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Conflict of Interest Disclosure
Conflicts of Interest
A Conflict of Interest occurs when an individual has an opportunity to affect educational content about healthcare products or services of a commercial interest with which she/he has a financial relationship.
There is no conflict of interest for this presentation.
Commercial Support
No commercial support for this seminar
Non-Endorsement of Products
Non-applicable
Source Documentation
Kerry Moore, RN, BS, CCRC
Director, Research
Le Bonheur Children’s Hospital/Children’s Foundation Research Institute
ICH Defines Source documents as:
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 copies, 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).
Additional Regulations Related to source documentation:
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 individualadministered 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.
21 CFR Sec. 312.62 Investigator recordkeeping and record retention
Paper
Electronic
Source Documents
Electronic – Source Documentation
1. Electronic-any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system
§ 21 CFR Part 11, Electronic Records; Electronic Signatures (1997)
§ Guidance for Industry: Part 11, electronic records, Electronic Signatures (Scope and Application, 2003)
§ Guidance for Industry: Electronic source Data in Clinical Investigations (2013)
Electronic Source Document Requirements
Validation of Computer System
Audit Trail for Electronic Records
Electronic Signatures
User and technical support
Paper - Source Documentation
Paper source documents should have the original signature of the person collecting the data on the form.
Can be pre-printed forms prepared for the study visit
Handwritten records
Key Elements in Source Documentation
1. Consent
2. Eligibility, Statement of Inclusion/Exclusion Review
3. Study Procedures/Intervention
4. Adverse Events
5. Drug Accountability
6. Specimen Collection, Handling & Storage
7. Interactive Voice/Web System Forms
8. Progress notes
Informed Consent Documentation
21 CFR 312.62 states “The case history for each individual shall document that informed consent was obtained prior to participation in the study.”
Best practice for informed consent documentation is to record on the source document worksheet that informed consent was obtained prior to a procedure required by the clinical investigation, or to record the time the consent was obtained and the time of the first study related procedure performed
Source Worksheet Examples/Informed Consent
Was informed consent obtained: Yes NoDate of informed consent: __________________________
Time of consent: ___________
Consent obtained by: _______
Was a copy given to the subject/parent: Yes No
Inclusion/Exclusion Criteria
Every subject source record should include an inclusion/exclusion checklist to show that the participant met all inclusion criteria and none of the exclusion criteria for the study. Prior to randomization, the PI should review the study criteria to determine eligibility and document this in the study record.
I certify that this subject meets all inclusion criteria and none of the exclusion criteria for this study. The subject is eligible for randomization._______________________________ ___________PI Signature Date
Source Document Worksheets
Many study teams develop protocol specific worksheets for each study
visit to include all procedures that need to be performed. All
worksheets should include the following information:
u Subject identifiers
u Protocol visit number and date of visit
u Subject’s state prior to the initiation of any study procedures
u Study medication accountability
u Adverse events
u Results of study specific evaluations
u Subject status at the time of study termination
Source Worksheet Examples
Vital Signs: Were Vital Signs Collected? Yes NoTime seated: __________ Time Performed:____________Blood Pressure: _________________ mmHg Right Arm Left Arm*SBP, DBP and HR obtained in sitting position on the same arm after the subject has been restingHeart Rate: __________________ beats/minRespiratory Rate: ______________breaths/min
Medical History Example
Medical History Normal Abnormal Start Date End Date Comments
Cardiovascular Yes 01/2010 Ongoing HTN
Respiratory Yes
Gastrointestinal Yes 06/2015 Ongoing GERD
Surgical Yes 12/2016 12/2016 Appendectomy
Other Yes 01/1995 Ongoing Allergy to PCN
Documentation of Physical Examinations
If physical exams are documented in electronic medical records and not on
paper, then that is the source document. This can be printed and added to the
source chart, or can be viewed in the EMR. If EMR is not available, the physical
examination worksheet is the source. Ensure all areas of the protocol defined
body systems are completed on the physical exam, and will match with the
Case Report Form.
Questionnaires and Surveys
1. All questionnaires and/or surveys must be IRB approved
2. All questionnaires and/or surveys must include the subject number, date of completion, visit number and who completed the form (ALCOA-C)
3. If the survey is completed electronically, the source document should note what survey was done, who and when the questionnaire/survey was completed and when the data was transmitted.
Documentation of Adverse EventsAssessment of AEs and SAEs should occur at every
subject encounter, including all study visits and phone contacts.
Source documents should include questions such as: u Have you had any new symptoms since your last visit?
u Have you been to the doctor or hospital?
u Did you stop the study drug when you had your cold, and did you re-start it?
Adverse Event Documentation Should Include:u Description of the eventu Start date
u Severity of the event (mild, moderate or severe)
u Is this a serious adverse event (difference between serious and severe)
u Is the event related to the investigational product?u Action taken with investigational product
u Were any non-drug therapies or medications taken for this event
u Is this an unanticipated event or an adverse event of special interest (AESI)
Investigational Product Accountability
IP Accountability Documentation/Logs should include the following:
§ IP number on each bottle
§ Date IP received at the site
§ Date IP dispensed to the subject
§ Which IP was assigned to the subject
§ How many pills were dispensed
§ Date of return of IP
§ How many pills were returned
§ Compliance
Documentation Examples
Progress Note:
01.25.2020-Subject 001 in clinic today for visit 2 for the lipid study. Subject reports no changes in medications but did have AE of nausea on 01.20.2020 that lasted for 24 hours, subject did not take any medications for this event. Subject returned study medication, 7 tabs returned, 7 taken since last visit, 100 % compliant with dosing. Dispensed drug kit # 01234 to subject today with instruction along with diary. Reviewed diary completion instructions. All study procedure were completed per protocol, labs were obtained without difficulty and shipped to central lab. Scheduled for visit 3 on 2.4.2020. Instructed subject to call study site with any questions, concerns or changes in health status.
Good Documentation Tips1. Every study visit and conversation with the subject should be
documented in the clinic/study/source file.
2. All documentation should be completed in black or blue ink.
3. White out should never be used.
4. All emails or faxes sent to the site related to a research subject should be printed and filed in the clinic/study/source file.
5. All documents included in the clinic/study/source file should be ALCOA-C compliant.
6. Corrections should be made with a single line thru the error, adding initials and the date, and noting the corrected information
ALCOA-C
Common Problems in Source Documentation
1. Missing Source Documentation, including incomplete or incorrect IP records
2. Incomplete Questionnaires
3. Incomplete Assessments (example-physical exams)
4. Use of white out
5. Unsigned and dated entries
6. Lack of documentation of adverse event assessment and attribution by the investigator
7. Lack of documentation related to investigational product-dispensing, subject compliance, product return, education and instruction
Source Document Verification
Guidelines include requirements for sponsors to verify source documentation.The purpose of clinical trial monitoring is to verify that the reported trial data are accurate, complete, and verifiable from source documents (ICH E6, 5.18.1b)Expectations:§ Record observations and all pertinent protocol related data§ Use the same standardized forms for all subjects across the
trial§ Source files should be organized, and show an accurate
case history of the subject’s participation in the study
Source Document Review
§ The CRA is responsible to verify personnel performing study specific tasks, ensuring the delegation is documented in the Delegation of Authority Log. This log is used by the CRA when reviewing source documents.
§ The CRA will verify that collected and recorded data was documented at the time the measurement was taken. All source documentation should correspond with the time frame, leaving no concern for data integrity.
§ The CRA will review all data points collected for the trial, no matter in what form. The CRA will ensure that data is legible and original.
§ The CRA will review the source document for accuracy. Any trends in data collection, such as inconsistencies, should be discussed.
Current Issues with Source Documentation Verification
1. With increased use of EMRs, clinical research coordinators enter information in the electronic system, including dose changes, assessment of adverse events or communication on labs, as directed by the PI. These entries are linked to the CRC, who is not delegated to perform these tasks on the trial. This creates an issue for auditors/monitors/CRAs and explanations are needed that this is the normal site practice.
2. Late data entry in the EMR for research procedures creates concern. How does the CRA verify or determine if a lab was reviewed during a visit or prior to randomization with electronic signature if the lab is electronically signed at a later date.
3. Auditors want a clear picture of what happened-the process- with each subject, from the time of consent and progressing in the trial.
