Statement on Clinical Research and Trials
Published on: September 16, 2010
Clinical research in hematology has never been more important, yet
clinical hematology investigators are facing unprecedented challenges. Constantly changing and often inconsistent
regulations, chaotic reimbursement policies, lack of insurance coverage of
routine care associated with clinical trials, increasing demands on physician
time, and scientific advances demonstrating the complex differences between
individual patients, all complicate clinical research in both benign and
opportunities and the obstacles in clinical research are not unique to
hematology, and include problems with how we organize, support and conduct
clinical research. The Institute of
Medicine (IOM) recently released a report that calls for an overhaul of the
National Cancer Institute’s (NCI) Cooperative Group Program. The report, “A National Cancer Clinical
Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group
Program,”1 identifies four overarching goals:
the speed and efficiency of the design, launch, and conduct of clinical
optimal use of scientific innovations
selection, prioritization, support, and completion of clinical trials
expanded participation of both physicians and patients in clinical
are all vital issues, and addressing these goals is important for all aspects
of hematology clinical research, not just those studies that are part of the
NCI cooperative oncology groups.
has identified a number of specific challenges facing clinical investigators in
both malignant and benign hematology, including:
of harmonization of existing policies
and regulations on clinical trial operations
insurance coverage for routine patient care
consent forms and language; and
support for benign hematology and rare diseases.
Each of these challenges is discussed in detail below, along with the Society’s
recommendations for overcoming each specific challenge.
Challenges & ASH Recommendations
The future of hematology requires that research in diverse areas of basic
science be translated into novel, decisive therapies that will effectively
prevent or cure serious blood diseases. Clinical
trials are pivotal in the research and treatment efforts of the Society's
members who combat hematologic cancers as well as a multitude of non-malignant
hematologic diseases and conditions.
However, there are a number of existing and potential barriers to conducting
clinical trials research:
Harmonization of Existing Policies and Regulations on Clinical Trial
government, through the Office of Protection from Research Risks (OPRR), within
the NIH and the Department of Health and Human Services (HHS), has promulgated
regulations and policies that govern the protections for human subjects who
participate in federally-funded research. The federal government also propagates
regulations governing human subject protections through the Food and Drug
Administration (FDA). Investigators must
comply with these complex regulations that not only lack harmonization between
different agencies but, in fact, sometimes appear to be inconsistent with each
other and with reimbursement policies established by the Centers for Medicare
and Medicaid Services (CMS). In
addition, most of these regulations were developed at a time when the vast
majority of clinical research studies were taking place at single institutions
and thus, rely heavily on local Institutional Review Boards (IRBs). Studies on the subject of research oversight
have documented the adverse effects of regulatory burden on clinical,
epidemiological, and health systems research.2
recognizes the importance of providing strict policies and regulations that
govern protections for human subjects who participate in federally-funded
clinical trials. At the same time,
concerns have been raised that the various agencies that fund or provide
oversight of clinical trials have instituted different regulations that are
often inconsistent and unnecessarily burdensome, especially for
multi-institutional trials. This has
inhibited the initiation of new trials and access to promising treatments for
patients. ASH encourages the Department of Health and Human Services (HHS) to
bring together leading researchers with experience in the operation of clinical
trials and representatives from NIH, FDA, CMS, and other agencies to determine
if changes could be made to better harmonize existing policies and regulations
on clinical trial operations.
One possible short-term goal for this harmonization process would
be the establishment of a
national IRB. The future of hematology
in particular requires that research in diverse areas of basic and clinical
science be integrated and translated into novel, decisive therapies that will
effectively prevent and treat serious diseases.
The integrated national IRB will lift the regulatory burden, ease the
administrative burden, and increase the harmonization of multi-institutional
trials, thus increasing access to promising
treatments for patients. The
centralized rules will increase collaboration between multiple investigators around
common themes to support novel clinical trials.
ASH recommends the establishment
of a national IRB that will ultimately accelerate the translation of biomedical
research discoveries into approved diagnostics and therapies.
Coverage for Routine Patient Care
many patients, standard therapy may not be beneficial. The tremendous advances in the treatment of
cancer and many other hematologic diseases have been made largely because
therapies have been tested in clinical trials and have been found to be
significant improvements over standard therapy.
Unfortunately, access to treatment through clinical trials is often
denied, as many insurance companies refuse to cover routine patient care costs
on the grounds that the care is “experimental.”
trial sponsors – either industry or government entities – must rightly assume
the responsibility for the research costs of a clinical trial, including data
collection and analysis, as well as providing the experimental agent free of
charge, patients depend upon their insurance plan to cover diagnostic or
supportive services – considered “routine care” – while enrolled in the
the state level, a number of laws have been enacted that address the issue of
clinical trials coverage in varying and inconsistent ways. This has created a patchwork of coverage that
varies depending upon the state of residence of the patient and the vast
majority of Americans still lack guaranteed access to clinical trial coverage. A provision of the 2010 health reform law
would require all health insurance plans in the United States, including those
offered in the Federal Employees Health Benefits Program, to cover the routine
patient costs associated with participation in clinical trials beginning in 2014.
under a proposed federal regulation implementing the health reform law, certain
health plans in existence as of March 23, 2010, when the health reform bill
became law, were deemed to be "grandfathered" plans, and thus were
exempted from many of the new law’s provisions. Included among the benefits
that are not applicable to grandfathered plans is coverage of routine patient
costs associated with participation in approved clinical trials. Only when a plan loses its grandfathered
status will it be required to abide by the provisions of the health reform law
that were not mandated on grandfathered plans, including coverage of clinical
research process is a lifeline for those with life-threatening illnesses, and
the failure of private and public insurers to cover the costs of routine
patient care not only denies patients of the best care available, but also
threatens the American clinical research enterprise as a whole. ASH
recommends applying the clinical trials provision of the health reform law
immediately to all insurers, including grandfathered plans, and removing
coverage of routine patient costs associated with participation in approved
clinical trials from the list of benefits that are not applicable to
Forms and Language
regulations require researchers to obtain and document
informed consent from patients participating in clinical trials. Rigorous
patient protection must be maintained.
However, many of these regulations were developed in an era when
multicenter studies were uncommon and communication and information technology
were very different from what they are today.
informed consent forms were clear, concise, short, and in marked contrast to
informed consent documents in current use.
The forms have become so long and complex that they are no longer
effective as documents that truly inform patients about the potential risks and
benefits of participating in research. This creates a burden for both the patient who needs to read and
understand the form and the physicians who needs to spend extra time explaining
the forms to the patient. This, in turn,
can deter both patients and physicians from engaging in clinical research.
shorter, simpler informed consent documents would be easier for clinical
investigators to present to patients, easier for those patients to understand,
and would do a better job of protecting the rights of the patients. They would also result in enhanced accrual to
clinical trials. Consistent with the recommendations in the recent IOM report on
NCI’s Cooperative Group Program, ASH recommends that federal regulators
clarify that patient consent forms for all clinical trials may be shortened
and/or include an abbreviated and simplified summary to enhance the provision
of informed consent.
for Non-malignant Hematology and Rare Diseases
development of diagnostic and treatment strategies requires access to numerous
patients to support clinical trials.
However, many hematologic diseases and conditions, particularly those
which are non-malignant, can be classified as rare disorders. As a result, in order to undertake clinical
trials in one of these diseases, patient data must be pooled since no single
center sees sufficient numbers of patients to constitute a valid sample size.ASH
urges the establishment of a mechanism of support for clinical research for
rare hematological diseases and disorders.
One such mechanism of support would be the creation
of national resource centers. National resource centers focusing on blood diseases would have
an important impact on research of these disorders. Collaborative networks of multiple academic
medical centers would work together to design and prioritize clinical trials
and coordinate the prospective recruitment and registration of patients with
hematologic disorders into available clinical trials at the national level.
1IOM. A National Cancer Clinical Trials
System for the 21st Century: Reinvigorating the NCI Cooperative Group Program.
Institute of Medicine. April 15, 2010.
to a Halt: The Effects of the Increasing Regulatory Burden on Research and
Quality Improvement Efforts. Clinical Infectious Diseases 2009; 49:328–35.
Founded in 1958, ASH represents over 16,000 clinicians
and scientists committed to the study and treatment of blood and blood-related
diseases. These diseases encompass
malignant hematologic disorders such as leukemia, lymphoma, and myeloma; and
non-malignant conditions including anemia and hemophilia; and congenital
disorders such as sickle cell anemia and thalassemia. In addition, hematologists have been pioneers
in the fields of bone marrow transplantation, gene therapy, and many drugs for
the prevention and treatment of heart attacks and strokes.
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