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Conflicts of interest

Bernard Lo, M.D.

September 16, 2010

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Views of audience

Investment company offers fund whose

selectors have personal stake in fund

going lower. Company also has shorted

fund. Should these interests be disclosed?

1.Yes

2.No

3.Not sure

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Views of audience

Should such a fund be banned (even if

interests aredisclosed)?

1.Yes

2.No

3.Not sure

My COI disclosure

No relationships with for-profit

companies

Chaired 2009 Institute of Medicine

report on COIs

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What is a conflict of interest?

Special relationships of trust,

dependency

Primary interest in well-being of

clients, patients, integrity of research

Secondary interest in personal gain ($,

professional advancement)

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What is a conflict of interest?

Unacceptable risk that primary interest

unduly influenced by secondary

interest

Points to consider

1. Arrangement may be problematic

even if no proof of bias Hard to tell if bias exists

2. Disclosure necessary but not

sufficient May not know what risks are or how to

reduce them

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Points to consider

4. COI policies should consider• Risk of relationship• Burdens and unintended adverse effects of

policies

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Spiral CT for lung cancer screening

Screened >31,000 high risk persons F/u Stage 1 cancers who had surgical

resection• 10 year estimated survival 92%

“Could prevent 80% of deaths from lung cancer”

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Spiral CT for lung cancer screening

Advocates have pushed states to pay

for screening NY bill would pay only at Cornell

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Spiral CT for lung cancer screening

$200 million NIH trial comparing CT

screening vs. CXR “Allowing hundreds of thousands to die is

unethical”

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Methodologic concerns

No concurrent control group

Lead time bias

Few patients followed for 5 years

Assume at all persons found to have

cancer would die without screening

Ignore false positive scans

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Financial relationships

$3.6 million from parent company of

cigarette manufacturer

Grant to Foundation for Lung Cancer PI, co-PI as officers Dean, vice-chair of overseers as directors

• Claim didn’t know origin of money

Gift announced publicly

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Financial relationships

Not disclose 10 patents on CT

screening in some articles and CME

lectures Claim not relevant Cornell receives royalties

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Financial relationships

Not disclose funding as required To NEJM

• Would not have published

On American Cancer Society grant• Prohibit funding if also tobacco support

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Points to consider

Voluntary disclosure ineffective Impetus for public disclosure of payments

Institutions have their own COI

Bright people find loopholes

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Concerns about COIs

Disagreements and errors inevitable Due to reasonable differences of opinion,

slip, or financial profit?

Disclosure not remove risk of bias

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Interactions between physicians and industry

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Academia-industry collaboration to develop new therapies

Antiretrovirals for HIV infection

Pulmonary surfactant

Imatinib, tyrosine kinase inhibitor for

CML

Rituximab, MAB against CD20 on B

cells

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Concerns about industry-sponsored clinical trials

Most trials now sponsored by industry

Academic investigators may lack Access to data Independent statistical analysis

Drafting of papers by medical writers

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Concerns about industry-sponsored clinical trials

1. Favorable conclusions

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Association between funding and conclusions

Investigator ties to manufacturer 3.6 times more likely to find drug effective

Sponsored by manufacturer 4.0 times more likely to find drug effective

JAMA 2003; 289: 454

BMJ 2003; 327: 1167

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Explanations for association

Publication bias against negative trials

Less rigorously designed Evidence not support this

Manufacturers sponsor trials that are

likely to succeed

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Concerns about industry-sponsored clinical trials

2. Methodologic flaws that favor study

drug

3. Not report negative findings

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Rosiglitazone allegations

Manufacturer failed to release to FDA

data showing cardiac risk

Audit of RECORD trial showed 12

endpoints on drug not counted

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Not report negative findings

Celecoxib 6-month data reported, showed benefit. 12-month data known, no benefit

BMJ 2002; 324: 1287

JAMA 2001; 2886: 2398

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Mission of drug companies

“Drug companies have to continue to

be successful businesses… But their

primary mission is products that save

lives and improve lives.”

“This is an area that’s different from

ice cream, bubble gum, and

automobiles.”

Responses to conflicts of interest

1. Disclosure To university

• Annually

• With grant submission (new NIH requirements)

To IRB To research subjects When submit, present, publish

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Responses to conflicts of interest

1. Disclosure To public

• Required for some companies by legal settlements

• Voluntary by some companies

• Some state laws

• New federal law (in 2013)

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Arguments for disclosure

“Sunshine the best of disinfectants”

May deter questionable behavior

But may also deter desirable behaviors

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Concerns about disclosure

Not specific or standardized Categories like “consultant” ambiguous –

scientific or marketing?

May be misinterpreted Discrepancies due to different requirements

Not prevent undue influence or bias Necessary but limited first step

Responses to conflicts of interest

1. Disclosure

2. Management of relationship

3. Prohibition

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Clinical trial investigators with significant conflicts of interest

Default or presumption is that may not

participate if financial stake in results Patent, royalties Stock options Management position in sponsor

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Clinical trial investigators with significant conflicts of interest

Exceptions permitted For safety of participants

• Inventor of medical device

For validity of study• Only lab that can conduct assay

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Clinical trial investigators with significant conflicts of interest

Limit role of conflicted investigator Not tasks that others can carry out

• Recruitment of subjects

• Data analysis

• Drafting of manuscript

May not be PI

Alternatively, may end conflicting role

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Contracts or grants forIndustry-sponsored clinical trials

Be willing to justify protocol and

conduct of trial

Register with clinicaltrials.gov

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Contracts or grants forIndustry-sponsored clinical trials

Access to complete raw data

Independent statistical analysis

Control decision to publish May give sponsor draft Short delay for patent finding

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Concerns about current policies

Responses out of proportion to

problems Overreaction to egregious cases Unfair suspicion

Burdensome for physicians Particularly for MDs who act with integrity

Other COI issues

Medical education

Development of practice guidelines

Clinical practice

Institutional COIs

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Take home message

Are policies proportional to problems? How likely and serious is the risk? What are the desirable and detrimental

consequences of policies?

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Take home message

Public and press concerns about

conflicts of interest