Clinical trials have major deficiencies in design and funding

7 April 2008

There are major shortcomings in the way clinical trials are designed, carried out and funded in the US, according to a study carried out by the Chronic Disease Prevention and Control Research Center (CDPCRC) in Houston.

The report of the multi-year EDICT (Eliminating Disparities in Clinical Trials) Initiative, conducted by the CDPCRC at Baylor College of Medicine in Houston and the Intercultural Cancer Council (ICC) provides an in-depth assessment of the state of clinical trials in the US and offers a nine-step action plan for improving the relevant policies of public, private and non-profit sponsors of clinical trials that affect how human studies are conducted.

Among the deficiencies cited are the exclusion or under-representation of women, older people and minorities in the vast majority of human research studies; insufficient training in disparities for members of institutional review boards (IRBs), who by law, must review the protocols for all clinical studies; and the duplication of effort in the diseases studied by government and private industry, resulting in insufficient attention and resources for diseases where there are significant disparities in outcomes and high case fatality rates.

Because identifying potential differences among groups treated with a therapeutic regimen is an important goal of human studies, the EDICT review singles out the under-representation of women, older people, minorities, disabled persons, and rural populations in clinical trials as the problem requiring immediate attention and change at a systemic level. Looking specifically at cancer clinical trials where a lot has been published about the composition of clinical trials, the report reveals that only 25 percent of those taking part in cancer studies in 2003 were over 65 years of age. Older Americans are also routinely left out of clinical trials studying diseases associated with aging, such as Alzheimer's disease, arthritis, and incontinence.

At the same time, the report finds that the biomedical research community has been unsuccessful in resolving the under-representation of women, older adults, and racial and ethnic minorities in clinical research studies, despite many efforts to improve the performance in this area.

One study cited in the report that examined the composition of clinical trials testing new cancer drugs between 1995-1999 found less than 10 percent of the patients studied collectively represented African Americans, Asian/Pacific Islanders, Hispanics and Native Americans.

"Although disparities in clinical trials has been discussed and debated extensively, this problem has generally been under-addressed and, as a result, has received little direct, systematic, or sustained intervention," said Dr Armin D Weinberg Director of Baylor College of Medicine's Chronic Disease Prevention and Control Research Center and EDICT's Principal Investigator. "This report is intended as a nationwide call to action and is provided as a blueprint for removing the barriers to clinical trial participation, which is a critical step to improving the health status of all Americans."

More than an issue of fairness, the EDICT report associates better designed clinical research studies with the increased ability of scientists to catalogue and understand the influence of genetic and non-genetic factors on individual and group responses to treatments, now possible as a result of the successful sequencing of the human genome.

Findings from the large amount of genetic data generated to date show that more than 90% of the observed genetic variations occur within rather than between groups. This underscores the fact that ethnicity — which incorporates multiple variables including genetics, economic, social, dietary, religious, and linguistic background — has biomedical consequences when studying health outcomes.

Accordingly, the EDICT report identifies a number of behavioural, social, economic, medical, and policy-related factors that must be addressed if the biomedical research community — government researchers, academic centres and other non-profit sponsors, and industry scientists — is to meet the complex healthcare needs of an ever more diverse US population. Among the factors singled out for corrective action are:

  • strict inclusion or exclusion eligibility criteria that excludes patients who have co-morbidities, those who speak languages other than English, and subjects over a certain age;
  • lengthy and complex consent forms and other clinical trials materials that 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 being in a clinical trial;
  • insufficient training for institutional review boards (IRBs), which results in the systematic approval of research protocols that do not provide for inclusion of underrepresented populations;
  • divergent federal policies about the level of participation of racial and ethnic groups in government-sponsored clinical trials; and
  • a significant duplication of effort in the diseases studied by government and private industry sponsors, resulting in insufficient attention and resources for diseases, such as liver and kidney cancers, where there are significant disparities in outcomes and high-case fatality rates.

The report, prepared through a collaborative process involving more than 300 representatives of public, private and non-profit stakeholders who worked in teams over several years, finds that extensive barriers to clinical trial participation exist at every level, requiring immediate and longer-term policy change. Towards this end, the EDICT report calls for implementation of a series of practical and realizable policy solutions to clinical trials disparities in the following areas:

  1. Implement regulatory changes to improve the way research trials are designed and conducted. The report calls on the Food and Drug Administration (FDA) to harmonize its policies so they are consistent with the NIH Revitalization Act of 1993, thereby mandating to require appropriate inclusion of under-represented populations in all clinical trials conducted to bring new drugs and devices to the market. 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.
  2. Increase the collaboration between government and industry in the design and implementation of clinical research. Because nearly 75 percent of the funding for clinical trials comes from industry sponsors, new initiatives that attract more women, older people, minorities, and rural populations into research studies are needed to ensure the generalization of results. This will entail creating new regulatory incentives for pharmaceutical industry trials to include underrepresented populations, as well as imposing penalties for non-compliance with federal policy on appropriate inclusion.
  3. Foster community involvement in clinical trials. Today, community organizations are usually left out of the clinical trials process, resulting in increased costs and additional resources for investigators to conduct population-relevant clinical trials and secure enrollment into these trials. Towards this end, the EDICT team recommends that investigators build a detailed plan for community engagement into the research protocol that includes demonstrated methods and measures for working with community organizations and institutions.
  4. Implement new policies so that peer-reviewed medical/science journals address the issue of the representation of trial subjects in clinical research studies. Although peer-reviewed medical/science journals 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. To change this situation, the EDICT team is calling on two chief editorial organizations for biomedical publications — the International Committee of Medical Journal Editors (ICJME) and the World Association of Medical Editors (WAME) — 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.
  5. Invest in specialized training for Institutional Review Boards. Although the mission of institutional review boards (IRBs) is to safeguard the rights, safety, and well being of all human research participants, IRB members often lack the training needed to recognize disparities, and thus regularly approve research protocols that do not provide for inclusion of under-represented populations. Accordingly, an important priority is to work through the HHS Office of Human Research Protections (OHRP), which oversees the regulation of IRBs, and the Association for the Accreditation of Human Protections Programs (AAHRPP) to add specific requirements that IRBs receive training in healthcare disparities.
  6. Reallocate research funding to avoid duplication and address disparities. The report reveals a major duplication of research efforts in some disease categories and insufficient attention and resources for diseases, such as liver and kidney cancers, where there are significant disparities in outcomes and high case fatality rates. 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 coordination. Based on this assessment, 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.
  7. Enhance public education about clinical trials. Lack of awareness about clinical trials, fear or mistrust of medical research, and the complexity of consent forms and other clinical trials materials are major barriers to patient accrual. Accordingly, the report calls for the 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.
  8. Implement participant navigation as a critical element of the clinical trials process. Modeled after the "navigator" program created at Harlem Hospital, patient navigation is a new tool that helps patients keep their appointments and solves their non-medical problems. 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.
  9. Assure insurance coverage of the costs associated with clinical trials. The costs associated with participating in a clinical trial are a concern to all patients and have remained a major barrier to patient accrual. Addressing this problem will require actions by both policy makers and the business community to identify and close any existing gaps and to produce and disseminate easy-to-understand information about what the insurance program actually covers.

Eliminating Disparities in Clinical Trials (EDICT) is a four-year initiative, funded with an unrestricted educational grant from Genentech, Inc. and conducted jointly by the Chronic Disease Prevention and Control Research Center at Baylor College of Medicine and the Intercultural Cancer Council. The goal of the EDICT project is to review relevant policies of public, private and non-profit sponsors of clinical trials to identify problems and prescribe solutions.

The report will be distributed widely to health policy makers, regulators, the public health community, clinicians, the pharmaceutical industry, and patient advocates with the goal of implementing a series of practical and realizable policy solutions to clinical trials disparities at the federal, state and institutional levels in the public, private and non-profit sectors.

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