[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]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of the Secretary


Findings of Scientific Misconduct

AGENCY: Office of the Secretary, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

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]
BILLING CODE 4150-31-P