Do the Right Thing:

Good Clinical Practice

for Clinical Research

Andrew A. Nierenberg, MD

Director, Bipolar Clinic and Research Program,

Director, Training and Education, MGH Research Institute

Massachusetts General Hospital

Professor of Psychiatry, Harvard Medical School

anierenberg@mgh.harvard.edu 617-724-0837

Thanks for Barbara E. Bierer, M.D. for some slides……

Employee Of Massachusetts General Hospital

Consultant For

Abbott Laboratories, Astra Zeneca, Basilea, BrainCells Inc., Bristol-

Myers Squibb, Cephalon, Clintara, Corcept, Eli Lilly & Co., Forest,

Genaissance, Genentech, GlaxoSmithKline, Hoffman LaRoche,

Innapharma, Janssen Pharmaceutica, Jazz Pharmaceuticals,

Lundbeck, Medavante, Merck, Naurex, Novartis, PamLabs, PGx

Health, Pfizer, Roche, Sepracor, Schering-Plough, Shire,

Somerset, Sunovion, Takeda, Targacept, Teva

Stockholder In Appliance Computing, Inc. (MindSite); Brain Cells, Inc., Medavante

Grant Support

From

AFSP, AHRQ, Bristol-Myers Squibb, Cederroth, Cyberonics, Forest

Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica,

Lichtwer Pharma, Eli Lilly, NARSAD, NIMH, Pfizer, Shire, Stanley

Foundation, Wyeth-Ayerst

Honoraria

From

MGH Psychiatry Academy in the past 3 years (Prior to 3 years

ago, honoraria from Bristol-Myers Squibb, Cyberonics, Forest

Pharmaceuticals, GlaxoSmithKline, Eli Lilly,, Shire, Wyeth-Ayerst),

No speaker bureaus since 2003

Andrew A. Nierenberg, MD Disclosure Statement

Other Income

MBL Publishing for past services as Editor-in-chief of CNS

Spectrums; Slack Inc. for services as Associate Editor of

Psychiatric Annals; Editorial Board, Mind Mood Memory,

Belvior Publications

Patents and

Copyrights

Copyright joint ownership with MGH for Structured Clinical

Interview for MADRS and Clinical Positive Affect Scale

Additional

Honoraria

ADURS, Brain and Behavior Foundation Colvin Prize,

University of :Pisa, University of Wisconsin at Madison,

University Texas Southwest at Dallas, Health New England and

Harold Grinspoon Charitable Foundation and Eli Lilly and

AstraZeneca, American Society for Clinical

Psychopharmacology and Zucker Hillside Hospital and Forest

and Janssen, Brandeis University, International Society for

Bipolar Disorder

Andrew A. Nierenberg, MD Disclosure Statement

What does it mean to do the right thing?

Hebrew Bible

Talmud

New Testament

Quran

Baruch Spinoza

https://linguisticcapital.wordpress.com/2011/12/02/resources-on-spinoza/

Spike Lee

Leaders are people who do the right thing; managers are people who do things right. Warren Bennis Read more at http://www.brainyquote.com/quotes/quotes/w/warrenbenn385287.html#MWfE4f4htmUzO3KD.99

Dharma

NYT May 26, 2015 • Fraud in a drug study

• Enrolling illiterate Hmong refugees in a drug study without their consent

• ….“reckless, if not willful, disregard” for dozens of patients;…in a clinical trial

NYT Editor Picks Comments

swm Providence, RI • …..This mistreatment of the participants in these

drug studies is appalling, if not criminal. As a person who conducts research with human subjects, I consider the treatment of each individual to be sacrosanct and if there are researchers who are mistreating their subjects they should be banned from conducting research.

What’s at stake?

• Everyone’s health

How to do the right thing

• Learn and know the regulations

• Comply with the regulations

• Act ethically always

• Use your moral compass

– For yourself

– For the others around you

• Seek help

Institutional support for Good Clinical Practice

Commitment to the Belmont principles

Respect

Beneficience

Justice

And beyond:

The community and the public

How can we help?

Support of and to the IRB

Division of Clinical Research at MGH

Human Research Program at BWH

Education and training

Compliance and monitoring

Continuous quality improvement

What issues will you encounter?

• Privacy

• Informed consent

• Integrity

– Interactions with participants

– Every data point

• Trust

The mandate for quality in Clinical Research

Ensure the ethical treatment and protection of research participants

Uphold public trust in the integrity of clinical research and research conduct

And thus: Strive for compliance with regulatory

requirements Improve the efficiency, quality and impact of

clinical research process and performance

Concerns

• Research misconduct (as defined by 42 CFR Part 93)

Falsification (making up results and reporting them)

Fabrication (manipulating research materials, data, or processes; or manipulating data such that the research is not accurately represented in the record)

Plagiarism (the appropriation of another person’s ideas, results, or words without giving that person appropriate credit)

Concerns

Ignorance Sloppiness Falsification/Fraud

Unintentional Intentional

• An honest difference of opinion or an honest error can result in the occurrence of isolated non-compliance (including GCP noncompliance). This is NOT research misconduct.

• Misconduct requires deliberate or repeated noncompliance

Ensure data validity

Ensure data are clear, interpretable, and maintained

Meet with the research and staff associates to review progress and data regularly

PIs should establish clear practices for all practices

PI Responsibility

Look at the data Look at the documentation Question what you see

And, if you don’t have time… Assign the responsibility to someone who does

The single most important tool is

Source Documentation Even if it annoys others

Even if inconvenient

Even if you need support

Image source: Jason Tester.

Support • Your IRB administrator

• QA/QI service

• Office of Interactions with industry

• Research compliance

– Mary Gervino, MGH

– Allison Moriarty, BWH

• And your Senior Vice Presidents

– Harry Orf, MGH

– Paul J. Anderson, BWH

Today you will hear

• Good clinical practice (GCP) approaches

– Necessary for industry sponsored trials

• Monitored (Clinical Research Organization, other)

• Essential for data integrity

– Essential for investigator-initiated trials

• Risks potentially higher

• Less obvious support

– Time proven approach to data integrity and reliability

Today you will hear

• IRB, consenting processes, reporting, adverse event reporting, quality assurance, monitoring…

• Research integrity, and misconduct (Office of interactions with Industry)