Regulatory changes, improved government-industry collaboration, community involvement, special training for Institutional Review Boards (IRBs), reallocation of research funding, public education and guaranteed insurance coverage are among the steps that need to be taken to iron out continuing disparities in both the populations and diseases addressed by clinical trials in the US.

These are the conclusions of a report from Eliminating Disparities in Clinical Trials (EDICT), a four-year project run by the Chronic Disease Prevention and Control Research Center (CDPCRC) at Baylor College of Medicine in Houston and the Intercultural Cancer Council. The initiative is backed by an unrestricted educational grant from Genentech.

The EDICT report found that women, older people, racial and ethnic minorities, the disabled and rural populations are underrepresented in US trials, demanding “immediate attention and change at a systemic level”. It also highlighted substantial duplication of research efforts by government and industry sponsors in some disease categories, with the result that conditions such as liver and kidney cancers, where there are high fatality rates and significant disparities in outcomes, are attracting insufficient attention and resources.

The neglect of older Americans is particularly marked in cancer studies, where the report revealed that only 25% of enrollees in 2003 were over 65 years of age. Older Americans are also routinely left out of clinical trials for diseases associated with aging, such as Alzheimer’s, arthritis and incontinence, it noted.

Thwarted efforts

Nor has the biomedical research community been successful in resolving the underrepresentation of women and minorities in clinical research, despite a number of efforts to improve performance in these areas, the report said. One study cited looked at the composition of clinical trials for new cancer drugs between 1995 and 1999, finding that fewer than 10% of the patients involved collectively represented African Americans, Asian/Pacific Islanders, Hispanics and Native Americans.

Although disparities in clinical trials have been “discussed and debated extensively”, the problem has “generally been under-addressed and, as a result, has received little direct, systematic or sustained intervention”, commented Dr Armin Weinberg, director of the CDPCRC at Baylor College of Medicine and EDICT’s principal investigator. Removing barriers to clinical trial participation is a “critical step to improving the health status of all Americans”, he added.

Among the behavioural, social, economic, medical and policy factors that must be addressed if the biomedical research community is to meet “the complex healthcare needs of an ever more diverse US population”, the EDICT report singled out:

- Strict inclusion or exclusion eligibility criteria that leave out patients who have co-morbidities or speak languages other than English, as well as subjects over a certain age
- “Lengthy and complex” consent forms and other clinical trial materials, which are difficult to read and are printed only in English
- Vague information about how Medicare, Medicaid and private health insurers reimburse for the routine costs associated with taking part in a clinical trial

- Inadequate training for IRBs, leading to “the systematic approval of research protocols that do not provide for inclusion of underrepresented populations”

- Divergent federal policies on the level of participation by racial and ethnic groups in government-sponsored clinical trials
- Significant duplication of effort in the diseases studied in clinical trials by government and private industry sponsors

The report found that “extensive barriers to clinical trial participation exist at every level, requiring immediate and longer-term policy change”. It called the implementation of “practical and realisable” policy solutions to clinical trial disparities in the following areas:

- Regulatory changes to improve trial design and conduct. The US Food and Drug Administration needs to harmonise its policies to achieve consistency with the National Institutes of Health (NIH) Revitalization Act of 1993, thereby mandating appropriate inclusion of under-represented populations in all clinical trials. The EDICT team also advocates expanding the application of the federal government’s CLAS (Culturally and Linguistically Appropriate Services) standards in clinical trials “as a necessary step to improve the way government-sponsored research is designed and conducted”.
- Increased collaboration between government and industry in the design and implementation of clinical research. With nearly 75% of the funding for clinical trials coming from pharmaceutical industry sponsors, this will need to include new regulatory incentives for industry trials to embrace underrepresented populations, as well as penalties for non-compliance with federal policy on appropriate inclusion.
- Fostering community involvement in clinical trials. Community organisations are usually left out of the clinical trial process, pushing up the costs and resources needed for investigators to conduct population-relevant studies, the EDICT team notes. It recommends that investigators build detailed plans for community engagement into research protocols, including demonstrated methods and measures for working with community organisations and institutions.

- More recognition by peer-reviewed medical/science journals. While these publications “have addressed significant issues where increased attention by the scientific community is warranted, the discussion of diversity, inclusion and representation in clinical trials has been missing from published studies”, the EDICT team comments. It calls on the International Committee of Medical Journal Editors and the World Association of Medical Editors to adopt standards “that require investigators to include in their manuscripts an analysis of how the subject population’s demographics correspond to those of the population that bears the greatest disease burden”.
- Specialised training for Institutional Review Boards. Although the function of IRBs is to safeguard the rights, safety and well-being of research participants, their members often lack the training to recognize disparities in research protocols, the report claims. “Accordingly, an important priority is to work through the HHS Office of Human Research Protections, which oversees the regulation of IRBs, and the Association for the Accreditation of Human Protections Programs to add specific requirements that IRBs receive training in healthcare disparities.”
- Reallocation of research funding to avoid duplication and address disparities. Addressing this problem “will require an honest broker to access areas of duplicative research, which is why EDICT recommends that the Institute of Medicine conduct a new study that will recommend strategies for eliminating duplication and promoting co-ordination”, the report notes. Based on this assessment, it adds, Congress will be able to ensure that federal research funding complements private sector funding and gives priority to diseases with the greatest disparities and the highest case fatality rates.
- Improved public education about clinical trials. Lack of awareness about clinical trials, along with fear or mistrust of medical research and the complexity of consent forms and other trial materials, are significant barriers to patient accrual, the report says. It calls for widespread development and implementation of culturally appropriate recruitment and retention plans, with an additional focus on community education provided in appropriate languages for non-English and limited-English speaking populations.
- Participant navigation should be a critical element of the clinical trial process. Modelled on the ‘navigator’ programme created at Harlem Hospital in New York City, patient navigation is a tool for helping patients keep their appointments and solve non-medical problems, the report explains. “Because of its potential to retain patients in medical research studies, an analogous process termed ‘participant navigation’ should become the accepted standard of practice for institutions conducting clinical trials,” it adds.

- Making sure the costs associated with clinical trial participation are covered by insurance. These costs are “a concern to all patients and have remained a major barrier to patient accrual”, the EDICT team comments. Addressing the problem will require “actions by both policymakers and the business community to identify and close any existing gaps and to produce and disseminate easy-to-understand information about what the insurance programme actually covers”.

The report on eliminating disparities in clinical trials will be distributed widely to health policymakers, regulators, the public health community, clinicians, the pharmaceutical industry and patient advocates.