SF Coordinating Center

Multicenter TrialsIndustry-sponored Trials

Steve Cummings, MD

Director, SF Coordinating Center

SF Coordinating Center

Outline

Multicenter studiesIndustry-sponsored trials

Being a site in an industry studyHow to work with industry

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NIH-style studies

Data Coordinating Center - Makes forms & manuals - Compiles data for analysis

Clinical sites - Recruit subjects - Transmits data to CC

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NIH-style studies

Data Coordinating Center - Makes forms & manuals - Compiles data for analysis

Clinical sites - Recruit subjects - Transmits data to CC

Other functions depend on the studyDesign, analysis, assessing clinical outcomes

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NIH-style studies

Overall PI Got the grant; leads the study

Clinical site PIs Run the sites; variable say re: the study

Steering Committee Represents all sites and CC Sets the policies; ultimate arbiter

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Publications Committee

Publications and Analysis CommitteeUsually a subset of the SCommDevelops guidelines for approvalReviews and approves proposals for

analyses, papers (and ancillary studies)

Democratic

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Reasons to be a siteNIH multicenter study

Participate in scientific investigation Use data; publish Get promoted Support staff

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Industry sponsored trials

Sponsor - Designs the trial - Chooses sites - Analyzes data

Clinical sites - Recruit subjects - Transmits data to CRO

CRO*CRO (hired by sponsor) - Creates the forms - Collects/collates data - Monitor sites

Sponsor

CRO = ‘Contract Research OrganizationCompanies that provide research services

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Most industry trials

Sponsor does it all Designs study, develops forms and

protocols Analyzes data; selects authors; write the

articles Investigators

Paid to recruit patients Investigator meetings No representation in decisions

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A few industry trials

More collaborative with investigators ‘Lead’ investigators involved in design Steering Committee (a few investigators) Publications Committee

Investigators Most still just paid to recruit patients Investigator meetings

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A few (ideal) industry trials

Steering Committee Minority representation from sponsor Real authority (official charter)

Changes in design. Stopping the trial.

Publications and Analysis Committee Minority representation from sponsor Publication guidelines (a contract) Develop and review analysis plans Review and approve papers

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Being a site in an industry trial

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Reasons to be a site in the typical industry trial

Funding for you and staff Profit (industry funds are worth more than

NIH funds) New treatment alternatives to patients A chance for correlative science? A step toward larger roles with the sponsor Appear on publications Value for promotion??

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What we (SFCC) look for in a site

Past performance Rapid recruitment of large numbers Responsive and involved colleagues

(Avoid complainers and nonresponders) Scientific expertise High quality work (clean data)

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What Industry looks for in sites

Past performance Number recruited Number recruited Not a ‘problem site’

Current capability to recruit Reputation of the investigator

Thought leader Active contributor: expertise, consulting,

productive writer.

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Would you like to be a site?

Get a reputation Become a local or national leader Recruit successfully

Borrow a reputation Have a mentor or experienced colleague

make contacts (Industry: Contact your local ‘rep’)

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Disadvantages of being a site in industry trials

Can lose money

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Disadvantages of being a site in industry trials

Can lose money Can lose a lot of money

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Competitive recruitment

Trials have set recruitment goal Industry pays per subject Those who recruit most make most

Possible to make $$$ Possible to lose $$$ The case of the “Lone Academic”

Top recruiter is often 1st author

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Disadvantages of being a site in industry trials

Can lose money Distraction from other types of work or

research Hassles

Site monitoring FDA inspections

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How to be a great clinical site

An excellent study coordinator A registry of patients (subjects)

Characteristics Consent to be contacted for research

Excellent responsive support Contracts office IRB

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Other types of support from industry

“IIT” grants Small Free drug for your own research Support for other types of studies

(epidemiology, cost-effectiveness studies) Educational funds

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Publications and industry

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Potential bias

Unrush to publish negative results Selection and emphasis of positive

results Spin control

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Anatomy of a pharma sponsor

Research or ‘Clinical Development’ unit Usually scientists Goal: FDA approval of a safe and effective

treatment Marketing

Usually business professionals Goal: make $ They usually have more $$ than Development Greater potential for bias

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PublicationsThe usual approach

Sponsors own the data Data are usually analyzed by

the sponsor’s statistician and medical writer a hired “Medical Communications” firm

External authors invited to author a paper They are given the analyses or a draft May write a draft or just ‘edit’ the sponsor’s draft

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An example of guests and ghosts

- Rofecoxib trials

- The communications company completed analyses (and drafts) then invited the 1st author

JS Ross, et al. JS Ross, et al. JAMA 2008;299:1800-12JAMA 2008;299:1800-12

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An example of guests and ghosts - Rofecoxib trials

- The communications company completed analyses (and drafts) then invited the 1st author

- The initial draft of papers were written by the sponsor and sent to the author for editing.

JS Ross, et al. JS Ross, et al. JAMA 2008;299:1800-12JAMA 2008;299:1800-12

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Concerns about guests and ghosts

“Some sponsors and contract communications companies analyze data and provide nearly complete draft articles for academic investigators who are then listed as 1st authors.”

DeAngelis & Fontanarosa. DeAngelis & Fontanarosa. JAMA 2008;299:1833-5JAMA 2008;299:1833-5

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JAMA Principles, 2008

“For profit companies…should not be solely or primarily involved in…conducting the data analysis, and preparing the manuscript reporting study results. These responsibilities should primarily…be performed by academic investigators who are not employed by the company…

DeAngelis & Fontanarosa. JAMA 2008;299:1833-DeAngelis & Fontanarosa. JAMA 2008;299:1833-55

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Other journals

NEJM asks: Who wrote the 1st draft? Who employs the statistician?

Several ask that a description in the the specific roles of sponsor be put in the paper

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Now for some heresies…

“Access to data” “Right to publish”

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Heresies

Access to the data

The ‘Right to Publish’

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Universities: investigators must have ‘access to the data’

“Access to data” is meaningless Sponsors employ the data analysts Sponsor’s team directs and selects

analyses Authors are rarely involved (or skilled) in

data analysis, rarely look at data output

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Universities: investigators must have ‘the right to publish’

“Right to publish” is usually meaningless Your data is one small part of the larger

trial; would be wrong to publish a part Hard to analyze and publish without

support for analysis and writing Investigators should not have a ‘right to

publish’ results that are wrong

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Other issues

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Industry studies and promotion

Participating as a site and coauthor gets little respect

Scientific leadership (lead authorship) in trials gets more respect

Grants from industry for independent research get less respect than the same research funded by NIH

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Potential conflicts of interest

Consultations ($1-4,000) Meetings to discuss development and design Design ways to promote the drug

Honoraria for speaking At grand rounds or conferences at Universities or

other institutions At meetings or dinners arranged by sponsors

Ownership or options on stock; patents

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AAMC Guidelines

Full disclosure $10,000 limit on payments to investigators on

company-sponsored trials ‘Rebutable’ presumption of conflict if

investigators hold financial interests in a sponsor

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The press

Commonly reports investigator’s financial relationship with sponsors

Have embarrassed investigators for receiving substantial industry funding

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An ideal approach to publications from from industry

Insist on a Publications Committee With guidelines as a contract Reviews plans and papers before submission Minority voting representation from the sponsor

Data available for analysis by independent statistician-analyst Some journals are insisting

Writing the paper No medical writers? Or writers assist investigators

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Thank you!