Findings of Research Misconduct

Two rather different cases …

Notice is hereby given that ORI has taken final action in the following case: Based on an investigation conducted by Advocate Health Care Network d/b/a Advocate Health Care (Advocate Health Care) and additional analysis conducted by ORI in its oversight review, ORI and Advocate Health Care found that Parag Patel, DO engaged in research misconduct in research supported by  grant U01 HL089458.

ORI and Advocate Health Care found that the Respondent engaged in research misconduct by directing or intimidating fellows and others to influence left ventricular ejection fraction (LVEF) scores of <= 35% and requesting attending physicians to reassess scores of LVEF to be reported as <= 35% for research subjects after being diagnosed with acute myocardial infarction, thereby causing and being responsible for falsification of research records. These falsifications made subjects eligible for enrollment into the Vest Prevention of Early Sudden Death Trial (VEST) when they otherwise may not have been eligible.

The Respondent, Advocate Health Care, and the U.S. DHHS want to conclude this matter without further expenditure of time or other resources and have entered into a Voluntary Settlement Agreement (Agreement) to resolve this matter. Respondent neither admits nor denies ORI’s and Advocate Health Care’s findings of research misconduct. This settlement does not constitute an admission of liability on the part of the Respondent.

Dr. Patel has voluntarily agreed for a period of 2 years, beginning on February 21, 2014:

(1) To have any U.S. Public Health Service (PHS)-supported research in which he is involved be supervised; Respondent agreed that prior to the submission of an application for PHS support for a research project on which the Respondent’s participation is proposed and prior to Respondent’s participation in any capacity on PHS-supported research, Respondent shall ensure that a plan for supervision of Respondent’s duties is submitted to ORI for approval; the supervision plan must be designed to ensure the scientific integrity of Respondent’s research contribution as outlined below; Respondent agreed that he shall not participate in any PHS-supported research until such a supervision plan is submitted to and approved by ORI; Respondent agreed to maintain responsibility for compliance with the agreed-upon supervision plan;

(2) That the requirements for Respondent’s supervision plan are as follows: A committee of 2-3 qualified physicians at the institution’s discretion, who are familiar with Respondent’s field of research, but not including Respondent’s supervisor or collaborators, will provide oversight and guidance; the committee will review primary data from Respondent’s participation in PHS-supported research on a quarterly basis and submit a report to ORI at 6 month intervals setting forth the committee’s meeting dates, Respondent’s compliance with appropriate research standards, and confirming the integrity of Respondent’s research contribution; and The committee will conduct an advance review of any PHS grant applications (including supplements, resubmissions, etc.), manuscripts reporting PHS-funded research submitted for publication, and abstracts; the review will include a discussion with Respondent of the primary data represented in those documents and will include a certification to ORI that the data presented in the proposed application/publication are supported by the research record; (3) That any institution employing him shall submit, in conjunction with each application for PHS funds, or report, manuscript, or abstract involving PHS-supported research in which Respondent is involved, a certification to ORI that the data provided by Respondent are based on actual experiments or are otherwise legitimately derived and that the data, procedures, and methodology are accurately reported in the application, report, manuscript, or abstract; and (4) To exclude himself voluntarily 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.

***

Notice is hereby given that ORI has taken final action in the following case: Based on evidence and findings of an investigation report by Mount Sinai School of Medicine (MSSM) transmitted to ORI in April 2010 and additional analysis conducted by ORI in its oversight review, ORI found that Li Chen, PhD, former Postdoctoral Fellow, Department of Gene and Cell Medicine, engaged in research misconduct in research that was supported by grants R01 DK062972 and P20 GM075019 and was submitted in grant applications R01 DK074695, R01 DK083286, P20 GM075019, and R01 NS062054.

ORI found that the Respondent intentionally, knowingly, and recklessly fabricated and falsified data reported in 4 publications, 1 submitted manuscript, and 4 grant applications:

  • Chen, L., & Woo, S.L.C. Complete and persistent phenotypic correction of phenylketonuria in mice by site-specific genome integration of murine phenylalanine hydroxylase cDNA. Proc. Natl. Acad. Sci. U.S.A. 102(43):15581-15586, October 2005 (hereafter referred to as PNAS 2005).
  • Chen, L., Thung, S.N., & Woo, S.L.C. Metabolic Basis of Sexual Dimorphism in PKU Mice After Genome-targeted PAH Gene Therapy. Mol. Ther. 15:1079-1085, June 2007; Retracted in December 2010 (hereafter referred to as Mol. Ther. June 2007).
  • Chen, L., & Woo, S.L.C. Correction in Female PKU Mice by Repeated Administration of mPAH cDNA Using phiBT1 Integration System. Mol. Ther. 15:1789-1795, October 2007; Retracted in December 2010 (hereafter referred to as Mol. Ther. Oct. 2007).
  • Chen, L., & Woo, S.L.C. Site-Specific Transgene Integration in the Human Genome Catalyzed by [Ouml]BT1 Phage Integrase. Hum. Gene Ther. 19:143-151, February 2008; Retracted in August 2010 (hereafter referred to as HGT 2008).
  • Chen, L., Roy, I., Prasad, P.N., & Woo, S.L.C. Nanoparticle-Based Gene Therapy for Metabolic Disorders: Hepatic Delivery of Minicircle DNA for Complete Correction of Phenylketonuria. Submitted for publication in Proc. Natl. Acad. Sci. U.S.A. (hereafter referred to as the PNAS 2008 manuscript).
  • R01 DK074695, “Genome-targeted PAH Gene Integration in PKU Mice and Sexual Dimorphism,’ Savio L.C. Wood, PhD, PI
  • P20 GM075019, “Growth, Differentiation & Genetic Alteration of Human ES Cells,’ Gordon M. Keller, PhD, PI
  • R01 NS062054, “Nanoparticle-medicated Gene Therapy for PKU,’ Savio L. Woo, PhD, PI
  • R01 DK083285, “Nanoparticle-Mediated Gene Therapy PKU,’ Savio L. Woo, PhD, PI

The Respondent fabricated figures reporting the chromosomal locations of integration sites, fabricated data reporting the use of PCR to determine integration frequencies, falsified data representing the detection of chromosomal translocations in human cells, and fabricated figures by falsely reporting the results of HPLC assays. The Respondent also falsified experimental data for LacZ stained liver sections and for H&E stained liver sections.

Specifically, ORI finds by a preponderance of the evidence that the Respondent engaged in misconduct in science and research misconduct by intentionally, knowingly, and recklessly:

1. fabricating and/or falsifying 19 figures by falsely reporting that PKU gene therapy experiments were successfully completed, when the available evidence shows the experiments were not performed; specifically the Respondent:

(a) fabricated figures where DNA sequencing was purportedly used to identify the chromosomal locations of integration sites for the PAH gene in mouse and human cells, reported in 7 figures:

  • PNAS 2005, Figure 2A
  • HGT 2008, Figures 3b and 3c
  • R01 NS062054, Figures 3 and 20
  • R01 DK074695, Figure 6
  • R01 DK083286, Figure 17
  • P20 GM075019, Figure 4

(b) fabricated data purportedly representing the use of PCR to determine integration frequencies for the PAH gene and the secreted embryonic alkaline phosphatase (SEAP) reporter gene, in mouse and human cells, reported in 11 figures:

  • PNAS 2005, Figures 2C and 3B
  • Mol. Ther. June 2007, Figures 2a and 5a
  • Mol. Ther. Oct. 2007, Figures 2d and 5a
  • HGT 2008, Figure 4 R01 NS062054, Figures 4b and 10a
  • R01 DK074695, Figure 7b
  • R01 DK083286, Figure 2b

(c) falsified figures representing the detection of chromosomal tranlocations in human cells, purportedly determined by PCR in 2 figures:

  • HGT 2008, Figure 5a
  • R01 NS062054, Figure 21a

2. fabricating the results of HPLC assays to show generally lowered blood levels of phenylalanine after PKU gene therapy and to show liver levels of BH4 when the Respondent did not have the HPLC data needed to support those claims; specifically the Respondent:

(a) fabricated serum phenylalanine graphs in:

  • PNAS 2005, Figure 4B; this false data also is presented in R01 DK074695, Figure 10b
  • Mol. Ther. June 2007, Figure 1a; this false data also is presented in R01 DK074695, Figure 11
  • R01 DK083286, Figure 3; this false data also is presented in Mol. Ther. June 2007, Figure 3, and R01 NS062054, Figure 7
  • Mol. Ther. Oct. 2007, Figure 4a; this false data also is presented in R01 NS062054, Figure 9a
  • PNAS 2008 manuscript, Figure 4

(b) fabricated graphs for BH4 levels in:

  • Mol. Ther. June 2007, Figure 5c; this false data also is presented in R01 NS062054, Figure 8c

3. falsely reporting the results of LacZ stained liver sections by reusing and relabeling an image and claiming that it represents different experiments; specifically, the same image was used to represent mice treated with a nanoplex gene delivery system in R01 NS062054, Figure 14b (right panel), and also to represent a wholly different experiment for mice treated with 10 injections of the phiBT1 integrase system alone in R01 NS062054, Figure 4c (right panel), and Mol. Ther. Oct. 2007, Figure 2b (D panel)

4. falsely reporting the results of H&E stained liver sections in R01 NS062054, Figure 6, by using the identical image to represent 4 different experimental treatments of H&E stained liver sections; specifically the Respondent reused and relabeled one image to represent liver sections from mice that received either 1 or 10 injections, with or without the phiBT1 integrase plasmid.

The Respondent failed to take responsibility for the fabrication and falsification described in ORI’s findings.

The following administrative actions have been implemented for a period of 3 years, beginning on April 11, 2014:

(1) Respondent is debarred from any contracting or subcontracting with any agency of the United States Government and from eligibility for, or involvement in, nonprocurement programs of the United States Government referred to as “covered transactions’ pursuant to HHS’ Implementation (2 CFR part 376 et seq.) of Office of Management and Budget (OMB) Guidelines to Agencies on Governmentwide Debarment and Suspension, 2 CFR part 180 (collectively the “Debarment Regulations’); and

(2) Respondent is prohibited 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.

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