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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.