Department of Health and Human Services February 2012 – Federal Register Recent Federal Regulation Documents

The U.S. Food and Drug Administration (FDA or the Agency) is announcing a public hearing to obtain input on a new paradigm we are considering. Under this paradigm, the Agency would approve certain drugs that would otherwise require a prescription for nonprescription use (also known as over-the-counter or OTC) under conditions of safe use. These conditions of safe use would be specific to the drug product and might require sale in certain pre-defined health care settings, such as a pharmacy. This public hearing is being held to obtain information and comments from the public on the feasibility of this paradigm and its potential benefits and costs.

The Health Resources and Services Administration (HRSA) is requesting nominations to fill five vacancies on the National Advisory Council (NAC) on the National Health Service Corps (NHSC). The NAC on the NHSC was established in 1978.

In compliance with Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, which requires 60 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. Proposed Collection: Title: 0917-0014, ``Indian Health Service Loan Repayment Program.'' Type of Information Collection Request: Revision of currently approved information collection, 0917-0014, ``Indian Health Service Loan Repayment Program.'' The LRP application has been revised so that it is now available in an electronically fillable and fileable format. Form(s): The IHS LRP Information Booklet contains the instructions and the application formats. Need and Use of Information Collection: The IHS LRP identifies health professionals with pre- existing financial obligations for education expenses that meet program criteria and who are qualified and willing to serve at, often remote, IHS health care facilities. Under the program, eligible health professionals sign a contract through which the IHS agrees to repay part or all of their indebtedness for professional training time in IHS health care facilities. This program is necessary to augment the critically low health professional staff at IHS health care facilities. Any health professional wishing to have their health education loans repaid may apply to the IHS LRP. A two-year contract obligation is signed by both parties, and the individual agrees to work at an IHS location and provide health services to American Indian and Alaska Native individuals. The information collected via the on-line application from individuals is analyzed and a score is given to each applicant. This score will determine which applicants will be awarded each fiscal year. The administrative scoring system assigns a score to the geographic location according to vacancy rates for that fiscal year and also considers whether the location is in an isolated area. When an applicant accepts employment at a location, they in turn ``pick-up'' the score of that location. Affected Public: Individuals and households. Type of Respondents: Individuals. The table below provides: Types of data collection instruments, Estimated number of respondents, Number of responses per respondent, Annual number of responses, Average burden hour per response, and Total annual burden hour(s).

Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the National Institute of Environmental Health Sciences (NIEHS), the National Institutes of Health (NIH) has submitted to the Office of Management and Budget (OMB) a request for review and approval of the information collection listed below. This proposed information collection was previously published in the Federal Register, Vol. 76, No. 202, on Wednesday, October 19, 2011, page 64954 and allowed 60 days for public comment. No public comments were received. The purpose of this notice is to allow an additional 30 days for public comment. The National Institutes of Health may not conduct or sponsor, and the respondent is not required to respond to, an information collection that has been extended, revised, or implemented on or after October 1, 1995, unless it displays a currently valid OMB control number. Proposed Collection: Title: DERT Extramural Grantee Data Collection. Type of Information Collection Request: New. Need and Use of Information Collection: In order to make informed management decisions about its research programs and to demonstrate the outputs, outcomes and impacts of its research programs NIEHS will collect, analyze and report on data from extramural grantees who are currently receiving funding or who have received funding in the past on topics such as: Key scientific outcomes achieved through the research and the impact on the field of environmental health science. Contribution of research findings to program goals and objectives. Satisfaction with the program support received. Challenges and benefits of the funding mechanism used to support the science. Emerging research areas and gaps in the research.

The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Notification to FDA of Issues that May Result in a Prescription Drug or Biological Product Shortage.'' This draft guidance relates to the Federal Food, Drug, and Cosmetic Act (FD&C Act), which requires sole manufacturers to notify FDA of a discontinuance of certain drug products and to the President's Executive Order 13588 of October 31, 2011, directing FDA to use all available administrative tools to expand the Agency's efforts to combat the problem of drug shortages. We are also requesting responsive comments from interested stakeholders on a specific question posed in this Federal Register document related to the draft guidance.

The Food and Drug Administration (FDA) is announcing the opening of a public docket to make available to the public a report of the pediatric studies of meropenem that were conducted in accordance with section 409I of the Public Health Service Act (PHS Act) and submitted to the Director of the National Institutes of Health (NIH) and the Commissioner of Food and Drugs.

The Food and Drug Administration (FDA) is announcing the availability of the final decision withdrawing approval of the breast cancer indication for AVASTIN (Bevacizumab). The Commissioner of Food and Drugs (the Commissioner) issued the decision following a June 2011 public hearing on a proposal to withdraw the approval.

This final rule sets forth a procedural framework for submission and review of initial applications for a Waiver for State Innovation described in section 1332 of the Patient Protection and the Affordable Care Act including processes to ensure opportunities for public input in the development of such applications by States and in the Federal review of the applications.

Notice is hereby given that the Office of Research Integrity (ORI) has taken final action in the following case: Michael W. Miller, Ph.D., State University of New York, Upstate Medical University: Based on the report of an investigation conducted by the State University of New York, Upstate Medical University (SUNY UMU) and additional analysis conducted by ORI in its oversight review, ORI found that Dr. Michael W. Miller, former Professor and Chair, Department of Neuroscience and Physiology, SUNY UMU, engaged in research misconduct in research supported by National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), grants R01 AA07568-18A1, R01 AA06916, and P50 AA017823-01. ORI finds that the Respondent engaged in research misconduct by falsifying and/or fabricating data that were included in grant applications R01 AA07568-18, R01 AA07568-18A1, R01 AA006916-25, and P50 AA017823-01 and in the following: Miller, M.W., Hu, H. ``Lability of neuronal lineage decisions is revealed by acute exposures to ethanol.'' Dev. Neurosci. 31(1-2):50-7, 2009 (``Dev. Neurosci. 2009'') Bruns, M.B., Miller, M.W. ``Functional nerve growth factor and trkA autocrine/paracrine circuits in adult rat cortex are revealed by episodic ethanol exposure and withdrawal.'' J. Neurochem. 100(5):1115-68, 2007 (``J. Neurochem. 2007'') A prepared manuscript submitted to PNAS for publication. As a result of its investigation, SUNY UMU recommended that Dev. Neurosci. 2009 and J. Neurochem. 2007 be retracted. Both publications have now been retracted: Dev. Neurosci. 2009 was retracted online on January 19, 2012, at: https://content.karger.com/ProdukteDB/ produkte.asp?Aktion=ShowPDF&ArtikelNr=323471&Ausgabe=0&Produk tNr=224107& filename=323471.pdf. J. Neurochem. 2007 was retracted online on January 23, 2012, at: https://onlinelibrary.wiley.com/doi/10.1111/j.1471- 4159.2012.07662.x/full. Specifically, ORI finds that the Respondent: Falsified Figure 5 in NIH grant application R01 AA07568- 18A1 by altering the bar graphs to make the experimental results appear valid and consistent with his hypothesis that ethanol exposure in-utero alters the transition of cells from Pax 6 expression to Tbr2 expression, which is critical to normal brain development. Specifically: a. In the VZ/SZ panel (upper row, right), Dr. Miller decreased the values by 50% for the bar graphs representing control and treated mice for ``Tbr2,'' ``both,'' and ``both/Ki-67,'' to falsely report an equivalent frequency of Tbr2 expressing cells in the right and left panels; this result was required for the experiment to appear valid; b. In the MGE panel (lower row, right), Dr. Miller altered the bar graphs representing control and treated mice for ``Ki-67,'' ``Pax6,'' and ``both'' to falsely report that ethanol increased the frequency of K-67+ cells and to report an equivalent frequency of Pax expressing cells in the right and left panels. Fabricated bar graphs in Supplemental Figure 2 in a manuscript submitted to PNAS and text in the manuscript also appearing in the grant application AA00616-25 to support the hypothesis that ethanol exposure during postnatal weeks 1 and 2 causes specific neuronal cell death in layers II/III and V of the cortex. Specifically, Dr. Miller: a. Fabricated bar graphs in Supplemental Figure 2 and related text in the PNAS manuscript to show that in select layers of the cortex, ethanol induced neuronal death occurred in post-natal day 10 (P10) mice; b. Included fabricated text in the PNAS manuscript and the grant application citing results of experiments using 15-25-day-old mice treated with ethanol during the second postnatal week, when these mice were never generated. Falsified Figure 6 in a manuscript submitted to PNAS by altering data points for the labeling index of caspase3 and TUNEL in cortex layers II/III and V after exposure to ethanol in postnatal day 7 (P7) mice, such that the two assays confirmed each other. The same data were also included as Figure 4 in NIH grant application R01 AA06916 and as Figure 7 in a poster presentation at the 2009 Research Society on Alcoholism. Falsified the figure legends and/or text in a published paper and multiple grant applications to support the primary hypothesis of the published paper that gestational alcohol exposure had an effect on brain development by affecting the way neurons differentiate and migrate into the cortex, rather than by changes to cell growth or death. Specifically, Dr. Miller falsely reported the number of animals (n) that were used in figure legends and/or text in the following: [cir] Figures 2 and 5, Dev. Neurosci. 2009, also included as Figures 3 and 4, respectively, in R01 AA07568-18; [cir] Figure 4 and Table 2 in P50 AA017823-01. Falsified Figures 4 and 6 in J. Neurochem. 2007 by altering bar graphs to increase the significance of the effect of ethanol exposure and/or withdrawal on NGF or trkA protein expression, thereby conforming with the paper's hypothesis that ethanol exposure and withdrawal affect the normal NGF/trkA circuits in cortical layer V. Specifically, Dr. Miller: a. Increased the value of the ethanol treated NGF expression in Figure 4 and decreased the value of withdrawal NFG to alter the difference between the two from approximately 2.2% to 11.6%, thereby falsely reporting significance where there was none; b. In Figure 6: (a) Increased the value of withdrawal trkA data by approximately 70% to falsely report significance with relation to the ethanol treated value and increase significance with relation to the control; (b) Increased the value of the ethanol treated phospho-trkA data by approximately 100% to increase the significance with relation to the control; (c) Falsely reported the results for Figure 6 as showing a nearly doubled ratio of p-trkA to total trkA after ethanol exposure when there was no increase at all. Dr. Miller has entered into a Voluntary Exclusion Agreement (Agreement). Dr. Miller neither admits nor denies committing research misconduct but accepts ORI has found evidence of research misconduct as set forth above. Dr. Miller has voluntarily agreed: (1) To exclude himself 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'' pursuant to HHS' Implementation (2 CFR part 376 et seq) of OMB Guidelines to Agencies on Governmentwide Debarment and Suspension, 2 CFR part 180 (collectively the ``Debarment Regulations'') for a period of one (1) year, beginning on February 6, 2012; (2) To have his research supervised for a period of two (2) years immediately following the one (1) year period of exclusion; Respondent agrees that prior to the submission of an application for U.S. Public Health Service (PHS) support for a research project on which the Respondent's participation is proposed and prior to the 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 agrees that he shall not participate in any PHS-supported research until such a supervision plan is submitted to and approved by ORI; Respondent agrees to maintain responsibility for compliance with the agreed upon supervision plan; the requirements for Respondent's supervision plan are as follows: i. A committee of 2-3 senior faculty members at the institution who are familiar with Respondent's field of research, but not including Respondent's supervisor or collaborators, will provide oversight and guidance for two (2) years immediately following the period of exclusion; the committee will review primary data from Respondent's laboratory on a quarterly basis and submit a report to ORI at six (6) month intervals setting forth the committee meeting dates, Respondent's compliance with appropriate research standards, and confirming the integrity of Respondent's research; and ii. 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 include a certification to ORI that the data presented in the proposed application/publication is supported by the research record; (3) That any institution employing him during the two (2) years during which the supervisory plan is in effect 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 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 a period of three (3) years, beginning on February 6, 2012.

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 Cancer Institute (NCI), 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. Proposed Collection: Title: A Multi-Center International Hospital- Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI). Type of Information Collection Request: Emergency. Need and Use of Information Collection: Incidence rates of certain lymphomas have increased in the United States and in many other parts of the world. The contribution of environmental, occupational, and genetic factors to the cause of lymphoma has generated a series of novel findings from epidemiological studies conducted in the United States that have attempted to explain this increase. However, none of the chemical associations have been conclusively established and the identification of the key, functional alleles in gene regions associated with risk of NHL requires further elucidation. Further, the ability to follow-up, confirm, and extend these observations in the United States is limited by the low prevalence and limited range of several important chemical and viral exposures and the high to complete linkage disequilibrium among key candidate genetic loci in Western populations. To optimize the ability to build on and clarify these findings, it is necessary to investigate populations that differ from those in the West in both exposure patterns and underlying genetic structure. A multidisciplinary case- control study of lymphoma in Asia, where lymphoma rates have also risen, provides an opportunity to replicate and extend recent and novel observations made in studies in the West in a population that is distinctly different with regard to patterns of key risk factors, including range of exposures, prevalence of exposures, correlations between exposures, and variation in gene regions of particular interest. It will also improve the ability to understand the causes of certain types of rare lymphoma tumors in the United States that occur at much higher rates in Asia. As such, AsiaLymph will confirm and extend previous findings and yield novel insights into the causes of lymphoma in both Asia and in the United States. The major postulated risk factors for evaluation in this study are chemical exposures (i.e., organochlorines, trichloroethylene, and benzene) and genetic susceptibility. Other factors potentially related to lymphoma, such as viral infections, ultraviolet radiation exposure, medical conditions, and other lifestyle factors will also be studied. Patients from 19 participating hospitals will be screened and enrolled. There will be a one-time computer-administered interview, and patients will also be asked to provide a one-time blood and buccal cell mouth wash sample and lymphoma cases will be asked to make available a portion of their pathology sample. Frequency of Response: Once. Affected Public: Individuals. Type of Respondents: Newly diagnosed patients with lymphoma or patients undergoing surgery or other treatment for non- cancer related medical issues who live in Taiwan and in Hong Kong, Chengdu and Tianjin, China will be enrolled at treating hospitals. The annual reporting burden is estimated at 5,302 hours (see Table below). There are $77,000 in Capital Costs, Operating Costs, and/or Maintenance Costs to report.

The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.

The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed collection of certain information by the Agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal Agencies are required to publish notice in the Federal Register concerning each proposed collection of information and to allow 60 days for public comment in response to the notice. This notice solicits comments on a survey entitled ``Improving Food Safety and Defense Capacity of the State and Local Level: Review of State and Local Capacities.'' The data collection will obtain knowledge of State and local capacities including food safety defense staffing and expertise, laboratory capacities, and information systems to support food and feed safety and defense.

HHS is soliciting public input on the draft National Plan to Address Alzheimer's Disease, which is available at https://aspe.hhs.gov/ daltcp/napa/NatlPlan.shtml.

Under the provisions of section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the Office of the Director, National Institutes of Health (NIH) has submitted to the Office of Management and Budget (OMB) a request to review and approve the information collection listed below. This proposed information collection was previously published in the Federal Register on Oct 5, 2011 and allowed 60 days for public comment. No public comments were received. The purpose of this notice is to allow an additional 30 days for public comment. The National Institutes of Health may not conduct or sponsor, and the respondent is not required to respond to, an information collection that has been extended, revised, or implemented on or after October 1, 1995, unless it displays a currently valid OMB control number. Proposed Collection: Title: STAR METRICS (Science and Technology for America's Reinvestment: Measuring the EffecTs of Research on Innovation, Competitiveness and Science). Type of Information Collection Request: Extension of OMB number 0925-0616, expiration date 03/31/2012. Need and Use of Information Collection: The aim of STAR METRICS is twofold. The goal of STAR METRICS is to continue to provide mechanisms that will allow participating universities and Federal agencies with a reliable and consistent means to account for the number of scientists and staff that are on research institution payrolls, supported by federal funds. In subsequent generations of the program, it is hoped that STAR METRICS will allow for measurement of science impact on economic outcomes (such as job creatfon), on knowledge generation (such as citations, and patents) as well as on social and health outcomes. Frequency of Response: Quarterly.~ Affected Public: Universities and other research institutions. Type of Respondents: University administrators.