Clinical Data Management - Class 10

DH308: NIRMAL PUNJABI
DH 308 – Class 10
3rd February 2023
Clinical Data
Management
- Nirmal Punjabi, Ph.D.
Welcome to the course. We will start at 11:05 am.

Today’s Agenda (Class 10)

• Revisit Class 9 Class 10:
• Clinical Data Planning • Clinical Data Management
• Protocol / Standard Operating
Procedure (SOP) • Clinical Data Planning
• Parameter selection • Case Report Forms
• Paper / EDC
• Case Report Forms
• Types
• Questions in CRF
• Selection of standard
instruments/CRF
• Number of Participant
• Estimation
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Clinical Data
Planning
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Good clinical research practice (GCP) ….

• Ethics:
• Ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP
and the applicable regulatory requirement(s).
• Trial risk vs trial benefit:

• A trial should be initiated and continued only if the anticipated benefits justify the risks.
• Trial participants:
• The rights, safety, and well-being of the trial subjects should prevail over interests of science and society.
• Information on the Medicinal Product:

• The available non-clinical and clinical information on an Investigational Product should be adequate to
support the proposed clinical trial.
• Good quality trials:

• Clinical trials should be scientifically sound, and described in a clear, detailed protocol.
• Compliance with the study protocol:

• A trial should be conducted in compliance with the protocol that has received prior institutional review
board (IRB)/independent ethics committee (IEC) approval/favorable opinion.
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Image Reference: ICH-GCP guidelines, WHO GCP guidelines
Good clinical research practice (GCP) …

• Medical decisions:
• The medical care given to, and medical decisions made on behalf of, subjects should always be the
responsibility of a qualified physician or, when appropriate, of a qualified dentist.
• Trial staff:
• Each individual involved in conducting a trial should be qualified by education, training, and experience
to perform his or her respective task(s).
• Informed consent:
• Freely given informed consent should be obtained from every subject prior to clinical trial participation.
• Clinical trial data:
• All clinical trial information should be recorded, handled, and stored in a way that allows its accurate
reporting, interpretation and verification.
• Confidentiality:
• The confidentiality of records that could identify subjects should be protected, respecting the privacy
and confidentiality rules in accordance with the applicable regulatory requirement(s).
• Good Manufacturing Practice:
• Investigational products should be manufactured, handled, and stored in accordance with applicable
good manufacturing practice (GMP). They should be used in accordance with the approved protocol.
• Quality assurance:
• Systems with procedures that assure the quality of every aspect of the trial should be implemented.
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Image Reference: ICH-GCP guidelines, WHO GCP guidelines
Clinical Data Planning

Case Report Forms
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Case Report Form

• ICH guidelines for Good Clinical • To collect data
Practice (GCP) • According to the ‘protocol’
• Case Report Form: “A printed, optical, • Easily Analyzable
or electronic document designed to • Fit the requirements of
record all of the protocol required statistical analysis plan
information to be reported to the • Minimize queries
sponsor on each trial subject”
• Types
• Paper based
• Electronic
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• Collection strategy
• Paper based forms
• Retrieval
• Manual Entry
• Double entry
(validation)
• Scanning
• With OCR
• Shape
• Text
• Color
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Image Reference: Wikipedia; https://restoringtrials.org/glossary/case-report-form-crf/; www.istock.com

• Collection strategy (ctd..)
• Electronic record
• Survey forms
• Tools
• Validation
05-02-2023 9
Image Reference: https://workspace.google.com/products/forms/; www.popularmechanics.com
CRF example 1-1
10
05-02-2023 Reference: https://www.who.int/tdr/diseases/tuberculosis/case-report-form.pdf
CRF example 1-2
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Reference: https://www.who.int/tdr/diseases/tuberculosis/case-report-form.pdf
CRF example 1-4
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CRF example 2
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Reference: Bellary et al, Perspect Clin Res. 2014 Oct-Dec; 5(4): 159–166. DOI: 10.4103/2229-3485.140555
CRF example 3
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CRF example 4
05-02-2023
Reference: Bellary et al, Perspect Clin Res. 2014 Oct-Dec; 5(4): 159–166. 15
DOI: 10.4103/2229-3485.140555
CRF example 5
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CRF example 6
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• CRF
• Design Considerations
• Follow the protocol • Clear questions
• Inclusion/Exclusion factors • Unambiguous Formatting/Positioning
• Main Events: Procedures • Reduce Error
• Parameters to • Improve efficiency
observe/monitor • Divide similar/related questions into
sections
• Frequency of Procedures
• Header and Footer
• Duration of study
• Id No.
• Participant
• Technical Team
• Page number
• Form Number
05-02-2023 • Signature 18
Image Reference:
Questions in CRF: Design Considerations

• Content/Information needed
• Accordance of the protocol
• Types of Question/Presentation
• Open: Text, number, symbols.
• Closed: Including binary and multiple choice.
• Mixed/Combination: Open and closed response.
• Analogue scales:
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CRF example 1-1
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CRF example 1-2
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CRF example 1-4
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Questions in CRF: Design Considerations

• Content: Accordance with Protocol
• Date, phase and identification of the trial.
• Identification of the Subject.
• Age, sex, height, weight and ethnic group of the Subject.
• Characteristics of the Subject (smoking, dietary, pregnancy, previous treatment etc.).
• Adherence to inclusion/exclusion criteria.
• Duration of disease, time to last breakout, etc.
• Dose, dosage schedule, administration of medical product, compliance record.
• Duration of treatment.
• Duration of observational period.
• Concomitant use of other medicines and non-medicinal interventions/therapy.
• Dietary regimens.
• Recording of efficacy parameters met, date and time.
• Recording Adverse Events, type, duration, intensity consequence and measures
taken.
• Reasons for withdrawal, breaking code.
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CRF Design: Questions in CRF

• Unambiguous
• Easy to understand
• Minimal Training
• Preference to closed-ended questions

• Provide list of options
• Add ‘Others ______’ or ‘Specify’, if applicable.
• Binary questions should be verified

• Provide option for ‘don’t know’ or ‘does not wants to disclose’ or ‘not
applicable’
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Questions in CRF
• Subjective questions (Improvement, Pain, )
• Clearly specify duration to be observed
• Note down the duration of the event
• Try to use validated protocol or ‘instruments’ that has been validated.
• Linked questions
• Proper information/guidelines should be provided to avoid confusion.
• Data Analysis
• Collect raw data or Avoid collapsing data
• Use appropriate units (mm/inch, ms, kg, mmol)
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Different sections/modules of CRF

• Screening Module
• Inclusion/exclusion criteria
• Date of written consent

• Medical History
• Demographic data
• Physical Examination
• Vital Signs
• Laboratory parameters
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Screening
• Screening Module
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Screening
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• Inclusion compliance & Baseline Data
• Verification of inclusion/exclusion criteria
• Vital Signs (BP, RR, Temperature, etc)
• Examinations (Basic tests)
• Laboratory tests
• Study Events (administration of therapy)
05-02-2023 29

• Visits/Logs
• Noting of examinations and other parameters as per study protocol
• Study Conclusion
• Withdrawal of patient
• Adverse Event
• Death
• Pregnancy
• Non-compliance with protocol
• “Lost to follow up”
05-02-2023 30

• Pharmacovigilance
related
• Concomitant drug data
• Drug
• Type/Name
• Form
• Dosage
• Quantity
• Frequency
• Route of Administration
• Documentation of
Adverse event and Serious
adverse events
• Endpoint
05-02-2023 31
Template Reference: University of Wisconsin-Madison
CRF: Example
05-02-2023 32
Reference: https://sengiclinical.com/
CRF: Example
05-02-2023 33
Reference: https://sengiclinical.com/
CRF list (non-exhaustive)
Screening or
Documentation of Eligibility form Randomization Demographic
Enrolment form
informed consent [inclusion and form information form
exclusion criteria]
Baseline Pre-existing and

Medical history Physical or general Concomitant
assessment or vital Adverse Events
form examination form medications form
signs form form
Serious Adverse
Study visit forms End of study form
Events form
05-02-2023 34
Case Report Forms: Design Considerations

Good Design practice: Traceability, Accountability
• MUST have
• Identifiers on each page
• Site Id
• Patient Id
• Form title
• Page number
• Verifier/Technical Team Name (Optional)
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CRF example 6
05-02-2023 36
Image Reference: Kilburn et al, Trials, 2014. https://doi.org/10.1186/1745-6215-15-379
Electronic Case Report Form

eCRF, Computerized CRF
Electronic Case Report Form

• Electronic acquisition of data
• Directly from the individual
• Directly at trial site
• Part of Electronic Data Capture (EDC)

• In some literature, referred as EDC.
• Benefits
• Address various challenges of paper based CRF
• Provides efficiency and reliability
• Reduction in queries
• No readability issues
• Real-Time Validation of data (Age Range, Missed entry, )
• Reduction of need for logistics and infrastructure (physical storage space)
• Traceability
• Faster sharing of data
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Challenge – 1 with conventional CRF

• Problems in Parsing of hand-written data
• Handwriting
• Corrections
• Additions
• …
05-02-2023 39
eCRF: Challenge -1 Solution

• Benefits • Benefits
• Reduction in queries • Validation of data (Age Range,
• Direct entry in standard font Missed entry, )
(no issues with readability of • Appropriate selection options
handwritten entries)
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Challenge - 2
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Image Reference: Kilburn et al, Trials, 2014. https://doi.org/10.1186/1745-6215-15-379
eCRF: Challenge 2 solution

• Benefits
• Branching Logic implementation
Gender
HIV Test
Male Female
Positive Negative
Next
Pregnant?
section Confirmatory
Next Section
Test
Yes No
Positive Negative
How many Next

months? section
05-02-2023 42
eCRF
• Best Practices
• Benefits
• Less requirement of physical
space or shipping logistics • Optimal Layout
• Faster sharing of data • Suitable Item Types
• Secured storage and sharing
• Correct Logic in
interconnected questions
• Challenges
• Data Security • Validation or Edit checks
• More time needed to properly
plan the questions. • Data Standards
05-02-2023 43

Clinical Data Management - Class 10

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DH308: NIRMAL PUNJABI

Welcome to the course. We will start at 11:05 am.

Today’s Agenda (Class 10)

Good clinical research practice (GCP) ….

• Trial risk vs trial benefit:

• Information on the Medicinal Product:

• Good quality trials:

• Compliance with the study protocol:

Good clinical research practice (GCP) …

Clinical Data Planning

Case Report Form

Clinical Data Planning

Clinical Data Planning

CRF example 1-1

CRF example 1-2

CRF example 1-4

Clinical Data Planning

Questions in CRF: Design Considerations

CRF example 1-1

CRF example 1-2

CRF example 1-4

Questions in CRF: Design Considerations

CRF Design: Questions in CRF

• Preference to closed-ended questions

• Binary questions should be verified

Different sections/modules of CRF

• Date of written consent

Different sections/modules of CRF

Different sections/modules of CRF

Different sections/modules of CRF

CRF list (non-exhaustive)

Baseline Pre-existing and

Case Report Forms: Design Considerations

Electronic Case Report Form

Electronic Case Report Form

• Part of Electronic Data Capture (EDC)

Challenge – 1 with conventional CRF

eCRF: Challenge -1 Solution

eCRF: Challenge 2 solution

How many Next

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