[Federal Register Volume 74, Number 127 (Monday, July 6, 2009)]
[Notices]
[Pages 31955-31957]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E9-15910]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Office of the Secretary
Findings of Scientific Misconduct
AGENCY: Office of the Secretary, HHS.
ACTION: Notice.
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SUMMARY: Notice is hereby given that the Office of Research Integrity
(ORI) and the Assistant Secretary for Health have taken final action in
the following case:
Judith M. Thomas, PhD, University of Alabama at Birmingham: Based
on a finding of scientific misconduct made by the University of Alabama
at Birmingham (UAB) on January 24, 2008, a report of the UAB
Investigation Committee, dated November 21, 2007, and additional
analysis conducted by ORI during its oversight review, the U.S. Public
Health Service (PHS) found that Dr. Judith M. Thomas, former Professor
of Surgery, UAB, engaged in scientific misconduct in research supported
by National Institute of Allergy and Infectious Diseases (NIAID),
National Institutes of Health (NIH), grants R01 AI22293, R01 AI39793,
and U19 AI056542, National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), NIH, grant U19 DK57958, and NIH/Novartis
Cooperative Research and Development Agreement 96-MH-01/NIHITC-0697.
The objective of the research was to test the effectiveness of
different agents, such as Immunotoxin FN18-CRM9 or 15-deoxyspergualin
(15-DSG), administered around the time of renal transplantation in non-
human primates, in preventing rejection of the transplanted kidney. To
determine whether or not the transplanted kidney was functioning (able
to sustain life) after the immunomodulating therapy, the animals were
to have both of their native kidneys removed at or shortly after the
time of transplant, so that their survival would depend solely on the
viability of the transplanted kidney. It was postulated that the use of
immunomodulating agents would increase tolerance of the host animal to
the grafted kidney and thus eliminate the necessity for chronic
administration of immunosuppressive medications commonly required to
prevent rejection in renal transplant recipients. Failure to remove
both native kidneys would render it impossible to assess the
effectiveness of the immunomodulating treatment, and could give totally
misleading results, suggesting that the treatment worked while in fact
survival was due entirely to the remaining native kidney.
PHS found that Respondent engaged in scientific misconduct by
falsifying reports of research results in NIH-supported experiments
with non-human primate (NHP) renal allograft recipients in 15
publications and in progress reports in two NIH research grant
applications. Specifically, PHS found that:
1. Respondent falsely reported in 15 publications that NHP renal
allograft recipients had received bilateral nephrectomies of their
native kidneys, while in fact many of the animals retained an intrinsic
kidney. Specifically:
A. Respondent falsely reported in eight publications \1\ that at
least 32 specific NHPs in a renal allotransplantation study had
received bilateral nephrectomies, while in fact an intrinsic kidney was
left in place in each animal, and generally, in seven additional
publications,\2\ Respondent falsely reported that all long term
surviving NHP renal allograft recipients had received bilateral
nephrectomies of their native kidneys. The publications referenced are
listed separately in the endnotes.
2. In seven publications,\3\ Respondent falsely reported
immunomodulating treatments given to NHP renal allograft recipients by
not reporting the administration of donor bone marrow to seven
recipients and not reporting administration of cyclosporine A to four
recipients. She also falsely reported (by overstating by 15%) dosages
of the immunomodulating agents that were given and/or duration by
overstating the exceptionalbriefer duration of immunomodulating
treatment given to four recipients and cited in at least eight
publications.\4\
3. In progress reports for NIH research awards R01 AI39793 and U19
DK57958, Respondent falsely claimed that long term surviving (LTS) NHP
renal
[[Page 31956]]
allotransplantation recipients had received bilateral nephrectomies and
falsely reported the immunomodulating therapies received by the graft
recipients. Specifically:
A. In the progress report in application 5 R01 AI39793-04,
submitted in approximately May 1999, Respondent repeated falsified
claims of successful LTS NHP allografts by citing two publications
(Transplantation 68:1660-1673, 1999 and Transplantation 68:215-219,
1999) that reported LTS in renal allograft recipients that were falsely
reported to have had bilateral intrinsic nephrectomies, while
laboratory records showed that at the most four of these animals had
bilateral nephrectomies.
B. In the progress report in application 5 U19 DK57958-02 submitted
in approximately May 2000, Respondent falsely reported that 10/13 LTS
NHP renal allograft recipients had received bilateral nephrectomies of
their native kidneys and falsified the immunomodulating treatment
received by four of the animals by failing to report the administration
of cyclosporine A (CSA) or donor bone marrow.
For the same award, in a progress report submitted in approximately
May 2002, Respondent falsely reported that all of the 16 animals in the
rhesus Ktx (kidney transplant) series had bilateral nephrectomies of
their native kidneys, but in fact at least nine of the animals did not
have the requisite bilateral nephrectomies.
In a competing renewal application 2 U19 DK057958-05, submitted on
about 03/10/2003, Respondent reported that 14 Ktx long term survivors
did not have an intrinsic kidney, while in fact at least 11 of those
animals had a remaining intrinsic kidney.
Both Dr. Thomas and PHS are desirous of concluding this matter
without further expense of time and other resources, and the parties
have entered into a Voluntary Exclusion Agreement to settle the matter.
Dr. Thomas accepted responsibility for the reporting described above,
but denied that she intentionally committed research misconduct. The
settlement is not an admission of liability on the part of the
Respondent.
Dr. Thomas has entered into a Voluntary Exclusion Agreement in
which she has voluntarily agreed, for a period of ten (10) years,
beginning on May 5, 2009:
(1) To exclude herself voluntarily from any contracting or
subcontracting with any agency of the United States Government and from
eligibility or involvement in nonprocurement programs of the United
States Government referred to as ``covered transactions'' and defined
by 2 CFR parts 180 and 376; and
(2) To exclude herself from serving in any advisory capacity to
PHS, including but not limited to service on any PHS advisory
committee, board, and/or peer review committee, or as a consultant.
FOR FURTHER INFORMATION CONTACT: Director, Division of Investigative
Oversight, Office of Research Integrity, 1101 Wootton Parkway, Suite
750, Rockville, MD 20852, (240) 453-8800.
John E. Dahlberg,
Director, Division of Investigative Oversight, Office of Research
Integrity.
Endnotes
1.
Asiedu, C.K., Dong, S.S., Lobashevsky, A., Jenkins, S.M., & Thomas,
J.M. ``Tolerance induced by anti-CD3 immunotoxin plus 15-
deoxyspergualin associates with donor-specific indirect pathway
unresponsiveness.'' Cell Immunol. 223(2):103-112, June 2003.
(Retraction required by UAB.)
Hutchings, A., Wu, J., Asiedu, C., Hubbard, W., Eckhoff, D.,
Contreras, J., Thomas, F.T., Neville, D., & Thomas, J.M. ``The
immune decision toward allograft tolerance in non-human primates
requires early inhibition of innate immunity and induction of immune
regulation.'' Transpl Immunol. 11(3-4):335-344, July-September 2003.
(Retraction required by UAB.)
Lobashevsky, A.L., Jiang, X.L., & Thomas, J.M. ``Allele-specific in
situ analysis of microchimerism by fluorescence resonance energy
transfer (FRET) in nonhuman primate tissues.'' Hum Immunol.
63(2):108-120, February 2002. (Retraction required by UAB.)
Thomas, J.M., Eckhoff, D.E., Contreras, J.L., Lobashevsky, A.L.,
Hubbard, W.J., Moore, J.K., Cook, W.J., Thomas, F.T., & Neville,
D.M. Jr. ``Durable donor-specific T and B cell tolerance in rhesus
macaques induced with peritransplantation anti-CD3 immunotoxin and
deoxyspergualin: Absence of chronic allograft nephropathy.''
Transplantation 69(12):2497-2503, June 27, 2000. (Retracted.)
Thomas, J.M., Contreras, J.L., Jiang, X.L., Eckhoff, D.E., Wang,
P.X., Hubbard, W.J., Lobashevsky, A.L., Wang, W., Asiedu, C.,
Stavrou, S., Cook, W.J., Robbin, M.L., Thomas, F.T., & Neville, D.M.
Jr. ``Peritransplant tolerance induction in macaques: Early events
reflecting the unique synergy between immunotoxin and
deoxyspergualin.'' Transplantation 68(11):1660-1673, December 15,
1999. (Retracted.)
Contreras, J.L., Eckhoff, D.E., Cartner, S., Frenette, L., Thomas,
F.T., Robbin, M.L., Neville, D.M. Jr., & Thomas, J.M. ``Tolerability
and side effects of anti-CD3-immunotoxin in preclinical testing in
kidney and pancreatic islet transplant recipients.'' Transplantation
68(2):215-219, July 27, 1999. (Retracted.)
Contreras, J.L., Wang, P.X., Eckhoff, D.E., Lobashevsky, A.L.,
Asiedu, C., Frenette, L., Robbin, M.L., Hubbard, W.J., Cartner, S.,
Nadler, S., Cook, W.J., Sharff, J., Shiloach, J., Thomas, F.T.,
Neville, D.M. Jr., & Thomas, J.M. ``Peritransplant tolerance
induction with anti-CD3-immunotoxin: A matter of proinflammatory
cytokine control.'' Transplantation 65(9):1159-1169, May 15, 1998.
(Retracted.)
Asiedu, C.K., Goodwin, K.J., Balgansuren, G., Jenkins, S.M., Le Bas-
Bernardet, S., Jargal, U., Neville, D.M Jr., & Thomas, J.M.
``Elevated T regulatory cells in long-term stable transplant
tolerance in rhesus macaques induced by anti-CD3 immunotoxin and
deoxyspergualin.'' J Immunol. 175(12):8060-8068, December 5, 2005.
(Retracted.)
2.
Thomas, J.M., Hubbard, W.J., Sooudi, S.K., & Thomas, F.T. ``STEALTH
matters: A novel paradigm of durable primate allograft tolerance.''
Immunol Rev. 183:223-233, October 2001. Review. (Retracted.)
Thomas, F., Ray, P., & Thomas, J.M. ``Immunological tolerance as an
adjunct to allogeneic tissue grafting.'' Microsurgery 20(8):435-440,
2000. (Retraction required by UAB.)
Hutchings, A., & Thomas, J.M. ``Transplantation: Tolerance.''
Current Opinion in Investigational Drugs 4(5):530-535, 2003.
(Retraction required by UAB.)
Hubbard, W.J., Eckhoff, D., Contreras, J.L., Thomas, F.T.,
Hutchings, A., & Thomas, J.M. ``STEALTH on the preclinical path to
tolerance.'' Graft 5(6):322-330, 2002. (Retraction required by UAB--
Journal has ceased publication.)
Hutchings, A., Hubbard, W.J., Thomas, F.T., & Thomas, J.M. ``STEALTH
in transplantation tolerance.'' Immunologic Res. 26:143-152, 2002.
(Retracted.)
Thomas, J.M., Asiedu, C., George, J.F., Hubbard, W.J., & Thomas,
F.T. ``Preclinical bridge to clinical tolerance.'' Current Opinion
in Organ Transplantation 6:95-101, 2001. (Retraction required by
UAB.)
Hubbard, W.J., Contreras, J.V., Eckhoff, D.E., Thomas, F.T.,
Neville, D.M., & Thomas, J.M. ``Immunotoxins and tolerance induction
in primates.'' Current Opinion in Organ Transplantation 5:29-34,
2000. (Retracted.)
3.
Asiedu, C.K., Dong, S.S., Lobashevsky, A., Jenkins, S.M., & Thomas,
J.M. ``Tolerance induced by anti-CD3 immunotoxin plus 5-
deoxyspergualin associates with donor-specific indirect pathway
unresponsiveness.'' Cell Immunol. 223(2):103-112, June 2003.
(Retraction required by UAB.)
Hutchings, A., Wu, J., Asiedu, C., Hubbard, W., Eckhoff, D.,
Contreras, J., Thomas, F.T., Neville, D., Thomas, J.M. ``The immune
decision toward allograft tolerance in non-human primates requires
early inhibition of innate immunity and induction of immune
regulation.'' Transpl Immunol. 11(3-4):335-344, July-September,
2003. (Retraction required by UAB.)
Thomas, J.M., Eckhoff, D.E., Contreras, J.L., Lobashevsky, A.L.,
Hubbard, W.J., Moore,
[[Page 31957]]
J.K., Cook, W.J., Thomas, F.T., & Neville, D.M. Jr. ``Durable donor-
specific T and B cell tolerance in rhesus macaques induced with
peritransplantation anti-CD3 immunotoxin and deoxyspergualin:
Absence of chronic allograft nephropathy.'' Transplantation
69(12):2497-2503, June 27, 2000. (Retracted.)
Thomas, J.M., Contreras, J.L., Jiang, X.L., Eckhoff, D.E., Wang,
P.X., Hubbard, W.J., Lobashevsky, A.L., Wang, W., Asiedu, C.,
Stavrou, S., Cook, W.J., Robbin, M.L., Thomas, F.T., & Neville, D.M.
Jr. ``Peritransplant tolerance induction in macaques: Early events
reflecting the unique synergy between immunotoxin and
deoxyspergualin.'' Transplantation 68(11):1660-1673, December 15,
1999. (Retracted.)
Contreras, J.L., Eckhoff, D.E., Cartner, S., Frenette, L., Thomas,
F.T., Robbin, M.L., Neville, D.M. Jr., & Thomas, J.M. ``Tolerability
and side effects of anti-CD3-immunotoxin in preclinical testing in
kidney and pancreatic islet transplant recipients.'' Transplantation
68(2):215-219, July 27, 1999. (Retracted.)
Contreras, J.L., Wang, P.X., Eckhoff, D.E., Lobashevsky, A.L.,
Asiedu, C., Frenette, L., Robbin, M.L., Hubbard, W.J., Cartner, S.,
Nadler, S., Cook, W.J., Sharff, J., Shiloach, J., Thomas, F.T.,
Neville, D.M. Jr., & Thomas, J.M. ``Peritransplant tolerance
induction with anti-CD3-immunotoxin: A matter of proinflammatory
cytokine control.'' Transplantation 65(9):1159-1169, May 15, 1998.
(Retracted.)
Asiedu, C.K., Goodwin, K.J., Balgansuren, G., Jenkins, S.M., Le Bas-
Bernardet, S., Jargal, U., Neville, D.M. Jr. & Thomas, J.M.
``Elevated T regulatory cells in long-term stable transplant
tolerance in rhesus macaques induced by anti-CD3 immunotoxin and
deoxyspergualin.'' J Immunol. 175(12):8060-8068, December 5, 2005.
(Retracted.)
4.
Includes those cited in Endnote 3 plus:
Thomas, J.M., Neville, D.M., Contreras, J.L., Eckhoff, D.E., Meng,
G., Lobashevsky, A.L., Wang, P.X., Huang, Z.Q., Verbanac, K.M.,
Haisch, C.E., & Thomas, F.T. ``Preclinical studies of allograft
tolerance in rhesus monkeys: A novel anti-CD3-immunotoxin given
peritransplant with donor marrow induces operational tolerance to
kidney allografts.'' Transplantation 64(1):124-135, July 15, 1997.
[FR Doc. E9-15910 Filed 7-2-09; 8:45 am]
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