Lecture 4

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Why does responsible conduct of research matter?

Bernard Lo, M.D.

August 18 and 26, 2010

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Kuklo case

Orthopedic surgeon in Army

Research on bone-growth product Recombinant human bone morphogenic

protein-2 Claimed benefit in soldiers with severe leg

injuries

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Kuklo allegations

Data fabricated Reported more cases than in Army records

Co-authors had not seen manuscript

prior to publication

Forged signatures of co-authors

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Kuklo allegations

Paid by manufacturer as consultant Almost $800,000 for two years Spoke on company’s behalf Taught other physicians Manufacturer did not sponsor study

• Denied knowledge of misconduct

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Kuklo case

Paid by manufacturer as consultant Did not get permission from Army Did not disclose payments to Army or

Washington University

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Reuben case

Peri-op analgesia with COX-2, NSAIDs Reduce opioid use, improve function Pre-emptive pre-op administration reduces

post-op and chronic pain Use for regional anesthesia or for intra-

articular injection Celecoxib + pregabalin superior to opioids

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Reuben case

Fabricated data in 21 / 72 articles Pleaded guilty to fraud charges Co-authors exonerated

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Reuben case

Served on speakers’ bureau for

manufacturer of celecoxib

Also research funding

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Editorial on impact of misconduct

Retraction does not correct problems

with meta-analyses, reviews, CME

Confirmatory studies unlikely to be

published

“We might be heading in wrong

direction or toward blind ends”

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Darsee case

109 papers as a fellow

Fabricated data in view of colleagues

Patients and collaborators did not exist

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Slutsky case

Faculty member in radiology

Fellow in cardiology

Resident in nuclear medicine

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Slutsky case

137 papers while a resident and fellow One paper every ten days

Two studies had same mean and SD for

different populations

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Why is research misconduct problematic?

Data and conclusions not valid Harm to science, other researchers Harm to patients

Wasted resources

Unmerited rewards

Undermines public trust and support

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Congressman Dingle

“Every time a researcher takes

taxpayer money and publishes

fabricated, falsified, or plagiarized

findings, the taxpayer has in effect

been swindled. Furthermore, given our

budget deficit, there is never enough

money to go around.”

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Consequences

When self-regulation fails, government

will step in NIH requires ethics training Conflict of interest disclosures when submit

grant

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Social science research

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How you will encounter misconduct?

Review manuscript or grant

As PI of large project

Serve on selection committee

Challenges to your work by others

Serve on investigation panel

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What would you do?

You review paper on prevention trial

for cancer. Accrual extremely rapid. Point estimate not vary across sites. Confidence interval very narrow.

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What would you do?

You decided to call the editor about

concerns but did put them in writing.

One month later you are sent a revised

manuscript for re-review Your concerns not raised with authors None of your concerns addressed.

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What would you do?

Decline to review the article

Recommend biostatistical review of the

article

Describe your concerns in a written

review

Other?

Why not?

Not your job

Don’t look for trouble

Don’t be a snitch or tattletale

Don’t ruin a career if you’re not sure

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Encounter misconduct as PI?

Progress too good to be true Enrollment at site >> other sites Phenomenal productivity

Data are too good to be true Discrepancy from other sites Variation too small

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Encounter misconduct on selection committee?

Plagiarism of personal essay 5.2% of resident essays match Internet

pages, previous essays, printed resources

Falsification of publication record 4.9% of residency and fellowship

applicants

Falsification of publication record

Article not in journal

Not an author

Change order of authors

List abstract as article

Change journal

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Federal definition of research misconduct

Fabrication

Falsification

Plagiarism

Must be intentional

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Research misconduct excludes

Unintentional “honest” error

Sloppiness, incompetence, laziness

Differences of opinion or interpretation

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Research misconduct excludes other ethical problems

Lack of IRB approval

Lack of informed consent

Financial mismanagement

Discrimination

Poor mentoring

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Federal definition of misconduct

Legal requirements set a minimum

standard

Ethical and professional standards

may be higher

How do people respond to plagiarism?

Using computer programs, identify 212

pairs of similar articles

Survey to authors, journal editors of

these articles

Science 2009; 323; 1293.

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Individual response to misconduct

“There is no way under the stars we

could have picked that up ourselves.”

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Individual response to misconduct

“It is my understanding that copying

someone else’s description virtually

word-for-word is considered a

compliment to the person whose words

were copied.”

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Individual response to misconduct

“I have no idea why the pieces are

similar, except that I am sure I do not

have a good enough memory to have

allowed me to ‘copy’ his piece.”

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Responses to allegations

I didn’t know it was wrong Course precludes this defense

It’s just a personal vendetta

This is just creative science

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Institutional response to alleged misconduct

Inquiry Is a full investigation warranted?

Investigation Is there misconduct?

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Criticisms of institutional inquiry

Self-interest Can be unconscious

Underestimate problems

Assumption of trust

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Institutional responses to allegations of misconduct

Both whistleblower and accused have

rights No retaliation Written charges Accused may respond to charges Right to have lawyer Timely decision

Federal response to allegations of misconduct

May conduct own inquiry or

investigation

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Consequences of research misconduct

Suspension of federal grant

Debarment from future grants

Institutional penalties Termination of employment

Civil and criminal liability

Questions about misconduct

Are you responsible for work of

colleagues in collaborative project? How much do you have to learn about their

specialty?

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Dilemmas for co-investigators

Value in multidisciplinary projects Encouraged by NIH Do not have expertise in other specialties

Accountable for misconduct of others Trust colleagues What review is reasonable to expect?

How to prevent misconduct

Close involvement during all phases of

research Look at primary data

• Challenges with direct computer entry of data

Data audits

Realistic expectations of progress and

productivity

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How to prevent misconduct

Know enough about other fields to ask

tough questions

Specify your exact role in project

Reconsider loose collaborations

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Take home points

Misconduct a serious offense, with

grave consequences

Address allegations of misconduct