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. They strike all races, although one racial group or another may have a higher incidence rate for a particular disease. 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. 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. 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. 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. In support of the Registry, NMDP manages a worldwide network consisting of more than 400 donor centers, recruitment groups, contract laboratories where tissue is typed, apheresis centers, 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. 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. NMDP has also signed cooperative agreements with national registries in 13 foreign countries. 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. These other registries, however, are relatively small; often specialize in donors from particular racial or ethnic groups; and are private, with no national requirements. 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 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, 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. 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. 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. 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. 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. 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. 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.) 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. 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 donorsthe incremental cost of adding these rare genetic types to the donor poolis 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. 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. 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. 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. 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. 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. 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 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, 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. 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. 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 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 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. 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. 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. 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. 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. 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. 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. 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. 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. 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) . 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 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). 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. 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. 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. (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. 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. At each stage of the search process, NMDP requires donors to sign informed consent statements for procedures performed at the donor and transplant centers. 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. 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. 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). 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. 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) 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. 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. The following staff members made important contributions to this work: Donna Bulvin, Charles Davenport, Donald Keller, Kelly Klemstine, Behn Miller, and Roseanne Price.

Summary: 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.