Bone Marrow Transplants
Despite Recruitment Successes, National Program May Be Underutilized
Gao ID: GAO-03-182 October 18, 2002
More than 30,000 people are diagnosed annually with leukemia or other blood, metabolic, or immune system disorders, many of whom may die without stem cell transplants, using stem cells from bone marrow or another source. When a patient needs a transplant of donated stem cells and no genetically compatible related donor is available, the National Bone Marrow Donor Registry may help the patient search for compatible stem cells from unrelated donors. The National Bone Marrow Registry Reauthorization Act of 1998 required, among other things, that the Registry carry out a donor recruitment program giving priority to minority and underrepresented donor populations, ensure efficiency of operations, and verify compliance with standards by organizations that participate in the Registry. From 1998, when the National Bone Marrow Registry Reauthorization Act was enacted, through 2001, the number of stem cell donors on the Registry increased for all racial and ethnic groups. Although the exact number of patients in need of transplants is not known, estimates suggest that about one-third of them use the Registry to search for donors. The organizations that are involved in transplantation and participate in the National Marrow Donor Program (NMDP) network generally adhere to NMDP's standards and procedures. In 2001, NMDP required 24 centers to take corrective actions because they did not meet its standards.
GAO-03-182, Bone Marrow Transplants: Despite Recruitment Successes, National Program May Be Underutilized
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Report to Congressional Committees:
United States General Accounting Office:
GAO:
October 2002:
Bone Marrow Transplants:
Despite Recruitment Successes, National Program May Be Underutilized:
Bone Marrow Transplants:
GAO-03-182:
Contents:
Letter:
Results in Brief:
Background:
NMDP Has Succeeded in Increasing Recruitment of Donors, Including
Minorities, but May Not Be Able to Equalize Access to Matches:
National Registry May Be Underutilized:
Organizations in the NMDP Network Generally Comply with Its Standards
and Procedures:
Concluding Observations:
Agency Comments:
Appendix I: Methods of Assessing Registry Utilization:
Method Based on Number of HLA-Identical Sibling Transplants:
Method Based on Number of Preliminary Searches:
Method Based on Incidence of Disease:
Appendix II: How NMDP Achieves Network Compliance
with Selected Standards and Procedures:
Informed Consent of Donors and Patients:
Criteria for Donor Selection:
Methods to Protect Confidentiality:
Marrow Collection and Transport:
Laboratory Standards:
Donor File Maintenance and Updates:
Appendix III: Comments from the Health Resources and
Services Administration:
Appendix IV: GAO Contact and Staff Acknowledgments:
Tables:
Table 1: Percentage Increase in Registry Donors, by Racial and Ethnic
Group, 1998 to 2000, and Current Proportion of Groups on the Registry
and in the Population:
Table 2: U.S. Patients‘ Utilization of the Registry, by Race and
Ethnicity, 1997 to 2000:
Table 3: Reasons for Preliminary Search Cancellation, January 2000
through September 2001:
Table 4: Reasons for Formal Search Cancellation, 1997 to 2000:
Table 5: Alternate Approach to the Analysis of U.S. Patients‘
Utilization of the Registry, by Race and Ethnicity, 1997 to 2000:
Table 6: Average Annual Unrelated Donor NMDP-Facilitated Transplants
and Estimated Number of Potential Recipients for U.S. Patients with
Selected Diseases Who Might Benefit from Unrelated Stem Cell
Transplants, by Race/Ethnicity, 1997 through 2000:
Figure:
Figure 1: Theoretical Probability of Patient‘s Finding at Least One
Matched Donor, by Racial and Ethnic Group, 1988 to 2001:
Abbreviations:
ABMTR: Autologous Blood and Marrow Transplant Registry:
CPI: Continuous Process Improvement:
HHS: Department of Health and Human Services:
HLA: human leukocyte antigens:
HRSA: Health Resources and Services Administration:
IBMTR: International Bone Marrow Transplant Registry:
NMDP: National Marrow Donor Program:
OIG: Office of Inspector General:
OPA: Office of Patient Advocacy:
PBSC: peripheral blood stem cells:
United States General Accounting Office:
Washington, DC 20548:
October 18, 2002:
Congressional Committees:
More than 30,000 people are diagnosed annually with leukemia or other
blood, metabolic, or immune system disorders, many of whom may die
without stem cell transplants, using stem cells from bone marrow or
another source.[Footnote 1] When a patient needs a transplant of
donated stem cells and no genetically compatible related (family) donor
is available, the National Bone Marrow Donor Registry (Registry) may
help the patient search for compatible stem cells from unrelated
donors. Founded in 1986, the Registry is the largest and most diverse
list of potential donors in the world. This list currently includes
more than 4 million donors.[Footnote 2] The Registry is operated by the
nonprofit National Marrow Donor Program (NMDP) under contract to the
Department of Health and Human Services‘ (HHS) Health Resources and
Services Administration (HRSA), with additional support from the U.S.
Navy.[Footnote 3] NMDP coordinates stem cell transplants through its
network of more than 400 participating organizations, domestic and
foreign, involved in transplantation, including donor centers, which
recruit and manage donors; laboratories; blood sample repositories;
bone marrow collection centers; and transplant centers. NMDP has
facilitated more than 14,000 transplants since 1987.
Concerns about the Registry have been raised by the HHS Office of the
Inspector General (OIG) and in our own work. These include the extent
to which the Registry provides equality of opportunity for patients of
all racial and ethnic groups to find compatible (matched) unrelated
donors, the extent to which it is utilized by those in need of stem
cell transplantation, and the effectiveness of the management of the
donor centers. We reported in 1992 that the proportions of African
American and Hispanic donors on the Registry were less than their
proportions in the U.S. population.[Footnote 4] This imbalance results
in a decreased likelihood of an individual from a minority group
finding a match and eventually receiving a transplant because matches
are more likely to be found from among donors of one‘s own group. In an
effort to address these concerns, a 1996 OIG report recommended that
HRSA and NMDP reexamine the method used to finance the donor centers
that recruit volunteers to join the Registry.[Footnote 5] It
recommended a performance-based method to pay donor centers for
specific activities including monetary incentives tied to performance
indicators and emphasizing recruitment and retention of donors,
especially those from racial and ethnic minority groups.
The National Bone Marrow Registry Reauthorization Act of 1998[Footnote
6] required, among other things, that the Registry carry out a donor
recruitment program giving priority to minority and underrepresented
donor populations, ensure efficiency of operations, and verify
compliance with standards by organizations that participate in the
Registry. In addition, the act required that we conduct a study of the
Registry, including an examination of the extent to which it has
increased representation of racial and ethnic minority groups so that a
member of such a group has a probability of finding a match comparable
to that of a person who is not a member of such a group. In conducting
this study, we addressed the following questions: (1) To what extent
have the program‘s recruitment efforts increased the enrollment of
donors, including those from racial and ethnic minority groups, since
the 1998 act took effect, and has the chance of finding a suitable
match increased? (2) To what extent is the Registry utilized to search
for and obtain transplants? (3) Are the donor centers and other
organizations in the NMDP network complying with its standards and
procedures?
To answer these questions, we analyzed NMDP data on racial and ethnic
representation on the Registry from 1998 through 2001 and, to provide a
broader context for examining these changes, also analyzed data on
racial and ethnic representation in relation to the patients who
searched the Registry from 1988 through 2001. In addition, we analyzed
data provided by the International Bone Marrow Transplant Registry
(IBMTR)[Footnote 7] on transplants from related donors from 1997
through 2000, which enabled us to estimate the demand for unrelated
donor transplants in the United States and relate this estimate to
Registry utilization by patients searching for donors during this
period; analyzed NMDP data on matches, canceled searches, and
transplants obtained for patients needing donors during this period;
reviewed NMDP‘s standards for participating in the Registry; and
reviewed evidence of compliance with the standards and procedures by
the organizations that participate. We also interviewed officials of
NMDP; HRSA; the Department of the Navy; the American Red Cross; and
selected donor, stem cell collection, and transplant centers. We did
not independently verify the accuracy of the data provided by NMDP. We
conducted our work from June 2001 through June 2002 in accordance with
generally accepted government auditing standards.
Results in Brief:
From 1998, when the National Bone Marrow Registry Reauthorization Act
was enacted, through 2001, the number of stem cell donors on the
Registry increased for all racial and ethnic groups. NMDP recruitment
efforts focused on minority groups appear to have been effective in
increasing the number of donors from these populations. Since 1998 the
number of donors on the Registry has increased by 36 percent, and
increases for minority groups ranged from 30 percent to 53 percent. The
total of more than 1 million minority donors listed in 2001 contrasts
with the approximately 80,000 we reported in 1992. The proportional
distribution of racial and ethnic groups on the Registry was much
closer to their proportional distribution in the U.S. population at the
end of 2001 than it was in our 1992 review. However, when viewed as a
percentage of each group‘s proportion of the U.S. population, African
Americans and Hispanics are underrepresented by 17 and 15 percent,
respectively. The underrepresentation of minorities is somewhat
mitigated by the Registry‘s efforts to have complete genetic
information needed for typing on a higher proportion of minority
donors, which facilitates more rapid matching. For all racial and
ethnic groups, the theoretical probability of finding a match has grown
as the Registry size has increased, but equal access to a match may not
be attainable. Differences among racial and ethnic groups in the rarity
and variability of the genes responsible for compatibility in
transplants may mean that the Registry cannot achieve equal probability
for all groups. Further, devoting many resources in pursuit of a small
number of rare genetic types may divert resources from other efforts,
such as recruiting Caucasians and other groups with more common genetic
types, which might more readily increase the number of matches.
Although the exact number of patients in need of transplants is not
known, estimates suggest that about one-third of them utilize the
Registry to search for donors. The number of transplants facilitated by
NMDP represents about one-tenth of those we estimate to be in need of
unrelated donor transplants. These figures suggest that the Registry
may be underutilized for both searching and facilitating transplants.
From 1997 through 2000, an estimated 44,740 U.S. patients were in need
of unrelated donor transplants. During this period, physicians for
approximately 15,000 U.S. patients conducted preliminary searches for
donors on the Registry, and about 4,000 of these patients obtained
unrelated donor transplants facilitated by NMDP. About 25 percent of
formal searches were not completed because stem cells were obtained
from donors or organizations without the involvement of NMDP.
The organizations that are involved in transplantation and participate
in the NMDP network generally adhere to NMDP‘s standards and
procedures. NMDP monitors the compliance and performance of these
organizations with its standards by using several systems of feedback
and incentives, including site visits. Centers that deviate from NMDP‘s
standards may be placed on probation or suspended or their
participation in the network may be terminated. In 2001, NMDP required
24 centers to take corrective actions because they did not meet its
standards. Further, NMDP reimburses donor centers for services based on
their performance by offering financial incentives to centers that
consistently meet donor recruitment goals and financially penalizing
centers that do not.
In its written comments on a draft of this report, HRSA stated that the
report provides an accurate and helpful overview of the status of the
National Bone Marrow Donor Registry. HRSA agreed that other efforts are
needed in addition to minority recruitment efforts in order to improve
minority access to unrelated donor transplants, but pointed out that
the Registry has complete genetic information needed for matching on
higher proportions of minority donors than it has for Caucasian donors.
We have clarified this information in the report. HRSA agreed that many
patients who could benefit from transplants do not utilize the Registry
but suggested a slightly modified method of determining the number of
patients in need of transplants. We accepted this suggestion, but note
that both approaches produce virtually identical estimates of overall
underutilization. (See app. I.) HRSA also noted that many factors
affect the time required to complete a search of the Registry and that
NMDP has completed medically urgent searches in less than a month. We
have included this clarification in the report. In addition, HRSA
provided technical comments, which we have incorporated as appropriate.
Background:
Most of the diseases treated by stem cell transplantation involve
abnormalities of the blood, metabolic, or immune systems. These
diseases include several forms of cancer as well as certain
nonmalignant diseases.[Footnote 8] They strike all races, although one
racial group or another may have a higher incidence rate for a
particular disease.[Footnote 9] Not all patients with diseases that may
be cured by stem cell transplants necessarily pursue them. Depending on
a number of donor and patient characteristics, from about 10 to 50
percent of patients are alive 5 years after transplants. The patients
who do not survive may succumb either to their diseases or to the
consequences of transplantation. Because of these low survival rates,
some patients and physicians may be reluctant to select this stressful
treatment under most or all circumstances. For most of the diseases
involved, other therapies are available that may be less invasive,
carry lower risk, or be the medically preferred initial treatment.
Nevertheless, some of these diseases are best treated by stem cell
transplantation, either initially or after other treatments have
failed.
Prior to stem cell transplantation, the patient‘s bone marrow and,
consequently, immune system are destroyed with radiation or
chemotherapy. The patient‘s bloodstream is then infused with healthy
stem cells from a donor. Healthy stem cells can be therapeutic because
they can develop into all the components of blood, including those
needed to replace the patient‘s immune system. In an ’autologous“
transplant, these cells come from the patient‘s own marrow. In a
’syngeneic“ transplant, the cells come from an identical twin. For many
diseases, the most common type of transplant is an ’allogeneic“
transplant, which consists of stem cells from a genetically compatible
donor.
Bone Marrow and Other Sources of Stem Cells for Transplantation:
Although bone marrow was initially the only source of stem cells for
transplantation, in recent years two other sources of stem cells,
umbilical cord blood and peripheral blood stem cells (PBSC), have also
been used. In 2001, 1,215 of the transplants facilitated by NMDP (70
percent) involved marrow, 42 (2 percent) involved cord blood, and 491
(28 percent) involved PBSC. Umbilical cord blood is collected from the
placenta and umbilical cord of a newborn and then preserved in a cord
blood bank until needed by a matched patient. The number of stem cells
typically obtained from cord blood is relatively small but is often
adequate for pediatric patients. For transplantation from cord blood,
the blood is volunteered when the blood is banked, not when it is used.
The Registry began an umbilical cord blood stem cell program in 1998.
Stem cells from peripheral blood may be obtained in numbers sufficient
for transplantation when the donor is treated with a drug that causes
the cells to leave the marrow and enter the bloodstream where they can
be extracted using a process where the stems cells are removed and the
remaining components of the blood are returned to the donor. A donor,
matched to a patient, may be asked to donate either bone marrow or
PBSC, depending on the preference of the patient‘s physician. The
Registry has offered PBSC to patients since 1999.
Matching Donor and Patient:
In addition to its dependence on such common determinants of treatment
success as patient age and disease severity, the outcome of a
transplant depends on the degree of match between donor and patient
with respect to particular blood cell proteins--the human leukocyte
antigens (HLA)--that are part of a person‘s genetic makeup.[Footnote
10] Each person has three primary pairs (one set of three from each
parent) of these antigens that play a major role in the compatibility
of a transplant. A matched donor is defined as one for whom each of
these six antigens has the same kind of HLA. If a matched donor cannot
be found, then a donor with certain types of mismatch may be used,
depending on the transplant center‘s preferences, although usually with
poorer results. In general, the more closely related two people are,
the more likely it is that their HLA will match. At one extreme,
identical twins always match, and, in fact, match on all antigens, not
just the six ordinarily focused upon. At the other extreme, members of
separate racial groups are relatively unlikely to match one another.
Full siblings can provide a six out of six match, resulting in what is
called an ’HLA-identical sibling transplant,“ but only about 30 to 40
percent of patients can be expected to have a matched sibling donor. As
a result, unrelated donors with matched HLA are sought from the
registries in which their HLA type has been recorded.
The definition of a match has been refined over time as scientific
understanding of HLA increases. HLA are being typed more precisely, so
more types of HLA can now be distinguished. Thus, some of today‘s
matches may be judged as mismatches in the future because better
matches are possible. This increasing refinement does not mean,
however, that finding a suitable match for transplantation is
inevitably becoming more difficult. Some kinds of mismatch may be less
dangerous than others. As a result, as research continues, there may be
fewer matches by today‘s standards, but relatively harmless mismatches
will be recognized as such and used. Further, there is evidence that
cord blood may not require as exact an HLA match as is usually sought.
The NMDP Network:
In support of the Registry, NMDP manages a worldwide network consisting
of more than 400 donor centers, recruitment groups,[Footnote 11]
contract laboratories where tissue is typed, apheresis
centers,[Footnote 12] cord blood banks, collection centers where marrow
is harvested, blood sample repositories, and transplant centers. More
than half of these organizations are donor (91) or transplant centers
(149). The relationship of these network components to NMDP varies.
Some, such as the recruitment groups, were designed to be parts of the
network and work with NMDP, whereas others, such as the transplant
centers, exist separately from the network and function independently
of NMDP except where specified by contract.
The NMDP network includes donor centers and other organizations in
foreign countries.[Footnote 13] The foreign donor centers merge their
files with the Registry, contributing more than one million donors.
These centers are required to comply with NMDP policies, program
standards, and other criteria, although fees for recruiting donors and
other financial incentives and payments that go to U.S. centers are not
paid to foreign centers.[Footnote 14] NMDP has also signed cooperative
agreements with national registries in 13 foreign countries.[Footnote
15] Although certain data on donors recruited into these registries are
not entered into the Registry‘s computer system, these foreign
registries will search their donor files on behalf of a U.S. patient
searching the Registry. In addition, 6 foreign apheresis centers, 18
foreign bone marrow collection centers, and 36 foreign transplant
centers are affiliated with the Registry. NMDP‘s affiliations with
foreign donor and transplant centers result in its facilitation of both
foreign-to-U.S. and U.S.-to-foreign donations.
The existence of these international affiliations with the Registry
does not prevent U.S. transplant centers from obtaining stem cells
through foreign registries directly, that is, without going through
Registry channels. Even domestically, the Registry is not a monopoly;
other U.S. registries also maintain lists of donors, conduct searches
for stem cells, or perform both of these functions.[Footnote 16] These
other registries, however, are relatively small; often specialize in
donors from particular racial or ethnic groups; and are private, with
no national requirements.
Operation of the NMDP Registry:
The Registry serves two groups of people, donors and patients. The
Registry‘s donor centers and recruitment groups recruit donors, who are
then managed by the donor centers. The Registry pays these centers and
groups for signing up donors. In view of the past underrepresentation
of minorities in the Registry, NMDP has initiated several recruitment
efforts to increase its racial and ethnic diversity. For example, it
provides free or low-cost minority-specific educational materials to
donor centers and recruitment groups. Probably the most important
aspects of managing donors are to maintain their commitment to donation
so that they are locatable and willing to donate when their stem cells
are requested, to keep records of how to contact them, and to drop from
the list any individuals who are too old[Footnote 17] or no longer able
or willing to donate.
A patient‘s first contact with the Registry occurs when his or her
physician or a transplant center conducts a free, preliminary search of
the Registry for stem cell donors and cord blood units. The preliminary
search, which takes about 24 hours, produces a list of donors and cord
blood units that are potentially suitable for that patient. However,
many patients for whom such searches are conducted are not necessarily
good candidates for stem cell transplants. For example, some searches
may be conducted for patients who are too sick for transplantation or
who are good candidates for less invasive therapies.
If the physician and patient decide to continue a search for an
unrelated donor (or unrelated cord blood) on the Registry, then more
information about the matching stem cells is required and a formal
search is begun. Only a physician affiliated with a transplant center
in the NMDP network may conduct a formal search of the Registry. The
Registry bills the transplant center a one-time activation fee of $600.
It also bills the center for the cost of the four or five testing
components of the search process, each of which costs more than $100.
Since several donors may have to be tested before one is selected for
the patient, these component charges may be made repeatedly, resulting
in a search costing thousands of dollars to the transplant center, and
more to the patient when the center adds its markups. Relatively few
insurance plans pay for searches; however, plans often pay for the
actual transplantation including the procurement of stem cells. The
details of the formal search and the subsequent steps in the process
possibly leading to transplantation depend on the additional
information needed; the results of laboratory tests; and the kind of
stem cells sought, whether stored blood from an umbilical cord or blood
or marrow from a living donor.
If a suitable donor or suitable cord blood unit is found, and if other
requirements in the process toward transplantation are
fulfilled,[Footnote 18] then either (1) the marrow is harvested from
the donor at a collection center, (2) PBSC are collected from the donor
at an apheresis center, or (3) the cord blood is shipped from a cord
blood bank. The stem cells are transported to the transplant center,
often by courier. The final step is the infusing of the patient‘s
bloodstream with the selected marrow, PBSC, or cord blood. The entire
process--from the initiation of the formal search to the transplant
(infusion)--typically requires many months and sometimes more than 1
year. However, some patients cannot wait this long for transplants
because their medical conditions are deteriorating.
During the search process, NMDP offers patient advocacy services
through two channels. Its Office of Patient Advocacy (OPA) provides
several services, including education, support, case management
intervention, financial assistance, and special advocacy projects. For
example, OPA publishes the Transplant Center Access Directory, a
patient guide listing all transplant centers in the NMDP network. The
directory describes each center‘s HLA matching criteria and lists the
diseases each typically treats with unrelated donor marrow transplants.
The directory also provides information on comparable search charges
and risk-adjusted patient survival data. In addition to the services
provided through OPA, NMDP requires that each transplant center have a
patient advocate on staff. The patient advocate must be familiar with
the center‘s transplant program and with issues of unrelated donor stem
cell transplantation and must not be a member of the transplant team.
OIG Review:
A 1996 OIG review raised concerns about donor center costs and
performance. Before the review, NMDP used two methods to finance donor
centers. NMDP paid for services at some donor centers through cost-
based contracts for direct expenses, such as labor and fringe benefits
and donor expenses. Other donor centers received payments from NMDP for
specified activities, such as donor recruitment and donor search
activities. The OIG recommended that HRSA and NMDP develop a payment
approach for all donor centers that more directly linked funding to
performance and emphasize recruitment and retention of donors,
particularly donors from racial and ethnic minority groups. Further,
the OIG recommended that HRSA and NMDP develop procedures to monitor
the performance of donor centers and other organizations in the NMDP
network.
NMDP Has Succeeded in Increasing Recruitment of Donors, Including
Minorities, but May Not Be Able to Equalize Access to Matches:
The program‘s recruitment efforts have apparently increased the number
of donors on the Registry since 1998 for all racial and ethnic groups,
and the theoretical probability of finding a match has increased
steadily over the life of the Registry. By 2001, the number of donors
from each minority group on the Registry had grown by at least 30
percent and was either greater than or no more than 2 percentage points
below its representation in the general population. However, when
viewed as a percentage of each group‘s population, African Americans
and Hispanics are still substantially underrepresented. For all racial
and ethnic groups, the theoretical probability of finding a match has
grown as the Registry size has increased, but equal access to a match
may not be attainable. Differences among racial and ethnic groups in
the rarity and variability of the genes responsible for compatibility
in transplants may mean that the Registry cannot achieve equal
probability for all groups. Further, the goal of equal access to a
match conflicts to some extent with attempts to maximize the overall
numbers of matches and transplants for the Registry.
Number of Donors on Registry Has Increased for All Groups:
The size of the Registry has increased since 1998 by 36 percent, and no
minority group increased by less than 30 percent. NMDP‘s efforts to
recruit minorities may have substantially increased the number of
donors from these populations. Percentage increases for minorities
ranged from 30 percent for Native Americans to 53 percent for
Hispanics. Caucasian donors increased 28 percent. (See table 1.) The
multiple race category had the largest increase, 123 percent, but this
may result in part from an increase in the use of that category by
those to whom it applies, rather than solely from an increase in the
availability of donors of that group.
Table 1: Percentage Increase in Registry Donors, by Racial and Ethnic
Group, 1998 to 2000, and Current Proportion of Groups on the Registry
and in the Population:
Race/ethnicity: African American; Number on Registry, September 30,
1998: 264,868; Number on Registry, December 31, 2001: 363,246;
Percentage change: 37; Percentage of donors on the Registry with known
race[A]: 10; Percentage of U.S. population[B]: 12.
Race/ethnicity: Asian/Pacific Islander; Number on Registry, September
30, 1998: 194,118; Number on Registry, December 31, 2001: 287,129;
Percentage change: 48; Percentage of donors on the Registry with known
race[A]: 8; Percentage of U.S. population[B]: 4.
Race/ethnicity: Caucasian; Number on Registry, September 30, 1998:
1,926,675; Number on Registry, December 31, 2001: 2,460,725; Percentage
change: 28; Percentage of donors on the Registry with known race[A]: 7;
Percentage of U.S. population[B]: 69.
Race/ethnicity: Hispanic; Number on Registry, September 30, 1998:
252,569; Number on Registry, December 31, 2001: 386,059; Percentage
change: 53; Percentage of donors on the Registry with known race[A]:
11; Percentage of U.S. population[B]: 13.
Race/ethnicity: Multiple race; Number on Registry, September 30, 1998:
34,443; Number on Registry, December 31, 2001: 76,937; Percentage
change: 123; Percentage of donors on the Registry with known race[A]:
2; Percentage of U.S. population[B]: 2.
Race/ethnicity: Native American; Number on Registry, September 30,
1998: 45,478; Number on Registry, December 31, 2001: 59,112; Percentage
change: 30; Percentage of donors on the Registry with known race[A]: 2;
Percentage of U.S. population[B]: 1.
Race/ethnicity: Other; Number on Registry, September 30, 1998: 13,089;
Number on Registry, December 31, 2001: 14,142; Percentage change: 8;
Percentage of donors on the Registry with known race[A]: 0[C];
Percentage of U.S. population[B]: 0[C].
Race/ethnicity: Declined to specify; Number on Registry, September 30,
1998: 4,629; Number on Registry, December 31, 2001: 6,498; Percentage
change: 40; Percentage of donors on the Registry with known race[A]: N/
A; Percentage of U.S. population[B]: N/A.
Race/ethnicity: Unknown[D]; Number on Registry, September 30, 1998:
623,659; Number on Registry, December 31, 2001: 902,802; Percentage
change: 45; Percentage of donors on the Registry with known race[A]: N/
A; Percentage of U.S. population[B]: N/A.
Race/ethnicity: Total; Number on Registry, September 30, 1998:
3,359,528; Number on Registry, December 31, 2001: 4,556,650; Percentage
change: 36; Percentage of donors on the Registry with known race[A]:
100; Percentage of U.S. population[B]: 100.
Note: N/A = not applicable.
[A] As of December 31, 2001.
[B] Based on 2000 U.S. Census.
[C] Rounds to zero.
[D] Some foreign registries that are part of the NMDP network do not
collect information on race or ethnicity.
Sources: NMDP and U.S. Bureau of the Census.
[End of table]
The total of more than 1,000,000 minority donors listed in 2001
contrasts with the approximately 80,000 we reported in 1992. As can be
seen in table 1, by 2001, the proportions of both African Americans and
Hispanics on the Registry were within 2 percentage points of their
proportions in the 2000 U.S. population. The proportions of other
minorities on the Registry were either approximately equal to or
exceeded their proportions in the population. While the differences
between Registry and population levels of representation for African
Americans and Hispanics reflect improved representation of these
groups, the 2-percentage point differences still indicate a substantial
underrepresentation in comparison with their proportions in the U.S.
population. Specifically, in 1992, the proportions of African Americans
and Hispanics, both at 4 percent of the Registry, were 8 and 5
percentage points lower, respectively, than their proportions in the
U.S. population (which were 12 and 9 percent, respectively). This
translated to a 67 percent underrepresentation for African Americans
and a 56 percent underrepresentation for Hispanics. The current 2-
percentage point differences on the Registry for these groups translate
to a 17 percent underrepresentation for African Americans and a 15
percent underrepresentation for Hispanics.[Footnote 19]
Theoretical Probability of Finding a Match Has Increased over Life of
Registry:
For all racial and ethnic groups the theoretical probability of a
patient‘s finding at least one matched donor has increased every year
since 1988 but has leveled off somewhat since 1998.[Footnote 20] The
increase in theoretical probability represents significant progress in
raising the likelihood of a match. It reflects inclusion in the
Registry of the most common genetic types over the period when the
Registry was small and new, and recruitment efforts were beginning. The
leveling off likely reflects the fact that for all groups, after years
of recruitment activity, improvement now occurs mainly when rare types
are added. (See fig. 1.):
Figure 1: Theoretical Probability of Patient‘s Finding at Least One
Matched Donor, by Racial and Ethnic Group, 1988 to 2001:
[See PDF for image]
Source: NMDP.
[End of figure]
Nevertheless, the theoretical probability of finding a match varies by
race, ranging in 2001 from under 60 percent for African Americans to
over 80 percent for Caucasians. This probability has always been higher
for Caucasian patients than for patients in any minority group, in
part, perhaps, because of Caucasians‘ greater numbers and level of
representation on the Registry. The theoretical probability of finding
a matched donor has been lowest for African American patients. This is
because, in addition to their smaller numbers and lower level of
representation on the Registry, their rarer and more varied HLA
combinations make matching harder.
Equal Access for All Groups May Be Unattainable:
Because of genetic differences among racial and ethnic groups, there is
reason to believe that patients from some minority groups, notably
African Americans, may never have the same probability of finding
matches, and therefore of access to transplants, as Caucasian patients,
regardless of the efforts made to recruit them. Any patient is more
likely to find a match in his or her own racial and ethnic group than
in another group, so patient matching rates depend, to some extent, on
the number of people in the patient‘s group on the Registry. All
minorities are at a disadvantage for this reason. Further, some
minority groups, such as African Americans, are known to have more rare
and more varied HLA combinations than do Caucasians. The likelihood of
finding a match from among a group of racially or ethnically defined
donors declines with the rarity and number of possible genetic types
found among the members of that group.
In addition to these factors related to finding a match, there are
other factors that may contribute to differences in access to a
transplant. Some of these depend on the characteristics of those who
volunteer for the Registry. For example, donors from different groups
may differ in their tendency to be available (locatable, willing, and
physically able) when called upon to actually donate. Other possible
factors involve the attitudes, health, medical care, resources, and
preferences of the patients. Patients of different groups may differ in
their tendency to engage the health care system at all, to seek help
early enough in their illnesses, or to search the Registry as opposed
to pursuing other options. It may be possible to effect changes in
these factors, thereby moving closer to the goal of equal opportunity
for all racial and ethnic groups.
However, not only is the goal of equal access to transplants for all
groups difficult to attain, but it also may conflict with the statutory
goal of maximizing the number of patients who find a match and thereby
maximizing the number of transplants facilitated. Recruiting donors
with the rare HLA combinations that may be needed for minorities is
difficult. Large numbers of donors must be recruited and retained in
the Registry in order to identify and add each rare genetic type to the
donor pool, so the cost of recruiting such donorsæthe incremental cost
of adding these rare genetic types to the donor poolæis large. Thus,
devoting many resources in pursuit of a small number of rare genetic
types may divert resources from other efforts, such as recruiting
Caucasians and other groups with more common genetic types, which might
more readily increase the number of matches.
Because of the difficulty encountered in finding matches for minority
patients, NMDP engages in a number of initiatives to increase the
Registry‘s diversity. It conducts outreach, recruitment, and
educational efforts directed towards minorities. In addition, NMDP has
initiated a program to pay the full costs of HLA tissue typing for
minority donors.
Although the difficulty in finding matches for minority patients may be
unavoidable, it may be mitigated somewhat by the efforts of the
Registry to increase the number of donors on whom it has complete HLA
typing. The vast majority of actual donations are obtained from by
donors whose HLA is fully typed.[Footnote 21] When only these donors
are considered, each minority constitutes a larger portion of the
Registry than its representation in the population. Therefore, because
access to a match depends upon, for the most part, the fully typed
donors on the Registry, access for minorities may be somewhat better
than might be assumed by looking at the Registry as a whole.
National Registry May Be Underutilized:
Although the exact number of patients in need of transplants from
unrelated donors is not known, the number of patients utilizing the
Registry to search for matches is about one-third of the estimated
number of patients in need of unrelated donor transplants. About one-
tenth of the number of patients estimated to be in need of unrelated
donor transplants obtain transplants facilitated by NMDP. These figures
suggest that the Registry may be underutilized for both searching and
facilitating transplants.[Footnote 22] Physicians for approximately
15,000 U.S. patients requested preliminary searches of the Registry
from 1997 through 2000. This number represents 34 percent of the 44,740
U.S. patients estimated to be in need of stem cell transplants from
unrelated donors in that 4-year period. About 4,000, or 27 percent, of
the patients whose physicians searched the Registry eventually received
transplants facilitated by NMDP. However, a significant proportion of
searches were not completed because stem cells were obtained from
donors or organizations without the involvement of NMDP.
Estimates Suggest about One-Third of Patients in Need Search the
Registry and about One-Tenth Receive Transplants
:
From 1997 through 2000, physicians carried out preliminary searches for
34 percent of the number of U.S. patients estimated to be in need of
transplantation from unrelated donors at any time during that period.
The number of transplants facilitated by NMDP for all U.S. patients was
9 percent of the number estimated to be in need. The precise number of
patients in need of unrelated donor transplants is not known. However,
there is a greater than 10 to 1 ratio between the number of such
patients estimated to be in need and the number of transplants
facilitated by NMDP. This suggests that the Registry may be
underutilized, as many more U.S. patients may need unrelated donor
transplants than obtain them through the Registry.[Footnote 23] The
ratio of the number of preliminary searches to the number of patients
in need varied by race and ethnicity. Among specific racial and ethnic
groups, the percentage of preliminary searches was highest for
Caucasian patients (35 percent), and was lowest for Hispanic patients
(24 percent) and Native American patients (24 percent). (See table 2.)
We do not know why these apparent disparities in search rates exist.
Table 2: U.S. Patients‘ Utilization of the Registry, by Race and
Ethnicity, 1997 to 2000:
Race/ethnicity: African American; Estimated number of patients without
matched sibling donor[A]
(patients in need): 5,397; Actual number of preliminary searches:
1,694; Ratio of number of preliminary searches to number of patients in
need: 0.31; Actual number (percentage) of preliminary searches
resulting in formal searches: 958 (57); Actual number (percentage) of
preliminary searches resulting in NMDP-facilitated transplants: 256
(15); Ratio of number of NMDP-facilitated transplants to number of
patients in need: 0.05.
Race/ethnicity: Asian/Pacific Islander; Estimated number of patients
without matched sibling donor[A]
(patients in need): 1,666; Actual number of preliminary searches: 439;
Ratio of number of preliminary searches to number of patients in need:
0.26; Actual number (percentage) of preliminary searches resulting in
formal searches: 270 (62); Actual number (percentage) of preliminary
searches resulting in NMDP-facilitated transplants: 96 (22); Ratio of
number of NMDP-facilitated transplants to number of patients in need:
0.06.
Race/ethnicity: Caucasian; Estimated number of patients without matched
sibling donor[A]
(patients in need): 30,929; Actual number of preliminary searches:
10,844; Ratio of number of preliminary searches to number of patients
in need: 0.35; Actual number (percentage) of preliminary searches
resulting in formal searches: 7,079 (65); Actual number (percentage) of
preliminary searches resulting in NMDP-facilitated transplants: 3,321
(31); Ratio of number of NMDP-facilitated transplants to number of
patients in need: 0.11.
Race/ethnicity: Hispanic; Estimated number of patients without matched
sibling donor[A]
(patients in need): 5,613; Actual number of preliminary searches:
1,366; Ratio of number of preliminary searches to number of patients in
need: 0.24; Actual number (percentage) of preliminary searches
resulting in formal searches: 840 (61); Actual number (percentage) of
preliminary searches resulting in NMDP-facilitated transplants: 317
(23); Ratio of number of NMDP-facilitated transplants to number of
patients in need: 0.06.
Race/ethnicity: Native American; Estimated number of patients without
matched sibling donor[A]
(patients in need): 329; Actual number of preliminary searches: 80;
Ratio of number of preliminary searches to number of patients in need:
0.24; Actual number (percentage) of preliminary searches resulting in
formal searches: 56 (70); Actual number (percentage) of preliminary
searches resulting in NMDP-facilitated transplants: 20 (25); Ratio of
number of NMDP-facilitated transplants to number of patients in need:
0.06.
Race/ethnicity: Other; Estimated number of patients without matched
sibling donor[A]
(patients in need): 806; Actual number of preliminary searches: 365;
Ratio of number of preliminary searches to number of patients in need:
0.45; Actual number (percentage) of preliminary searches resulting in
formal searches: 213 (58); Actual number (percentage) of preliminary
searches resulting in NMDP-facilitated transplants: 39 (11); Ratio of
number of NMDP-facilitated transplants to number of patients in need:
0.05.
Race/ethnicity: Total; Estimated number of patients without matched
sibling donor[A]
(patients in need): 44,740; Actual number of preliminary searches:
15,231[B]; Ratio of number of preliminary searches to number of
patients in need: 0.34; Actual number (percentage) of preliminary
searches resulting in formal searches: 9,623c (63); Actual number
(percentage) of preliminary searches resulting in NMDP-facilitated
transplants: 4,056[D] (27); Ratio of number of NMDP-facilitated
transplants to number of patients in need: 0.09.
AFor Caucasians, the number of HLA-identical sibling transplants
multiplied by the number of patients expected to be without matched
sibling donors for each such transplant was derived from data obtained
from the Statistical Center of the IBMTR and Autologous Blood and
Marrow Transplant Registry (ABMTR). (The analysis has not been reviewed
or approved by the Advisory Committees of the IBMTR and ABMTR.) See
appendix I for a description of this method of estimation. For each of
the other groups, the number was derived by assuming that the group‘s
need is the same as it is for Caucasians and in proportion to the
group‘s representation in the U.S. population.
[B] Includes 443 preliminary searches, not included elsewhere in the
column, from patients of unknown race/ethnicity.
[C] Includes 207 formal searches, not included elsewhere in the column,
from patients of unknown race/ethnicity.
[D] Includes 7 transplants, not included elsewhere in the column, from
patients of unknown race/ethnicity.
Source: GAO analysis of data from the Statistical Center of the IBMTR
and ABMTR and NMDP.
[End of table]
About one-fifth of the number of patients estimated to be in need
formally searched the Registry (9,623 out of 44,740). Less than one-
tenth of those estimated to be in need ultimately received NMDP-
facilitated transplants. The numbers and percentages of preliminary
searches that progressed to formal searches from 1997 through 2000 are
presented by racial and ethnic group in table 2. The overall rate of
progression from preliminary to formal search is 63 percent. Further,
4,056 of the 15,231 U.S. patients (27 percent) for whom preliminary
searches were conducted from 1997 through 2000 eventually received
NMDP-facilitated transplants. This number corresponds to 9 percent of
the number of patients estimated to be in need of unrelated transplants
during that period.
Reasons for Cancellation Vary and Include Obtaining Stem Cells from a
Provider Other than NMDP:
Reasons for cancellation of preliminary searches or formal searches
vary. Although clinical reasons, such as a change in medical condition,
are the most commonly cited explanations for cancellation of both
preliminary and formal searches,[Footnote 24] another relatively
frequent reason is that stem cells are obtained from a provider other
than NMDP, such as a related donor or another registry. (See tables 3
and 4.) We do not know the proportion of these cases that used a
related donor, and some cases may not have been able to find a
potential match at NMDP. However, it is likely that in at least some of
these cases, NMDP might have facilitated a transplant if the patient‘s
transplant center had not selected another registry to provide the stem
cells, thus representing another kind of possible underutilization of
NMDP. Lack of donor availability--not finding any potential matches--
and financial reasons are not commonly cited as reasons for
cancellation of either kind of search, although it is possible that
patients with limited financial resources or insurance may not be
encouraged to make preliminary searches.
Table 3: Reasons for Preliminary Search Cancellation, January 2000
through September 2001:
Reason for cancellation: No donor available; Number of preliminary
search cancellations: 105; Percentage of preliminary search
cancellations: 7.
Reason for cancellation: Another provider; Number of preliminary search
cancellations: 317; Percentage of preliminary search cancellations: 20.
Reason for cancellation: Patient stable; Number of preliminary search
cancellations: 383; Percentage of preliminary search cancellations: 25.
Reason for cancellation: Financial reasons; Number of preliminary
search cancellations: 114; Percentage of preliminary search
cancellations: 7.
Reason for cancellation: Personal reasons[A]; Number of preliminary
search cancellations: 187; Percentage of preliminary search
cancellations: 12.
Reason for cancellation: Deterioration/death; Number of preliminary
search cancellations: 160; Percentage of preliminary search
cancellations: 10.
Reason for cancellation: Other; Number of preliminary search
cancellations: 284; Percentage of preliminary search cancellations: 18.
Reason for cancellation: Total; Number of preliminary search
cancellations: 1,550; Percentage of preliminary search cancellations:
100.
Note: These data are based on a survey, conducted by OPA, of
individuals making preliminary searches.
[A] Personal reasons for preliminary search cancellations include
decisions made by physicians and patients.
Source: NMDP.
[End of table]
Table 4: Reasons for Formal Search Cancellation, 1997 to 2000:
Reason for cancellation: No donor available; Number of formal search
cancellations: 131; Percentage of formal search cancellations: 3.
Reason for cancellation: Another provider; Number of formal search
cancellations: 1,200; Percentage of formal search cancellations: 25.
Reason for cancellation: Financial reasons; Number of formal search
cancellations: 22; Percentage of formal search cancellations: 0.
Reason for cancellation: Personal reasons[A]; Number of formal search
cancellations: 733; Percentage of formal search cancellations: 15.
Reason for cancellation: Deterioration/death; Number of formal search
cancellations: 2,096; Percentage of formal search cancellations: 44.
Reason for cancellation: Alternative therapy; Number of formal search
cancellations: 357; Percentage of formal search cancellations: 7.
Reason for cancellation: Other; Number of formal search cancellations:
262; Percentage of formal search cancellations: 5.
Reason for cancellation: Total; Number of formal search cancellations:
4,801; Percentage of formal search cancellations: 100.
APersonal reasons for formal search cancellations include decisions
made by physicians, patients and patients‘ families.
Source: NMDP.
[End of table]
Several factors may influence a decision to obtain stem cells from a
provider outside the NMDP network, including the source of stem cells
preferred by the physician, the costs involved, and the timeliness of
the response. Outside providers may need to be used when the physician
sees cord blood as a viable alternative source to bone marrow or PBSC
because some cord blood banks do not list their cord blood units with
NMDP.[Footnote 25]
Search and procurement costs can also be a factor. Administrators of
transplant centers that have done non-NMDP-affiliated transplants told
us that other registries charge less for searches than NMDP does. For
example, we were told that only a few other registries worldwide charge
a search activation fee in addition to their charges for the specific
medical procedures needed to confirm that a particular donor is healthy
and matched to the patient. In addition, the cost of stem cell
procurement at NMDP tends to be higher. One transplant center director
told us that the center pays about $13,000 for stem cells obtained
directly from overseas registries and about $21,000 for NMDP stem
cells. However, even when NMDP is not paid for a formal search or for
stem cells, it may still have been utilized. An official at NMDP
informed us that it is possible for a transplant center to determine
the NMDP-affiliated registry at which a foreign (but not domestic)
potential match is registered on the basis of a preliminary search and
to contact the foreign registry directly to obtain the stem cells.
Moreover, that official stated that some transplant centers may do this
regularly. Thus, although NMDP may not be recorded as having
facilitated the transplants that result, its role in helping to locate
donors in such cases means that its utilization is somewhat greater
than the record suggests.
Timeliness can be another factor. A few center administrators mentioned
that NMDP takes longer to provide stem cells than do other registries.
For example, one administrator told us that the time it takes to obtain
a donor sample for testing at the transplant center--an important
component of the overall search process--can be a week longer for NMDP
than for a foreign registry, depending on whether NMDP judges the
search to be urgent. Waiting this additional week can be frustrating
for those at the transplant center who are anxious to determine whether
they have a confirmed match or will have to continue searching. Another
director told us that stem cells from non-NMDP providers are more
likely to be received by the date the transplant center requests them
than are stem cells from NMDP. NMDP has attempted to shorten its time
from formal search initiation to transplant and reports that its median
time has decreased from 4.8 months from 1992 through 1993 to 3.7 months
in 2000. The optimal time frames for patients vary. Some may not be
urgent, but NMDP has shown that it is possible to complete urgent
searches in less than a month and reports that it expects to begin
offering urgent searches as an option to transplant centers.
Organizations in the NMDP Network Generally Comply with Its Standards
and Procedures:
Organizations that participate in the NMDP network generally comply
with the standards and procedures it has established. In order to
encourage adherence, NMDP uses various mechanisms to monitor compliance
and performance. These include site visits, the Continuous Process
Improvement (CPI) program, and incident reports, as well as a financial
incentive system designed to improve the performance of donor centers.
The results of the selected site visits, analysis of CPI measures, and
incident report summaries we reviewed show that the organizations in
the NMDP network generally adhere to NMDP‘s standards and procedures.
In general, NMDP ensures compliance by taking action against
noncompliant organizations. (See app. II for examples of how NMDP uses
these systems to achieve compliance with respect to selected
activities.) In 2001, NMDP required 24 donor and transplant centers to
take corrective actions because they did not meet its standards. The
incentive system encourages compliance by linking donor center
reimbursement to performance.
NMDP Monitors Network Compliance and Performance:
NMDP uses several mechanisms to encourage the compliance and
performance of the participating organizations in its network. NMDP
staff members conduct site visits to donor centers to monitor the
centers‘ compliance with NMDP‘s standards and procedures and to provide
feedback about the results. It also employs the CPI program to assess
and provide feedback at donor, transplant, and bone marrow collection
centers. Further, NMDP monitors incident reports from donor,
transplant, and collection centers and may take corrective action
including, in serious cases, suspension or termination.
According to NMDP officials, NMDP staff members conduct site visits at
donor centers approximately every 2 years to assess donor center
compliance with program standards and procedures. NMDP staff members
review the organization of the program (such as its support and
staffing structure), recruitment activities (such as performance
against goals and donor drive compliance), donor management activities
(such as management of patient-related donor search requests,
confidentiality procedures, and records management), and billing and
reimbursement to determine adherence to NMDP‘s standards and
procedures. They also compare performance against goals for various
recruitment activities. Upon completion of these visits, NMDP staff
members discuss the results with the center staff and provide a summary
report. Centers that are noncompliant are advised of the problems and
are required to submit corrective action plans to NMDP that address the
problems. Our review of donor center site visit reports indicates that
the reports identified problems and the corrective actions required of
the centers to meet NMDP criteria.
Since 1998, NMDP has conducted additional site visits at transplant
centers to verify the accuracy of the data that the transplant centers
submit electronically to NMDP. NMDP staff members compare the data from
the centers‘ records with the data from NMDP‘s computer system. During
these visits, NMDP staff members may also review other activities, such
as the signing of patient consent forms. The site visits are scheduled
for each transplant center every 4 years. NMDP plans to issue its first
annual report on the results of the first cycle of site visits in
September 2002.
NMDP monitors the operations and performance of its centers through the
CPI program. The program includes nine goals to increase the efficiency
of key activities in the search and donation process and measures
performance against these goals. For example, at donor centers, NMDP
measures the timeliness of registering new donors, resolving search-
related requests, and processing requests for HLA blood typing. At
transplant centers, NMDP measures the time it takes to resolve and
report confirmatory testing results. NMDP also monitors post-transplant
data submission through CPI. These outcome data are used in research
studies to analyze outcomes for donors and patients. NMDP also monitors
the accuracy and timeliness with which donor and transplant centers
submit donor and patient blood samples to NMDP‘s research repository.
NMDP provides regular feedback to donor and transplant centers
concerning their performance on CPI measures. For example, each center
receives a monthly report summarizing the results of its activities,
along with those of all other centers, in the previous month. The
reports allow centers to analyze how consistently they perform and to
compare their results to those of other centers in the network. NMDP
also conducts a year-end analysis to provide feedback to centers.
Through its CPI program, NMDP monitors whether organizations in its
network meet goals for timeliness and may recommend corrective actions
for centers that do not meet these goals.[Footnote 26] A year-end
analysis of the CPI program shows that during 2001 almost half (44 of
91) of donor centers met all nine CPI goals for the search process. In
addition, 20 more donor centers met eight of nine goals, and 9 others
met seven of nine goals. According to NMDP, the remaining 18 donor
centers (20 percent) that met six or fewer goals were the focus of
technical assistance to improve their performance. Our analysis shows
that 5 of the 91 donor centers (5 percent) were placed on review or
probation for failing to meet CPI goals in 2001.
Our analysis also shows that NMDP placed 18 of the 129 transplant
centers (14 percent) on probation. Eight of these were placed on
probation for failure to meet CPI goals for the search process, seven
for failure to meet CPI measures concerned with timely submission of
recipient follow-up information, and three for problems related to the
accuracy and timeliness of submissions of donor and patient research
blood samples.
NMDP supplements these activities with incident reports, which are
written accounts of deviations from policies and standards that are
categorized by the nature of a deviation and include, but are not
limited to, categories such as confidentiality concerns, customer
service, and product transport. NMDP uses incident reports to track
deviations from its standards by recording the specifics of incidents.
NMDP staff members follow up and investigate incidents. In addition, an
NMDP committee reviews a summary report of incidents twice a year to
identify developing trends that may affect an individual center or the
entire network. Since NMDP reviews center participation annually, the
committee may follow up on deviations from NMDP‘s standards or take
action such as probation, suspension, or termination during the
reapplication process. We reviewed a summary of incidents categorized
by type of problem and the corrective actions taken to resolve them.
For example, one incident involved an operating room staff member
administering less appropriate blood, rather than the donor‘s own
blood, which was available for that purpose, during a marrow harvest.
NMDP monitored an investigation at the hospital to ensure that the
problem would be addressed.
Donor Center Reimbursement Is Linked to Performance:
To improve the operation of its donor centers, NMDP ties their
reimbursement to their performance. In 1997, NMDP instituted a new
reimbursement system that links payment to performance on CPI goals for
all donor centers.[Footnote 27] NMDP pays donor centers a fee for each
activity to recruit donors for the Registry, such as signing up donors,
typing their tissues, maintaining their files, and other activities
related to confirming that the donors identified as potential matches
for a searching patient actually match and are medically cleared for
donation. NMDP pays each donor center a recruitment fee of $28 and $10
for every minority and Caucasian donor, respectively, recruited up to
the number specified in its recruitment goal. NMDP establishes annual
recruitment goals for each donor center based on the demographics of
the local population. When donors are recruited, the donor centers that
do not register a specific percentage of the new donors within a
certain period incur financial penalties. For example, the CPI goal for
registering new donors is to register at least 85 percent of them
within 35 days of the date on which they volunteer. NMDP would reduce
the total recruitment fee it pays to donor centers that register less
than 85 percent of new donors within this time frame. NMDP data show
that in May 2001, 98 percent of all donor centers met this goal. In
addition, NMDP pays incentives to donor centers for retaining donors at
various points in the donation process.
Concluding Observations:
In spite of progress in recruiting minority donors, racial and ethnic
disparities in the Registry remain, due in part to differences in the
genetic variability within groups. Thus, differences among racial and
ethnic groups in the probability of obtaining transplants will likely
continue. Many in need of transplants may not search the Registry;
those that do often do not obtain them, and for those that obtain them,
the transplants may not be facilitated by NMDP. Although NMDP enhances
the quality of its network by actively monitoring the compliance and
performance of the component organizations, it has not attained the
level of utilization that might be expected.
Agency Comments:
In its written comments on a draft of this report, HRSA stated that the
report provides an accurate and helpful overview of the status of the
National Bone Marrow Donor Registry. HRSA agreed that recruitment of
donors cannot be the sole strategy for improving access to unrelated
donor transplants for minority patients or those with unusual antigens,
and cited the need for other efforts to supplement recruitment
activities. However, HRSA noted that the Registry consists of two
distinct groups of donors, those who are fully HLA typed and those who
are less than fully typed. Since the vast majority of actual donors are
selected from the fully typed portion, minority racial and ethnic
groups therefore make up a larger proportion of the Registry than their
representation in the U.S. population. We have noted in the report
that, because of this, access for minorities may be somewhat better
than might be assumed by looking at the Registry as a whole.
With regard to underutilization of the Registry, HRSA agreed that many
patients who could benefit from unrelated donor transplants never
consult the Registry or do so too late in the course of their
illnesses. HRSA suggested a slightly modified method for estimating the
number of patients in need. We modified table 2 in accordance with its
suggestions, but note that both approaches produce virtually identical
estimates of overall utilization. (See app. I.):
Finally, HRSA noted that many factors affect the time required to
complete a search of the Registry. While searches frequently take many
months and the median search time has decreased, NMDP has completed
medically urgent searches in less than a month, on a pilot basis, and
reports that it expects to begin offering urgent searches as an option
to transplant centers. We have revised the report to include this
clarification. HRSA also provided technical comments, which we
incorporated as appropriate. HRSA‘s comments are reprinted in appendix
III.
We are sending this report to the Administrator of HRSA, the NMDP Chief
Executive Officer, and other interested persons. We will also make
copies available to others upon request. In addition, the report will
be available at no charge on the GAO Web site at http://www.gao.gov.
If you or your staff members have any questions about this report,
please call me at (202) 512-7119. Key contributors to this assignment
are listed in appendix IV.
Janet Heinrich
Director, Health Care--Public Health Issues:
List of Committees:
The Honorable Robert C. Byrd
Chairman
The Honorable Ted Stevens
Ranking Minority Member
Committee on Appropriations
United States Senate:
The Honorable Edward M. Kennedy
Chairman
The Honorable Judd Gregg
Ranking Minority Member
Committee on Health, Education,
Labor, and Pensions
United States Senate:
The Honorable C.W. Bill Young
Chairman
The Honorable David Obey
Ranking Minority Member
Committee on Appropriations
House of Representatives:
The Honorable W.J. ’Billy“ Tauzin
Chairman
The Honorable John D. Dingell
Ranking Minority Member
Committee on Energy and Commerce
House of Representatives:
[End of section]
Appendix I Methods of Assessing Registry Utilization:
Registry utilization is the extent to which patients in need of
unrelated stem cell transplants search the Registry or obtain NMDP-
facilitated transplants. In determining utilization, it is necessary to
use indirect methods to calculate the number of patients in need
because it is impossible to determine this number directly. For
example, although we may be able to obtain data on the number of
patients who have been diagnosed with certain blood and immune system
diseases, we are unable to determine the number for whom stem cell
transplants are the best treatment.
One measure of the utilization of the Registry is the extent to which
the number of patients obtaining transplants facilitated by the
Registry is as high as it could be. The maximum possible utilization of
the Registry would be indicated if the number of U.S. patients
conducting preliminary searches was approximately equal to the
estimated number of patients needing unrelated donor transplants. A
second measure of utilization is the extent to which patients search
the Registry.
The method we used to assess the two aspects of utilization--searching
the Registry and obtaining an NMDP-facilitated transplant--is also used
by NMDP. It involves estimating the number of patients in need of
unrelated donor transplants by using data on the number of HLA-
identical sibling transplants obtained from IBMTR.[Footnote 28] This
method and two alternative methods that are also used by NMDP to assess
utilization by U.S. patients, one based on the number of preliminary
searches conducted and the other based on the incidence of disease, are
described here.
Method Based on Number of HLA-Identical Sibling Transplants:
For the years from 1997 through 2000, we estimated the number of
Caucasian patients in need of unrelated donor transplants based on the
average annual number of Caucasian HLA-identical sibling transplants
performed during those years. To obtain this estimate, we multiplied
the number of HLA-identical sibling transplants, for Caucasians, by the
number of patients of that group that genetic theory predicts--on the
basis of the average number of children born to the women of that
group--are in need of unrelated donor transplants for every Caucasian
HLA-identical sibling transplant in the United States.
The average number of children born to Caucasian women over a lifetime
during the years from 1989 through 1995 was 1.7925.[Footnote 29]
Subtracting the individual who is in need of a transplant gives n =
0.7925 as the number of siblings available to be transplant donors. The
likelihood of a match between two siblings is 25 percent because each
child inherits one-half of each parent‘s HLA genes, resulting in a one
out of four chance of having the same HLA genes as a sibling has.
Therefore, the probability that no sibling HLA identically matches the
one in need is P = (0.75)N . For a Caucasian patient, P = (0.75)0.7925
= 0.796134.
The number of patients in need of unrelated stem cell transplants is
equal to the number of sibling donor transplants multiplied by P/(1 -
P). Therefore, for every HLA-identical sibling transplant recorded for
a Caucasian patient, there will be 0.796134/(1 - 0.796134) = 3.90518
patients in need of unrelated donor transplants. Because there were
7,920 sibling transplants performed for Caucasian patients from 1997
through 2000, we estimate that 3.90518(7,920) = 30,929 Caucasian
patients were in need of stem cell transplants during that period. The
estimates for other racial and ethnic groups are presented in table 2.
Because minorities generally have less access to health care[Footnote
30] and may therefore have less access to sibling transplants
specifically, these estimates were obtained by assuming that each
minority group‘s need for unrelated donor transplants is proportional
to the Caucasian group‘s need. The estimates were obtained by
multiplying the number of persons in the minority group by the
proportion of Caucasians in need of unrelated donor transplants. This
approach implicitly assumes that differences across groups in fertility
rates are of negligible importance in computing the numbers of patients
in need of unrelated donor transplants.
An alternative approach assumes that minorities and Caucasians have
equal access to HLA-identical sibling transplants. Based on this
assumption, this approach derives the needs of minorities for unrelated
donor transplants directly from their observed numbers of HLA-identical
sibling transplants. In doing so, it allows for the possibility that
each group has its own disease incidence rates and that the differences
among groups in their relative levels of sibling donations reflect
these rates, not differences in access. (See table 5.) This approach,
while utilizing somewhat different assumptions from the method above,
produces a virtually identical estimate of the underutilization of the
Registry (10 percent versus 9 percent).
Table 5: Alternate Approach to the Analysis of U.S. Patients‘
Utilization of the Registry, by Race and Ethnicity, 1997 to 2000:
Race/ethnicity: African American; Estimated number of patients without
matched sibling donor[A,B]
(patients in need): 1,880; Actual number of preliminary searches:
1,694; Ratio of number of preliminary searches to number of patients in
need: 0.90; Actual number (percentage) of preliminary searches
resulting in formal searches: 958 (57); Actual number (percentage) of
preliminary searches resulting in NMDP-facilitated transplants: 256
(15); Ratio of number of NMDP-facilitated transplants to number of
patients in need: 0.14.
Race/ethnicity: Asian/Pacific Islander; Estimated number of patients
without matched sibling donor[A,B]
(patients in need): 1,355; Actual number of preliminary searches: 439;
Ratio of number of preliminary searches to number of patients in need:
0.32; Actual number (percentage) of preliminary searches resulting in
formal searches: 270 (62); Actual number (percentage) of preliminary
searches resulting in NMDP-facilitated transplants: 96 (22); Ratio of
number of NMDP-facilitated transplants to number of patients in need:
0.07.
Race/ethnicity: Caucasian; Estimated number of patients without matched
sibling donor[A,B]
(patients in need): 35,964; Actual number of preliminary searches:
10,844; Ratio of number of preliminary searches to number of patients
in need: 0.30; Actual number (percentage) of preliminary searches
resulting in formal searches: 7,079 (65); Actual number (percentage) of
preliminary searches resulting in NMDP-facilitated transplants: 3,321
(31); Ratio of number of NMDP-facilitated transplants to number of
patients in need: 0.09.
Race/ethnicity: Hispanic; Estimated number of patients without matched
sibling donor[A,B]
(patients in need): 1,593; Actual number of preliminary searches:
1,366; Ratio of number of preliminary searches to number of patients in
need: 0.86; Actual number (percentage) of preliminary searches
resulting in formal searches: 840 (61); Actual number (percentage) of
preliminary searches resulting in NMDP-facilitated transplants: 317
(23); Ratio of number of NMDP-facilitated transplants to number of
patients in need: 0.20.
Race/ethnicity: Native American; Estimated number of patients without
matched sibling donor[A,B]
(patients in need): 97; Actual number of preliminary searches: 80;
Ratio of number of preliminary searches to number of patients in need:
0.82; Actual number (percentage) of preliminary searches resulting in
formal searches: 56 (70); Actual number (percentage) of preliminary
searches resulting in NMDP-facilitated transplants: 20 (25); Ratio of
number of NMDP-facilitated transplants to number of patients in need:
0.21.
Race/ethnicity: Other; Estimated number of patients without matched
sibling donor[A,B]
(patients in need): 290; Actual number of preliminary searches: 365;
Ratio of number of preliminary searches to number of patients in need:
1.26; Actual number (percentage) of preliminary searches resulting in
formal searches: 213 (58); Actual number (percentage) of preliminary
searches resulting in NMDP-facilitated transplants: 39 (11); Ratio of
number of NMDP-facilitated transplants to number of patients in need:
0.13.
Race/ethnicity: Total; Estimated number of patients without matched
sibling donor[A,B]
(patients in need): 41,179; Actual number of preliminary searches:
15,231[C]; Ratio of number of preliminary searches to number of
patients in need: 0.37; Actual number (percentage) of preliminary
searches resulting in formal searches: 9,623 (63); Actual number
(percentage) of preliminary searches resulting in NMDP-facilitated
transplants: 4,056 (27); Ratio of number of NMDP-facilitated
transplants to number of patients in need: 0.10.
Note: This table presents an alternate approach to that given in table
2.
[A] Number of HLA-identical sibling transplants multiplied by the
number of patients expected to be without matched sibling donors for
each such transplant was derived from data obtained from the
Statistical Center of the IBMTR and Autologous Blood and Marrow
Transplant Registry (ABMTR). (The analysis has not been reviewed or
approved by the Advisory Committees of the IBMTR and ABMTR.):
[B] Numbers based on the HLA-identical sibling transplants of the
designated race/ethnicity plus a portion of those of unknown race/
ethnicity. These unknowns submitted record forms that did not ask about
race/ethnicity. The unknowns can be assumed to be similar in racial/
ethnic distribution to the other patients, and so we distributed them
among the racial/ethnic groups according to that distribution. It can
therefore be assumed that there is no racial bias in this estimation
method.
[C] Includes 443 preliminary searches, not included elsewhere in the
column, from patients of unknown race/ethnicity.
Source: GAO analysis of data from the Statistical Center of the IBMTR
and ABMTR and NMDP.
[End of table]
Method Based on Number of Preliminary Searches:
The second method used by NMDP to assess Registry utilization is based
simply on the annual number of patients conducting preliminary
searches. In order to use this method, one must assume that this number
directly represents those in need of unrelated donor transplants. One
cannot assess the extent to which those in need search the Registry on
the basis of this number since the number itself is the number of
patients searching. However, one can assess the extent to which those
in need obtain NMDP-facilitated transplants by considering the annual
percentage of patient searches that result in NMDP-facilitated
transplants. This method yields an estimate of the patients searching
who obtain NMDP-facilitated transplants of 27 percent. (See table 5.):
Although this approach has been used by NMDP as a way of assessing
utilization, officials at NMDP observe that the validity of this
approach to utilization assessment is limited by the freedom with which
patients can choose whether to search. These officials point out that
preliminary searches are performed for some patients who are not good
candidates for transplant and that other patients who should submit
preliminary searches probably do not. Because of the lack of
correspondence between the number of patients in need and the number
performing preliminary searches, this estimate is not likely to be as
accurate as the other two.
Method Based on Incidence of Disease:
The third method used by NMDP is based on an estimate of the annual
number of U.S. patients newly diagnosed from 1997 through 2000 with
selected diseases that might benefit from unrelated stem cell
transplants.[Footnote 31] The estimated number of potential recipients
for each disease is obtained from disease incidence estimates, with
adjustments for the likelihood that (1) the patient is young enough to
benefit from transplantation, (2) disease severity is not so great as
to make transplantation futile, and (3) an HLA-identical sibling donor
is available, thereby making unrelated donor transplant unnecessary.
The ratio of the annual number of NMDP-facilitated transplants for U.S.
patients diagnosed with these selected diseases during this period to
the estimated number of new U.S. patients with the diseases is used to
assess utilization.[Footnote 32] (See table 6.) The ratio, for all
patients with the selected diseases, corresponds to an estimated
percentage of candidates obtaining transplants--10 percent--that is
very close to the estimate obtained by the first method. The validity
of this third method is constrained by the limited number of diseases
for which data are available.
Table 6: Average Annual Unrelated Donor NMDP-Facilitated Transplants
and Estimated Number of Potential Recipients for U.S. Patients with
Selected Diseases Who Might Benefit from Unrelated Stem Cell
Transplants, by Race/Ethnicity, 1997 through 2000:
Race/ethnicity: African American; Acute lymphocytic leukemia: 8; Acute
myelogenous leukemia: 12; Chronic myelogenous leukemia: 18; Non-
Hodgkin‘s lymphoma: 4; Total: 42.
Race/ethnicity: Caucasian; Acute lymphocytic leukemia: 121; Acute
myelogenous leukemia: 197; Chronic myelogenous leukemia: 161; Non-
Hodgkin‘s lymphoma: 68; Total: 547.
Race/ethnicity: Hispanic; Acute lymphocytic leukemia: 24; Acute
myelogenous leukemia: 12; Chronic myelogenous leukemia: 14; Non-
Hodgkin‘s lymphoma: 2; Total: 52.
Race/ethnicity: Native American; Acute lymphocytic leukemia: 1; Acute
myelogenous leukemia: 1; Chronic myelogenous leukemia: 1; Non-Hodgkin‘s
lymphoma: 0; Total: 3.
Race/ethnicity: Asian/Pacific Islander; Acute lymphocytic leukemia: 6;
Acute myelogenous leukemia: 5; Chronic myelogenous leukemia: 4; Non-
Hodgkin‘s lymphoma: 1; Total: 16.
Race/ethnicity: Other; Acute lymphocytic leukemia: 2; Acute myelogenous
leukemia: 1; Chronic myelogenous leukemia: 2; Non-Hodgkin‘s lymphoma:
0; Total: 5.
Race/ethnicity: Total number of NMDP-facilitated transplants; Acute
lymphocytic leukemia: 162; Acute myelogenous leukemia: 228; Chronic
myelogenous leukemia: 200; Non-Hodgkin‘s lymphoma: 75; Total: 665.
Race/ethnicity: Estimated number of new U.S. patients with selected
diseases who might benefit from unrelated stem cell transplants; Acute
lymphocytic leukemia: 1,359; Acute myelogenous leukemia: 662; Chronic
myelogenous leukemia: 761; Non-Hodgkin‘s lymphoma: 4,081; Total: 6,863.
Race/ethnicity: Percentage of new patients who receive NMDP-facilitated
transplants; Acute lymphocytic leukemia: 12; Acute myelogenous
leukemia: 34; Chronic myelogenous leukemia: 26; Non-Hodgkin‘s lymphoma:
2; Total: 10.
Sources: GAO analysis of data from NMDP and the National Cancer
Institute‘s Surveillance, Epidemiology, and End Results program.
[End of table]
[End of section]
Appendix II How NMDP Achieves Network Compliance with Selected
Standards and Procedures:
NMDP requires that the organizations participating in its network
comply with its standards and procedures. This appendix discusses how
NMDP achieves the compliance by network organizations with standards
and procedures for obtaining the informed consent of donors and
patients, donor selection criteria, confidentiality of records,
collection and transportation of marrow, laboratory standards, and
maintenance of donor files in the Registry.
Informed Consent of Donors and Patients:
At each stage of the search process, NMDP requires donors to sign
informed consent statements for procedures performed at the donor and
transplant centers.[Footnote 33] A volunteer must sign an informed
consent form before being listed as a donor on the Registry, and also
before the collection of blood for initial and follow-up testing,
infectious disease testing, and participation in research. In addition,
consent must be obtained before notifying the transplant center that a
donor is willing to proceed to marrow donation and before the
administration of anesthesia. Consent must also be obtained before
collecting blood specimens for research and before any proposed
procedure for which the donor has not previously given consent.
According to NMDP officials, during each donor center site visit, NMDP
staff members review about 35 randomly selected donor files. NMDP staff
members check that each donor has signed all appropriate consent forms
for the stages of the recruitment and search process the donor has
completed. According to an NMDP official, since NMDP began performing
site visits in 1998, missing or unsigned donor consent forms occurred
in only a few cases, indicating that a high level of compliance has
been achieved. The number of missing consent forms is not readily
available because cumulative data are not permanently stored.
Transplant centers are responsible for obtaining informed consent from
each transplant patient, for collecting research blood samples that are
sent to the NMDP repository, and for submitting baseline and follow-up
data to the Registry. Some of the centers have separate consent forms
specifically for the research samples and clinical data, whereas others
incorporate consent for the research samples and clinical data into the
informed consent document the patient signs for the transplant.
NMDP is currently collecting information on how transplant centers are
handling the informed consent process for the research samples and
clinical data submitted to NMDP. This information will be analyzed, and
NMDP will evaluate whether changes in policies or procedures should be
made to the consent process for obtaining NMDP data and research blood
samples.
Criteria for Donor Selection:
In order to be considered for stem cell donation, donors must be from
age 18 through 60 and in good health. Individuals with serious illness
or those who are significantly overweight are disqualified. The donor
must provide a medical history and acknowledge in writing that the
history is accurate. Pertinent donor medical information is evaluated
for acceptance or deferral according to NMDP medical eligibility
standards and criteria set by the medical director at the local donor
center.
NMDP monitors whether registered donors have filled out the appropriate
medical history questionnaires, but NMDP does not store cumulative data
on the number of missing medical history questionnaires. During each
donor center site visit, NMDP staff members check a random number of
health history questionnaires. However, NMDP is limited in how it
monitors the donor selection process. Although NMDP tracks the number
of donors who are unavailable for medical reasons, it cannot determine
whether an unavailable donor‘s medical condition was preexisting, and
therefore should have been caught in the health screening at the time
the donor volunteered, or whether the donor‘s health changed during the
period between registration and a request for testing prior to
donation.
Methods to Protect Confidentiality:
NMDP requires that each participating donor center have a system for
safeguarding donor confidentiality. The Registry identifies donors by
code number only. Donor centers maintain donor identity and location
and limit access to this information by using locked file cabinets and
locked rooms.
NMDP also requires that each participating transplant center have a
system of confidentiality in place to protect the privacy of patients.
It provides that transplant patient identification should not appear on
papers or publications, and the patient‘s name and location should not
be disclosed to the donor(s).
Marrow Collection and Transport:
Organizations responsible for marrow collection and transport must meet
certain participation criteria in order to be affiliated with NMDP.
Among other things, participating cord blood banks must be accredited
and licensed or registered by the Food and Drug Administration for
collection of autologous blood. Marrow collection centers must provide
emergency and intensive care services and must be accredited by the
Joint Commission on Accreditation of Healthcare Organizations. In
addition, each collection center must have a licensed medical director,
an experienced marrow collection team that regularly collects bone
marrow, and a designated site for management of collection activities.
NMDP has established standards to ensure the proper collection and
transportation of marrow. These require that bone marrow collection
centers have experienced personnel to collect marrow and adequate
resources to support collection and management activities. In addition,
NMDP requires that collection centers maintain written standard
operating procedures and policies for collecting, testing, labeling,
and transporting marrow.
Laboratory Standards:
Laboratories responsible for HLA tissue typing must meet certain
criteria in order to be affiliated with NMDP. Participating HLA typing
laboratories must be accredited by the American Society for
Histocompatibility and Immunogenetics (ASHI)[Footnote 34] or the
European Foundation for Immunogenetics for techniques required by NMDP.
Laboratories must also comply with all state and federal regulations,
including the Clinical Laboratory Improvements Amendments of 1988 (or
their non-U.S. equivalent) for infectious disease testing, blood
typing, red cell antibody screening, and other tests required by NMDP.
As part of NMDP‘s quality control program, participating laboratories
must type blind samples provided by NMDP. The laboratories must
maintain monthly error rates less than or equal to 1.5 percent. If a
laboratory fails to meet quality control and quality assurance
standards established by ASHI or NMDP, NMDP may require that laboratory
to submit a corrective action plan. After the period allowed for
corrective action, the laboratory‘s contract with NMDP may be
terminated if it still does not meet the standards.
From February 2000 through April 2002, NMDP suspended five laboratories
responsible for HLA tissue typing. The length of suspension ranged from
1 to 9 weeks, and reasons for suspension were related to electronic
communication problems, overdue samples, and poor turnaround time.
Donor File Maintenance and Updates:
NMDP‘s central database is updated when new donors are recruited and
when information on existing donors changes or donors are deleted from
the Registry. Information about newly recruited donors includes donor
identification numbers, demographic data, and the donors‘ HLA types.
According to NMDP procedures, domestic donor centers submit data on
donors daily through NMDP‘s central database.
[End of section]
Appendix III Comments from the Health Resources and Services
Administration:
SEP 12 2002:
TO: Janet Heinrich:
Director, Health Care - Public Health Issues:
FROM: Administrator:
SUBJECT: General Accounting Office Draft Report ’Bone Marrow
Transplants: Despite Recruitment Success, National Program May Be
Underutilized“ (GAO-02-994):
Thank you for the opportunity to provide comments on the subject draft
report. Attached please find HRSA‘s comments.
Questions may be referred to John Gallicchio on (301) 443-3099.
Betty James Duke
Signed by Betty James Duke
Attachment:
HRSA Comments on the Draft GAO Report: ’Bone Marrow Transplants:
Despite Recruitment Successes, National Program May Be Underutilized“
(GAO-02-994):
General Comments:
The Health Resources and Services Administration (HRSA) appreciates the
opportunity to review the draft of the report: ’Bone Marrow
Transplants: Despite Recruitment Successes, National Program May Be
Underutilized“ (GAO-02-994). The report provides an accurate and
helpful overview of the status of the National Bone Marrow Donor
Registry, with respect to the study mandated in the National Bone
Marrow Registry Reauthorization Act of 1998. The report notes the
substantial progress that has been made in achieving the statutory
goals for the Registry, and recognizes that the challenges facing the
Registry today are not amenable to simple solutions. We are enclosing
HRSA‘s substantive comments on the draft report and a number of
technical comments for your consideration as you develop the final
report. We shared the draft report with HRSA‘s National Marrow Donor
Program (NMDP) and have incorporated their suggestions in our comments.
We would like to comment on four aspects of the draft report. The first
is progress in improving minority access to transplants through the
Registry. The report notes that recruitment efforts focused on minority
populations have increased the representation on the Registry of the
major minority population groups to levels approximately equal to their
shares of the U.S. population, and that for all racial and ethnic
groups the likelihood of finding a match through the Registry has
increased as the Registry has grown. Still, the likelihood of finding a
match differs by race, with African Americans having the lowest
probability of finding a match, in large part because of their greater
variety in HLA types. The report concludes that some minority groups,
especially African Americans, may never achieve the same probability of
finding a match as Caucasians, and that attempting to close the gap
through recruitment of donors with rare HLA types is expensive and may
divert resources from another statutory goal for the program,
increasing the overall number of patients who find a match and receive
a transplant through the Registry.
We agree that recruitment of donors cannot be the sole strategy for
improving access to unrelated donor transplants for minority patients,
or for other patients with unusual HLA types. Also important are
leaming which less-than-perfect HLA matches may still lead to
successful transplants, and how to more effectively manage
complications that arise in unrelated donor transplants; improving the
retention of donors who have joined the Registry; encouraging patients
who may need an unrelated donor transplant (and their physicians) to
begin a search of the registry soon after their diagnosis; providing
expert assistance in difficult searches; and increasing the
effectiveness of umbilical cord blood as a source of blood stem cells
for patients who cannot find a matched adult donor. The Registry is
actively involved in all these areas. We think these efforts, along
with continued recruitment of donors to replace those who are lost to
attrition and to add:
unique HLA types to the Registry, can result in further improvements in
access for all populations. The appropriate level of recruitment in the
future will depend, among other things, on whether the cost of tissue
typing continues to decline.
With respect to current minority representation on the Registry, we
would note that the Registry donor file is comprised of two distinct
components defined by the amount of HLA typing data available. The
larger portion (3,081,642 as of June 30, 2002) has donors fully typed
for HLA-A, -B and -DR. The remainder (35%) is typed only for HLA-A and
-B. The vast majority of actual donors (>98%) are selected from the
fully typed portion. In this most active portion of the donor file,
each racial and ethnic group, with the exception of Caucasians,
comprises a larger proportion of the file than their representation in
the U.S. population.
The report also concludes that the Registry is underutilized. We agree
that many patients who could benefit from an unrelated donor transplant
never consult the Registry or do so too late in the course of their
illness. Many of the ongoing efforts listed above aim to increase
utilization of the Registry as well as increase the probability that a
patient will find a matching donor on the Registry. We question,
however, one specific GAO finding, that the percentage of patients in
need of an unrelated donor transplant who search the Registry is much
greater for African American, Hispanic and American Indian patients
than for Caucasians. The method used to estimate the number of patients
in need, as reported in Table 2, may involve an incorrect assumption.
The calculation used data from the International Bone Marrow Transplant
Registry reporting the race of related donor transplant recipients. GAO
combined these data with fertility data to compute an estimated number
of transplant candidates without matching sibling donors. This approach
assumes that all appropriate candidates for sibling transplant are in
fact transplanted. That is, there are no disparities in access to
related donor transplant between racial and ethnic groups. Since many
studies have found that minorities do not have the same access to
health care as Caucasians, this assumption may be incorrect.
Finally, we wish to comment on the time required to complete a search
of the Registry. The report notes that the median search time has been
decreasing, but that searches still frequently take many months and
sometimes over a year. The median search time for all patients is a
convenient way to present data, but many factors affect search duration
including the optimal timeframe for transplantation for each patient.
For example, a transplant center may initiate a search for a patient at
the same time they enroll the patient in a clinical trial of a new
pharmaceutical agent. If the patient responds, he or she may not be a
transplant candidate for several years but the transplant center may
want to identify a potential donor, in case the patient‘s clinical
condition changes suddenly. In situations like this, a search may be
ongoing for a long period of time without disadvantaging the patient.
Alternatively, a patient with acute leukemia may need a transplant as
soon as a suitable donor can be identified and prepared for donation.
Decreasing search times for those patients who need to proceed to
transplant rapidly is a major priority of the program. The NMDP has
shown in a pilot project that it is possible to complete medically
urgent searches in 14-21 days. Drawing on the lessons of the pilot
project, the NMDP has made numerous procedural changes and beginning in
September,
2002 will offer transplant centers the option of requesting that an
urgent search be completed in 21 days or 45 days. The percentage of
these urgent searches completed in the requested timeframe will be a
more useful measure of performance than an overall median search time.
[End of section]
Appendix IV: GAO Contact and Staff Acknowledgments:
GAO Contact:
Marcia Crosse, (202) 512-3407:
Acknowledgments:
The following staff members made important contributions to this work:
Donna Bulvin, Charles Davenport, Donald Keller, Kelly Klemstine, Behn
Miller, and Roseanne Price.
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FOOTNOTES
[1] The first source of stem cells for transplant was bone marrow, but
now stem cells from the bloodstream or from umbilical cord blood can
also be used. We use the term stem cell transplant to include both bone
marrow transplants and transplants involving one of these newer sources
of stem cells.
[2] We use the term donors throughout this report to refer to potential
donors on the Registry, most of whom have not donated stem cells, only
expressed their willingness to do so.
[3] The Navy was instrumental in the founding of the Registry and has
maintained its interest in stem cell donation over the years. HRSA and
the Navy each contributed a little less than 20 percent of the
Registry‘s fiscal year 2002 funding (about $21 million and $20.5
million, respectively), with program revenue and private sources
providing the rest of the total of about $108 million.
[4] U.S. General Accounting Office, Bone Marrow Transplants: National
Program Has Greatly Increased Pool of Potential Donors, GAO/HRD-93-11
(Washington, D.C.: Nov. 4, 1992).
[5] HHS OIG, National Marrow Donor Program: Financing Donor Centers,
OEI-01-95-00123 (Washington, D.C.: December 1996).
[6] Pub. L. No. 105-196, 112 Stat. 631 (1998).
[7] IBMTR is not a donor registry; it records data about transplants
performed.
[8] Almost 90 percent of the transplants coordinated by NMDP are for
types of cancer, including, in descending order of frequency, chronic
myelogenous leukemia, acute myelogenous leukemia, acute lymphocytic
leukemia, myelodysplastic disorders, and non-Hodgkin‘s lymphoma. The
nonmalignant diseases most commonly treated by stem cells obtained
through NMDP are aplastic anemia and several varieties of inherited
disorders of the metabolic, immune, and blood systems.
[9] For example, the age-adjusted incidence rate per 100,000 patients
with acute myelogeneous leukemia over the period from 1995 through 1999
is higher for Caucasians (3.7) than for African Americans (2.9). In
contrast, for patients with myeloma, the rate is higher for African
Americans (11.5) than for Caucasians (5.2).
[10] An antigen is a protein found on the outside of most cells in the
body that induces the formation of antibodies. There are a number of
antigens in the human body, and HLA are a set of these.
[11] Recruitment groups actively seek donors, sometimes ones of a
particular ethnic or racial heritage.
[12] Apheresis is a technique for separating blood into its components,
using a machine that draws blood from a vein in a donor‘s arm; filters
out the desired product, such as PBSC; and returns the remaining blood
to the donor.
[13] There are seven such donor centers. Three of these are in Germany,
and the others are located in the Netherlands, Israel, Sweden, and
Norway.
[14] HRSA consults with the Department of State on proposed membership
of foreign organizations.
[15] These countries are Australia, Austria, Canada, the Czech
Republic, England, France, Ireland, Italy, Japan, Singapore, Spain,
Switzerland, and Taiwan.
[16] For example, the American Bone Marrow Donor Registry of
Mandeville, Louisiana, is composed of a Patient Advocacy Office that
coordinates and processes search requests and a Donor Services Division
that educates, recruits, and maintains the records of donors. Moreover,
it has regional components, also called registries. Other U.S.
registries include the Caitlin Raymond International Registry of
Worcester, Massachusetts, and the Gift of Life Foundation of Boynton
Beach, Florida. In addition, there are a number of U.S. cord blood
banks including ones in New York, New Jersey, Missouri, and
Massachusetts (part of the Caitlin Raymond International Registry).
[17] Donors are considered too old to donate at age 61.
[18] These include confirmation of donor availability and willingness,
satisfactory results of laboratory tests done on the donor, and the
patient‘s desire to continue the search.
[19] For example, the African American difference of 2 percentage
points is 17 percent of that group‘s 12 percent share of the
population.
[20] This probability was computed in 2001 by considering all patients
who had searched the Registry by that time and, using NMDP‘s matching
criteria, asking what proportion of these would have found a match
during each year of the Registry‘s existence, given the donors on the
Registry during that year. This theoretical probability has advantages
over the observed proportion of matches as a measure of access by
patients. One is that a large and representative number of searching
patients are repeatedly applied to the Registry over its history so
that any fluctuations cannot be a result of fluctuations in the numbers
or kinds of patients searching from year to year. Another advantage is
that today‘s definition of a match has been applied throughout the
years covered so that any fluctuations cannot be a result of changes in
that definition over the years.
[21] A fully typed donor is one for whom all crucial antigens are
determined at the time the donor volunteers.
[22] See app. I for an explanation of how we estimated the number of
patients in need.
[23] NMDP has used a similar method of estimation and draws a similar
conclusion about possible underutilization.
[24] Cancellation of a preliminary search means that 45 days have
occurred since the search without a formal search having been
initiated. Cancellation of a formal search means that the transplant
center has submitted a particular form indicating a desire to terminate
the search and included a reason for doing so.
[25] Although several blood banks list their cord blood units with
NMDP, others, including the largest, the New York Blood Center, do not,
and thus NMDP cannot facilitate transplants from those banks.
[26] Under CPI, NMDP allows up to three notices of noncompliance with a
particular standard and sets interim goals to be met within a specified
review period after each notice. After a third notice, centers are
placed on probation. Failure to meet the requirements of the
probationary period may result in termination.
[27] The HHS OIG recommended that HRSA standardize contracts between
NMDP and donor centers for donor services to improve the cost
efficiency of the centers and to link payment to performance. HRSA
included this requirement in its 1997 contract with NMDP to operate the
Registry.
[28] This registry, located in Milwaukee, registers bone marrow
transplants, not donors like the other registries discussed in this
report. The data used in our estimations were obtained from the
Statistical Center of IBMTR and Autologous Blood and Marrow Transplant
Registry (ABMTR). The analysis has not been reviewed or approved by the
Advisory Committees of the IBMTR and ABMTR.
[29] We determined this average by taking the median Caucasian
fertility rate for the years from 1989 through 1995. Fertility rates
for non-Hispanic Caucasians were not available for earlier years. We
did not include rates for years after 1995 because we do not think many
of the transplants occurring during the years 1997 through 2000 were
done for patients born after 1995. Because fertility rates tended to be
higher before about 1973, when some of the patients seeking transplants
during the period of our analysis, 1997 through 2000, were born, the
use of the 1989 through 1995 rates results in an underestimation of the
average number of siblings and a consequent overestimation of the
number of patients in need of unrelated donor transplants. The effect
of this consideration of the 1989 through 1995 rates is counterbalanced
to an unknown extent because (1) the fertility rates count half
siblings and dead siblings as well as living full siblings and (2) the
fertility rates count all of a woman‘s live births, including those
that occur after the patient needs a transplant. The effect of these
two counterbalancing considerations is to overestimate of the number of
siblings available to donate and underestimate the number of patients
in need. The net effect of the choice of 1989 through 1995 rates and
the considerations concerning the fertility rates on the estimation of
the number of patients in need is not known.
[30] See, for example, R.M. Mayberry, F. Mili, and E. Ofili, ’Racial
and Ethnic Differences in Access to Medical Care,“ Medical Care
Research and Review, vol. 57, Supplement 1 (2000), pp. 108-145.
[31] R.P. Gale, ’Potential Utilization of a National HLA-Typed Donor
Pool for Bone Marrow Transplantation,“ Transplantation, vol. 42, no. 1
(1986), pp. 54-58.
[32] We have not related the number of potential recipients estimated
in this third way with the numbers of preliminary searches for patients
with the selected diseases, only with the numbers of transplants.
[33] Informed consent refers to the process of helping an individual
weigh the risks against the benefits of a procedure or treatment. By
signing a form, an individual consents to undergo a procedure after
being fully informed of the risks and benefits.
[34] ASHI is an accrediting body that has established standards that
all histocompatibility laboratories must meet if their services are to
be considered acceptable.
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