Ethics for Addiction Research

Catherine Striley, PhD, MSW, MPEResearch Assistant Professor, Dep’t of Psychiatry

For 2010 Alcohol Research Training Summer School

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DisclosuresFunding from NIDA, Department of Justice, Administration for Children and Families, Pinney and Associates No financial interests or consulting to disclose

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Ethics of Human Subjects Research

“Without people who are willing to place themselves at risk to advance our knowledge, we will be frozen in our current state of understanding” (Drazen 2006, p.1061).

Human Research Participants:The Four Principles

►Respect for Autonomy

►Nonmaleficence►Beneficence

►Justice

Freedom of people to make intentional decisions independent from controlling influences

Obligation to do no harmHelping others and promoting good

Impartial, equitable and appropriate treatment of all – the fair distribution of benefits, risks and costs

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Protecting ParticipantsRegulatory requirements for additional protections for “vulnerable populations” “place a heavy burden on researchers and IRB members who may want to protect participants (and minimize institutional liability) but may not know how best to accomplish these goals” (Anderson & Dubois 2006)“Concern” not paternalism (Ruof, 2004)

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Integrity or Responsible Conduct:

“Integrity… is the use of honest and verifiable methods in proposing, performing, and evaluating research and reporting research results with particular attention to adherence to rules, regulations, guidelines and commonly accepted professional codes or norms” (ORI RFA-NR-07-001)Responsible research conduct refers to “intellectual honesty in formulating, conducting and presenting research”  (NIH, 1997).

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Standards in Science“The social mechanisms of science do more than validate what comes to be known as scientific knowledge.  They also help to generate and sustain the body of experimental techniques, social conventions, and other “methods” that scientists use in doing and reporting research.  Some of these methods are permanent features of science; others evolve over time or vary from discipline to discipline.  Because they reflect socially accepted standards in science, their application is a key element of responsible scientific practice.”

On Being a Scientist: Responsible Conduct in Research, National Academy Press, Washington DC, 1995, p. 4

Definition of Research MisconductResearch misconduct means fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results. (42 C.F.R. Part 50, Subpart A and Part 93).

(a) Fabrication is making up data or results and recording or reporting them.

(b) Falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record.

(c) Plagiarism is the appropriation of another person's ideas, processes, results, or words without giving appropriate credit.

(d) Research misconduct does not include honest error or differences of opinion.

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Nine Core Areas of RCR Education (ORI) for all

Collaborative scienceConflicts of interestData managementMentor-trainee responsibilitiesPeer reviewPublication practices/authorshipResearch misconductUse of animal subjectsUse of human subjects

Rates of Questionable Research Conduct

Fanelli, 2007 Meta-analysis of 21 studiesSeparated out plagiarism from misconduct (fraud,fabrication)1.97% of scientists admitted fabrication, falsification or other modification of data33.7% admitted questionable conductBelieved that 14% of colleagues committed misconduct, 72% questionable conductConservative estimates

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Questionable Research Practices

Questionable Research Practices don’t reach the level of misconductPast three years behaviorMartinson, Anderson and DeVries. Scientists behaving badly. Nature, 2005; 435(9): 737-8

Rate Practice12.5% Overlook others’

use of flawed data15.3% Drop observation or

data points based on gut feeling

10.8% Withheld details of methodology or results in papers or proposals

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Anyone can commit misconduct

Field has moved from an emphasis on the pathological to the “normal” scientist committing questionable acts of conduct

Chart from Dr. N. Steneck, 7/24/06 presentation for Mentoring conference

Striley 10/08 14

Rates of Misconduct

About 1 in 2 scientists report knowing of or witnessing some misconduct in science, up to 25% included fraud or fabrication (Ranstam 2000; Geggie 2001)

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Paul Kornak Case

He enrolled people in clinical trials – who should have been ineligible – using fraudulent lab work– Posed as a Dr.

One participant had impaired kidney and liver function, and died as a direct result of the study medication when he should have been excluded.Stratton Veterans Affairs Medical Center in Albany, where he worked, is now under investigation

Research coordinator sentenced to 6 years in federal prison for “criminally negligent homicide” Mr. Kornak also must pay over $600,000 in restitution and was debarred from receipt of federal funds for life

Dr. Hwang Woo-Suk: Hope of World to Suspended Prison Term

2004: Science article2005: Science article2004: Nature alleges unethical ooctye donationOct. 26 2009 WooSuk Hwang receives 2 year suspended prison sentence for embezzlement and bioethics law violations

Trial lasted 40 months!

More from the News…Fabrication– “A prominent Massachusetts anesthesiologist

allegedly fabricated 21 medical studies that claimed to show benefits from painkillers like Vioxx and Celebrex, according to the hospital where he worked.”

– “Baystate Medical Center, Springfield, Mass., said that its former chief of acute pain, Scott S. Reuben, had faked data used in the studies, which were published in several anesthesiology journals between 1996 and 2008.”

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Our Job 1: Ensure the rigor of the science

Participants put themselves at risk assuming that society, if not they themselves, will benefitIf the science is not rigorous, no one will benefitThe science will then have nothing but risk for the participants and is not ethical

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Our Job 2: Protect those who volunteer

Regulatory requirements for additional protections for “vulnerable populations” “place a heavy burden on researchers and IRB members who may want to protect participants (and minimize institutional liability) but may not know how best to accomplish these goals” (Anderson & Dubois 2006)“Concern” not paternalism (Ruof, 2004)

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• 1928: PHS Syphilis Prevalence study (n < 2000) African-Americans in Mississippi• 25% positive

1929 Aggressive treatment approach initiated with Mercury and Bismith. Cure rate is less than 30 percent, treatment requires months and side effects are toxic, sometimes fatal.1929 Oslo Study retrospective study of white men w/ untreated syphilis – Found both cardiovascular damage and neurological damage

1932 Tuskegee begins, PI Dr. Taliaferro Clark, PHSProspective study of living patientsn=399 African-American men, n-201 controlNo money for treatment due to stockmarket crash

Tuskegee Study Facts 1

Centers for Disease Control, http://www.cdc.gov/nchstp/od/tuskegee/time.htmThe Tuskegee Syphilis Study: A Hard Lesson LearnedJones, J. Bad Blood: The Tuskegee syphilis experiment: A tragedy of race and medicine. NY: The Free Press, 1981

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Subjects were poor, illiterate, rural, African American menIncentives – Free physical exams– Free transportation by Nurse Rivers– Hot meals on exam days– Free treatment for minor ailments– Burial stipends

No informed consentCenters for Disease Control, http://www.cdc.gov/nchstp/od/tuskegee/time.htmThe Tuskegee Syphilis Study: A Hard Lesson LearnedJones, J. Bad Blood: The Tuskegee syphilis experiment: A tragedy of race and medicine. NY: The Free Press, 1981

Tuskegee Facts 2

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Tuskegee Facts 3

1936 Paper published about study with wide criticism following– Decision made to continue to study men until

death1945 Penicillin widely used to treat syphilis From 1947 to 1962 127 Black medical students rotate through study

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Tuskegee Case

Examine using “So Far No Objections” framework – developed by James Dubois, PhD, DSc, Department

Chair and Center Director, Center for Health Care Ethics, Saint Louis University

S – Stakeholders – competing interestsF – Facts – known and unknown N – Norms – what is relevant, conflicting? O – Options – possible? attractive?

(Available at: www.emhr.net “A Framework for Analyzing Ethics Cases”)

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ProblemsPaternalisticBad blood was assumed to be the right term, but subjects didn’t know this termParticipants didn’t know what they had or what was being done to themTreatment was available– Participants were denied treatment by other providers

because they were in the studyThere was no need for the science– The course of untreated syphilis was known

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Tuskegee: Resolution1968 Peter Buxtun and others raise concern about study ethics 1969 CDC and AMA support continuing the study 1972 NY Times front page article1972 Study ends. 1973 Lawsuit filed by NAACP– 9 million in reparations – Treatment– Many were already dead – all had suffered

1997 May 16th President Clinton Apologizes on behalf of the Nation.

CASE: Eastell“leading bone specialist”One of 6 authors of study of Actonel (Proctor & Gamble)No access to data– Signed journal form that did have access– His letter to Journal of Bone and Mineral Research stated

that only a P&G statistician had data access Errors in the study also admittedA co-author taped him saying “The only thing that we have to watch all the time is our relationship with P&G. Because we have….grant, which is a good source of income, we have got to really watch it.”

– The Guardian, Boseley, 9-18-09

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Online Case for Study

Query, Video-presentation, Query (QVQ): A New Method for Teaching RCR in a Case-based Format by Sara Vollmer University of Alabama at Birmingham, Department of Philosophy and Center for Ethics and Values in the Scienceshttp://www.uab.edu/researchintegrityandimages/case_study/default.html 27