Almost Ready: Before a Study Starts

1
Almost Ready Before a Study Starts

• HIC/YCCI/GCA
• June 26, 2008

2
Introduction

• Joint session as a response to a survey conducted
  this spring by HIC and YCCI
• Weve divided our presentation into two sections
• You Have an Idea
• Your Idea was funded/supported

3
You have an idea What do you do first?

• Process is not totally linear!
• Be a toddler and learn how to parallel play!

4
You Have An Idea How will you fund it?

• Do you have a funding source? http//info.med.yale
  .edu/ysm/grants/funding_opportunities/
• Types of Funding Sources
• Federally Funded
• Foundation Funded
• Industry Funded
• Departmentally Funded and other
• State

5
You have an Idea How will you design it?

• Design The general framework by which the study
  will be undertaken.
• Two main categories
• Observational
• Experimental
• Study subjects balance of feasibility and
  generalizability
• Do you have these patients within your clinical
  population?
• Statistical Issues There is uncertainty when a
  sample is used to describe what is happening in a
  population
• Sample size Power Calculations
• Plan for Analysis of Each Aim

6
You have an Idea Do you have enough money
resources?

• If your design is feasible/sound and you have
  access to the patient population, can the
  proposed funding source and site afford your
  idea?
• Do you have a budget? Is the study feasible for
  your site?
• Per Patient Costs (SOC vs. Research)
• Additional Costs (e.g. Pharmacy, IRB review,
  recruitment, subject payments)
• Do you need labs? What kind, prep and rationale,
  shipping?
• Does your protocol require specialized
  nutritional needs/interventions?
• Data management needs storage needs for data and
  supplies
• Hidden costs
• Internal and external budget development
• Personnel needs (Who, What, When, Why?)
• Appropriate Venue, i.e. site visits (Where?)
• Indirect (FA) costs

7
You have an idea So you like to write?Pre-HIC
considerations

• Aims or Study Objective and Research Plan need to
  match and be feasible in humans
• What are the regulatory requirements for your
  project? To which IRB will you submit?
• Does your research include a test article? Do you
  need an IND or IDE from the FDA?
• Do you need to complete/gather other regulatory
  documents, e.g. FDA 1572 form, CVs, lab norms,
  financial disclosure(s)?
• Do you need to write Standard Operating
  Procedures for your site or a Manual of Operating
  Procedures for your study?
• All human subjects research needs a Data and
  Safety Monitoring Plan. How will you secure your
  data?

8
You have an idea Its all in the data!

• How will you collect your data? Electronic or
  paper
• Case report formsthe deliverable of the study.
  Do you need to develop your own or is the sponsor
  providing them?
• Source documentsany document where data is first
  recorded. Identify the source documents that will
  be needed for your study. Are there gaps in what
  is institutionally available?
• What are your database needs?
• Desktop toolsExcel or Access
• Low-end Web Based Solutionsweb-based forms
  designed by research team with the help of
  informatics
• High-end Web Based Solutionse.g. Trial DB, a
  secure system that can generate sophisticated
  forms secure entry of PHI data on web needs a
  bioinformatics designer.

9
You have an idea Where can you get help?

• Yale Center for Clinical Investigations has
  service units to assist with your idea
  http//www.ycci.yale.edu
• Applicable Service Units include
• Biostatistical Support Unit (James Dziura, PhD
  staff)
• Budget Development Unit (Lynn Mezzanotte Lane
  Campbell)
• Protocol Development Regulatory Support Unit
  (Melody Sacatos)
• Bioinformatics (Pradeep Mutalik)
• CONTACT Theresa Katz, Protocol Process
  Committee Coordinator 785-6335 or
  theresa.katz_at_yale.edu

10
GCA What Do We Need?

• PI/Dept. to notify their GCA reviewer of possible
  study
• PI/Dept. to provide paperwork or email
  contract.med_at_yale.edu
• A company protocol if Industry sponsored
• A company contact if industry sponsored
• A scope of work if PI initiated
• The Proposal Summary and Transmittal Form
• A Department Contact
• The HIC protocol
• A budget (may not be immediately available)

11
Federally sponsored clinical trials

• Often driven by RFP
• May require subcontracting
• Talk to your GCA reviewer

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GCA What Do We Do?

• Start a file and enter study into our database
• Verify contract/grant terms
• Verify regulatory compliance
• Compare and integrate informed consent and
  contract language
• Negotiate with sponsor and come to resolution
• Wait for final budget, if still under review,
  making sure delineation has been made between
  standard of care and research services
• Sign contract/grant

13
GCA What Drives the Process

• Protecting the University from risk
• Ensuring that any Yale inventions are protected
• Making sure the University/PI is not making
  promises it cant keep
• Defining confidential information in a logical
  fashion
• Safeguarding rights to publication

14
GCA What Do Sponsors Want?

• Just about everything and on their terms
• Publication review
• Broad licensing terms
• Coverage for subject injury
• Payment based on enrollment
• Indemnification protection
• but primarily, they want fast turnaround

15
GCA What Do We Aim For?

• Establishing relationships with each Sponsor as
  it is likely we will deal with them again soon
• A Win-Win for Yale and the Sponsor
• A fair and equitable budget to cover trial costs
  and sometimes hidden costs
• Coverage of costs for treatment of adverse events

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You Have An IdeaHIC 1

• You may not be sure if your idea needs HIC review
• Some studies are exemptbut the exemption must
  be applied for
• A medical records review needs to come to HIC
• Your idea has some aspects that you think pose
  human subject protection questions
• Your study may be controversial, or it may have
  issues in getting consent, or you may be
  establishing a repository and need to determine
  its parameters.

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You Have an IdeaHIC 2

• Youre not sure where to start for HIC approval
• Is there a process? How do you find out what
  the process is?
• Your idea includes people not associated with
  Yale
• Yales approval generally covers only Yale
  agents or employees arrangements must be made

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You Have an Idea--HIC 3

• Are you a resident, fellow or trainee?
• Youll need a faculty sponsorthe application
  has a place for the faculty sponsor to agree and
  sign.
• Do you meet faculty guidelines for being PI?
• Guidelines are available on our web site. If you
  dont meet them, special permission must be
  sought.
• GCA has an exemption form posted on their
  website.
• CALL US FOR A CONSULT

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Your Idea Was FundedHIC 1

• Find a primary reviewer
• review the list on the website. You may choose
  someone in your area, or someone whose background
  is similar to the research area your protocol
  involves all members know the human subjects
  protections
• Call them and ASK if they would be a primary
  reviewer. Committee members are volunteers the
  first person you ask may already be committed to
  primary review other protocols.
• Discuss with them how they will work with
  youwhat communication system is needed.

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Your Idea Was FundedHIC 2

• Have everyone on your protocol complete the
  required training
• If someone is listed on your protocol, they must
  complete human subjects protections training and
  HIPAA training for researchers

21
Your Idea Was FundedHIC 3

• Check the HIC web site for the most current forms
• evolving practice and regulation mean that forms
  often require updating. Pull the form from the
  website for each submission.
• Develop all the materials youll need ads, phone
  scripts, information sheets, informed consent
  documents, wallet cards
• If you develop materials after approval, they
  must be submitted as an amendment.

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Your Idea Was FundedHIC 4

• Identify all review requirements before/in
  addition to HIC
• PRC? MRRC? PPRC? RSC? YCCI? WHVA?
• In a complex system, more than HIC review is
  often required. Check the HIC Protocol
  Application instructions.
• Plan the timeframe
• Its longer than youd like. The more you know
  the process and the more organized you are, the
  faster it goes.

23
Your Idea Was FundedHIC 5

• When Completing your protocol application
• Use the most current form
• As noted earlier, forms change. Check the web.
• Get all the necessary signatures
• Everyone on the protocol. The faculty sponsor if
  there is one. The department chair. Or chairs, if
  the study involves more than one department. The
  primary reviewer.
• Include the relevant portions of the grant
• The cover page, aims and human subjects sections
  only.

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Your Idea Was FundedHIC 6

• Complete the protocol-related COI questions
• Dont check the boxes in advance for the
  researchers, and just have them sign. Each person
  on the protocol must sign and check their own
  box.
• Indicate ALL funding sources
• Studies often have multiple funders. The HIC
  needs to know all funders for each protocol. Our
  information must match G C information. This
  also helps the researcher identify whether or not
  they have a protocol-related COI.

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Your Idea Was FundedHIC 7

• Make sure the informed consent information
  matches the protocol
• Do the procedures match? Does the In Case of
  Injury language match the contract?
• Do you need a Certificate of Confidentiality?
• Make the correct number of copies
• Check the How Many Copies Instruction on the
  website.
• Include all required materials.
• The HIC can no longer hold documents while
  awaiting further materials.

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Your Idea Was FundedHIC 8

• Dont forget HIPAA requirements
• Do you need a waiver?
• Do you need a RAF?
• Do you need a combined consent/RAF?

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Your Idea Was FundedHIC 9

• Check our website http//info.med.yale.edu/hic/
  
• Bookmark our forms page
• http//info.med.yale.edu/hic/forms/index.html
• Call when you have questions
• 785-4688

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Your Idea Will Be Supported GCA

• You have HIC approval
• A fully negotiated contract is in place
• Study enrollment can begin
• Contact GCA by email to request setup of an At
  Risk Account
• GCA will forward the request to the ASU who will
  check compliances and setup the account
• Upon receipt of the first check, the account will
  be taken off of the At Risk list

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Your Idea was funded The Protocol

• Does your protocol contain all procedures and/or
  interventions? Do you need an amendment before
  implementation?
• Did you answer yes to the question on the HIC
  application, Will your research study require
  clinical care services to human subjects that may
  be billable to the subject, the sponsor, or other
  third party payer? If so, did you complete the
  form(s) on the YMG website at http//yalemedicalgr
  oup.org/comply/alert/Research.htm
• Once HIC approved, have you registered your trial
  on clinicaltrials.gov? Needed for applicable
  trials and for publication in journals belonging
  to the International Committee of Medical Journal
  Editors (ICMJE)

30
Your idea was funded Implementation

• Study meetings with your team early often.
• Who will do what and when? If the YCCI/HRU,
  contact your Protocol Coordinator to help
  facilitate.
• Delegation of AuthorityCommunicate with PI
  ensure accountability for each study component in
  accordance with GCP or as applicable to your
  study.
• Does everyone on the team have the proper
  training and understand the protocol? (Remember
  to document all training!)
• Do you have all CRFs, study and regulatory
  binder(s), test articles (e.g. IDS), storage for
  files/kits, shipping materials, and SOPs/MOPPs as
  applicable?
• Have you re-contacted all parties involved to
  give them enough time to plan for your study?
  Timely communication is KEY!
• Parallel play again! Team members may meet with
  different departments/service units and then
  report back to study team/PI.

31
Your idea was funded Specifics of Implementation

• YNHH CLIA approved labs, if needed Have you
  filled out the Dept of Lab Medicine Request for
  Services or Specimens Form with your T account
  (hospital charging)?
• Research Labs Have you contacted the University
  Lab and discussed requirements, labeling,
  processing, and analysis?
• If YCCI Core Lab, contact Ralph Jacob at 54422.
• Recruitment Have you covered your bases or do
  you need more modalities?
• Does the team need to conduct a mock
  visit/session? (Often helpful for complicated
  studies esp. those involving multiple
  interventions and/or scanning.)

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Your idea was funded Where can you get help?

• Yale Center for Clinical Investigation has
  service units to assist you with study
  implementation.
• Applicable service units include
• Education Training of Research Staff (Gina
  DAgostino)
• Recruitment Marketing (Kelly Burton Tracy
  Yale)
• Hospital Research Unit (Shelley Britt Bill
  Hofmann)
• Church St. Research Unit (Diane Wall)
• YCCI Core Lab (Ralph Jacob)
• Bionutrition Core (Donna Caseria Mary Savoye)
• CONTACT Theresa Katz, Protocol Process
  Coordinator at 785-6335.
• References Woodin, K.E. (2004).The CRCs Guide
  to Coordinating Clinical Research. Boston,
  MA Thomson Centerwatch.
• Dziura, J. (2007). YCCI
  Pilot Project Award Orientation. September 20,
  2007.

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Your idea was funded Best of Luck!

• If necessary, have a debriefing after your first
  study visit.
• If debriefing not necessary, have a celebration!
• Best of luck with all your current future
  studies!