Department of Health and Human Services February 2013 – Federal Register Recent Federal Regulation Documents

The U.S. Department of Health and Human Services announces establishment of the 2015 Dietary Guidelines Advisory Committee (hereafter referred to as the Committee or 2015 DGAC). The 2015 DGAC is an expert advisory committee that has been established to assist the Department of Health and Human Services (HHS) and the U.S. Department of Agriculture (USDA) perform a single, time-limited task.

Notice is hereby given that the Office of Research Integrity (ORI) has taken final action in the following case: Bryan William Doreian, Ph.D., Case Western Reserve University: Based on the admission of the Respondent, ORI found that Dr. Bryan William Doreian, former postdoctoral fellow, Department of Dermatology, Case Western Reserve University (CWRU), engaged in research misconduct in research supported by National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), grant T32 HL07887 and National Institute of Neurological Disorders and Stroke (NINDS), NIH, grant R01 NS052123. ORI found that the Respondent engaged in research misconduct by falsifying data that were included in: Doreian, B.W. ``Molecular Regulation of the Exocytic Mode in Adrenal Chromaffin Cells.'' Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, August 2009; hereafter referred to as the ``Dissertation.'' Doreian, B.W., Fulop, T.G., Meklemburg, R.L., Smith, C.B. ``Cortical F-actin, the exocytic mode, and neuropeptide release in mouse chromaffin cells is regulated by myristoylated alanine-rich C- kinase substrate and myosin II.'' Mol Biol Cell. 20(13):3142-54, 2009 Jul; hereafter referred to as the ``Mol Biol Cell paper.'' Doreian, B.W., Rosenjack, J., Galle, P.S., Hansen, M.B., Cathcart, M.K., Silverstein, R.L., McCormick, T.S., Cooper, K.D., Lu, K.Q. ``Hyper-inflammation and tissue destruction mediated by PPAR- [gamma] activation of macrophages in IL-6 deficiency.'' Manuscript prepared for submission to Nature Medicine; hereafter referred to as the ``Nature Medicine manuscript.'' As a result of the Respondent's admission, the Respondent will request that the following paper be retracted: Mol Biol Cell. 20(13):3142-54, 2009 Jul. ORI finds that Respondent falsified numerical values in the Mol Biol Cell paper, the submitted Nature Medicine manuscript, and the Dissertation by altering the number of samples or the experimental results to improve the statistical results. Specifically, ORI finds that Respondent: 1. Falsified the quantification of immunofluorescence for the ratio of phosphorylated to unphosphorylated MARCKS protein in response to different stimuli in Figure 2 of the Mol Biol Cell paper and in Figure 12 of the Dissertation by falsifying the sample number as n=15. 2. Falsified the quantification of immunofluorescence for filamentous actin in response to different stimuli in Figure 3 of the Mol Biol Cell paper and in Figure 13 of the Dissertation by falsifying the sample number as n=15. 3. Falsified the quantification for the effect of blebbistatin on catecholamine release as determined by patch clamp analysis in Figure 22 of the Dissertation by stating that 14 cells had been assayed when only 8 cells had been assayed. 4. Falsified the Pearson's cross-correlation analysis in Figure 7 of the Mol Biol Cell paper and in Figure 25 of the Dissertation, used to calculate the degree of spatial correlation between pan-chromogranin A/B (CgA/B) and the endosomal membrane, by stating that 20 or more cells had been tested for each condition when only 9-18 cells had been tested for each condition. 5. Falsified RT-PCR values for iNOS and TNF-alpha expression recorded on spreadsheets and presented in Figures 5e and 5f of the Nature Medicine manuscript showing the effect of hyper-inflammatory macrophage generation on tissue destruction, by falsifying the numeric values to fit the hypothesis of the manuscript. 6. Falsified ELISA graphs for the concentration of TNF-[alpha] in the aAB IL-6 mice and their controls in Figure 6j of the Nature Medicine manuscript showing the effect of rosiglitazone treatment in the mice, by multiplying the experimental values by 100 to match the magnitude of the values presented in Figures 21, 6h, and 6i of the Nature Medicine manuscript. 7. Falsified the RT-PCR results presented in the Nature Medicine manuscript for quantification of iNOS and TNF-[alpha] RNA expression by claiming that the results represent the rmean of three identical experiments when the three experiments were normalized differently to yield the desired result. Specifically, false results were presented for peritoneal macrophages treated in vivo with rosiglitazone and/or inhibitors of PPAR[gamma] signaling Figures 1g, 1h, and 1i, and for iNOS RNA expresssion in IL6-/- macrophages treated in vitro with either SOCS3 antisense oligonucleotides in Figure 2g or the STAT3 decoy in Figure 2j. Dr. Doreian has entered into a Voluntary Settlement Agreement and has voluntarily agreed for a period of three (3) years, beginning on January 15, 2013: (1) To have his research supervised; Respondent agreed that prior to the submission of an application for U.S. Public Health Service (PHS) support for a research project on which his participation is proposed and prior to his participation in any capacity on PHS- supported research, Respondent shall ensure that a plan for supervision of his duties is submitted to ORI for approval; the supervision plan must be designed to ensure the scientific integrity of his research contribution; he 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 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; (3) 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; and (4) To request that the following paper be retracted: Mol Biol Cell. 20(13):3142-54, 2009 Jul.

The Food and Drug Administration (FDA or we) is extending to May 13, 2013, the comment period for the notice entitled ``Request for Comments and Information on Initiating a Risk Assessment for Establishing Food Allergen Thresholds; Establishment of Docket,'' that appeared in the Federal Register of December 14, 2012 (77 FR 74485). In that document, we requested comments relevant to conducting a risk assessment to establish regulatory thresholds for major food allergens as defined in the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA). The document requested comments (including data) that we can use to design and carry out a quantitative risk assessment for establishing regulatory thresholds for major food allergens. We are extending the comment period in response to a request from an industry association.

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``S10 Photosafety Evaluation of Pharmaceuticals.'' The draft guidance was prepared under the auspices of the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. The draft guidance includes criteria for initiation of and triggers for additional photosafety testing and should be read in conjunction with the ICH M3(R2) guidance, section XIV(14) Photosafety Testing. The purpose of the draft guidance is to recommend international standards for photosafety assessment and to harmonize such assessments that support human clinical trials and marketing authorization for pharmaceuticals.

This notice announces two new membership appointments to the Advisory Panel on Hospital Outpatient Payment (HOP, the Panel). The two new appointments to the Panel will each serve a 4-year period. The new members will have terms that begin on February 1, 2013 and continue through January 31, 2017. The purpose of the Panel is to advise the Secretary of the Department of Health and Human Services and the Administrator of the Centers for Medicare & Medicaid Services concerning the clinical integrity of the Ambulatory Payment Classification groups and their relative payment weights. The Panel also addresses and makes recommendations regarding supervision of outpatient services. The advice provided by the Panel will be considered as we prepare the annual updates for the hospital outpatient prospective payment system.

In compliance with Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995 which requires 30 days for public comment on proposed information collection projects, the Indian Health Service (IHS) is publishing for comment a summary of a proposed information collection to be submitted to the Office of Management and Budget (OMB) for review. This proposed information collection project was previously published in the Federal Register (77 FR 69865) on November 21, 2012, and allowed 60 days for public comment, as required by 3506(c)(2)(A). No public comment was received in response to the notice. The purpose of this notice is to allow 30 days for public comment to be submitted directly to OMB. Proposed Collection: Title: 0917-0002, ``IHS Contract Health Service Report.'' Type of Information Collection Request: Extension, without change, of a currently approved information collection, 0917- 0002, ``IHS Contract Health Service Report.'' While there were minor text changes (i.e., updating of statute/regulatory citations), there were no significant changes to the form. Form: IHS 843-1A. ``Order for Health Services.'' Need and Use of Information Collection: The IHS Contract Health Service (CHS) Program, located in the Office of Resource Access and Partnerships, needs this information to certify that the health care services requested and authorized by the IHS have been performed by the CHS provider(s) to have providers validate services provided; to process payments for health care services performed by such providers; and to serve as a legal document for health and medical care authorized by IHS and rendered by health care providers under contract with the IHS. Affected Public: Patients, health and medical care providers or Tribal Governments. Type of Respondents: Health and medical care providers. Burden Hours: The table below provides: Types of data collection instruments, Estimated number of respondents, Number of responses per respondent, Average burden hour per response, and Total annual burden hours.

In compliance with the requirement of Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, for opportunity for public comment on proposed data collection projects, the National Institutes of Health (NIH) will publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Written comments and/or suggestions from the public and affected agencies are invited to address one or more of the following points: (1) Whether the proposed collection of information is necessary for the proper performance of the function of the agency, including whether the information will have practical utility; (2) The accuracy of the agency's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) The quality, utility, and clarity of the information to be collected; and (4) Minimize the burden of the collection of information on those who are to respond, including the use of appropriate automated, electronic, mechanical, or other technological collection techniques or other forms of information technology. To submit comments in writing, request more information on the proposed project, or to obtain a copy of the data collection plans and instruments, contact: Jose Galvez, Office of the Director, National Cancer Institute, 2115 East Jefferson Street, Rockville, MD 20852 or call non-toll-free number 301-443-6141 or Email your request, including your address to: jose.galvez@nih.gov. Comments regarding this information collection are best assured of having their full effect if received within 60 days of the date of this publication. Proposed Collection: The Clinical Trials Reporting Program (CTRP) Database, 0925-0600, Expiration Date 3/31/2013EXTENSION, National Cancer Institute (NCI), National Institutes of Health (NIH). Need and Use of Information Collection: The Clinical Trials Reporting Program (CTRP) is an electronic resource that serves as a single, definitive source of information about all NCI-supported clinical research. This resource allows the NCI to consolidate reporting, aggregate information and reduce redundant submissions. Information is submitted by clinical research administrators as designees of clinical investigators who conduct NCI-supported clinical research. The designees can electronically access the CTRP Web site to complete the initial trial registration. Subsequent to registration, four amendments and four study subject accrual updates occur per trial annually. OMB approval is requested for 3 years. There are no costs to respondents other than their time. The estimated annualized burden hours are 38,500.