The Management of Scientific Integrity within Academic Medical Centers

The Management of Scientific Integrity within Academic Medical Centers

Peter J. Snyder

Lifespan Hospital System & Alpert Medical School of Brown University, Providence, RI

Linda C. Mayes

Yale University School of Medicine, New Haven, CT

William E. Smith

Chief Judge, United States District Court for the District of Rhode Island, Providence, RI

Table of Contents

Cover image

Title page

Copyright

Dedications

Foreword

About the Authors

Acknowledgments

Chapter 1. Introduction: Research Misconduct in Biomedical Research Institutions

Chapter 2. Research Integrity: The Legal and Regulatory Landscape

1. Introduction

2. The Institutional and Agency Process

3. Other Legal Consequences for Researchers Engaging in Research Misconduct

4. Process-Based Challenges

5. Other Types of Claims Arising Out of Institutional Proceedings

6. Litigation over Records

7. Summary

Case Studies

Introduction

A Note on the Presentation of Nine Research Integrity Case Studies

Chapter 3. Question of Data Manipulation in Failure to Replicate Findings in Published Manuscript

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 4. Violation of Institutional and Public Health Service Policies Governing the Care and Use of Animals in Research: Cultural Barriers in the Academic Workplace

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 5. Research Assistants Coming Forward with Concerns about Perceived Behavior of Principal Investigator

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 6. Questionable Mentorship and Oversight of Federal Grant Funding

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions For Discussion

Chapter 7. Submission of Fraudulent Data to a Peer-Review Journal: What Is the Role of the Lab Head/Mentor?

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Interview with Dr Alatas

6. Interview with Dr Perkasa

7. Synthesis and Formulation

8. Resolution

9. Commentary

Questions for Discussion

Chapter 8. Plagiarism versus Data Shared between Junior and Senior Investigators

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 9. Misappropriation and Use of Data from a Multisite and Multi-investigator Study

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 10. Determining the Extent of Data Fabrication Following an Apparent Single Incident

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 11. Anonymous Allegations of Scientific Misconduct

1. Presenting Complaint

2. Background and History

3. Relevant Evidence

4. Case Management and Adjudication

5. Synthesis and Formulation

6. Resolution

7. Commentary

Questions for Discussion

Chapter 12. Management of Research Integrity within Academic Medical Centers: A Summary and Suggested Best Practices

1. Themes Illustrated in the Case Material

2. Recommendations and Best Practices

3. Conclusion

Appendix 1. Federal Policy on Research Misconduct

Appendix 2. Lifespan System-wide Policy

Appendix 3. Policies and Procedures for Dealing with Allegations of Academic Misconduct at Yale University

Index

Copyright

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Dedications

For my wise and loving mother, Susan J. Etkind, who has always been a wonderful supporter of my career and interests.

Peter J. Snyder

To Marion Mayes, my model for courage and resilience and Dr. Lawrence Cohen, my teacher and colleague in matters of research integrity.

Linda C. Mayes

For Christine, Katie and Allie who make it all worthwhile.

William E. Smith

Foreword

As you thumb through the Table of Contents, the introductory chapters, or quickly skim through one of the detailed case studies presented in this book, you may be considering whether this volume—and its central topic—is of clear relevance to your professional practice as a scientist, clinician/scientist, academic medical center (AMC) administrator, graduate or postgraduate trainee, or scholar of modern research process. This book is unique in its presentation of issues, the competencies of its coauthors, and it is absolutely central to the culture, function, and reputation of any AMC, or medical research institute.

In my current role, I lead a large hospital Network, in one of the biggest population centers in North America. The Mount Sinai Health System and Network includes seven separate hospital campuses, a prestigious medical school (The Icahn School of Medicine of Mount Sinai), and multiple out-patient facilities. We credential over 6000 clinicians and scientists across 32 departments and 15 academic institutes. Research and innovation are core values and differentiating factors for our Health System and Network. Our commitment to these, as at other AMCs, is as central as our commitment to clinical excellence. At any one moment in time, there are many hundreds of professionals actively engaged in scientific research across virtually every facility and discipline within our system. All of this combined effort, and all of the scholarly productivity and successes of our faculty, would be rendered meaningless without constant vigilance over, and careful management of, research integrity. Our entire research enterprise, both as an individual medical system, but also as an entire academic society, hinges on our ability to protect and enhance the veracity of the scientific process.

We now live in an age in which research misconduct cases are regularly hitting the news and in which public trust in science and in fact in the overall quality and outcome of intervention and care within the medical profession is at an all-time low. Federal funding of science, is also greatly diminished. All of these critical environmental factors underscore the need to effectively manage ethical misconduct. Without a well-supported and active research integrity process and system in place, the pursuit of scientific discovery within an academic medical institution and indeed within our society is rendered meaningless. We need to clearly and openly look at these issues and commit to making our oversight and adjudication better.

In this volume, Professors Peter J. Snyder and Linda C. Mayes have formed a unique partnership, with Federal District Court Judge William E. Smith, to explore the application of NIH research integrity policy within hospital and AMC environments, and to better understand how the internal institutional management of misconduct affects—and is affected by—the United States’ jurisprudence. The authors accomplish this large task through the presentation of a provocative introduction, an authoritative chapter on the legal and regulatory systems that guide the management of research conduct, the presentation of eight complex case studies, and by a summary chapter that provides best practices for those charged with such a large set of responsibilities. In choosing their anonymous cases for presentation, the authors have shown convincingly that, in most instances, there are rarely clear-cut right or wrong decisions to be made, but rather ambiguities and uncertainties that must be handled with care, consistency, wisdom, and high ethical standards; and where appropriate transparency and disclosure.

All three coauthors bring a wealth of experience, talent, good judgment, and knowledge to their work and to this book. Snyder, Mayes, and Smith have each enjoyed very productive and distinguished careers and the reader will most certainly benefit from their collective experience and advice. This volume will stimulate much discussion in the classroom (e.g., for graduate courses in science and ethics) and it will be a useful resource for both practicing scientists and for those who must serve their institutions by managing the oversight of research conduct.

Arthur A. Klein, M.D., President,     The Mount Sinai Health Network, Executive Vice President—Mount Sinai Hospital, Executive Vice President—Icahn School of Medicine, New York City, NY, USA

About the Authors

Prof. Peter J. Snyder has served as the Research Integrity Officer, as well as the Institutional Official, for the Lifespan Hospital System (Providence, RI) since 2008. He oversees the ethical conduct of research for approximately 350 investigators across a system of five hospitals that form the core teaching campuses for the Alpert Medical School of Brown University. Dr Snyder is the Chief Research Officer for this academic health system, and he also serves as a Professor of Neurology within the medical school. Dr Snyder has maintained an active research program for more than 20 years, and he has published widely in the fields of clinical neuropsychology, cognitive neuroscience, neuropharmacology and the history of the neurosciences. Dr Snyder is the Senior Associate Editor for Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association (published by Elsevier).

Prof. Linda C. Mayes has served as the Special Assistant to the Dean, Yale School of Medicine (New Haven, CT) since 2008. In this role, she is also responsible for management of scientific integrity for the Yale School of Medicine. Dr Mayes is the Arnold Gesell Professor of Child Psychiatry, Pediatrics, and Psychology in the Yale Child Study Center, and her research integrates perspectives from child development, behavioral neuroscience, psychophysiology and neurobiology, developmental psychopathology, and neurobehavioral teratology. She has published widely in the developmental psychology, pediatrics, and child psychiatry literature. Dr Mayes is also trained as an adult and child psychoanalyst and she coordinates the Anna Freud Centre bridge program in social and developmental neuroscience and developmental psychopathology at the Yale Child Study Center. She is also a distinguished Visiting Professor in Psychology at Sewanee: The University of the South.

The Hon. William E. Smith is the Chief United States District Court Judge for the District of Rhode Island. He has served on that court for over 12 years. Judge Smith has developed an expertise and interest in the intersection between rapid advances in science and the work of the courts, in both the civil and criminal law. He has presided over a number of cases involving highly complex fields of scientific evidence. In addition, Judge Smith teaches various courses at the Roger Williams School of Law (Bristol, RI), including a course on the law of scientific and expert evidence; in addition, he serves on the board of The National Courts and Science Institute, an organization devoted to increasing the level of scientific knowledge and competency within the judiciary.

Acknowledgments

The authors would like to acknowledge the support, advice, expertise, and generosity of a number of individuals who helped make this published volume possible.

From the outset, a book on this controversial topic—including the presentation of detailed case studies—seemed to be a daunting task. Dr Snyder would first like to thank the General Counsel for the Lifespan Hospital System (Providence, RI), Kenneth Arnold, Esq., for his unfailing encouragement throughout this project. Ken has been an important mentor to Dr Snyder, and the organization and structure of this book (including our approach to the creation of anonymous case studies) resulted directly from Ken’s questions and advice. Dr Snyder would also like to thank Therese Flynn-Eckford, Esq., who played the leading role in authoring the research misconduct policy provided in Appendix 2, for her advice and expertise. Dr Snyder would also like to thank Dr Tim Babineau, the President and Chief Executive Officer for the Lifespan Hospital System, for his consistent and unfailing support of the biomedical research mission of our institution (presently ranked 9th in the country, in terms of federal funding for research to private hospitals), and Ms Peggy McGill, Administrative Director for the Lifespan Office of Research Administration, for her wisdom and the often-needed patient advice of an older sister! Dr Snyder also thanks Dr Jack Elias, Dean of the Alpert Medical School of Brown University, for his dedication to advancing biomedical research across the entire Brown community, including its affiliated hospitals. Sophie Van Horne (Brown, 2014), a characteristically talented Brown University undergraduate student, assisted in compiling background material for this volume. Finally, Dr Snyder’s spouse, Amy L. Snyder, M.D., and two children (Molly and Jacob), provided all the love, encouragement, and good humor to allow any writer to forge ahead with such a difficult project.

Dr Linda Mayes would first like to thank Dean Robert Alpern and Deputy Dean Carolyn Slayman of the Yale School of Medicine for the opportunity to work on matters of scientific integrity and conduct for the School of Medicine. In her role as Special Advisor to the Dean, Dr Mayes has become deeply appreciative of the complex social nature of research and the often conflicting motivations researchers are faced with. She is very grateful to her faculty colleagues who have voluntarily given hundreds of hours to carefully considering the many questions and allegations that come to a research integrity office. Indeed, her faculty colleagues continue to be exemplary teachers on how to thoughtfully and in a balanced matter hear the many sides of any scientific misconduct allegation. Dr Mayes also gratefully acknowledges her colleagues in the Yale General Counsel’s office who provide support and guidance for Dr Mayes and the faculty committees reviewing the different allegations and concerns presented for consideration to Dr Mayes’ office. Specifically, Robert Bienstock, Esq., senior associate general counsel and Harold Rose, Esq., senior associate general counsel, each in the Yale General Counsel’s office have provided advice and review for a number of the issues and anonymous case descriptions in this volume and are both generous teachers and colleagues. Dr Mayes also gratefully acknowledges Marion Mayes, her mother, who consistently encouraged curiosity, fairness, and an appreciation for the richness of all human endeavors.

Chief Judge William Smith would like to first thank Dr Snyder for initially suggesting the collaboration that resulted in this book. It is because of his vision about the value of a work like this, and what a nonscientist might bring to the project, that Judge Smith became involved. Judge Smith is enormously grateful to his Research Assistant/Law Clerk, Michael Pabian, who took the laboring oar in the research for, drafting and editing of the Legal Landscape chapter and who contributed tremendous value to the rest of the work through his thoughtful comments and suggestions. Michael’s acute legal mind, writing prowess, and incredible work ethic is second to none, and Judge Smith could not have done this without him. Michael was able to work on this project through the generous support of his law firm, Ropes and Gray, which allowed him to work for the judge for over a year as part of its New Alternatives Program. Thank you to Ropes and Gray for making him available. Judge Smith would also like to thank his intern, Scott Hefferman, a soon-to-be law student for his research and editing assistance as well. And finally, Judge Smith would like to thank Christine, Katie, and Allie Smith for all of their love and support in this and every project he has undertaken.

All three authors thank our editor at Elsevier B.V., Ms Halima Williams, for her active engagement as a partner in this effort—and for believing that this book will serve as an important resource for those who protect the veracity of the scientific process within academic medical centers.

Chapter 1

Introduction

Research Misconduct in Biomedical Research Institutions

Abstract

As we age, we look for simple lifestyle changes that might serve to protect our health and stave off dreaded diseases. And, at the same time, many adults enjoy a delicious glass of wine with a good meal. If we could pair together a plateful of cardiac health along with a glass of a full-bodied Cabernet Sauvignon? Fantastic! Over the past 20  years, there have been numerous reports concerning the benefits of moderate alcohol consumption (particularly red wine in first reports) in maintaining cardiac health, decreasing the risk of certain forms of cancer, and even as an incremental lifestyle protective factor for slowing the progression of age-related memory decline and Alzheimer’s disease. The basic relationship(s) between modest alcohol ingestion and positive health effects have now been replicated by dozens of laboratories and clinical investigators, and so the risk of a false-positive association (a Type I error) between alcohol and/or other ingredients of alcoholic beverages (e.g., resveratrol), and certain health benefits, is unlikely. What remains unclear, however, is the strength of this relationship. That is, just how much benefit is derived from the glass or two of wine with dinner?

Keywords

academic medical center; ethics; fraud; plagiarism; research misconduct; scientific integrity

The management of research misconduct is central to the entire mission of an academic medical center. Without clear, transparent policies and procedures to guide the oversight of research ethics and scientific integrity, the veracity of the entire research enterprise is lost. The conduct of research is a human activity, and subject to the same human failings and errors of judgment that appear occasionally in any other field of human endeavor. In this chapter we describe the singular importance that the oversight of research integrity plays in the well-being of an academic medical center, and the we describe the rationale for this book and the chapters to follow.

As we age, we look for simple lifestyle changes that might serve to protect our health and stave off dreaded diseases. And, at the same time, many adults enjoy a delicious glass of wine with a good meal. If we could pair together a plateful of cardiac health along with a glass of a full-bodied Cabernet Sauvignon? Fantastic! Over the past 20  years, there have been numerous reports concerning the benefits of moderate alcohol consumption (particularly red wine in first reports) in maintaining cardiac health (cf. Lavy et al., 1994; Bognar et al., 2013), decreasing the risk of certain forms of cancer (cf. Surh et al., 1999; Luo et al., 2013), and even as an incremental lifestyle protective factor for slowing the progression of age-related memory decline and Alzheimer’s disease (cf. Russo et al., 2003; Wang et al., 2006; Pasinetti, 2012). The basic relationship(s) between modest alcohol ingestion and positive health effects have now been replicated by dozens of laboratories and clinical investigators, and so the risk of a false-positive association (a Type I error) between alcohol and/or other ingredients of alcoholic beverages (e.g., resveratrol), and certain health benefits, is unlikely. What remains unclear, however, is the strength of this relationship. That is, just how much benefit is derived from the glass or two of wine with dinner?

One well-respected researcher to pose this question was Dipak K. Das, M.D., the former director of the cardiovascular research center at the University of Connecticut Health Sciences Center (Farmington, Connecticut). Dr Das had a reputation for scholarly contributions to this field, built over many years, with a specific focus on the health benefits of resveratrol, a naturally occurring phenol that is abundant in red wine. Dr Das had authored or coauthored more than 100 scholarly articles on this general topic, and his work had been highlighted in numerous popular magazines and television news programs (e.g., CBS network’s 60 Minutes). Although his general findings and conclusions have been replicated by other independent research groups, Dr Das’s data seemed to suggest that red wine might be a powerful, key dietary approach to slowing the ravages of sedentary lifestyles and aging—even being referred to by the Science Daily website as exercise in a bottle (03 July, 2011: http://www.sciencedaily.com/releases/2011/06/110630131840.htm). Were his data too good to be true?

In early 2012, following a lengthy internal investigation by the university’s Research Integrity Officer (RIO) and an appointed review committee, and in response to an anonymous tip in 2008, the institution found 145 separate instances of fabricated or falsified data by Dr Das, leading to the issuances of notification to 11 separate journals, in an attempt to correct the scientific record by asking these journals to publish ‘retractions’ of his papers. As a result of this investigation, the university declined and returned nearly $1,000,000.00 in Federal grant funding, closed his laboratory, and terminated his tenured professorship.

Another example was the work of psychologist Diederik Stapel, professor of cognitive social psychology and dean of the School of Social and Behavioral Sciences at Tilburg University in the Netherlands as well as founder of the Tilburg Institute for Behavioral Economics Research. Staple was regarded as one of Europe’s top researchers with his findings about implicit contextual cues that motivate social behavior included findings such as how the presence of wine glasses changes meal behavior and table manners, that messy environments promote social discrimination, and that meat eaters are more antisocial than vegetarians. Widely published with over 250 peer-reviewed articles, book chapters, and conference proceedings, Professor Stapel was well-known and widely sought out as a collaborator given his innovative questions and ability to accomplish seemingly complex data collections in a timely manner. In 2011, an extensive investigation revealed that Professor Stapel had consistently fabricated data since at least 2004 with at least 55 published papers containing fraudulent data. In a pattern that appears to have extended well over a decade, Dr Stapel would team up with a student or colleague to design a study to test one of the collaborator’s hypotheses. Dr Stapel would carry out the study and process the data. He provided his collaborator with a data file ready for analysis that was in reality entirely fabricated. In August 2011, three of Stapel’s Ph.D. students brought forward allegations of data fabrication because they had been unable to obtain raw data from Dr Stapel when they repeatedly requested the files. Indeed, a number of his students graduated with their doctorates without ever completing an experiment. The investigation spread beyond Tilburg University to include the University of Amsterdam where Dr Stapel received his doctorate and the University of Groningen where he was employed prior to his professorship at the Tilburg University. The University of Amsterdam revoked his doctorate and Stapel resigned his professorship in the midst of ongoing investigations revealing more instances of complete data fabrication (Jarrett, 2013).

What motivated both of these scientists? What might compel an accomplished, well-trained scientist to