M' Joyce Heinrich

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Introduction

• M. Joyce Heinrich
• Administrative Director T.A.B.S. Research Review
  Committee

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• Clinical Evaluations

• Regulatory Requirements

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Purpose

• The purpose of my presentation today is two fold.
  
• First - to provide you with an overview of the
  FDAs regulatory requirements for conducting
  clinical studies on an investigational device.
• Secondly - to review the general responsibilities
  of Investigators involved in clinical research
  studies involving human subjects.

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• First

• Regulatory Requirements

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What Regulations?

• IDE

• GCP

• 21 CFR Part 820

• FDA

• 21 CFR Part 812

• IRB

• PMAA

• 21 CFR Part 50

• 510(k)

• 21 CFR Part 54

• 21 CFR Part 56

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What are they?

• GCP

• Good Clinical Practices
• GCP refers to the regulations and
  requirements that must be complied with while
  conducting a clinical study.

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Primary Regulations -

• 21 CFR Part 812 - Investigational Device
  Exemptions
• 21 CFR Part 50 - Protection of Human Subjects
• 21 CFR Part 54 - Financial Disclosure by Clinical
  Investigators
• 21 CFR Part 56 - Institutional Review Boards
• 21 CFR Part 820, Subpart C - Design Controls of
  the Quality System Regulations

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• IDE

• IDE - Investigational Device Exemption
• An IDE allows the investigational device to be
  used in a clinical study in order to collect
  safety and efficacy data required to support a
  Premarket Notification Submission to the Federal
  Food and Drug Administration (FDA).
• This Premarket Notification may be either a
  Premarket Approval Application (PMAA) or a 510(k)
  Notification.

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• IRB

• IRB - Institutional Review Board
• An IRB is a board, committee or other group
  formally designated to review, to approve the
  initiation of, and to conduct periodic review of
  biomedical research involving human subjects.
• The primary purpose of such a review is to assure
  the protection of the rights, safety and welfare
  of human subjects.

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• Clinical Evaluation

• Requirements

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Clinical evaluations of devices that have not
been cleared for market requires

• An approved investigational device exemption
  (IDE) by an institutional review board (IRB) (and
  by the FDA if the device is a significant risk
  device)
• Informed consent from all patients
• Labeling for investigational use only
• Monitoring of the study and
• Records and reports.

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• Second

• Clinical Investigator
• Responsibilities

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Clinical Investigator

• A clinical investigator is defined as an
  individual who actually conducts a clinical
  investigation (21 CFR Sections 312.3 and 812.3).
• The FDAs regulations further defines such
  investigators as people under whose immediate
  direction a medical device is administered to a
  human subject in a clinical trial.

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Investigators Role

• An investigators role in a clinical study is
  crucial to determining the safety and
  effectiveness of the test device in a clinical
  study.
• An investigator can, and often do, delegate some
  of the work involved in the study to their staff.
• A clinical investigator must sign an
  Investigators Agreement which is a commitment
  to conduct the clinical study in accordance with
  the study plan / protocol and all relevant FDA
  regulations.

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• Responsibilities

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In general, clinical investigators are
responsible for

• ensuring that the investigation is conducted
  according to the Investigators Agreement
• protecting the rights of subjects
• obtaining informed consent from each subject
• controlling the device being investigated
• retaining specific records and issuing specific
  reports
• assuring that an IRB is provided information for
  initial and continuing review of the study.

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• Records

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Device Study Records

• In conducting clinical investigations,
  investigators agree to maintain accurate,
  complete and current records (21 CFR Part
  812.140).

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These records include

• all correspondence with other investigators and a
  studys IRB, sponsor, monitor and the FDA
• protocol for the study (including any information
  about any deviations from the protocol)
• informed consent forms from each subject, or
  written records as to why a patient was exposed
  to a device without an informed consent form

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• information about the receipt, use and
  disposition of a device being studies
• each subjects case history, including all
  information about each patients condition as he
  or she entered the study and progress during the
  study, information related to each subjects
  exposure to the device (with dates and times of
  each exposure).
• Any other records that the FDA may request.

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Federal regulations require clinical
investigators to retain records for two years
after the latter of the following dates

• the date the investigation is terminated or
  completed or
• the date that records are no longer required to
  support a premarket approval application or a
  notice of completion of a product development
  protocol.

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• Reports

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Device Study Reports

• Clinical investigators must provide to sponsors,
  monitors, IRBs and FDA, if requested, certain
  reports at various times during the clinical
  study.
• The clinical study reports are not the same as
  the clinical study records.

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These reports include

• Unanticipated adverse device effects (to sponsor
  and IRB as soon as possible, but no longer than
  10 days after the event
• withdrawal of IRB approval (to sponsor no later
  than 5 days after receiving notice from IRB)
• progress reports (to sponsor, monitor and IRB no
  less than annually)
• deviations from the investigational plan /
  protocol in an emergency to protect a subject (to
  sponsor and IRB no later that 5 working days
  after the emergency)

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• use of a device without informed consent (to
  sponsor and IRB no later than 5 working days
  after the occurrence)
• final report (to sponsor and IRB no later than 3
  months after the investigators work on the study
  ceases) and
• accurate, complete and current information about
  any aspect of the investigation (to IRB or FDA
  upon request).

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• Case Report
• Forms

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Case Report Forms for this Study include

• Inclusion / Exclusion Questionnaire for LILT Soft
  Tissue Injury Clinical Study
• Consent to Assessment / Treatment
• Informed Consent Form
• Clinical Case Report Form
• Medical History Form
• Pre-Treatment Medical Examination Form

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Clinical Case Report Forms -(continued)

• Treatment Plan
• Visual Analog Scale Form
• Progress Summary Form
• Patient Daily Diary
• Adverse Effect Report
• Patient Termination Report

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Definitions Associated with IDE Studies
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• Thank you