Lisa Janssen Carlson, PharmD, BCOP, discusses some background and history of regulations for the conduct of clinical trials.
From a historical perspective, there are shortcomings in clinical trial data because of the limited diversity of oncology clinical trials, explained Lisa Janssen Carlson, PharmD, BCOP, investigational drug services manager at UCSF Health, during a presentation at the Hematology/Oncology Pharmacy Association Annual Conference 2024 in Tampa, Florida. Although the field has done a good job of standardizing clinical trials, there is room for growth in the inclusivity of the clinical trial space.
“There are many regulatory organizations who have developed how we should conduct clinical trials. They work with the sponsors on approving and optimizing how they each conduct their clinical trial of interest. The sponsor then hires a clinical research organization to help operationalize the trial across the sites, whether internationally or throughout our country. The [contract research organizations] work in collaboration with the providers or the principal investigators and the health system, and they bring the trial to the site,” Carlson said during the session. “Really, what we are looking at is trials for our patients in our practice sites. So that's where the patient is really at the center of the clinical trial framework.”
However, Carlson noted that patient interest in being a part of a clinical trial is also an essential piece of the puzzle. Without patient willingness, greater inclusivity in clinical trials remains challenging.
“They have to want to be in a clinical trial, and being in a clinical trial can be quite demanding,” Carlson said during the session. “Where we've run into issues in the past is with distrust [because of] some historical examples that prevent people from wanting to be in a clinical trial.”
To assess the current state of inclusivity in oncology clinical trials, Carlson explained that she looked at clinical trials posted on clinicaltrials.gov in 2022. She found that there were about 470,000 studies overall in 2022 that included an intervention (i.e., a treatment).
“As oncology pharmacists, we know that cancer always has a wide number of approvals every year in that space,” Carlson said during the session. “So, about a third of the approvals in 2022 were for a cancer indication.”
Carlson looked at the clinical trial participant diversity of 10 agents that the FDA approved or expanded the indication of in 2022 as a result of these trials. For the clinical trial diversity of a few of those approvals, adagrasib (Krazati; Mirati Therapeutics, Inc) consisted of 8% African American participants, 4.5% Asian, 2.7% Hispanic, and 83% White. Similarly, lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Advanced Accelerator Applications USA) consisted of 7% African American participants, 2% Asian, 1.7% Hispanic, and 87% White. For mirvetuximab soravtansine-gynx (Elahere; ImmunoGen, Inc), 0% were African American, 2% were Asian, 2% were Hispanic, and 96% were White.
“The percent of White or Caucasians in the trials largely is much greater than the other races identified in the trials’ snapshot,” Carlson said during the session. “Obviously, there's a lot of room for improvement to expand our external validity when we're conducting clinical trials.”
When addressing diversity, equity, and inclusion (DEI) in clinical trials, it’s important to consider the implementation of programs, guidelines, and policies that can help improve DEI and encourage representation and participation of diverse populations within clinical trials, according to Carlson. Additionally, DEI not only addresses inclusion of different racial and ethnic groups, but also inclusion of different gender identities, religions, cultures, and socioeconomic statuses, as well as inclusion of participants from urban vs rural areas and inclusion of people with disabilities.
Much of the regulations for the conduct of clinical trials present today have been developed as a result of various efforts to address problems in how clinical trials were conducted in the past. For example, the Nuremberg Code was drafted in 1947 after the Nuremberg War Crime Trials, which prosecuted physicians and scientists for war crimes against humanity conducted during World War II. The charges against physicians and scientists were based on the experiments they conducted on prisoners held in concentration camps.
“Obviously, [individuals in the concentration camps] did not provide any consent,” Carlson said during the session. “From the Nuremberg Code, it established internationally that there must be voluntary participation and willing consent to be in a clinical trial. It's not a lot of regulation, but it was the first international documentation that was an agreement for that type of practice in a study.”
The Declaration of Helsinki of 1964 was another regulatory document addressing the conduct of clinical trials, according to Carlson. This declaration established that the benefits when conducting a trial must be greater than the risks, research has to be conducted by medical scientists, and there has to be an independent review committee for any research that is conducted.
Another regulatory document that impacts clinical trials today was the Belmont Report from 1976, which attempts to summarize the basic ethical principles identified by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Carlson explained that the report looks at the ethical principles that should underlie the conduct of clinical trials involving human subjects, and it outlines the need for informed consent, an assessment of the risk of harm and the likelihood of benefit, and the fair and equitable selection of participants.
In 2023, the FDA and National Institutes of Health (NIH) released a guidance on how to incorporate DEI into clinical trials. Specifically, the guidance provides a framework for a diversity plan that is focused on racial and ethnic characteristics.
“The National Institute on Minority Health and Health Disparities at the NIH put together a strategic plan to dig a little bit deeper,” Carlson said during the session. “They've included statements about ensuring appropriate representation of minorities and other health disparity populations in NIH-funded research. Then, as far as the components from the initial phase to conclusion, [they note the importance of] promoting evidence-based community engagement, dissemination, and implementation of minority health and health disparities research best practices. Grant funding is largely based on that statement.
Additionally, the FDA also has a DEI guidance for industry. In this guidance, the FDA provides recommendations for conducting their clinical trials for new drugs or devices and states that industry sponsors must have a race and ethnicity plan.
“There’s no exclusions there,” Carlson said during the session. “Also, the plan has to describe challenges and successes—we want to learn what works, what didn't work, and how we can improve it. Basically, it's to help improve the external validity of the population and results of the clinical trial.”
REFERENCE
Carlson LJ, Murphy JA, MacDonald EA. Diving into DEI: Increasing Inclusivity and Fostering Diversity in Clinical Trials Presented at: Hematology/Oncology Pharmacy Association Annual Conference 2024; Tampa, Florida; April 3-6, 2024.
