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

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Irritable Bowel SyndromeClinical Evaluation of Drugs for Treatment.'' This guidance is intended to assist the pharmaceutical industry and investigators who are developing drugs for the treatment of irritable bowel syndrome (IBS), specifically the IBS indications for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C). The guidance describes the evolution of patient-reported outcome (PRO) measures as primary endpoints for IBS clinical trials, and sets forth provisional endpoints and trial design recommendations that sponsors may apply to IBS clinical trials as PRO measurements continue to evolve. The guidance also discusses the future development of IBS PRO instruments. This guidance finalizes the draft guidance published in March 2010.

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 study entitled ``Experimental Study on Consumer Responses to Nutrition Facts Labels With Various Footnote Formats and Declaration of Amount of Added Sugars.''

Notice is hereby given that the Office of Research Integrity (ORI) has taken final action in the following case: Juan Ma, Ph.D., Brigham and Women's Hospital and Harvard Medical School: Based on evidence and findings of an inquiry conducted jointly by Brigham and Women's Hospital (BWH) and Harvard Medical School (HMS) and additional evidence gathered by the Office of Research Integrity (ORI) during its oversight review, ORI found that Dr. Juan Ma, former Research Fellow, BWU, engaged in research misconduct in research supported by National Cancer Institute (NCI), National Institutes of Health (NIH), grant 5 P01 CA120964. ORI found that the Respondent knowingly and intentionally fabricated and falsified data in portions of figures in an unpublished manuscript titled ``TSC1 loss synergizes with KRAS activation in lung cancer development and confers rapamycin sensitivity'' by M.-C. Liang, J. Ma, L. Chen, P. Kozlowski, W. Qin, D. Li, T. Shimamura, M.L. Sos, R. Thomas, D. Neil Hayes, M. Meyerson, D.J. Kwiatkowski, and K.-K. Wong, submitted to the Journal of Clinical Investigation (JCI) on August 5, 2008, and in revised form on October 21, 2008 (hereafter referred to as the ``JCI manuscript''). Specifically, Respondent committed research misconduct by knowingly and intentionally: Falsifying and/or fabricating those portions of the immunoblots in JCI manuscript Figure 1C, to show that in TsclL/L and TscL/+ mouse lung cancer cells compared with KRAS induced lung cancer cells, there were reduced Tsc1 and Tsc2 protein levels, reduced phospho-AKT-S473 levels, and increased phospho-S6-S249/244 levels, consistent with the hypothesis that introduction of the Tsc1L gene resulted in mTORC1 activation. Falsifying and/or fabricating those portions of the immunoblots in Figure 3A of the JCI manuscript to show data consistent with the hypothesized TNS null signaling lung tumor cells: Functional loss of Tsc1/Tsc2, high phospho-S6-S249/244 levels, and low phospho- AKT-S473, with recovery of phospho-AKT-S473 after Rapamycin treatment. Falsifying and/or fabricating those portions of the immunoblots in Figure 3B of the JCI manuscript by (i) adding a band in the Tsc2 lane for control cells for the IP blot, and (ii) weakening the Tsc2 band for one of the tumor lysates. Falsifying and/or fabricating immunoblots in Figures 5A and 5B of the JCI manuscript so that the data appeared to indicate that TSC reconstitution in TSC null (TNS) cell lines led to reduction of pS6-S240/244 levels during serum deprivation (in the absence of growth factors), as well as increased pAKT(S473) levels in response to serum stimulation. The JCI manuscript was accepted by JCI on December 8, 2008, but it was withdrawn by one of the authors on January 6, 2009. ORI found that Respondent's knowing and intentional falsification and fabrication of data constitutes research misconduct within the meaning of 42 CFR 93.103. The following administrative actions have been implemented for a period of three (3) years, beginning on May 12, 2012: (1) Any institution that submits an application for U.S. Public Health Service (PHS) support for a research project on which Respondent's participation is proposed or that uses him in any capacity on PHS-supported research must concurrently submit a plan for supervision of his duties to the funding agency for approval; the supervisory plan must be designed to ensure the scientific integrity of his research contribution; Respondent must ensure that a copy of the supervisory plan is also submitted to ORI by the institution; Respondent will not participate in any PHS-supported research until such a supervisory plan is submitted to ORI; (2) Respondent will ensure that any institution employing him submits, in conjunction with application for PHS funds or any report, manuscript, or abstract of PHS-funded research in which he is involved, a certification that the data provided by him are accurately reported in the application or report; Respondent must ensure that the institution send the certification to ORI; this certification shall be submitted no later than one month before funding and concurrently with any report, manuscript, or abstract; and (3) 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.

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 the availability of a draft guidance for industry entitled ``Pathologic Complete Response in Neoadjuvant Treatment of High-Risk Early-Stage Breast Cancer: Use as an Endpoint to Support Accelerated Approval.'' FDA's accelerated approval regulations permit approval of a new drug to treat a serious disease on the basis of an effect on a surrogate endpoint reasonably likely to predict the clinical benefit of the drug. This draft guidance is intended to assist applicants in designing trials to support marketing approval of drugs to treat breast cancer in the neoadjuvant (preoperative) setting using pathologic complete response (pCR) as a surrogate endpoint that could support approval under the accelerated approval regulations. Despite advances in systemic therapy of early-stage breast cancer over the past few decades, there remains a significant unmet medical need for certain high-risk or poor prognosis populations of early-stage breast cancer patients. This guidance is intended to encourage industry innovation and expedite the development of breakthrough therapies to treat high- risk early-stage breast cancer.

This document corrects technical and typographical errors that appeared in the final rule, interim final rule, published in the Federal Register on March 27, 2012, entitled ``Patient Protection and Affordable Care Act; Establishment of Exchanges and Qualified Health Plans; Exchange Standards for Employers.''

The Centers for Medicare & Medicaid Services (CMS), is announcing the launch of the ``CMS Provider Screening Innovator Challenge.'' This Challenge is sponsored by CMS and is presented as part of the Partnership for Program Integrity Innovation program, and will be administered by the National Aeronautic and Space Administration's (NASA) Federal Center of Excellence for Collaborative Innovation. This Challenge addresses our goals of improving our abilities to streamline operations, screen providers, and reduce fraud and abuse. Specifically, the challenge is an innovation competition to develop a multi-State, multi-program provider screening software application which would be capable of risk scoring, credentialing validation, identity authentication, and sanction checks, while lowering burden on providers and reducing administrative and infrastructure expenses for States and Federal programs. More information pertaining to the Medicaid and CHIP programs can be found at www.medicaid.gov.

This proposed notice with comment period acknowledges the receipt of an application from the Community Health Accreditation Program (CHAP) for continued recognition as a national accrediting organization for hospices that wish to participate in the Medicare or Medicaid programs.

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Meetings with Industry and Investigators on the Research and Development of Tobacco Products.'' This guidance describes FDA's current policies and recommendations with respect to Agency meetings with tobacco manufacturers, importers, researchers, and/or investigators relating to their plans to conduct research to inform the regulation of tobacco products, or support the development or marketing of tobacco products. The guidance is intended to assist persons seeking a meeting with FDA to discuss the research and development of tobacco products. This guidance does not pertain to other types of meetings or meeting requests with Center for Tobacco Products (CTP) staff.