Clinical Data Management Responsibilites

							Roles & Responsibilities of the
Research Team




 Developed by Center for Cancer Research, National Cancer Institute
           Endorsed by the CTN SIG Leadership Group
                Objectives
• Define the role of the Principal Investigator
• Describe the purpose of FDA Form 1572
• Define the role of an Investigator-Sponsor
• Discuss the responsibilities associated with
  study coordination
• Discuss the responsibilities associated with data
  management
• Describe the purpose and contents of a DARF
  (drug accountability record form)
All staff involved in clinical
research must adhere to the
regulations and understand
the guidelines that govern
clinical research.
           Site Perspective
• Research Team           • Support Staff
  – Investigator            – Clinical/Staff
  – Study Coordinator /       Nurse
    Research Nurse          – Pharmacist
  – Data Manager
  – Study Subject
     Principal Investigator (PI)
         Responsibilities…
• Leads the team that conducts a clinical
  investigation and is ULTIMATELY
  accountable for the conduct of the trial
• Balances patient coming first with
  protocol coming first


                 Patient                Protocol
                 comes                   comes
                  first                   first
    …PI’s Responsibilities…
• Ensures the investigation is conducted
  according to:
  – Investigational plan (protocol)
  – For IND studies, Investigator statement (FDA
    Form 1572)


• Ensures the subjects’:
  – Rights, safety & welfare are protected
    …PI’s Responsibilities…

• Supervises sub-investigators/educates staff
  – Protocol
  – Investigational product
  – Trial related duties & functions

• Assesses time & resources for study
  conduct
  …PI’s Responsibilities…

• Prepares and maintains adequate
  case histories (i.e.: medical
  records/source documents)
• Maintains regulatory binder
• Discloses financial interest (with own
  organization, sponsor, and/or FDA)
     …PI’s Responsibilities…
• Obtains informed consent from each subject
   – Documents consent obtained prior to participation
     in the study

• Reports immediately all serious and
  unexpected adverse events to IRB and
  sponsor as applicable

• Maintains a record of accreditation for all
  clinical laboratories used during the
  investigation
    …PI’s Responsibilities…
• Assures IRB reviews for:
  – Initial protocol and all amendments
  – Continuing reviews
  – Serious adverse events
  – Data Safety Monitoring Board (DSMB)
    reviews

• Ensure integrity of research data
    …PI’s Responsibilities…
• Controls investigational drug/product:
  – Supervises administration of drug
  – Restricts access to drug
  – Records distribution of drug
     • Dates
     • Dose & Quantity
     • Subjects
  – Returns or disposes of all unused or
    partially-used product
      …PI’s Responsibilities
• Makes records available for inspection,
  as applicable (e.g.: FDA, OHRP,
  Sponsor, IRB, CCR OCD)

• Complies with record-keeping & record
  retention requirements
  – Case histories, source documents, consents
  – Retain for 2 years after NDA approved or, 2 years
    after investigation is discontinued, or as directed
    by the sponsor
 FDA Form
1572 (page 1)
• Statement of
  Investigator Form
  1572
• Legal agreement
  between the PI and
  the FDA for all
  studies that use an
  IND
• ONE 1572 per
  protocol (CTEP
  studies are
  exception)
• Updated as needed
 FDA Form
1572 (page 2)
  Investigator's
  pledges
Site Management Organization
           (SMO)
An independent contractor that assumes 1 or
more of the duties of a clinical investigator, not
the transfer of responsibilities:
 – Preparation and maintenance of case
   histories
 – Ensuring compliance with IRB review
 – Submitting protocol amendments to IRB
 – Maintain a record of accreditation for all
   laboratories used during the study
 – Completing case report forms
 – Submitting data to sponsor
     Sponsor - Investigator
•   A physician who both initiates and
    conducts an investigation and under
    whose immediate direction the
    investigational drug is administered or
    dispensed.

•   Must adhere to regulations and
    guidances for BOTH the Investigator
    and the Sponsor.
     Associate/Sub-Investigator
        Responsibilities …
• Assists in conducting the investigation
  according to the investigational plan
  (protocol)

• Assists in obtaining informed consent

• Provides accurate/adequate case
  histories
 …Associate/Sub-Investigators
      Responsibilities
• Discloses financial interests

• Reports immediately all “serious and
  unexpected” adverse events to the PI

• Reports all adverse events to the PI
Clinical Trial Nurse (CTN)

Primary responsibility is to coordinate
daily activities of the trial = hands on
control of the trial.

AKA: Study Coordinator, Research
Nurse
CTN Responsibilities: Overview
• Study coordination
• Maintain the integrity of the protocol
• Documentation
   – Patient data
   – Deviations & violations
• Education
   – Patient, Staff, Self
• Data
   – Input, output, QA
   – Analyze data for reporting & presentation
      CTN Responsibilities…
• Coordinates study:
  – Recruiting
  – Screening and scheduling patients
  – Securing informed consent
  – Study conduct
  – Initiation, monitoring and close-out visits
  – Coordination of lab pick-ups, supplies, etc.
     …CTN Responsibilities…
• Maintains accurate and appropriate source
  documentation, including phone conversations

• Reports adverse events - constant vigilance for
  any AEs

• Manages case report forms (CRFs) including
  data QA & QC

• Directs patient care
  – Provides patient care as indicated
    …CTN Responsibilities…
• Ensures drug accountability & inventory
  – Assure subject drug compliance

• Retains records as per regulations

• Archives records as appropriate

• Maintains regulatory files
    …CTN Responsibilities…
• Assists PI in preparing protocols and
  consents, continuing reviews, and
  publications

• Knows the deadlines for IRB and
  Sponsor/FDA reporting

• Documents deviations & violations when
  necessary
     …CTN Responsibilities…
• Provides staff/clinical nurse education
  – Schedule in-services for all appropriate
    nursing units
  – Present information in a concise manner
    focusing on what the clinical nurses need to
    know (drug administration and PKs)
  – Provide worksheets, as appropriate
  – Keep staff informed about amendment and
    general protocol progress
   … CTN Responsibilities…
      Patient Education
• Provides patient education:
  – Disease
  – Clinical Trials & Research: phases, patient
    role
  – Importance of compliance with treatment
    and procedures
  – Specific protocol for patient
     • Study objectives
     • Schema: calendars & visual aids
     • Side effects & management
  – Expectations for patient
     • cure, control, palliation or no benefit?
      Data Manager (DM)
Individual responsible for organizing
and collecting the data in a clinical trial.
       DM Responsibilities:
           Overview
•   Source document collection
•   Data abstraction
•   Data entry
•   Provide periodic reports from database
•   Case Report Form development
•   Prepare for audits/monitoring visits
     DM Responsibilities…
• Collects source documents needed for
  data abstraction
• Abstracts research data from patient’s
  medical record/source documents to the
  case report form (paper or electronic)
• Enters data into database(s)
• Conducts self-audits to ensure data
  quality
      …DM Responsibilities
• Manages protocol related data (i.e.:
  understanding what forms are still
  outstanding and what documentation is
  missing)
• Understands the various databases used
  and how to resolve problems associated
  with the different systems
• Provides periodic reports from database
• Prepares for audits/monitoring visits
Study Subject’s Responsibilities

• Adheres to protocol specific schedule of
  events

• Notifies research staff if unable to comply with
  protocol criteria (e.g.: exclusionary meds,
  keeping appointments, patient diaries, etc.)

• Notifies research staff of change in status
  (e.g.: new phone #, adverse event, etc.) in a
  timely manner
  Support Staff Responsibilities:
       Staff/Clinic Nurse
• Provides direct patient care including
  treatment and patient education
• Adheres to protocol
• Documents all patient encounters
• Collects specimen as per protocol
• Informs PI/CTN of patient or protocol
  related issues/concerns
  Support Staff Responsibilities:
           Pharmacist
• Prepares drugs as per protocol
• Stores investigational products as per
  protocol
  – For multiple studies using same IND agent,
    needs to provide separate/distinct storage
    in pharmacy
• Maintains accurate drug accountability
  records
  – Receipts of drug shipment/invoices
  – Drug accountability record form (DARF)
Example
  of a
 DARF
         Helpful Hints:
      Know Your Protocols
• Eligibility criteria
• Drug preparation & administration
• Schema, requirements, follow-up
  – PKs, research tests, restaging, drug return
• Dose limiting toxicity and/or dose
  modifications
• Reporting requirements
• Results (responses, toxicities)
               Helpful Hints:
             Know the Disease

• Etiology            • Disease Staging
• Epidemiology        • Treatment Options
• Signs and             – What is standard
  Symptoms                therapy?
• Screening and       • Disease Trajectory
  Diagnosis           • Clinical Trials
• Pathology Grading     elsewhere for the
                        same disease
 Regardless of Your Role:
Be Your Own Best Advocate
• Protect your time & get organized
• Learn as much as you can about:
   – clinical trials
   – oncology
   – your particular drug(s)
   – your database/software programs
• Know how/where to get training & do it
• Join a professional organization & get
  involved
• Teach something new & you will learn
• Teach someone new & you will grow
       Module Evaluation

The CTN SIG would greatly appreciate your
feedback on this learning module. Please
complete the evaluation form and fax to
Elizabeth Ness at 301-496-9020.