oversight

NIH-Funded Research: Therapeutic Human Fetal Tissue Transplantation Projects Meet Federal Requirements

Published by the Government Accountability Office on 1997-03-10.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

                 United States General Accounting Office

GAO              Report to the Chairmen and Ranking
                 Minority Members, Committee on Labor
                 and Human Resources, U.S. Senate, and
                 Committee on Commerce, House of
                 Representatives
March 1997
                 NIH-FUNDED
                 RESEARCH
                 Therapeutic Human
                 Fetal Tissue
                 Transplantation
                 Projects Meet Federal
                 Requirements




GAO/HEHS-97-61
      United States
GAO   General Accounting Office
      Washington, D.C. 20548

      Health, Education, and
      Human Services Division

      B-276018

      March 10, 1997

      The Honorable James M. Jeffords
      Chairman
      The Honorable Edward M. Kennedy
      Ranking Minority Member
      Committee on Labor and Human Resources
      United States Senate

      The Honorable Thomas J. Bliley, Jr.
      Chairman
      The Honorable John D. Dingell
      Ranking Minority Member
      Committee on Commerce
      House of Representatives

      Therapeutic human fetal tissue transplantation is a promising area of
      research that may have application for a broad range of diseases, such as
      juvenile diabetes and leukemia. Current federally funded research projects
      use fetal tissue—cells from electively aborted fetuses—to treat patients
      with Parkinson’s disease. Although this research holds promise for
      treating diseases, concerns have been raised about the acceptance of fetal
      tissue transplantation; that is, some women might choose to conceive for
      the sole purpose of aborting their fetuses, so that tissue could be provided
      to treat family members or to supply fetal material for financial gain.

      In March 1988, the Department of Health and Human Services (HHS)
      imposed a moratorium on the use of federal funds for research projects on
      therapeutic human fetal tissue transplantation until a panel, appointed by
      HHS, could study the ethical issues involved.1 In the fall of 1988, the panel
      concluded that the use of human fetal tissue in research is acceptable
      public policy, but the moratorium remained until the President ordered it
      lifted in January 1993. At the same time, the Secretary, HHS, directed the
      National Institutes of Health (NIH) to develop interim guidelines for the
      support and conduct of such research projects “to ensure that federal
      funding of human fetal tissue transplantation research does not encourage
      the choice of abortion.” In June 1993, the NIH Revitalization Act of 1993
      (P.L. 103-43) was enacted, a part of which establishes the conditions under
      which federally funded therapeutic human fetal tissue transplantation
      research can take place.2

      1
       During the moratorium, private funding was used for therapeutic transplantation studies.
      2
       The NIH interim guidelines were withdrawn when P.L. 103-43 was enacted.



      Page 1                                            GAO/HEHS-97-61 Fetal Tissue Transplantation
B-276018




The NIH Revitalization Act of 1993 requires us to carry out a compliance
review of research on fetal tissue transplantation conducted or supported
by HHS. Specifically, the act requires that we (1) determine compliance
with informed consent and other documentation and (2) report on any
violations occurring in the acquisition of human fetal tissue for use in
transplantation.

To determine compliance with the requirements of the act, we met with
federal officials and with project personnel at two institutions awarded
grants for federally funded research on therapeutic human fetal tissue
transplantation. The federal officials gave us information from NIH’s Office
for Protection from Research Risks (OPRR),3 Office of Science Policy, and
the National Institute of Neurological Disorders and Stroke (NINDS). This
information included project funding and status, as well as institutional
procedures for ensuring protection for human subjects.

We visited the project personnel at the University of Colorado Health
Sciences Center in Denver, Colorado, and the Mount Sinai Medical Center
in New York City, as well as its affiliated site at the University of South
Florida in Tampa, Florida.4 We spoke with the principal investigators and
the chairs of the institutional review boards.5 In addition, we examined
documents used for the research projects, including consent forms and
statements of the attending physicians. In reviewing such documents, we
were mindful of the confidentiality granted to the project participants and
of the integrity of the double-blind research methodology. These
double-blind research projects were designed so that neither the recipients
nor the researchers who evaluate the outcome of the transplant surgery
knew which patients were in the experimental group and which in the
control group. In our workpapers, we did not record the names of the
donors or recipients, nor any of the dates on which the transplantations
took place. We reviewed the relevant documents to ensure that the proper
number of forms were present and that consent had been obtained on or
before the dates that transplantations were performed.


3
 OPRR has the responsibility for ensuring that institutions awarded grants for research on fetal tissue
transplantation comply with the act’s requirements for informed consent and other human subject
protection.
4
 The University of South Florida is “affiliated” because it receives funding from Mount Sinai’s NIH
award. We needed to visit South Florida because it had relevant documents.
5
 Institutional review boards are responsible for examining research proposals and ongoing studies in
order to ensure protection of human subjects from risks. These boards, composed mainly of scientists
at institutions doing the research, are required to report to the NIH any violations or unanticipated
problems involving risks to subjects.



Page 2                                             GAO/HEHS-97-61 Fetal Tissue Transplantation
                   B-276018




                   We conducted our review from October 1996 to December 1996 in
                   accordance with generally accepted government auditing standards.


                   In general, the requirements of the act are being complied with. The act’s
Results in Brief   documentation requirements—pertaining to informed consent of donors
                   and “donees” (recipients) and compliance statements made by institutions,
                   researchers, and attending physicians—were met. HHS did not submit
                   annual reports on the program’s activities, however, as required by the act.
                   But the agency did submit a combined report on January 29, 1997,
                   describing the activities from fiscal years 1993 through 1995.

                   There have been no reported violations in the acquisition of human fetal
                   tissue for use in transplantation, according to NIH and our verification
                   efforts.


                   Between fiscal years 1993 and 1996, NIH awarded over $6 million for five
Background         extramural projects involving therapeutic human fetal tissue research.
                   Two projects—at the University of Colorado Health Sciences Center and
                   the Mount Sinai Medical Center—involved actual transplantation of fetal
                   tissue. These projects accounted for about $5.9 million of the funds. Both
                   were funded by NINDS, which expects to continue funding these projects in
                   fiscal year 1997. The remaining three projects—at Yale University School
                   of Medicine, University of Colorado Health Sciences Center, and Columbia
                   University College of Physicians and Surgeons—totaling about $280,000,
                   were funded through NIH’s National Center for Research Resources (NCRR)
                   grants at General Clinical Research Center (GCRC) sites. For these three
                   projects, funds were not spent to transplant fetal tissue, but to clinically
                   observe Parkinson’s patients before and after transplant surgery. (For
                   more detailed funding information, see app. I).

                   No intramural projects involving therapeutic human fetal tissue
                   transplantation have been funded. At the time of our review, no new
                   projects on therapeutic human fetal tissue transplantation were being
                   proposed for funding by January 1997.




                   Page 3                               GAO/HEHS-97-61 Fetal Tissue Transplantation
                          B-276018




                          The act contains the following eight requirements for research on human
Ongoing Projects          fetal tissue transplantation:
Have Complied With
the Requirements of       (1) Informed consent of the donor: The woman providing the tissue
                          must make a signed written statement, declaring that she is donating fetal
the Act                   tissue for research, without any restrictions on, or awareness of, who the
                          tissue recipient will be.

                          (2) Attending physician statement: The physician responsible for
                          obtaining the tissue from the woman involved must make a signed written
                          statement declaring that

                      •   in the case of tissue obtained through an induced abortion, consent for the
                          abortion preceded consent for the tissue donation, the timing of the
                          abortion was not solely for purposes of obtaining the tissue, and the
                          abortion was performed in accordance with state law;
                      •   the woman gave informed consent, as described in (1) above; and
                      •   the donor was given full disclosure of any interest the physician has in the
                          research use of the tissue and any known medical risks and privacy risks
                          associated with the tissue donation.

                          (3) Principal researcher statement: The individual with the principal
                          responsibility for conducting the research must make a signed written
                          statement indicating awareness that the tissue obtained is human tissue,
                          that it may have been obtained through a spontaneous or induced abortion
                          or a stillbirth,6 and that it was donated for research purposes. The
                          statement also must indicate that the researcher

                      •   has provided such information to others with responsibilities for the
                          research,
                      •   will obtain written acknowledgment from the tissue recipient of the
                          receipt of such information, and
                      •   has not been involved in the timing of, or method used, in the abortion.

                          (4) Informed consent of the recipient: The individual to be a recipient
                          of a transplantation of tissue must provide written acknowledgment, as
                          described in (3) above.




                          6
                           Due to concerns about the quality of the tissue, only tissue obtained from induced abortions is used in
                          research on therapeutic human fetal tissue transplantation.



                          Page 4                                             GAO/HEHS-97-61 Fetal Tissue Transplantation
B-276018




(5) Availability of statements for audit: The head of each agency or
entity conducting the research must certify to the Secretary of HHS that the
required statements (1 to 4) will be available for audit by the Secretary.

(6) Compliance with state law: The recipients of funding for research
on fetal tissue transplantation must agree to conduct research in
accordance with applicable state law.

(7) HHS annual report: HHS is required to submit annual reports to the
House Committee on Commerce and the Senate Committee on Labor and
Human Resources, describing the fetal tissue transplantation activities
carried out during the preceding fiscal year and discussing whether those
activities were carried out in accordance with the law.

(8) Tissue purchase and donation restrictions: The purchase of
human fetal tissue is prohibited. In addition, donated tissue can not be
transplanted into a recipient specified by the donor, such as a relative of
the donor, nor can a person acquiring tissue pay costs associated with the
abortion. Violators are subject to fines or imprisonment or both.

In general, the research projects we reviewed were in compliance with the
requirements of the act. See table 1 for a summary of our methodology and
findings, which verify compliance.




Page 5                               GAO/HEHS-97-61 Fetal Tissue Transplantation
                               B-276018




Table 1: GAO Verification of
Compliance With Requirements   Requirement of the act               Methodology and findings
of the Act                     (1) Informed consent of donor        We checked for the inclusion of the required statements
                               (2) Attending physician              on the forms used by the projects,a and verified that the
                                  statement                         required forms were in the project files and were properly
                               (3) Principal researcher             executed. Documentation for both projects met the
                                  statement                         requirements of the law.
                               (4) Informed consent of
                                  recipient
                               (5) Availability of statements       We checked whether the institutions involved in this
                                  for audit                         research had submitted institutional assurances to NIH
                                                                    that covered the audit requirements. Each institution
                                                                    involved had submitted such an assurance.
                               (6) Compliance with state law We checked whether the institutions involved in this
                                                             research had submitted institutional assurances to NIH
                                                             that covered the state law requirements. Each institution
                                                             involved had submitted such an assurance.
                               (7) HHS annual report                We checked on HHS submission of reports to the
                                                                    Congress. HHS was not in compliance with the annual
                                                                    requirement. The agency submitted a combined report
                                                                    covering fiscal years 1993-95 in January 1997.
                               (8) Tissue purchase and              We checked with NIH’s OPRR and the funded institutions’
                                  donation restrictions             institutional review boards. No violations had been
                                                                    reported or detected.
                               a
                                 Each project had several participating institutions, but only one institution for each project was
                               listed as the funded institution.



                               We found that the two research projects on fetal tissue transplantation
                               adhered to the documentation requirements for the protection of human
                               subjects. Our examination of the four forms used by each of the two
                               projects conducting fetal tissue transplantation research indicated that the
                               requirements of the law were met. During our visits to the project sites, we
                               also verified that the forms had been appropriately executed for each
                               project. All of the forms that were required were present, signed, dated,
                               and witnessed.

                               To date, NIH’s OPRR has not performed audits on the two projects
                               conducting fetal tissue transplantation research because there have been
                               no complaints reported. According to OPRR, NIH funds approximately 15,000
                               studies involving human subjects and OPRR can only carry out about five
                               compliance site visits each year. Therefore, site visits tend to be made to
                               institutions with some indication of problems.

                               We also found that the Secretary, HHS, had not submitted annual reports to
                               your Committees as required. NIH prepared draft annual reports for fiscal




                               Page 6                                              GAO/HEHS-97-61 Fetal Tissue Transplantation
                  B-276018




                  years 1993, 1994, and 1995 and forwarded them to the Secretary in May
                  1994, June 1995, and August 1996, respectively. HHS submitted a combined
                  report, covering fiscal years 1993 through 1995, on January 29, 1997.


                  A draft of this report was reviewed by NIH officials. They agreed with our
Agency Comments   findings related to therapeutic human fetal tissue transplantation research.
                  Based on these officials’ technical comments, we changed the report
                  where appropriate.


                  We are sending copies of this report to other interested Members of
                  Congress, and will make copies available to others on request. Please call
                  me on (202) 512-7119 if you or your staff have any questions about the
                  issues discussed above. Other major contributors include Rosamond Katz,
                  Erwin Bedarf, Ann White, and Robert Crystal.




                  Bernice Steinhardt
                  Director, Health Services Quality
                    and Public Health Issues




                  Page 7                               GAO/HEHS-97-61 Fetal Tissue Transplantation
Appendix I

NIH Funding of Award Institutions for
Research on Fetal Tissue Transplantation,
FYs 1993-96

                      NIH                                                                     Total NCRR Total NINDS              Total FYs
Award institution     sponsor   FY 1993             FY 1994          FY 1995         FY 1996a FYs 1993-96 FYs 1993-96              1993-96
Yale University
School of Medicine                                                                                                                $213,357
                      NCRR
                                                                                                                             b
                      (GCRC)    $97,325             $76,693           $36,007          $3,332           $213,357
University of
Colorado Health
Sciences Centerc                                                                                                                  3,855,445
                                      d                                                                        b
                      NINDS                       1,019,956        1,326,627        1,507,573                        3,854,156
                      NCRR
                                      d                       d                                d                             b
                      (GCRC)                                               1,289                           1,289
Columbia University
College of
Physicians and
Surgeons                                                                                                                            66,890
                      NCRR
                                      d                       d                                                              b
                      (GCRC)                                           26,424          40,466             66,890
Mount Sinai Medical
Centerc,e                                                                                                                         2,028,049
                                      d                       d                                                b
                      NINDS                                           952,070       1,075,979                        2,028,049
Total                           $97,325          $1,096,649       $2,342,417       $2,627,350           $281,536    $5,882,205   $6,163,741
                                          a
                                              Only preliminary information was available for FY 1996.
                                          b
                                              Total not applicable here.
                                          c
                                              These funds were used for a research project involving transplant surgery.
                                          d
                                              No funding.
                                          e
                                              The University of South Florida was funded through this award.

                                      Source: Office of Science Policy, NIH.




(108299)                                  Page 8                                               GAO/HEHS-97-61 Fetal Tissue Transplantation
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