Responsibilities of the Principal Investigator in an IndustrySponsored Trial

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Responsibilities of the Principal Investigator
in an Industry-Sponsored Trial

• SOM Clinical Trials Office
• December 10, 2008

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Principal Investigator the definition

• An individual who is responsible and ultimately
  accountable for the design, the conduct
  (including obtaining informed consent, following
  the protocol, collecting data, reporting adverse
  events, ensuring subject safety, etc.),
  monitoring and reporting of a clinical research
  study at a site.

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FDA Form 1572 and Investigator Agreement

• By signing the 1572 and/or the IRBs Investigator
  Agreement, the PI agrees
• To conduct the study in accordance with the
  current protocol.
• That no subjects will be recruited or entered
  into the study until s/he has received the signed
  IRB approval stating that the protocol is open to
  enrollment.
• To personally conduct or supervise the described
  investigation.
• To obtain informed consent from all subjects
  prior to conducting any study-related procedures.
• How does this work in practice?

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It meansobtaining proper informed consent

• After evaluating one of your patients, you
  determine he would fit the inclusion/exclusion
  criteria for your new study with the exception
  that he is taking an ACE inhibitor for
  hypertension.
• You discuss the study with him and he is
  agreeable to participate and to switch to another
  medication for treating his hypertension.
• Tell me if you should consent this potential
  subject and if so, how and when you should
  consent him?

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Form FDA 1572 -Investigator Agreement (cont)

• That any materials used to recruit subjects will
  be approved by the IRB prior to use.
• That any modifications to the protocol or consent
  form will not be initiated without prior written
  approval from the IRB.
• What does this mean?

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It means. following the approved protocol

• Ensure every inclusion / exclusion criterion is
  satisfied before subject is enrolled
• Follow the protocol as written, do not make
  adjustments based upon your clinical evaluation
  of the subject (unless in the case of immediate
  safety)
• Therapeutic misconception

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Form FDA 1572 -Investigator Agreement (cont)

• To record and report adverse events that occur in
  the course of the investigation (in accordance
  with the DSMP of the approved protocol)
• What does this mean?

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It means.reporting adverse events

• Define adverse event
• If conducting a drug study do only drug related
  adverse events need to be reported?
• Define serious adverse event
• Are all severe events serious?
• When is expedited reporting required?
• To whom must you report?
• Follow your DSMP!

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FDA Form 1572 - Investigator Agreement (cont)

• To ensure that all associates, colleagues, and
  employees assisting in the conduct of the study
  are adequately trained in the conduct of the
  study and adequately informed of their
  obligations in the conduct of the study.
• To delegate responsibilities for the conduct of
  the study appropriately.
• To ensure that a compliant IRB performs initial
  and continuing review and approval of the
  investigation.

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FDA Form 1572 -Investigator Agreement (cont)

• To maintain adequate and accurate records and to
  make those records available for inspection.
• What does this mean?

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It means. maintaining case histories

• Investigators are required to prepare and
  maintain adequate and accurate case histories on
  each study subject. This includes at a minimum
• Data collection forms
• Signed and dated consent forms
• Medical records
• basic subject identification
• eligibility criteria
• statement that informed consent obtained before
  participation

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It means. maintaining all regulatory
documentation

• All documentation regarding the trial
• E.g., all correspondence to and from the IRB, all
  signed consents
• Keep everything
• Keep it organized
• If it isnt documented, it didnt happen.
  Charting by exception is not acceptable for
  research.

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It means.retaining all research records

• The investigator is required to retain and store
  all records pertaining to clinical research
• FDA
• 2 years following the date a marketing
  application is approved for the drug for the
  indication for which it is being investigated, or
  if no NDA submitted, 2 years after investigation
  is discontinued and the FDA is notified
• NIH
• 3 years after completion of the study
• HIPAA
• 6 years from date of last contact

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FDA Form 1572 -Investigator Agreement (cont)

• For drug / biologic / medical device trials
• To inform any potential subjects that the
  drug/biologic/medical device is being used for
  investigational purposes and to ensure that the
  requirements relating to informed consent and IRB
  review are met.
• To understand fully the potential risks and side
  effects associated with the study
  drug/biologic/medical device and/or study
  procedures.

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FDA Form 1572 -Investigator Agreement (cont)

• To comply to all pertinent requirements in 21 CFR
  312. If a device trial, agree to comply with all
  pertinent requirements in 21 CFR 812.
• To ensure test article accountability
• What does this mean?

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It means.complete accountability and control of
the investigational agent

• The investigational drug/biologic/medical device
  can be used only as specified in the protocol and
  is to be handled / administered only under the
  supervision of the physician approved to do the
  study.
• If not yet approved for marketing by the FDA, the
  investigational product must be labeled as such.
• FDA requires the PI to establish a record of
  receipt, use, and disposition of all
  investigational agents.
• The drug/biologic/medical device must be kept in
  a secure place.

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FDA Form 1572 -Investigator Agreement (cont)

• Requires compliance with all federal, state,
  local and institutional regulations governing
  clinical trials.
• This is includes accurate billing of clinical
  research procedures
• No double-billing (Medicare fraud)

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• How can the
• SOM Clinical Trials Office help?

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SOM Clinical Trials Office

• Directives from the Deans office
• Provide clinical research training, education and
  mentoring to clinical research staff
• Provide support services and resources to
  clinical research personnel
• Promote ongoing clinical research process
  improvement efforts

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SOM Clinical Trials Office Training, Education
and Mentoring

• Services offered to any/all research personnel
• Clinical research mentoring
• 1 on 1
• Individually tailored training
• Utilizes projects to which the mentee is assigned
• Fall series
• 10 15 individual topics offered in 1-2 hour
  sessions running from September through December
  annually
• Continuing education credit offered

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SOM Clinical Trials Office Training, Education
and Mentoring

• Brown bag series
• Held every other month
• Topics cover issues pertinent to the conduct of
  clinical research at UVa
• Topics have included, e.g., budgeting clinical
  trials, clinical research subject billing
  process, obtaining informed consent when the
  subject does not speak / understand English,
  waiver of informed consent, Clinical Data
  Repository, understanding MRI and utilizing the
  research MRI, investigational pharmacy process
• Continuing education credit offered

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SOM Clinical Trials Office Training, Education
and Mentoring

• Audio conference participation
• As they become available
• Topics have included, e.g., informed consent
  process, budgeting clinical trials, Medicare
  rules as they apply to clinical trials, medical
  device trials
• Post Approval Monitoring education
• Conducted at the request of a post-approval
  monitor following a PAM review
• Tailored to the specific findings of the PAM
  review
• Clinical research orientation manual
• Available online via the SOM CTO website
• Hard copy available

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SOM Clinical Trials Office Training, Education
and Mentoring

• Clinical research tips

• Recent Tip from the SOM Clinical Trials Office
• Notes-to-File
• A Note-to-File is a tool to explain some
  discrepancy in the conduct of a research study
  or to clarify a decision made in regards to some
  aspect of the study.   It is important that it
  not become a device to allow a research
  investigator or coordinator to ignore protocol
  or to allow lax conduct of a study.  The tool
  should only be used when a discrepancy occurs or
  it is felt that a more thorough clarification is
  needed -  it is not a device to allow the
  discrepancy.

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SOM Clinical Trials Office Training, Education
and Mentoring

• Clinical Research Resource Manual
• A compilation of contact information for clinical
  research resources at UVa
• Available online via the SOM CTO website (hard
  copy also available upon request)
• Current Code of Federal Regulation (CFR) manuals
• Revised manuals available each year (May)
• Made available to research personnel upon request

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SOM Clinical Trials OfficeSupport Services

• Support services
• IND / IDE submission and maintenance
• Administrator for clinicaltrials.gov registration
• Study budget development and negotiation
• Case Report Form (CRF) and/or source document
  development
• Certificates of Confidentiality
• Regulatory document organization
• Study start-up, conduct, and/or close-out
  consultation
• On-site monitoring
• Preparation for, participation in, and response
  to sponsor and/or FDA audits
• General consultation

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SOM Clinical Trials OfficeProcess Improvement
Efforts

• Clinical research process improvement /
  documentation efforts
• E.g., clinical trial billing process, category B
  device Medicare reimbursement process, conducting
  trials utilizing the ED as the point of first
  contact, maintaining confidentiality as dictated
  by a Certificate of Confidentiality
• Standard operating procedures
• http//www.healthsystem.virginia.edu/internet/cto/

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SOM Clinical Trials Office

• For e-mail notification of SOM CTO offerings and
  for posting questions to the group, join the
  clinical research professional e-mail list
• https//list.mail.virginia.edu/mailman/listinfo/uv
  a-crps

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SOM Clinical Trials Office

• General consultation
• Contact our staff with any of your questions
• Telephone [phone]
• E-mail uvaclintrials_at_virginia.edu
• Pager 982-3500 ID 4370
• SOM CTO website
• http//www.healthsystem.virginia.edu/internet/cto/