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###### Department of Health and Human Services

###### Office of the Secretary

# 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                               ( print 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,                                   ( print 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