Speaker: Greater diversity needed in clinical trials
Conference raises need for pediatric studies
More subject diversity is needed in clinical trials to reduce the risk of adverse outcomes, according to the keynote speaker at the Clinical Trials in Georgia conference.
Valerie Montgomery Rice, MD, dean and executive vice president of the Morehouse School of Medicine, emphasized that more complete study results require diverse groups of research subjects.. By 2040, Montgomery Rice says, minorities will be the majority in the U.S. and will be the largest consumers of healthcare.
During a clinical trial, "there is a responsibility to ensure the safety and efficacy for all who will receive the drug, device or biologic," Montgomery Rice says. "But it doesn't happen nearly as often as it should. It's not intentional, but it is important to close this gap."
She identifies "the gap" as barriers keeping some populations from entering clinical trials, including:
- lack of access to medical care;
- mistrust of the study and its proposed goals;
- inconvenience — the study facility may not be in an accessible location;
- lack of information about the trial, or not even knowing the trial is going on;
- fear of participation.
And, according Montgomery Rice, principal investigators must work to bridge the gap and build community relationships in order to recruit a more diverse subject population.
The National Institutes of Health developed the Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research as part of the NIH Revitalization Act of 1993, stating that NIH-funded studies must recruit women and minorities. The guidelines state that, in Phase III trials, "they must be included in numbers adequate to allow for valid analyses of differences in intervention effect," unless a compelling rationale has been established otherwise (for example, a drug being tested for conditions not seen in women).1 However, Montgomery Rice says a gap still exists in privately funded studies.
Drugs and devices do not work the same on everyone — men and women, young and old, and different races and ethnicities all experience different outcomes. For example, a 2006 study in the Journal of the American Medical Association found that daily aspirin regimens have different protective effects for men and women — cutting the stroke risk in women but reducing heart attack risk for men.2 And BiDil showed a benefit in African-American heart failure patients that was not seen in any other ethnic group.
"Despite [these] instances of specific health concerns disproportionately affecting varied populations, minority participation in clinical trials remains a challenge," Montgomery Rice says.
To increase diversity in research, the entire clinical landscape must be changed, she says. The clinical landscape includes:
- Physicians: They can "recruit PIs from a community network of physicians who care for a diverse population every day," she says.
- Physician-scientists: There should be more opportunities for physicians to become researchers.
- Research staff: "Create a team that is capable of engaging and retaining diverse populations," Montgomery Rice says.
- Research subjects:"Establish bilateral communication and commitment that aligns the needs of the community with the research agenda. This reduces barriers and creates opportunities," she says.
Recruiting principal investigators with strong community ties can also increase minority participation. Those who serve diverse populations build relationships with the subjects. "It is well known that by increasing the number of PIs who serve diverse populations, one can increase the recruitment of diverse populations," Montgomery Rice says.
"It is the responsibility of all who participate in research to recruit diverse subjects," she says.
Expanding pediatric clinical trials
Though federal mandates have ensured that more clinical research has included children, there is still much progress to be made, the chief researcher at Children's Healthcare of Atlanta (CHOA) said at the Clincal Research in Georgia conference.
"Children represent 25% of our population, yet fewer than 10% of registered clinical trials include children," says Paul Spearman, MD, who is also vice chair for research, Emory University Department of Pediatrics.
The Pediatric Research Equity Act of 2003 requires companies filing license applications for new drugs or devices to assess safety and effectiveness in children if the new drug will have a meaningful benefit. The Best Pharmaceuticals for Children Act of 2002 provides six-month patent extensions and other incentives for testing new medications in children. In February of this year, the Institutes of Medicine released its "Safe and Effective Medicines for Children" report, which analyzed the effects the two pieces of legislation had on clinical trials and that significant strides have been made, including 400 labeling changes.3
To promote more pediatric clinical trials, Spearman suggests the steps that his organizations have followed:
- striking master research agreements with contract research organizations and major pharma;
- recruiting a clinical/translational research leader;
- expanding outpatient research unit facilities; and
- establishing a Task Force for Clinical Research Processes between the CHOA and Emory University.
"Clinical trials in children is a national priority," Spearman says. "We all have a mandate to study new therapies in children."
Enhancing best practices
Speakers at the Clinical Research in Georgia conference also discussed the following:
— Creating informed consent materials that are more accessible and understandable to clinical trials subjects.
Studies have shown that only 86% of study subject read informed consent forms, says Harry Cremisi, MD, medical director at Morley Research Consortium and Opus Institutional Review Board, and chairman of medical education Southern Piedmont Region at Novant Health, all in Charlotte, NC. Some issues to understanding the forms, he says, are patients feeling intimidated, low literacy, language barriers, participants not knowing what to ask, and patients feeling as though the trial is their only hope for treatment.
"Inadequate informed consent is not uncommon, and high-complexity trials pose special concerns," Cremisi says.
More guidelines are needed to ensure that informed consent is simple for patients to understand, he says. Possible guidelines include testing to ensure that participants have functional literacy and know enough about the trial to participate, having flexible informed consent templates, and being aware of consent and assent for certain subject populations.
"We are concerned for what patients are truly understanding," he says. "It's a very, very slippery slope."
— Making research sites more attractive to clinical trial sponsors.
A good foundation for trial sites includes appropriate staff to support research, appropriate accommodations with adequate space, and proper training for staff, says Cheryl Lutz, Southeast director of site management (Atlanta)of contract research firm Quintiles.
Other qualities for a successful site include good quality standing, experience and capability to do the trial, enrollment history, similar trials site conducted (screen failure, patient dropout rate, query rate, protocol deviations), turnaround time for critical documents, number of competing trials in enrollment at that site, and type of IRB.
— Expanding a research program.
The key to starting or expanding a good research program is to prioritize human subjects protection, comply with federal regulations, and contribute to medical science with quality data, says Joan Dorin, R.Ph., of director of clinical research at WellStar Research Institute in Atlanta. A good infrastructure includes a centralized research office for oversight of all research activities; research application process for all investigators; diligent regulatory compliance oversight; streamlined processes with legal and system compliance; and building the research organization from within.
- National Institutes of Health. Inclusion of Women and Minorities in Clinical Research. http://grants.nih.gov/grants/funding/women_min/outreach_qa.htm#1055
- Berger JS, et al. Aspirin for the Primary Prevention of Cardiovascular Events in Men and Women. JAMA. 2006;295(3):306-313.
- Institute of Medicine. Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act. http://www.iom.edu/Reports/2012/Safe-and-Effective-Medicines-for-Children/Report-Brief.aspx