What makes a successful Principal Investigator of a Clinical Trial Craig Pfister, BS, CCRP Temple Un

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What makes a successful Principal Investigator of
a Clinical Trial?Craig Pfister, BS, CCRP
Temple UniversityNovember 16, 2004

• What measures success?

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The Clinical Trial A Collaborative Relationship

• Good Clinical Science
• Good Statistical Design
• Sound Ethical Conduct
• Integrity Quality
• Understanding the roles and responsibilities of
  the Sponsor, Investigator, and Regulatory
  Authorities

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• Study Sponsor
• In house Study Team
• Medical monitor
• Study Management
• Clinical Research Associate

• Investigative Site
• Principal Investigator
• Research Coordinator

Research Subjects
FDA

• Academic Health Center
• IRB
• Sponsored Projects
• Additional Committees

OHRP
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Objectives

• Review the commitments of the principal
  investigator that must be adhered to when
  implementing a clinical trial consistent with the
  ICH/GCP guidelines.
• Identify the roles and responsibilities of the
  principal investigator during the conduct of a
  clinical trial.
• Describe 3 ways the principal investigator can
  influence the research process to better protect
  human research participants.

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Principal Investigator Responsibilities

• Responsibilities are assigned by federal
  regulations and ethical conduct
• 21 CFR 50 Protection of Human Subjects
  Informed Consent
• 21 CFR 56 Institutional Review Board
• 21 CFR 312, Subpart D Responsibilities of the
  Sponsor and Investigator

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Investigator Responsibilities

• CFR 312.60 General Responsibilities of
  Investigator
• An investigator is responsible for ensuring that
  an investigation is conducted according to the
  signed investigator statement, the
  investigational plan, and applicable regulations
  for protecting the rights safety and welfare of
  subjects under the investigators care and for the
  control of drugs under investigation.

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Investigator Responsibilities

• A Serious Commitment
• Statement of Investigator
• Form FDA 1572
• This is a legally binding document!

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Investigator Responsibilities
Investigator

• 1572 is a legally binding agreement
• Principal Investigator
• Sponsor
• Food and Drug Administration (FDA)
• Ensure Protections for study participant

Ensure Accountability
Sponsor
FDA
Ensure Protections
Study participant
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Statement of Investigator-1572

• 9. COMMITMENTS
• I agree to conduct the study(ies) in accordance
  with the relevant, current protocol(s) and will
  only make changes in a protocol after notifying
  the sponsor, except when necessary to protect the
  safety, rights, or welfare of subjects.
• I agree to personally conduct or supervise the
  described investigation(s).
• I agree to inform any patients, or any persons
  used as controls, that the drugs are being used
  for investigational purposes and I will ensure
  that the requirements relating to obtaining
  informed consent in 21 CFR Part 50 and
  institutional review board (IRB) review and
  approval in 21 CFR Part 56 are met.
• I agree to report to the sponsor adverse
  experiences that occur in the course of the
  investigation(s) in accordance with 21 CFR
  312.64.

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Statement of Investigator-1572

• I have read and understand the information in the
  investigator's brochure, including the potential
  risks and side effects of the drug.
• I agree to ensure that all associates,
  colleagues, and employees assisting in the
  conduct of the study(ies) are informed about
  their obligations in meeting the above
  commitments.
• I agree to maintain adequate and accurate records
  in accordance with 21 CFR 312.62 and to make
  those records available for inspection in
  accordance with 21 CFR 312.68.
• I will ensure that an IRB that complies with the
  requirements of 21 CFR Part 56 will be
  responsible for the initial and continuing review
  and approval of the clinical investigation....
• I agree to comply with all other requirements
  regarding the obligations of clinical
  investigators and all other pertinent
  requirements in 21 CFR Part 312.

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Investigator Responsibilities The Crux of
the Issue

• Good
• Clinical
• Practices

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Good Clinical Research Practices

• What are GCPs?
• Define the industry standards for researching and
  developing a new product regulated by the FDC
  Act and governed by FDA.
• An international ethical and scientific quality
  standard adopted by industry for designing,
  conducting, monitoring, recording, and reporting
  trials involving human research participants
• GCP standards have their origin in several
  milestone ethical principles

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Good Clinical Research Practices

• Why is compliance so important?
• Yes, regulations are absolutely binding!
• No, regulations are not difficult to follow!
• Compliance with the GC(R)P standard provides
  public assurance that rights, well-being, and
  confidentiality of clinical participants are
  observed and consistently protected
• Tarnished reputations are hard to reverse

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Good Clinical Research Practices

• Ethical/Scientifically Relevant Research
• Participate in research trials designed with
  reputable scientific quality
• Know the pre-clinical and clinical information of
  the investigational product
• Regulatory Compliance
• Prepare and obtain IRB approval prior to study
  conduct
• Submit regulatory documents to the sponsor (i.e.
  Investigator C.V./medical license, financial
  disclosure, 1572)
• Maintain communication with the IRB and the
  sponsor for the duration of the study (i.e. IND
  Safety Letters, Annual Reports)

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Good Clinical Research Practices

• Qualified Staffing and Adequate Facilities
• Allocate sufficient time to properly conduct the
  trial
• Delegate study related tasks to qualified staff
  members and document
• Confirm study staff understands and is competent
  to complete study related tasks
• Medical decisions are always the responsibilities
  of a qualified individual
• Subject Recruitment/Protection
• Demonstrate, recruit, and enroll the appropriate
  subject population
• Obtain valid informed consent from each study
  subject prior to study procedures
• Respect study participants rights to not
  participate or to withdraw from a clinical trial
• Ensure confidentiality of records that could
  identify the research subject

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Good Clinical Research Practices

• Study Conduct/Protocol Adherence
• Conduct the study in compliance with the IRB
  approved study protocol
• Complete comprehensive and accurate source
  documentation - that is legible!!!
• Clinical trial information should always be
  recorded handled, and stored in a way that will
  afford and ensure accurate reporting monitoring,
  interpretation, and verification
• Report and follow-up all adverse and serious
  adverse events experienced during the course of
  the study and at least 30 days after completion

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Good Clinical Research Practices

• Clinical Trial Documentation/Necessity
• Report and follow-up all adverse and serious
  adverse events experienced during the course of
  the study and at least 30 days after completion
• Ensure accuracy completeness and legibility of
  Case Report Forms (CRFs)
• Retain essential documents until notified by the
  sponsor to destroy
• Be compliant and cooperative with sponsor QA
  groups and regulatory authorities

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Crossroads to Success
Do the

• Awareness
• Sensitivity
• Application

right thing
Quality research
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Investigator Responsibilities

• Awareness
• Responsibilities to the study participants
• Responsibilities to the Institutional Review
  Board
• Responsibilities to the sponsor
• Responsibilities to the regulatory authorities
• Responsibility to complete the trial following
  Good Clinical (Research) Practices (ICH/GCP)

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Investigator Responsibilities

• Sensitivity
• Rights, safety, and well being of the research
  participants
• Integrity to the conduct of the clinical trial
• Importance for reporting AEs and SAEs
• Quality of data produced is credible
• Requirements of the IRB
• Respectful to the confidential sensitivity in
  conducting clinical research (patient and
  sponsor)
• Initiatives of the regulatory authorities

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Investigator Responsibilities

• Application
• Investigators must personally supervise all
  research activities
• Implement study procedures that are safe and
  accommodating for study participants
• Communicate progress of research activities with
  research participant, IRB, study staff, and
  sponsor
• Accept absolute responsibilities for all study
  conduct at the investigative site

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In Summary

• The two primary goals of GCPs
• To ensure the quality and integrity of the data
  obtained from clinical research.
• To protect the rights and welfare of human
  research subjects participating in clinical
  research.

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How can I impact the research process?

• Awareness of the FDA regulations and
  GC(R)P guidelines
• Sensitivity to the ethical conduct of
  clinical research
• Application able to implement a clinical
  trial with an awareness and sensitivity to the
  clinical research process.

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Clinical Trials-Outcome

• SCIENTIFIC
• Characterize the new drug by answering the
  following questions posed by the sponsor
• Safety - are the side effects acceptable?
• Tolerability - will the drug be taken?
• Efficacy - Can the drug work?
• Effectiveness - does the drug work under specific
  conditions?
• Efficiency - does it provide sufficient value?

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THANK YOU

• Craig J. Pfister, BS, CCRP
• Temple University
• Office Of Clinical Trials
• cpfister_at_temple.edu
• Phone [phone]