The Protocol making it your guide

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The Protocol making it your guide

• Clinical Trials Quality Assurance
• Compliance Office
• School of Medicine
• Presenter Sheda Moori

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Unappealing Aspects of Protocols

• A large amount of paper
• Incredibly long and complex title
• Technical language
• Confidential and controlled document

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Grant vs. Protocol

• A grant is a document that details the rationale
  and request for funding of research.
• A protocol is a document that details structure,
  procedures and organization for research.
• A protocol can be a part of a grant made
  available via an agreement/contract or created
  by the investigator.
• Grant funding can occur with the inclusion of a
  developed protocol or development may occur later
  in the process.
• IRB submission of a grant for review and approval
  of 1 research plan (protocol) at a time.

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The Research in the Protocol

• Categories
• Biomedical
• Study of the normal and abnormal physiology and
  development of humans.
• Behavioral
• Study of behavior of individuals or groups.
• Social
• Study of social and economic systems for use in
  planning public policy.
• Cost and benefits of alternate ways of providing
  health, educational or welfare services at
  national, state or local level

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The Research in the Protocol

• Objectives
• Collect Information
• Initiate possible methods of prevention
• Evaluate Instruments and techniques for diagnosis
• Test Interventions (drug, device, biologic,
  procedure)

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The Research in the Protocol

• Ethics of including humans in the research
• Is there true science?
• Does the research provide direct benefit?
• Does it minimize the risk?
• physical
• general welfare
• Does the research respect the person?

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Protocol Content

• Title page
  
• Signature page
• Content page
• List of Abbreviations and Definitions
• Summary
• Background/Rationale
• Research Objectives and Purpose
• Study Design
• Subject Population/Recruitment
• Research Intervention
• Randomization/Blinding
• Summary of Data to be collected
• Statistical Consideration
• Subject Compliance and Withdrawal
• Interim Analysis and Data Monitoring
• Ethical Considerations
• Finance and Insurance
• Reporting and Dissemination
• AppendixTables and References

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Todays Focus

• Make the protocol your guide
• How to read the protocol
• Understanding the protocol
• How to utilize the protocol

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Reading a protocol

• Grouping the sections of the protocol
• Why is the research being conducted?
• How will the research be conducted?
• What will be done with the data collected?
• Handle the housekeeping sections of the
  protocol last.

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Reading a protocol

• Why is this research being conducted?
• Summary
• Background/Rationale
• Research Objectives
• The history of the research

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Reading a protocol

• Why is this research being conducted?
• Investigator brochure
• Package inserts
• Articles
• Part of the protocol (usually provided by a
  sponsor of a protocol)

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Reading a protocol

• How will the research be conducted?
• Study Design
• Subject Population/Recruitment
• Subject Compliance/Withdrawal
• Research Intervention
• Randomization
• Methods to Avoid Bias
• Summary of Data to be Collected
• Your Instructions

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Reading a protocol

• How will the research be conducted?
• Procedures
• Observational
• Efficacy (only response in Phase I studies)
• Safety
• Maintain Integrity and Avoid Bias
• keep the research honest
• Note Repository/Database procedures for future
  research are not relevant to a current
  protocols research objective and require a
  separate consenting process.

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Reading a protocol

• How will the research be conducted?
• Manuals
• Memos
• Case report forms (blank)

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Reading a protocol

• What will be done with the data collected?
• Statistical Consideration
• Interim Analysis
• Data Monitoring
• Collect Data Accurately

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Reading a protocol

• What will be done with the data collected?
• Be aware of possible changes in the research.
• Interim analysis/DSMB
• Review and approval of changes in protocol
• Alert subjects to relevant changes (via consent)

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Reading a protocol

• Handling the housekeeping sections last
• Abbreviations Definitions
• Ethical Considerations
• Financing and Insurance
• Reporting and Dissemination
• AppendixTables and References
• Save for Last!

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Reading a protocol

• Housekeeping Considerations
• Consider the ethical, regulatory, practical and
  medical center policies as you read.
• Make sure results can be duplicated.
• Decrease the risk of flawed data and ineffective
  research.
• Integrate clinical standards with research
  standards.

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Understanding a protocol

• Title of protocol
• The Body System/ Disease Process/Behavior/Policy
• Intervention/Technique/Method/
• Instrument/Procedure
• Clinical research terms
• Additional reading
• Ask questions

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Understanding a protocol

• Title of the Protocol
• A Multi-center, Randomized, Phase III Active
  Control Study Comparing (investigational
  intervention) and (standard intervention) in
  (subject population)
• Structure of the research

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Understanding a protocol

• Walk the path of the researcher
• Knowledge of the Body system/Disease
  process/Behavior/Policy
• Knowledge of the Intervention/Technique/Method/
• Instrument/Procedure

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Understanding a protocol

• Additional Reading
• Duke Medical Center Library Online
  (http//www.mclibrary.duke.edu)
• Medline

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Understanding a protocol

• Defining research terms
• Get to know the context and intent
• Protocol glossary (protocol specific)
• CTQA coordinator guidebook (http//medschool.duke.
  edu/compliance)
• Several online clinical research glossaries

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Understanding a protocol

• Speak up and ask questions
• The protocol is not a perfect document.
• Responsibility/Accountability
• Milgram experiment (Obedience to Authority Study)
• Genovese syndrome (Bystander effect)
• The Seinfeld finale (Is Doing Nothing
  Something?)
• Healthcare professionals are held to a higher
  standard.

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Utilizing a protocol

• Research set-up
• Reconciling
• Explaining the research

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Utilizing a protocol

• Example 1
• A coordinator is given a protocol written by a
  Duke investigator and it is his/her
  responsibility to obtain IRB approval and
  implement the research within the clinical
  setting.

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Utilizing a protocol

• Example 1
• A coordinator is given a protocol written by a
  Duke investigator and it is his/her
  responsibility to obtain IRB approval and
  implement the research within the clinical
  setting.
• The protocol becomes the map of the
  scientific/clinical details for writing the
  consent, creating the IRB summary and designing
  the structure of the research within the clinic
  (budget, facility needs, personnel, etc.)

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Utilizing a protocol

• Example 2
• Per the agreement for a pharmaceutically-sponsored
  protocol, the research has competitive
  enrollment. Once the overall target enrollment
  has been met via all sites, the study will end
  regardless of individual site enrollment numbers.
  This same protocol has details of long-term
  safety procedures that must be performed for
  early withdrawal.

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Utilizing a protocol

• Example 2
• Per the agreement for a pharmaceutically-sponsore
  d protocol, the research has competitive
  enrollment. Once the overall target enrollment
  has been met via all sites, the study will end
  regardless of individual site enrollment numbers.
  This same protocol has details of safety
  procedures that must be performed for early
  withdrawal..
• The protocol becomes evidence that there is an
  inconsistency in the procedures for the research.
  
• Questions that need to be addressed--What will
  happen to active subjects if the overall study is
  stopped? The safety procedures per the protocol
  are required.who will pay for these procedures
  if the study prematurely ends?

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Utilizing a protocol

• Example 3
• A nephrology protocol requires the use of a
  dialysis center and its staff. The staff will be
  asked to collect and document data per the normal
  dialysis visit for the research.

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Utilizing a protocol

• Example 3
• A nephrology protocol requires the use of a
  dialysis center and its staff. The staff will be
  asked to collect and document data per the normal
  dialysis visit for the research.
• The coordinator becomes the instructor for the
  staff and the protocol becomes the textbook.

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Utilizing a protocol

• Example 4
• The sponsor of a protocol sends safety reports
  regarding adverse events at other sites. Several
  reports of pneumonia are detailed. Pneumonia was
  not documented as a possible adverse event for
  the research.

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Utilizing a protocol

• Example 4
• The sponsor of a protocol sends safety reports
  regarding adverse events at other sites. Several
  reports for pneumonia are detailed that was not
  listed as a possible adverse event for the
  research.
• Comparing these reports to the protocol details
  the continuing occurrence of an unexpected
  adverse event that could also be study-related.

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Utilizing a protocol

• Example 5
• An OB-GYN research group is interested in a
  pharmaceutically-sponsored protocol involving
  cervical dysplasia.

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Utilizing a protocol

• Example 5
• An OB-GYN research group is interested in a
  pharmaceutically-sponsored protocol involving
  cervical dysplasia.
• The objective of past protocols become the
  research resume for the group.

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Summarize

• A protocol can seem intimidating.
• Approach the protocol answering the 3 main
  questions.
• Walk the path of the researcher.
• Do some additional reading, define terms and ask
  questions.
• Be acquainted with all the procedures required.
• Learn to use the details of the protocol to help
  with set-up and explanation of the research.

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Final Thoughts

• Not a nursing order
• Overall understanding for an easier process
• Scientific and Practical Review

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Final Thoughts

• Its the protocol, stupid!

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Contact Us

• Clinical Trials Quality Assurance Section
• Compliance Office--School of Medicine
• 2200 West Main Street
• Suite 720 Wachovia Plaza at Erwin Square
• Durham, NC 27705
• Shedas phone number [phone]
• Shedas email moori001_at_mc.duke.edu
• Fax [phone]
• Website http//medschool.duke.edu/compliance