Multicenter Trials Industry-sponored Trials Pilot Studies

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Multicenter TrialsIndustry-sponored TrialsPilot
Studies

• Steve Cummings, MD
• Director, SF Coordinating Center

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Outline

• Multicenter studies
• Industry-sponsored trials
• Pilot studies for trials

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Dr. D

• Large dermatology practice
• Interest in psoriasis
• Wants to participate in multicenter trials of new
  treatments

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Multicenter studies

• Anatomy
• Physiology
• How to work with them
• Example MrOS

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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 study Design,
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 Committee
• Usually a subset of the SComm
• Develops guidelines for approval
• Reviews and approves proposals for analyses,
  papers (and ancillary studies)
• Democratic

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Industry sponsored trials
Sponsor - Designs the trial - Chooses sites
- Analyzes data
Sponsor
CRO
CRO (hired by sponsor) - Creates the forms -
Collects/collates data - Monitor sites
Clinical sites - Recruit subjects - Transmits
data to CRO
CRO Contract Research Organization Companies
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
• Example Denosumab (FREEDOM) Trial

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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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Reasons to be a siteNIH multicenter study

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

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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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Publications and industry
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Publications

• Sponsors own the data
• Data analyzed and drafted by
• The sponsor statistician and medical writer
• A hired CME firm
• External authors invited to author a paper
• Provided analyses or draft
• May write a draft or edit the sponsors draft

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Now for some heresies

• Access to data
• 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
• Sponsors 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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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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Pilot studies
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Why pilots

• Feasibility
• To determine if you can do it.
• To convince funders you can do it
• To improve the study
• More efficient
• Prevent screw-ups

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Example T trial

• Green tea has been associated with lower risk
  of breast cancer
• Inexpensive and safe
• Proposal
• Large randomized trial to test green tea extract
  vs. placebo X 3 years
• Randomize women who attend mammography units and
  have high breast density to capsules of placebo
  or green tea

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T trial

• Easy to recruit from the Center
• Breast density can be assessed on the mammogram
• No need for exclusions
• 45,000 women get mammography / year
• Periodically mail study supplements to home
• Follow-up by internet and future mammography
  visits
• Ascertain cancer by emailed or phoned self-report
  or periodic search of the SEER registry

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T trial

• Idea has been enthusiastically received
• A group has met to develop a proposal to NCI
• What type of pilot data would we need?

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Pilot studies

• To test feasibility of recruitment
• Survey participants
• Conduct a pilot trial
• To test the feasibility of interventions,
  procedures and measurements
• How much green tea to have an effect?
• Side effects of large doses of the extract?
• Will women adhere?

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Pilot studies

• To determine power
• Variability of the main measurement
• Rates of outcome in real participants
• To estimate costs and need for staffing

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Pilot studies

• To determine power
• Variability of the main measurement
• Rates of outcome in real participants
• To estimate costs and need for staffing

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How big should pilots be?

• It depends
• Sample size estimates sometimes useful
• Traditions and guesses
• NCI phase I trials start with 3
• Dry runs 3 to 10 of same age, health
• Usually depends on resources and time

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Do pilots need control groups?

• It depends
• New treatments
• Determining the highest tolerable dose of green
  tea?
• Determining the effect of green tea on breast
  density?
• Feasibility?
• Generally irrelevant (e.g., potential
  participants eligibility and willingness to
  enroll).

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Funding for pilots

• Small and quick
• Local institution
• Academic Senate
• CTSI grants
• Disease foundations
• Industry reps
• Mentors
• Can often be done with volunteer help

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IRB approval for pilots

• Pilots involving people (or medical records)
  generally need IRB approval
• Testing questionnaire or strength testing devise
  with staff?

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A real example

• Dr. B plans to administer a detailed survey to
  over 3,000 women who have received care at a the
  High Risk Breast Center
• She has extensively developed a 15 page
  questionnaire
• What type of pilots would you suggest?

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Thank you!