NIH-Funded Research: Therapeutic Human Fetal Tissue Transplantation
Projects Meet Federal Requirements (Letter Report, 03/10/97,
GAO/HEHS-97-61).

Pursuant to a legislative requirement, GAO reviewed the fetal tissue
transplantation research funded by the National Institutex of Health
(NIH) under the NIH Revitalization Act, focusing on: (1) compliance with
informed consent and other documentation; and (2) any violations
occurring in the acquisition of human fetal tissue for use in
transplantation.

GAO noted that: (1) in general, the requirements of the act are being
complied with; (2) the act's documentation requirements, pertaining to
informed consent of donors and "donees" (recipients) and compliance
statements made by institutions, researchers, and attending physicians,
were met; (3) the Department of Health and Human Services did not submit
annual reports on the program's activities, however, as required by the
act; (4) but the agency did submit a combined report describing the
activities from fiscal years 1993 through 1995; and (5) there have been
no reported violations in the acquisition of human fetal tissue for use
in transplantation, according to NIH and GAO's verification efforts.

--------------------------- Indexing Terms -----------------------------

 REPORTNUM:  HEHS-97-61
     TITLE:  NIH-Funded Research: Therapeutic Human Fetal Tissue 
             Transplantation Projects Meet Federal Requirements
      DATE:  03/10/97
   SUBJECT:  Reporting requirements
             Medical research
             Noncompliance
             Informed consent (medical law)
             Ethical conduct
             Health research programs
             Agency reports

             
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Cover
================================================================ COVER


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

Fetal Tissue Transplantation

(108299)


Abbreviations
=============================================================== ABBREV

  HHS - Department of Health and Human Services
  NIH - National Institutes of Health
  OPRR - Office for Protection from Research Risks
  NINDS - National Institute of Neurological Disorders and Stroke
  NCRR - National Center for Research Resources
  GCRC - General Clinical Research Center

Letter
=============================================================== LETTER


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

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. 

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


--------------------
\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. 

\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. 


   RESULTS IN BRIEF
------------------------------------------------------------ Letter :1

In general, the requirements of the act are being complied with.  The
act's 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. 


   BACKGROUND
------------------------------------------------------------ Letter :2

Between fiscal years 1993 and 1996, NIH awarded over $6 million for
five 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. 


   ONGOING PROJECTS HAVE COMPLIED
   WITH THE REQUIREMENTS OF THE
   ACT
------------------------------------------------------------ Letter :3

The act contains the following eight requirements for research on
human fetal tissue transplantation: 

(1) Informed consent of the donor:  The woman providing the tissue
must make a signed written statement, declaring that she is donating
fetal 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. 

(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. 



                                Table 1
                
                  GAO Verification of Compliance With
                              Requirements
                               of the Act

Requirement of the act  Methodology and findings
----------------------  ----------------------------------------------
(1) Informed consent    We checked for the inclusion of the required
of donor                statements on the forms used by the
(2) Attending           projects,\a and verified that the required
physician statement     forms were in the project files and were
(3) Principal           properly executed. Documentation for both
researcher statement    projects met the requirements of the law.
(4) Informed consent
of recipient

(5) Availability of     We checked whether the institutions involved
statements for audit    in this research had submitted institutional
                        assurances to NIH that covered the audit
                        requirements. Each institution involved had
                        submitted such an assurance.

(6) Compliance with     We checked whether the institutions involved
state law               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     We checked with NIH's OPRR and the funded
and donation            institutions' institutional review boards. No
restrictions            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 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. 


--------------------
\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. 


   AGENCY COMMENTS
------------------------------------------------------------ Letter :4

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


---------------------------------------------------------- Letter :4.1

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


NIH FUNDING OF AWARD INSTITUTIONS
FOR RESEARCH ON FETAL TISSUE
TRANSPLANTATION, FYS 1993-96
=========================================================== Appendix I

                                                                          Total
               NIH                                              Total     NINDS     Total
Award          sponso      FY                            FY  NCRR FYs       FYs       FYs
institution    r         1993   FY 1994   FY 1995    1996\a   1993-96   1993-96   1993-96
-------------  ------  ------  --------  --------  --------  --------  --------  ========
Yale                                                                             $213,357
 University
 School of
 Medicine
               NCRR    $97,32   $76,693   $36,007    $3,332  $213,357        \b
                (GCRC)      5
University of                                                                    3,855,44
 Colorado                                                                               5
 Health
 Sciences
 Center\c
               NINDS       \d  1,019,95  1,326,62  1,507,57        \b  3,854,15
                                      6         7         3                   6
               NCRR        \d        \d     1,289        \d     1,289        \b
                (GCRC)
Columbia                                                                           66,890
 University
 College of
 Physicians
 and Surgeons
               NCRR        \d        \d    26,424    40,466    66,890        \b
                (GCRC)
Mount Sinai                                                                      2,028,04
 Medical                                                                                9
 Center\c,e
               NINDS       \d        \d   952,070  1,075,97        \b  2,028,04
                                                          9                   9
=========================================================================================
Total                  $97,32  $1,096,6  $2,342,4  $2,627,3  $281,536  $5,882,2  $6,163,7
                            5        49        17        50                  05        41
-----------------------------------------------------------------------------------------
\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. 


*** End of document. ***