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
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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
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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-ResearchGlossary/ArticleStandard/Article/detail/648647?ref=25