Writing a Clinical Trial Protocol: Where to Begin

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Writing a Clinical Trial Protocol Where to Begin
September, 2008

• Randall F. Holcombe, MD
• Director, Office of Clinical Research Trials

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STEP 1 Where to start Ideas!

• Has this been done before?
• Is it safe?
• Is this novel? Will it advance science?
• Will this pass peer-review?
• Can you answer the questions youre asking?

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Step 2 Literature Search

• Needed for background
• Needed for justification
• Needed to confirm others are not doing the same
  or have done the same
• Needed to refine the original idea
• Without refining, the trial may resemble garbage
  in garbage out

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Step 3 Getting Things Down On Paper

• Types of trials
• Components
• The Protocol
• Informed Consent
• Budget
• CRFs
• Resources
• Trial resources

THE HARDEST STEP!!!
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Types of Trials

• Retrospective/prospective
• Observational/interventional
• Phase I, II, III, IV
• Feasibility/pilot
• Correlative

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Types of Trials (cont)

• Phase I
• Earliest human studies designed to define dose
  and evaluate toxicity
• Usually small (14-20 subjects)
• Phase II
• First studies to investigate therapeutic
  effectiveness once dose and toxicities are known
• Typically targeted for a specific disease type or
  specific population

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Types of Trials (cont)

• Phase III
• A randomized trial comparing a new therapy to an
  established therapy
• May be very large (hundreds to thousands of
  participants)
• Phase IV
• Clinical use studies often required by FDA
• Evaluates potential long term toxicities

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Components The Protocol

• Hypothesis
• Background
• Clinical Relevance
• Specific Aims and Objectives
• Methodology
• Outcome Measures
• Statistics/Sample Size

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Components Informed Consent

• Capacity (or ability) to make the decision
• Or, an approved surrogate
• Disclose information on the treatment, test, or
  procedure in question, including the expected
  benefits and risks, and the likelihood (or
  probability) that the benefits and risks will
  occur
• Ability to comprehend the relevant information
• Language issues
• Consent is voluntary, without coercion or duress

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Informed Consent

• Informed consent is a process
• An approved informed consent document is signed
  as part of the process
• Requirement for a witness
• Availability for participant to ask questions
• Site specific requirements
• Bill of rights
• Medical record documentation

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The Belmont Report

• Report of the National Commission for the
  Protection of Human Subjects in Biomedical and
  Behavioral Research (1976)
• Principles
• Respect for Persons
• Beneficence
• Justice

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The Belmont Report

• Respect for Persons
• Voluntariness, ability to understand the
  information
• Requirement for informed consent
• Beneficence
• Minimize harms and maximize benefits
• Justice
• Select subjects equitably
• Avoid exploitation of vulnerable populations

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Components - Budget

• Define real costs
• Think about research activities vs. routine care
• Who is paying for what?

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Budget and Billing Concerns

• Are all patients being handled similarly?
• Are Medicare guidelines being followed for
  components identified as routine care?
• Avoid the study covers if insurance doesnt
  trap
• Identify hidden charges related to clinical care
  activities
• Phlebotomy, room charges, clinical supplies

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Components CRFs

• Case Report Forms
• Collects the data used for reporting and
  monitoring
• Think about which data you want
• Think about which data you really need
• Extraneous data collection results in data
  overload on the back end
• Design forms that will be easy to use

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Resources

• Nursing
• Clinical and research
• Data management
• Quality assurance
• IRB maintenance, audits
• Account management
• Special needs
• Dietary, exercise lab, etc.

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Resources (cont)

• Everything on the prior slide costs money

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Step 4 Approval Process

• Concept proposal, LOI, grant
• Scientific review
• IRB
• Contracting
• Site and initiation meetings

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Step 5 GET STARTED!!