|
Items in cart [1] |
Questions? Call 888-624-8373 |
| Copyright © 2009. National Academy of Sciences. All rights reserved. Terms of Use and Privacy Statement |
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
Conflict of Interest in Medical Research, Education, and Practice
CONFLICT OF INTEREST IN MEDICAL RESEARCH, EDUCATION, AND PRACTICE
Bernard Lo and Marilyn J. Field, Editors
Committee on Conflict of Interest in Medical Research, Education, and Practice
Board on Health Sciences Policy
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
OCR for page R2
Conflict of Interest in Medical Research, Education, and Practice
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, N.W. Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract No. N01-OD-4-2139, TO # 201 of the National Institutes of Health, Contract No. 63229 of the Robert Wood Johnson Foundation, The Greenwall Foundation, the ABIM Foundation, Contract No. S07-2 of the Josiah Macy Jr. Foundation, Contract No. 1007182 of the Burroughs Wellcome Fund, and also the endowment fund of the Institute of Medicine, all contracts between the National Academies. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for the project.
Library of Congress Cataloging-in-Publication Data
Conflict of interest in medical research, education, and practice / Bernard Lo and Marilyn J. Field, editors ; Committee on Conflict of Interest in Medical Research, Education, and Practice, Board on Health Sciences Policy.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-309-13188-9 (hardcover)
1. Business and medicine. 2. Conflict of interests. I. Lo, Bernard. II. Field, Marilyn J. (Marilyn Jane) III. Institute of Medicine (U.S.). Committee on Conflict of Interest in Medical Research, Education, and Practice. IV. National Academies Press (U.S.)
[DNLM: 1. Conflict of Interest. 2. Biomedical Research—ethics. 3. Education, Medical—ethics. 4. Ethics, Clinical. W 50 C748 2009]
RA394.C665 2009
174.2—dc22
2009020634
Additional copies of this report are available from the
National Academies Press,
500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.
Copyright 2009 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2009. Conflict of Interest in Medical Research, Education, and Practice. Washington, DC: The National Academies Press.
OCR for page R3
Conflict of Interest in Medical Research, Education, and Practice
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
OCR for page R4
Conflict of Interest in Medical Research, Education, and Practice
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
OCR for page R5
Conflict of Interest in Medical Research, Education, and Practice
COMMITTEE ON CONFLICT OF INTEREST IN MEDICAL RESEARCH, EDUCATION, AND PRACTICE
BERNARD LO (Chair), Professor of Medicine and Director,
Program in Medical Ethics, University of California, San Francisco
WENDY BALDWIN, Director,
Poverty, Gender and Youth Program, Population Council
LISA BELLINI, Associate Dean for Graduate Medical Education and Associate Professor of Medicine,
University of Pennsylvania
LISA A. BERO, Professor,
Department of Clinical Pharmacy and Institute for Health Policy Studies, University of California, San Francisco
ERIC G. CAMPBELL, Associate Professor,
Institute for Health Policy and Department of Medicine, Massachusetts General Hospital and Harvard Medical School
JAMES F. CHILDRESS, Hollingsworth Professor of Ethics,
Department of Religious Studies and
Professor of Medical Education and Director,
Institute for Practical Ethics, University of Virginia
PETER B. CORR, General Partner,
Celtic Therapeutics Management Company, L.L.P.
TODD DORMAN, Associate Dean and Director,
Continuing Medical Education, and
Professor of Anesthesiology,
Johns Hopkins Medical Center
DEBORAH GRADY, Professor of Medicine and Director,
Women’s Health Clinical Research Center and
Associate Dean for Translational Research,
University of California, San Francisco
TIMOTHY S. JOST, Robert L. Willett Family Professor of Law,
Washington and Lee University School of Law
ROBERT P. KELCH, Executive Vice President for Medical Affairs,
University of Michigan and
Chief Executive Officer,
University of Michigan Health System
ROBERT M. KRUGHOFF, President,
Consumer CHECKBOOK/Center for the Study of Services
GEORGE LOEWENSTEIN, Herbert A. Simon Professor of Economics and Psychology,
Department of Social and Decision Sciences, Carnegie Mellon University
JOEL PERLMUTTER, Elliot Stein Family Professor of Neurology and Professor of Radiology and Physical Therapy,
Washington University School of Medicine in St. Louis
NEIL R. POWE, Professor of Medicine,
Epidemiology, and Health Policy and Management and
Director,
Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins School of Medicine and Bloomberg School of Public Health
OCR for page R6
Conflict of Interest in Medical Research, Education, and Practice
DENNIS F. THOMPSON, Alfred North Whitehead Professor of Political Philosophy,
Department of Government and
Professor of Public Policy,
John F. Kennedy School of Government, Harvard University
DAVID A. WILLIAMS, Chief of the Division of Hematology/Oncology, Director,
Clinical and Translational Research, Children’s Hospital Boston and
Leland Fikes Professor of Pediatrics,
Harvard Medical School
Committee Consultants and Background Paper Authors
JASON D. DANA, Assistant Professor,
Department of Psychology, University of Pennsylvania
MICHAEL DAVIS, Senior Fellow,
Center for Study of Ethics in the Professions and
Professor of Philosophy,
Humanities Department, Illinois Institute of Technology
JOSEPHINE JOHNSTON, Research Associate,
Hastings Center, Garrison, New York
IOM Staff
MARILYN J. FIELD, Senior Program Officer
FRANKLIN BRANCH, Research Associate
ROBIN E. PARSELL, Senior Program Assistant (from January 2008)
AFRAH ALI, Senior Program Assistant (until November 2007)
ANDREW POPE, Director,
Board on Health Sciences Policy
OCR for page R7
Conflict of Interest in Medical Research, Education, and Practice
Acknowledgments
In preparing this report, the committee and project staff benefited greatly from the assistance and expertise of many individuals and groups. Important information and insights came from four public meetings that the committee organized to collect information and perspectives from a range of academic, professional, consumer, patient, and other organizations and individuals. A number of speakers at these meetings also shared their knowledge at other times during the course of the study. Appendix A includes the agendas of the public meetings and a list of organizations that submitted written statements of views.
The committee appreciates the contributions of the authors of the background papers that appear as Appendix C (Michael Davis at Illinois Institute of Technology and Josephine Johnston at the Hastings Center) and Appendix D (Jason Dana at University of Pennsylvania). Our project officer at the National Institutes of Health, Walter Schaffer, was always helpful in getting our questions answered. We also called on Daniel Wolfson at the American Board of Internal Medicine Foundation for information. In addition, Ariel Winter of the Medicare Payment Advisory Commission helped by answering questions about the commission’s work. Mary Nix at the Agency for Healthcare Research and Quality provided data from the National Guidelines Clearinghouse that we could not obtain online. An undoubtedly incomplete list of others who assisted the committee’s work includes David Atkins, James Bernat, Carol Blum, David Blumenthal, Deborah Briggs, Laura Brockway-Lunardi, Robert Campbell, Roger Chou, Vivian Coates, Allan Coukel, Bette Crigger, Susan Ehringhaus, Brian Eigel,
OCR for page R8
Conflict of Interest in Medical Research, Education, and Practice
Susan Gilbert, Marianne Hockema, Cato Laurencin, Jeffrey Leiden, Martha Liggett, Kathleen Lohr, Peter Lurie, Charlene May, Jennifer Padberg, James Severson, Mark Sommerfeld, Gabriel Sullivan, and Myrl Weinberg.
The committee and project staff also appreciate the work of copy editor Michael Hayes. Within the National Academies, we particularly acknowledge the assistance of Clyde Behney, Judy Estep, Robert Giffin, Janice Mehler, Abbey Meltzer, Amy Packman, Donna Randall, Bronwyn Schrecker, and Jackie Turner.
OCR for page R9
Conflict of Interest in Medical Research, Education, and Practice
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published reports as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Claudia R. Adkison, Emory University School of Medicine
Robert Baron, University of California, San Francisco School of Medicine
Paul Citron, Medtronic, Inc. (Retired)
F. Sessions Cole, Washington University School of Medicine
Peter Densen, University of Iowa Carver College of Medicine
Thomas J. Fogarty, Fogarty Engineering
Leo T. Furcht, University of Minnesota
Linda Golodner, National Consumers League
Henry T. Greely, Stanford University Law School
Allen S. Lichter, American Society of Clinical Oncology
Joseph Loscalzo, Brigham and Women’s Hospital
Alan Nelson, American College of Physicians Foundation
OCR for page R10
Conflict of Interest in Medical Research, Education, and Practice
Philip A. Pizzo, Stanford University School of Medicine
Richard Schilsky, University of Chicago Medical Center
Larry J. Shapiro, Washington University in St. Louis School of Medicine
Harold Sox, Annals of Internal Medicine and American College of Physicians
Jeremy Sugarman, Johns Hopkins Medical Institutions
P. Roy Vagelos, Merck & Co., Inc. (Retired)
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by David Challoner, University of Florida, and Judith L. Swain, National University of Singapore and University of California, San Diego. Appointed by the National Research Council and the Institute of Medicine, these individuals were responsible for making certain that an independent examination of this report was carried out in accordance with the institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
OCR for page R11
Conflict of Interest in Medical Research, Education, and Practice
Preface
Hardly a week goes by without a news story about conflicts of interest in medicine. While this committee met, colleagues and friends sent me many news reports and journal articles on the topic. These reports—even if one expects that initial news reports may not always have the stories quite straight—served as continual reminders that conflicts of interest create deep concerns about the integrity of medicine and medical research and raise questions about the trustworthiness of physicians, researchers, and medical institutions.
As I look back over our deliberations, several themes stand out. First, as with all Institute of Medicine (IOM) reports, the committee was charged with making recommendations that were based on evidence and convincing reasons. Although the committee members were aware of powerful anecdotes and had personal beliefs about the issues, we repeatedly asked whether the evidence supported our conclusions and recommendations. If it did not, we developed a reasoned case on the basis of the committee’s experience and the judgment of the committee members about the arguments for the use of different approaches presented in the literature or in statements submitted to the committee. Second, it is a challenge to craft policy recommendations that strike the right balance between addressing egregious cases and creating burdens that stifle relationships that advance the goals of professionalism and generate knowledge to benefit society. The committee tried to consider the possibility that well-intentioned policies may have unintended adverse consequences. Third, regulation alone may have limited effectiveness in the absence of a culture of professionalism
OCR for page R12
Conflict of Interest in Medical Research, Education, and Practice
and other incentives that are aligned to promote professional behavior. The committee considered how a variety of organizations—including those that accredit health care institutions and license health care professionals, publish the findings of medical research, use practice guidelines, and pay for medical care—can buttress the conflict of interest policies implemented by institutions that carry out medical research, provide education and patient care, and develop practice guidelines.
This report cannot and did not attempt to resolve all issues related to conflicts of interest in medicine. In view of our expansive charge, we tried to address central questions rather than the many details of this complex topic. For example, we focus on conflicts that involve financial interests because they are at the heart of concerns and debates about conflicts of interest. Furthermore, because relationships with pharmaceutical, medical device, and biotechnology companies have created the greatest concern and were central in the discussions that led the IOM to pursue this study, we focused on those relationships. The committee expects that many of the recommendations and analyses in our report will also apply more generally to professional and institutional relationships with other commercial entities, such as insurers and vendors of nonmedical products.
The committee could not resolve some important issues like harmonizing the different requirements for the disclosure of financial relationships because they would require much more time and additional expertise. Instead, to standardize aspects of disclosure policies and procedures, the committee recommended a focused consensus development process that would involve multiple stakeholders on the issue.
Our committee was diverse, involving members with different professional backgrounds and areas of expertise. These different perspectives led to spirited discussions and debates. Each of us listened to points of view and information that we had not previously considered. We tried to listen to and understand other viewpoints and be open to new perspectives, even if in the end we did not agree on all issues. Appendix F describes the different views on one issue, a proposal by some committee members for broader requirements for public disclosure. In general, the committee hoped that by explaining our reasoning on difficult issues our audiences would better appreciate the multiple considerations that a sound conflict of interest policy should address.
As chair, I want to personally thank the committee members for their hard work and their willingness to engage on difficult topics. I am deeply grateful to them for the time and effort that they took from their busy schedules to devote to this project. This report is truly a collaborative effort and is much the better, I think, for the back-and-forth discussions. I also want to personally thank our IOM staff for their tremendous efforts in making this report possible. Robin Parsell skillfully handled meeting
OCR for page R13
Conflict of Interest in Medical Research, Education, and Practice
and other logistics, and Franklin Branch provided research assistance in many areas. Marilyn Field was unstinting in her background research, drafting and revising of the manuscript, and high standards for our work. And I want to thank Lindsay Parham, my research assistant at the University of California at San Francisco, for her expert help with background research.
Bernard Lo, M.D., Chair
Committee on Conflict of Interest in Medical Research, Education, and Practice
OCR for page R14
Conflict of Interest in Medical Research, Education, and Practice
This page intentionally left blank.
OCR for page R15
Conflict of Interest in Medical Research, Education, and Practice
Contents
SUMMARY
1
1
INTRODUCTION
23
Overview and Themes of the Report,
27
Historical and Policy Context,
33
Organization of Report,
43
2
PRINCIPLES FOR IDENTIFYING AND ASSESSING CONFLICTS OF INTEREST
44
What Is a Conflict of Interest?,
45
What Are the Purposes of Conflict of Interest Policies?,
48
Why Not Examine the Motives of the Decision Maker or the Validity of the Decision?,
50
Should Policies Also Require That Professionals Avoid the “Appearance of Conflict of Interest”?,
52
How Can Conflicts of Interest Be Assessed?,
52
How Can Conflict of Interest Policies Be Evaluated?,
56
Conclusion,
60
3
POLICIES ON CONFLICT OF INTEREST: OVERVIEW AND EVIDENCE
62
Overview of Conflict of Interest Policies,
64
Disclosure: An Essential but Insufficient Element of Policy,
67
Prohibiting or Eliminating Conflicts of Interests,
79
OCR for page R16
Conflict of Interest in Medical Research, Education, and Practice
Evaluating and Managing Conflicts of Interest,
80
Recommendations,
87
4
CONFLICTS OF INTEREST IN BIOMEDICAL RESEARCH
97
Collaboration and Discovery in Biomedicine,
98
Industry Funding and Relationships in Biomedical Research,
101
Concerns About Relationships with Industry,
102
Responses to Concerns About Conflicts of Interest in Research,
110
Recommendations,
116
5
CONFLICTS OF INTEREST IN MEDICAL EDUCATION
122
Background and Context,
124
Learning Environments in Medical Schools and Residency Programs,
127
The Learning Environment in Accredited Continuing Medical Education,
140
Ghostwriting, Speakers Bureaus, and Independence of Publications and Presentations,
153
Recommendations,
157
6
CONFLICTS OF INTEREST AND MEDICAL PRACTICE
166
The Broader Context: Physician Payment, Self-Referral, and Conflicts of Interest in Medical Practice,
167
Industry Promotional Activities and Practicing Physicians,
170
Responses to Concerns About Industry Relationships and Conflicts of Interest in Community Practice,
175
Recommendations,
183
7
CONFLICTS OF INTEREST AND DEVELOPMENT OF CLINICAL PRACTICE GUIDELINES
189
Background and Context,
190
Groups That Develop Clinical Practice Guidelines,
196
Financial Relationships in Guideline Development,
198
Policies on Conflicts of Interest in Clinical Practice Guideline Development,
204
Recommendations,
210
8
INSTITUTIONAL CONFLICTS OF INTEREST
216
What Are Institutional Conflicts of Interest?,
218
Extent of Institutional Relationships with Industry,
219
Responses to Institutional Conflicts of Interest,
221
Special Challenges in Managing Institutional Conflicts of Interest,
224
Recommendations,
226
OCR for page R17
Conflict of Interest in Medical Research, Education, and Practice
9
ROLE OF SUPPORTING ORGANIZATIONS
230
How Supporting Organizations Can Influence Medical Institutions,
232
Recommendations,
235
REFERENCES
240
APPENDIXES
A
Study Activities
285
B
U.S. Public Health Service Regulations: Objectivity in Research (42 CFR 50)
295
C
Conflict of Interest in Four Professions: A Comparative Analysis
302
D
How Psychological Research Can Inform Policies for Dealing with Conflicts of Interest in Medicine
358
E
The Pathway from Idea to Regulatory Approval: Examples for Drug Development
375
F
Model for Broader Disclosure
384
G
Committee Biographies
392
INDEX
401
OCR for page R18
Conflict of Interest in Medical Research, Education, and Practice
This page intentionally left blank.
OCR for page R19
Conflict of Interest in Medical Research, Education, and Practice
Boxes, Figures, and Tables
BOXES
3-1
Model of Steps Used to Identify and Respond to a Conflict of Interest,
65
3-2
Risks and Potential Benefits to Consider in Assessing the Severity of a Researcher’s Conflict of Interest,
83
4-1
Examples of Biased Reporting in Clinical Research,
107
5-1
AAMC Recommendations on Site Access by Sales Representatives,
134
5-2
Example of a Solicitation of Industry Support (Educational Grants) for a Large Accredited Continuing Medical Education Program,
146
5-3
Settlements Involving Educational Activities and Speaking and Writing Arrangements,
149
6-1
Excerpts from Statements on Gifts by American Medical Association and American College of Physicians,
177
6-2
Summary of Selected Recent Revisions in the PhRMA Code on Interactions with Healthcare Professionals,
180
6-3
Examples of Prosecutions Involving Kickbacks to Physicians,
182
7-1
Cases and Controversies Involving Conflicts of Interest in Guideline Development,
200
OCR for page R20
Conflict of Interest in Medical Research, Education, and Practice
7-2
Examples of Financial and Conflict of Interest Information Excerpted from Summaries in the National Guideline Clearinghouse,
202
7-3
Examples of Conflict of Interest Policy Descriptions Excerpted from Summaries in the National Guideline Clearinghouse,
206
7-4
Policies of American College of Chest Physicians on Industry Funding of Guideline Development,
208
7-5
Other Strategies for Limiting Bias in Clinical Practice Guideline Development,
209
8-1
Cases and Controversies Involving Institutional Conflicts of Interest,
217
9-1
Examples of Methods That Supporting Organizations Can Use to Strengthen Conflict of Interest Policies,
236
E-1
Case Example of Successful Collaboration in Drug Discovery and Development,
379
FIGURES
5-1
Sources of income reported by respondents (accredited providers of continuing medical education) to ACCME annual survey, 1998 to 2007,
128
6-1
Percent change in average net physician income, adjusted for inflation, 1995 to 2003,
168
E-1
Defining biomedical research from idea to market,
377
TABLES
S-1
Report Recommendations in Overview,
16
1-1
Timeline of Selected Events Relevant to the Evolution of Conflict of Interest Principles, Policies, and Practices,
36
1-2
Selected Reports on Conflict of Interest Released Since 2000,
42
2-1
Criteria for Assessing the Severity of Conflicts of Interest,
53
2-2
Criteria for Evaluating Conflict of Interest Policies,
57
OCR for page R21
Conflict of Interest in Medical Research, Education, and Practice
3-1
Percentage of Medical Schools Requiring Further Disclosures for Researchers with a Significant Financial Interest in Their Research,
69
3-2
Percentage of Medical Schools Citing Different Management Policy Options When Researchers Have a Significant Financial Interest in Their Research,
84
3-3
Candidate List of Categories of Financial Relationships with Industry to Be Disclosed,
93
4-1
Checklist for Reporting Clinical Trials from CONSORT 2001 Statement,
114
5-1
Third-Year Medical Students’ Interactions with Drug Companies,
130
5-2
Share of Total Accredited Continuing Medical Education Income, Instruction Hours, Participants, and Activities Accounted for by Major Types of ACCME-Accredited Providers,
141
5-3
Income, Expenses, and Source of Support as Percentage of Income, by Type of Accredited Provider of Continuing Medical Education, 2007,
144
7-1
Basic Elements of Process for Developing Evidence-Based Practice Guidelines,
193
7-2
Number of Clinical Practice Guidelines in the National Guideline Clearinghouse by Selected Types of Sponsors, as of March 16, 2009,
197
C-1
Summary of the Responses of Four Professions to Conflicts of Interest,
356
OCR for page R22
Conflict of Interest in Medical Research, Education, and Practice
This page intentionally left blank.
