are not typically performed. Some minorities learned English as a second language, so it may be more difficult for them to comprehend what is required of them for the clinical study. In addition, some may live in rural regions that are not close to clinical sites. They may have to depend on public transportation to get to and from the clinic.

Experience may also be a factor. Some immigrant minorities may not understand or trust clinical research. Some minority groups have had less education and exposure to the concept of clinical studies. This lack of experience means that it may not occur to them to ask their doctors about this option and it may make it harder for them to understand the risks/benefits of participation in a clinical study. 

O’Donnell: Another issue is the pool of physicians in some minority communities. There are some that may not be trained in ICHGCP (International Council on Harmonization Good Clinical Practice). Others are often reluctant to refer patients for any number of reasons. There is no partnership between the family doctor and the investigator that includes the sharing of information and treatment plans. Finally, many physicians feel that pharmaceutical investigators are participating in a clinical study for reasons that may not be in the best interest of the patient.

Dominic Clavell: All of those are good observations. One possible fix might be for sponsors and CROs to implement a diverse patient population strategy on most studies. At PAREXEL, we have spent many years working to develop strong relationships with diverse physicians, sites, and patient groups. By working closely with patient groups, sponsors and CROs will better understand that minority patients are more than willing to participate in clinical trials. We just need to ensure that we are creating the easiest path for patients to find and participate in ongoing projects. Patients understand the benefits and the opportunities that clinical trials present to themselves as well as the community as a whole. With assistance from industry groups and other diverse clinical research partnerships, we can continue to include them in that journey. 

Miseta: Do pharma companies tend to select the most readily available groups of patients, which may not be the most diverse group?

Gretchen Goller: I think “readily available” is a subjective term. Oftentimes, the issue is not availability. In a CISCRP (Center for Information and Study on Clinical Research Participation) study conducted in 2015, black Americans were shown to have a “higher willingness to participate, higher confidence in finding a clinical trial, and higher likelihood of trying to participate.”

I do believe this issue is having the positive effect of changing the way in which we reach out to patients. If you want to change your mindset to be more inclusive of all ethnicities, you also have to alter and customize your approach to patients of different ethnicities. This includes diversifying how you tailor your messaging, your methods of outreach, and your inclusion of the patient’s family and community. The entire focus of your approach may need to be different for each ethnic group. As with any communication plan, educational curriculum, or marketing plan, your focus should be on the audience and the customers that comprise that audience. We have been remiss as an industry in customizing our messaging, outreach, and education to the very heterogeneous world we live in.

Also, in that same CISCRP study, the results showed black Americans place greater weight on convenience and time availability, while Hispanics are more likely to turn to family for advice regarding participation in a clinical trial. If we armed ourselves with information such as this, it might change the approach we use to reach differing populations.

Iwasaki: The selection process is actually funneled by investigators, not pharma companies. The investigators typically contact and discuss candidates for potential participation in a clinical study.

Pharma companies tend to select sites that have performed well for them in the past in terms of quick patient enrollment. Those sites are usually well trained in good clinical practices, so it potentially lowers the risk of issues in the study as well. However, those sites may not be in areas where minorities live and work, so the “readily available” group may not be as diverse.

Miseta: What are some of the problems/risks of having various ethnic groups underrepresented in clinical trials?

Iwasaki: Although rarely reported, some drugs affect various ethnic groups differently in regards to safety or efficacy measures. For this reason, Japanese regulators require pharma to conduct studies in Japan prior to drug approval to confirm that results observed in non-Japanese study participants are also seen in Japanese patients. Differences in drug response based on race have seldom been reported, but this subject has not been sufficiently studied.

Goller: At a very simple level, we need to identify when there are differences in response – whether in terms of efficacy or adverse events – across different ethnic groups. We need to ensure that physicians have all the data needed to appropriately treat their patients. If you take a look at the FDA Drug Trial Snapshots, you can see the latest approved drugs and the ethnic makeup of their sample sizes. You would be amazed to see how far we need to go in this area as an industry. If you were a specific ethnicity and you were informed that there was not one person (or very few) included in the trial process leading up to that approval, you would not be confident in how well that therapy would treat you. In fact, with limited information, you must be concerned that it could have adverse effects on your health. This absolutely must change, and the way to do that is to ensure that all ethnic groups are included in our research.   

Miseta: We all know a big problem in drug development is the time and cost of the clinical trial process. What can pharma do to better address the patient diversity problem without increasing the time and cost of trials?

Goller: That’s a good question, and volumes of information have been published around the topic. One of the major problems is time. Time can be addressed, partly by including more ethnic groups in the trials. If appropriately addressed, this can broaden the potential patient population which can, in turn, shorten enrollment times. I believe the solution is making smart, data-driven decisions in order to maximize the return on investment. 

Clavell: I agree with Gretchen. The industry really needs to look at this problem the other way around. Facilitating access to the broadest possible spectrum of patients would actually speed up recruitment and, therefore, would not have a negative impact on cost or time.  However, it is evident that physicians are the gateway to patients – after all, they are ultimately responsible for recruiting patients into any trial. Therefore, pharmaceutical companies can target regions/cities with higher minority populations and identify trial investigators that have access to these populations. Minority physicians may also have a positive impact on minority enrollment in clinical trials.

Iwasaki: I would add that economies and efficiencies can be achieved at every step of clinical research but will require close collaboration between pharma, clinical study sites, investigators, and regulators. Despite the FDA’s recommendation to simplify study design, protocols are getting more complex, which leads to more data collected, more data verified, more complex database design. Ultimately this makes for more expensive trials. A few efficiencies we might achieve are simplifying study protocols, avoiding duplication of effort, reducing monitoring and source verification costs, and of course improving the rate of subject recruitment. The protracted patient enrollment period is a major determinant in spiraling study costs. Increasing the rate of patient participation in studies to reduce the enrollment period and excluding non-performing clinical sites will reduce the overall cost.

Miseta: What can CROs do to help with addressing the issue? What about the sites and the investigators?

O’Donnell: It is important to select the right sites – those with a history of successful recruitment that includes minority groups. If we had a national database of sites with diverse populations, it would help to increase awareness for CROs. Then we should develop relationships with sites that have access to a large number of minority patients and we can educate and support them. We can make the enrollment of diversity a priority and perhaps look at population specific trials or protocols with different population arms.

In addition, it may be that protocols don’t take into account minority population (genetic) differences. As a result, the criteria included in the protocol can be too restrictive. So we need to ensure the protocol is well-written, with a simplified study design and realistic enrollment restrictions.

Clavell: To put it simply, the most successful studies are those where the strategy begins to be implemented as soon as the project is awarded. Using geospatial analysis and proprietary investigator demographic data, CROs can ensure they are recruiting those sites that have the greatest access to a diverse patient population with the relevant indication in the appropriate regions.

Goller: CROs need to devote more time and effort into not only understanding the disparity of ethnic representation but also into building relationships with minority health organizations. In addition, they need to be prepared to present solid recruitment plans and strategies that will address these concerns as a standard part of their new trial proposals. Sites and investigators need to work within their communities to ensure they are raising awareness of clinical trials and their importance across different ethnic groups. They should also work with community leaders to identify opportunities to reach ethnic groups they may not have reached in the past.

Miseta: What can industry groups and patient advocacy organizations do to help resolve the problem?

Clavell: The Consortium of Diversity in Clinical Research is one such group that is assisting in creating an easier path for patients to identify and participate in projects. Additionally, PAREXEL collaborates with patient advocacy groups for difficult and competitive indications like lupus and diabetes. Patient support groups represent trusted sources of information for patients and can provide access to hard-to-reach patients. Partnership opportunities with patient advocacy groups may include email blasts, print advertisements in group newsletters or magazines, or a study spotlight on the patient advocacy group’s website and, at times, in-person meetings.

 Goller: Patient advocacy groups can be instrumental in reaching out to patients and gaining their insights about what is needed in specific indications. There is often a disconnect in the industry around understanding the patient and their needs, experience, and perspective. Working with advocacy groups can inform the sponsor/CRO about what patients care about. If we develop deep relationships with patient advocacy groups, we can work with them to guide protocol development, messaging to patients, and how to create a clinical trial experience that is tailored to their indication. The industry as a whole needs to do a better job of forming relationships with advocacy groups early during the drug development process.

O’Donnell: Patients are searching for an unbiased list of all available treatments. For that reason, patient advocacy groups need to be well informed, have lists of alternative treatment options, and have easy access to all information and lists of available trained investigators by location.

Academic institutions should also be involved for many reasons. They have a culturally diverse patient and staff base and are recognized by many patients as experts in their respective fields. Unfortunately, they are also more expensive for pharma in terms of both cost and time.

I believe a task force that includes NIH, pharma, academia, and CROs would help. They could provide educational social network links, investigate genetic differences, and inform advocacy groups and the public with ongoing updates. There will be a cost to this effort, and perhaps the NIH could partner with pharma to provide funding. This effort should be culturally sensitive, include well rounded information, and be transparent.  If the focus is solely on pharmaceutical treatments, there will be an immediate distrust of the overall effort.

Miseta: Could better social media campaigns be a big part of the solution?

Iwasaki: The use of social media has its benefits, and has become a resource for people looking to find solutions to their issues. It can provide insights on the illness and trial information for patients seeking possible cures or studies that are working on medications for their illnesses. The issue is that minorities need to be connected to the social media platform that is right for them in terms of language and culture.

Goller: I agree they can definitely be a part of the solution. But they are one tool within the toolbox of strategies that may work. How successful they can be is dependent on the indication and patient population you are trying to reach. 

Clavell: There are a number of opportunities to leverage social media for clinical trial recruitment. Integrating social platforms into the online advertising strategy can help attract participants and raise awareness among key patient populations. Culturally sensitive visual aids can lead to a better understanding of the patient’s disease state, as well as the study and associated procedures.