Blank Sponsor Sheet Form Source Documentation Source Documentation Objectives At by hyw14090

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									Source Documentation
           Source Documentation
Objectives: At the conclusion of this discussion,
  participants will be able to:
   – Define source document and source data
   – Identify what data from nuclear medicine is
     considered to be source data
   – Define the acronym “ALCOA” and what it means to
     the FDA and sponsor
   – Understand the difference between the source
     document and the Case Report Form (CRF)
   – Document the informed consent process as required
     by 21CFR312 and GCP
        Source Data: GCP Definition

1.51 Source Data: All information in original records and
   certified copies of original records of clinical findings,
   observations, or other activities in a clinical trial
   necessary for the reconstruction and evaluation of the
   trial. Source data are contained in source documents
   (original records or certified copies).
   Source Document: GCP Definition

1.52 Source Documents: Original documents, data, and
   records (e.g., hospital records, clinical and office charts,
   laboratory notes, memoranda, subjects' diaries or
   evaluation checklists, pharmacy dispensing records,
   recorded data from automated instruments, copies or
   transcriptions certified after verification as being accurate
   and complete, microfiches, photographic negatives,
   microfilm or magnetic media, x-rays, subject files, and
   records kept at the pharmacy, at the laboratories, and at
   medico-technical departments involved in the clinical
   trial).
              Practical Definition
•   The FIRST place you write something down
•   All scan data, in DICOM or printed format
•   All radiopharmacy records
•   Well counter print-outs
•   Documents that you sign
•   Worksheets and logs
•   Notes about the patient ANYWHERE
         The FIRST Place…scenarios

• You go back to the hot lab to assay the residual activity
  in the syringe after injection. You write the activity and
  time down….where?
• You get a phone call about the patient’s creatinine level.
  You write it down…where?
• You inject at 11:06, and start scanning at 12:22. You
  write it down…where?
• You are taking vital signs. You take three blood
  pressures because the first one was just after the patient
  laid down and it was high. You write this down…where?
              Where NOT to Write

• Your hand

• A scrap of paper in your lab coat pocket

• A document that has information about another patient
                 Where TO Write

• Worksheet provided by the sponsor

• Data sheet created for a specific purpose

• Blank sheet of paper for that patient
                 But Just in Case…

• If you write on a scrap paper, sign and date it, include it
  in the case record.

• If you write on a piece of paper that relates to another
  patient, write an explanation on the paper, sign and date
  it, and include it in the case record.

• If you write on your hand, never wash it again, and
  present your hand to the FDA at inspection which will
  take place 2-5 years later.
             What is the Big Deal?

Good source document “hygiene” prevents:

• Transcription errors

• Memory lapses

• Recreating data points to fit a predetermined idea

• The appearance of fraud
ALCOA principle

•   Attributable
•   Legible
•   Contemporaneous
•   Original
•   Accurate
                     Attributable

• Who wrote it?

• Is this person authorized by the Principal Investigator to
  perform clinical trial duties?

• What are this person’s credentials for recording the
  data?

• Will you know who wrote this down in 10 years?
Delegation of Responsibility Log




                Sample provided by Cellectar, Inc.
                         Legible

• To be avoided….”What does this say?”

• Avoid nuclear medicine terms that don’t translate to all of
  medicine

• Avoid departmental slang

• Will you be able to interpret this in 10 years?
               Contemporaneous

• Is the data being recorded at the time it is measured?

• If there is a correction, when was the correction and by
  whom?

• If there is a significant gap between the recording of the
  data and the gathering of the data, why?

• Never ever ever back-date something….
                       Original
• The FIRST place it was written down
• Transcriptions are not original
• CRFs are not original
   – 21CFR says CRFs are part of case history
   – Per GCP, CRFs should NOT be original recording
   – Industry standard: verify all CRF data with source
     document
• Copies are not original
   – Copies can be altered
                      Accurate

• Don’t ever guess….
• Don’t ever guess…
• Don’t ever guess…
   – The most well-intentioned guess can defeat a study.
   – Missing data points should be recorded as missing.
• Are there conflicting data recorded elsewhere?
         Source Document Hygiene

• Write in ink (never pencil or erasable ink)
• Blue or black is best (blue has advantages)
• Never ever ever ever EVER use white-out
• Correct errors and changes with the following technique:
   – Draw one line through the original entry
   – Write the correct entry beside the original
   – Initial and date the change
   – The original entry and the new entry should both be
     legible
Examples of Corrections
    Scan Data as Source Documents

• DICOM files
   – Time and date stamps
   – Isotope used
   – Parameters such as matrix, bed position, scan speed
   – Name of scan
   – Patient identifiers
• Avoid distractions
      Equipment QC Documentation

• Is your camera working like it’s supposed to?
• Is your treadmill or glucometer or refrigerator or infusion
  pump calibrated?
• Has your uniformity correction been done within the
  manufacturer’s recommended guidelines (or sponsor
  prescribed timeline)?
• Is your energy correction accurate?
• Did you perform daily QC, and did it meet predetermined
  specifications?
     Radiopharmacy Documentation

• How long are your patient dosing logs kept?
• Where is the dose calibrator QC kept?
• Did you follow the sponsor’s protocol for assaying the
  dose before and after the injection?
       Dose Calibrators & Well Counters
• Original print-outs are source documents
• Annotate: Sign and Date




                        Nuclear M. Technologist, 25 Jan 2010
              Numbers on a Page

• 82
   – Pulse?
   – Respiration?
   – Systolic blood pressure?
   – Glucose level?
   – Age?
   – Millicuries? Microcuries?
   – Volume of urine sample?
• Record full data, sign and date entries
• Duplicate measurements okay; record accurately
         Forms, Worksheets, CRFs

• Case Report Form (CRF)
“A printed, optical, or electronic document designed to
   record all of the protocol-required information to be
   reported to the sponsor for each trial subject”
“A record of clinical study observations and other
   information that a study protocol designates must be
   completed for each subject”
• Provided by the sponsor
• NOT source document (per industry standard and GCP)
• Must be checked against the source document


                                      CDISC v. 8.0, 2009
        Forms, Worksheets, CRFs
• Worksheets
   – Frequently provided by sponsor
   – May look like copy of CRF
   – Should be signed and dated
   – Usually study-specific
• Forms
   – Frequently provided by sponsor
   – May look like copy of CRF
   – Should be signed and dated
   – May be generalized to all studies for that company
FDA Inspection Manual
        From the FDA Inspection Manual

Source Documents
a. Describe the investigator's source documents in terms
   of their organization, condition, completeness, and
   legibility.
b. Determine whether there is adequate documentation to
   ensure that all subjects were alive and available for the
   duration of their stated participation in the study.
    From the FDA Inspection Manual
c. Determine whether the records contain:
    – Observations, information, and data on the condition
      of the subject at the time of entry into the clinical
      study, as required by the protocol;
    – Documentation of the subject's exposure to the test
      article, as required by the protocol;
    – Observations and data on the condition of the subject
      throughout participation in the investigation, including
      results of lab tests, development of unrelated illness,
      and other factors which might alter the effects of the
      test article; and
    – Identification of key personnel involved in collecting
      and analyzing data at the site.
    From the FDA Inspection Manual
Case Report Forms (CRFs)
a. Describe the process for obtaining and recording
   information in CRFs.
    – Who obtained and recorded the information;
    – The source of the information (e.g., were data
      transcribed from another document or were data
      recorded directly onto the CRF); and
    – Whether corrections were made to the CRF data
      entries. If corrections were made, determine who
      made them, the reason(s) for the changes, and
      whether the clinical investigator was aware of these
      changes.
    From the FDA Inspection Manual
b. Compare the source documents with the CRFs and any
  background information provided (e.g., data tabulations
  provided by the sponsor) per the assignment
  memorandum and sampling plan (if applicable).
Determine whether:
• The study subjects met the eligibility criteria
  (inclusion/exclusion);
• Protocol-specified clinical laboratory testing (including
  EKGs, X-rays, eye exams, etc.) was documented by
  laboratory records;
• All adverse events were documented and appropriately
  reported
         Case History Requirement
21CFR312.62(b):
Case histories. An investigator is required to prepare and
  maintain adequate and accurate case histories that
  record all observations and other data pertinent to the
  investigation on each individual administered the
  investigational drug or employed as a control in the
  investigation. Case histories include the case report
  forms and supporting data including, for example, signed
  and dated consent forms and medical records including,
  for example, progress notes of the physician, the
  individual's hospital chart(s), and the nurses' notes. The
  case history for each individual shall document that
  informed consent was obtained prior to participation in
  the study.
            Key point: Case History

  The case history for each individual shall document
  that informed consent was obtained prior to
  participation in the study.
• Clinic notes or nuclear medicine chart must provide
  documentation that the patient is willingly involved in the
  study, has had time to review the consent form, and has
  had an opportunity to ask questions and have their
  concerns addressed.
• Forms and pre-printed clinic notes are okay, as long as
  they are signed and dated appropriately.
  Sample Documentation of Consent

“The informed consent for the XXXXXX study was
presented to the subject. The subject was given the
opportunity to ask and have all questions answered. The
consent form was signed and a copy was given to the
subject.” (Signature/Date)
    Source Documentation Scenarios

• You go back to the hot lab to assay the residual activity
  in the syringe after injection. You write the activity and
  time down….where?
• You get a phone call about the patient’s creatinine level.
  You write it down…where?
• You inject at 11:06, and start scanning at 12:22. You
  write it down…where?
• You are taking vital signs. You take three blood
  pressures because the first one was just after the patient
  laid down and it was high. You write this down…where?
                         References

• FDA Inspection Manual
  http://www.fda.gov/downloads/ICECI/EnforcementActions/Bioresear
  chMonitoring/ucm133773.pdf
• ICH GCP
   http://www.ich.org/cache/compo/276-254-1.html
• 21CFR312
  http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.
  cfm?CFRPart=312
• CDISC Glossary
  http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/
  CRO%2FSponsor/CDISC-Clinical-Research-
  Glossary/ArticleStandard/Article/detail/648647?ref=25

								
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