GAO General Accounting Office
Washington, D.C. 20548
Health, Education, and Human Services Division
April 24, 1996
The Honorable Ron Wyden
United States Senate
Dear Senator Wyden:
Rapid advances in biomedical research and technology are producing
a continuous stream of new, and often expensive, medical devices,
drugs, and therapies. Health insurers' decisions about whether
and when to provide coverage for these new medical products and
treatments play a pivotal role in determining their availability
for use in general medical practice. In recent years, conflict
over insurers' coverage decisions of new medical treatments has
led to litigation and to a variety of federal and state legislation
and regulations that mandates insurance coverage of some new medical
Some of the most visible and contentious coverage decisions have
involved the treatment of breast cancer with high-dose chemotherapy
supported by autologous bone marrow transplantation (ABMT). In
this procedure, bone marrow or stem cells from the blood are taken
from the patient and then reinfused after high doses of chemotherapy
have been administered. The high-dose chemotherapy is toxic to
the bone marrow which produces the blood cells that fight infections.
ABMT following the chemotherapy treatment helps restore the patient's
ability to produce the blood cells that fight infection.
Most experts say that more research is needed before definitive
conclusions can be reached about the treatment's effectiveness
compared with conventional chemotherapy. Proponents of insurance
coverage of the procedure say it provides breast cancer patients
with access to a promising, potentially life-saving treatment.
Critics say that the public is not well-served by the proliferation
of an unproven treatment that is costly and possibly harmful,
and that such proliferation hinders clinical research to determine
if the treatment is effective.
To illustrate the issues raised when demand grows for coverage
of a new treatment in advanced clinical trials, you asked that
we provide you with information regarding insurance coverage of
ABMT for breast cancer. Specifically, you asked that we address
(1) the factors that have influenced insurers in deciding whether
to cover the treatment, (2) the status of the research on ABMT
for breast cancer and the consensus on what is known about its
effectiveness, and (3) the consequences of the increased use and
insurance coverage of the treatment while it is still being evaluated
in clinical trials.
To develop this information, we conducted structured interviews
with officials responsible for medical coverage decisions at 12
health insurance companies, including some of the nation's largest
insurers. These companies also included a mix of indemnity
and managed care plans. We also obtained information from researchers
and oncologists at major research centers, large urban hospitals,
and community hospitals. Others we obtained information from included
the American Society of Clinical Oncology; the National Association
of Insurance Commissioners; patient and women's health advocates,
including the National Breast Cancer Coalition; state health officials;
technology assessment organizations; and the National Cancer Institute
(NCI). We also reviewed state and federal legislation and regulations
regarding insurance coverage of ABMT, as well as relevant scientific
literature, and visited a large, private transplant center. The
National Institutes of Health (NIH) and the Office of Personnel
Management (OPM) provided formal comments on a draft of this report.
We did our fieldwork and analysis from April to December 1995
in accordance with generally accepted government auditing standards.
As agreed with your office, unless you release its contents earlier,
we plan no further distribution of this report for 30 days. At
that time, we will send copies to other congressional committees
and members with an interest in this matter, the Secretary of
Health and Human Services; the Director, NIH; and the Director,
This report was prepared by William Reis, Assistant Director;
Joan Mahagan; and Jason Bromberg under the direction of Mark Nadel,
Associate Director. Please contact me on (202) 512-7119 or Mr.
Reis on (617) 565-7488 if you or your staff have any questions
on this report.
Sarah F. Jaggar
Director, Health Financing
and Public Health Issues
[The text of the report follows. Ed.]
Results in Brief
Although it is widely considered an experimental therapy, many
health insurers are covering ABMT following high-dose chemotherapy
for breast cancer. The 12 insurers we spoke with said they based
their decision to cover the treatment on the preliminary clinical
evidence, but also on factors like fear of litigation and adverse
The use of ABMT for breast cancer has increased rapidly in recent
years, from an estimated 522 patients in 1989 to an estimated
4,000 in 1994. At least seven states now require insurers to cover
ABMT for breast cancer, and other states have such legislation
under consideration. Medicaid covers the treatment in some states,
and OPM has required that all beneficiaries of the Federal Employees
Health Benefits Program be covered.
Despite its increased coverage and use, most experts say they
do not yet know whether ABMT for breast cancer is effective, and
for which patients, compared with conventional therapy. Randomized
clinical trials sponsored by NCI are expected to provide the most
definitive answers, but these will not be completed for several
years. In the meantime, there have been sharp disagreements among
researchers, physicians, NCI, insurers, and patients about the
appropriate use of the treatment before definitive research results
are available. At one end are those who argue that the preliminary
evidence supports a policy of widespread use and universal insurance
coverage of the treatment. At the other end are those who feel
that the treatment should largely be restricted to patients enrolled
in randomized clinical trials until the treatment's effectiveness
has been clinically proven.
The NCI-sponsored trials have been slow to accrue patients. Many
experts expressed concern to us that the wide availability of
ABMT has impeded the ability to complete these randomized clinical
trials, which require a control group of patients who receive
conventional therapy. There is also concern that a substantial
portion of patients receiving ABMT are doing so outside of any
research setting, which may further slow down the effort to learn
whether the treatment is effective.
If ABMT is ultimately shown to be preferable to conventional therapy
for some groups of breast cancer patients, then those patients
will have benefited from the early diffusion of this technology.
If it is not, however, then the widespread availability of the
treatment before its effectiveness has been established will mean
that many patients may have been unnecessarily subjected to an
aggressive and toxic treatment. The diffusion of the treatment
also has implications for health care costs: ABMT typically costs
anywhere from $80,000 to over $150,000, compared with approximately
$15,000 to $40,000 for conventional chemotherapy.
Breast cancer is the second leading cause of cancer deaths among
American women. The American Cancer Society estimates that there
will be 184,300 new cases of breast cancer diagnosed in US women
in 1996 and that 44,300 women will die from the disease. One in
eight women will develop breast cancer during her lifetime.
Breast cancer is generally classified into four main stages based
on the size of the tumor and the spread of the cancer at the time
of diagnosis. Mortality rates are strongly related to the stage
of the disease at the time of detection. Stage I patients have
an excellent chance of long-term survival, while stage IV (metastatic)
breast cancer is usually fatal. A wide variety of treatments exists
for breast cancer patients, including surgery, chemotherapy, radiation
therapy, and hormone therapy. The particular treatments used depend
on the stage and characteristics of the cancer and other aspects
of the patient and her health.
ABMT is a therapy that allows a patient to receive much higher
dosages of chemotherapy than is ordinarily possible. Because high-dose
chemotherapy is toxic to the bone marrow (which supports the immune
system), methods have been developed for restoring the bone marrow
by reinfusing stem cells (the bone marrow cells that mature into
blood cells) taken from the patient before chemotherapy. Stem
cells are removed from the patient's blood or bone marrow, then
concentrated, frozen, and sometimes purged in an attempt to remove
any cancerous cells. The patient then undergoes chemotherapy at
dosages 2 to 10 times the standard dosage. To restore the ability
to produce normal blood cells and fight infections, the patient's
concentrated stem cells are thawed and reinfused after chemotherapy.
When the transplant is done from the blood rather than the bone
marrow, the procedure is often referred to as peripheral blood
stem cell transplantation.
ABMT is an expensive treatment although the cost per patient has
been falling in recent years. Aside from financial costs, the
treatment is usually very unpleasant for the patient and may pose
significant risks. The high doses of chemotherapy are very toxic,
leading to treatment-related morbidity and mortality rates that,
while declining, are still higher than for conventional chemotherapy.
There may also be problems in restoring the patient's ability
to produce normal blood cells and thereby fight infections. ABMT
is being evaluated in the treatment of a number of types of cancer
other than breast cancer and is considered standard therapy for
treating certain types of leukemia and lymphoma under certain
Many clinical trials have been conducted to assess ABMT for breast
cancer, but most of these studies have been phase I and phase
II trials, which most experts agree have been of limited use in
firmly establishing the effectiveness of ABMT compared with conventional
therapy. NCI is currently sponsoring three randomized clinical
trials that seek to determine whether ABMT is better than current
standard therapy in comparable breast cancer patients. These trials
seek to ultimately involve a total of about 2,000 women at more
than 70 institutions around the country.
1. The 12 health insurers were Aetna Health Plans, Anthem Health
Plan of Florida, Blue Cross and Blue Shield of Oregon, CNA Insurance,
Harvard Pilgrim Health Care, HealthGuard of Lancaster, HealthPartners,
Kaiser Permanente, Mutual of Omaha, Prudential HealthCare Group,
United HealthCare (formerly Meta Health), and United HealthCare
2. Also, Martin S. Tallman, md, Assistant Professor of Medicine
at Northwestern University Medical School, assisted us by providing
a technical review of a draft of this report.
3. In this report we refer to autologous bone marrow transplantation
(ABMT), which is commonly used to refer to all autologous stem
cell rescue, whether the transplant is of the bone marrow or the
peripheral stem cells of the blood. "Autologous" transplants
refer to transplants through which patients receive their own
marrow or peripheral stem cells. "Allogeneic" transplants
refer to transplants through which patients receive marrow donated
by another person. This report addresses only autologous transplants
for breast cancer.
4. A clinical trial is a medical experiment in which procedures
or drugs are tested on human subjects to assess their safety or
effectiveness. Phase I trials are designed to determine the dose
that can be given with an acceptable level of toxicity. Phase
II trials seek to evaluate the response in specific tumor types.
Phase III trials seek to assess a treatment's effectiveness by
comparing patients receiving the experimental treatment with patients
receiving a conventional treatment In a randomized phase III trial,
patients are randomly assigned either to a control group receiving
standard treatment or to one or more experimental groups receiving
the treatment being tested.
5. The Autologous Blood and Marrow Transplant Registry-North America,
begun in 1991, collects treatment information on ABMT recipients
from 128 participating centers, primarily in North and South America.
The database is used to help identify trends in the use and outcomes
of ABMT for several types of cancer, including breast cancer.
The estimates of ABMT use given here extrapolate from Registry
data, which the Registry estimates represent about half of all
breast cancer ABMTs in the United States.
6. WP Peters, MC Rogers: Variation in approval by insurance companies
of coverage for autologous bone marrow transplantation for breast
cancer, N Engl J Med 330(7):473-477, 1994.
7. Some of the oncology experts we spoke with included Karen Antman,
md, Columbia University; Lois Ayash, md, the Dana Farber Cancer
Institute; Craig Henderson, md, the University of California,
San Francisco; Roy Jones, md, the University of Colorado Cancer
Center, William Peters, md, the Karmanos Cancer Institute; Edward
Stadtmauer, md, the University of Pennsylvania; and James Vredenburgh,
md, Duke University Medical Center. We also spoke with researchers
at other large and small cancer centers around the country. Technology
assessment experts we consulted included Naomi Aronson, phd, the
Blue Cross and Blue Shield Association's Technology Evaluation
Center Jeffrey Lerner, phd, ECRI; and William McGivney, phd, Aetna.
8. For example, WP Peters, M Ross, JJ Vredenburgh, and others:
High-dose chemotherapy and autologous bone marrow support as consolidation
after standard-dose adjuvant therapy for high-risk primary breast
cancer. J Clin Oncol 11(6):1132-1143, 1993.
9. ECRI, High-Dose Chemotherapy With Autologous Bone Marrow Transplantation
and/or Blood Cell Transplantation for the Treatment of Metastatic
Breast Cancer (Plymouth Meeting, Pa.: Health Technology Assessment
Service, ECRI 1995).
10. Blue Cross and Blue Shield Association Technology Evaluation
Center, High-Dose Chemotherapy With Autologous Stem Cell Support
in the Treatment of Breast Cancer, TEC Assessments, Vol. 9, No.
33 (Chicago: Blue Cross and Blue Shield Association Technology
Evaluation Center, Assessment Program, Nov. 1994).
11. Autologous Bone Marrow Transplantation as a Treatment for
Breast Cancer, statement of Dr. Bruce Cheson, Head of the Medicine
Section, Clinical Investigations Branch, Division of Cancer Treatment,
NCI, NIH, Department of Health and Human Services, before the
House of Representatives, Committee on Post Office and Civil Service,
Subcommittee on Compensation and Employee Benefits (Aug. 11, 1994).
12. Denise S. Wolf, "Who Should Pay for 'Experimental' Treatments?
Breast Cancer Patients v. Their Insurers," American University
Law Review, Vol. 44, No. 5 (June l995), pp. 2029-2107.
13. Case No. 219692 (California Superior Court, Dec. 28. 1993).
14. The states with legislation enacted were Florida, Georgia,
Massachusetts, Minnesota, New Hampshire, Rhode Island, and Virginia.
The states where similar legislation is known to have been introduced
are California, Connecticut, Louisiana, Missouri, New Jersey,
New York, and Ohio.
15. Florida, Georgia, Massachusetts, New Jersey, and Texas provided
coverage, while Minnesota, New Hampshire, Tennessee, and Virginia