DH308: NIRMAL PUNJABI

DH 308 – Class 7
25th January 2023

Clinical Data
Management
- Nirmal Punjabi, Ph.D.

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

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Today’s Agenda (Class 7)

• Revisit Class 6 Class 7:
• Clinical Data Management • Clinical Data Management
• Clinical Data Planning
• Clinical Data Planning
• Clinical Research Theme / Idea
• FINER
• Budget
• Sources • Ethics
• Hypothesis • Regulations
• PICOT • Standard Terms
• Examples
• Practical Case: Exceptions
• Hypothesis v/s Research Question

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Clinical Data
Planning
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Clinical Data Planning

What all should be planned? & Dependencies

• Research • Technical Details

Theme/Hypothesis/Clinical • Defining Outcomes
Trial • Dosing Type
• Budget
• Methods
• Regulation
• Ethical Clearance • Parameters
• Historical
• Baseline
• Type of Trial • Monitored
• Randomization ??
• Blinded ??
• Multi-Centre ??
• …..
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Clinical Data Planning

What all should be planned? & Dependencies

• Research • Technical Details

Theme/Hypothesis/Clinical • Defining Outcomes
Trial • Dosing Type (For Drugs)
• Budget
• Methods
• Regulation
• Ethical Clearance • Parameters
• Historical
• Baseline
• Type of Trial • Monitored
• Randomization ??
• Blinded ??
• Participants
• Multi-Centre ?? • Selection Criteria
• ….. • Informed Consent
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Participant

Inclusion / To monitor the After Intervention

Exclusion Criteria current status / Placebo

Screening Baseline Parameters

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Clinical Data Management

Study Startup Study Conduct Study Close Out

• Collection planning • Collection of data • Data Quality
• Design Case Report forms validation
• Data cleaning
• Deciding tools for • Send for Analysis
collecting data • Collection/documen
• Defining codes OR tation of adverse
rules/conditions for events
special case
• Building/Selecting • Reports
database
• Testing of database
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Clinical Data Planning

Clinical Trial Budget

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Clinical Data Planning

• Trial Budget
• Estimate for money needed to conduct the clinical trial
• Proportional to the scale/scope of the Trial
• What is the hypothesis? How many?
• How many participants are needed to validate/invalidate it?
• How many sites are needed to recruit participants?
• What is the time duration?
• What parameters will be measured to determine safety and clinical outcomes?
• What are the per-patient costs in terms of testing (imaging, labs, etc.), intervention (drugs, devices),
and personnel time to screen, enroll, measure outcomes, follow subjects, and data entry?
• Who is running/coordinating the trial and what are their costs/expenses?
• What is the cost involved for statistical analysis?
• What is the cost involved in management (database, quality validation) of data?

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Clinical Data Planning

What all should be planned? & Dependencies

• Trial Budget
• Major Heads

• Clinical Trial Personnel • Testing Cost • Infrastructure Cost

• Salary • Screening • Number of centers
• Scientific Team • Baseline • Testing Facility
• Administrative Team • Parameters of study • Storage
• Training • Samples

• Participant • Data Management Cost • Travel

• Renumeration for • Storage: Physical and Digital • Scientific Team
participating • Digitalization cost • Audit Team
• Insurance • Clinical Trial Management • Meetings
System
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Clinical Data Planning

What all should be planned? & Dependencies

• Trial Budget
• Major Heads

• Adverse Events • Intervention Cost • Regulatory Cost

• Compensation • Cost of drug/device • Application Fees
• Modification • Consumables • Audit
• Regulatory • Validation

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Clinical Data Planning

What all should be planned? & Dependencies

• Trial Budget: Practical Considerations

• Optimum Parameters: Each test adds to the cost
• Optimum Data Points for each parameter

• Use of Expensive Testing should be technically rationalized

• Imaging modalities
• Genetic Testing

• Intervention Wastage / Expiry / Damaged

• More sites require more budget

• Complexity: Timeline 13
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Clinical Data Planning

Ethics

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History of Development of Human Research

Protections
1. Public Health Service Syphilis Study ’32-’71
• Better known as the “Tuskegee Syphilis Study”
• Originally designed to make treatment available to African-American men
with syphilis, even though there was no known effective treatment
• Issues:
1. Men were recruited without their consent
2. Misinformation about procedures, ie spinal taps
3. After penicillin was proven an effective treatment ’40’s), men were denied antibiotics
and prevented treatment from military and local physicians
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History of Development of Human Research

Protections
2. US Food, Drug and Safety Act (1938)

• 107 people died after taking sulfanilamide, a cold remedy that contained
anti-freeze.
• This act enforces manufacturers to demonstrate drug safety.
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History of Development of Human Research

Protections
3. Nuremberg Code (1947)
• Result of the trial of Nazi doctors and scientists from WWII – no guidelines
for human research
• Guidelines:
1. Need for informed consent
2. Research should be based on prior animal work
3. Risks should be justified by anticipated benefits
4. Only qualified scientists must conduct research
5. Physical and mental suffering must be avoided
6. No research where death/severe injury is expected
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History of Development of Human Research

Protections
3. Nuremberg Code (….)
• Problems:
1. Little impact on research done in the US – thought to condemn Nazis
2. No strength of the law behind it
3. Only applied to non-therapeutic human subject research
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History of Development of Human Research

Protections
4. Declaration of Helsinki (1964)
• Code of ethics developed by the World Medical Association (now known
and World Health Org)
• Broader than Nuremberg Code
• Geared towards therapeutic medical research
• Recommended informed consent
• Precursor to Institutional Review Board requirement
• Journals required all published research to follow Declaration’s guidelines
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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
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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
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Clinical Data Planning

Regulations

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Regulations
• Institutional Review Board / Institutional Ethics Committee

• Health Insurance and Portability Act (HIPAA)

• Privacy
• Security
• Federal Information Security Management Act (FISMA)
• Information security; US government agencies and their contractors
• General Data Protection Regulation (GDPR)

• The International Council for Harmonisation of Technical Requirements for

Pharmaceuticals for Human Use (ICH)
• MedDRA
• 21 CFR (Code of Federal Regulations), Part 11
• Electronics Record; Computer systems used in Clinical Trials 23
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Protected Health Information (PHI)-HIPAA18

• Protected health information (PHI) is any information in the medical record or
designated record set that can be used to identify an individual and that was
created, used, or disclosed in the course of providing a health care service such as
diagnosis or treatment

• HIPAA18: 18 identifiers

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HIPAA18
• 1. Names;
• 2. All geographical subdivisions smaller than a State, including street
address, city, county, precinct, zip code, and their equivalent geocodes,
except for the initial three digits of a zip code, if according to the
current publicly available data from the Bureau of the Census: (1) The
geographic unit formed by combining all zip codes with the same three
initial digits contains more than 20,000 people; and (2) The initial three
digits of a zip code for all such geographic units containing 20,000 or
fewer people is changed to 000.
• 3. All elements of dates (except year) for dates directly related to an
individual, including birth date, admission date, discharge date, date of
death; and all ages over 89 and all elements of dates (including year)
indicative of such age, except that such ages and elements may be
aggregated into a single category of age 90 or older;
• 4. Phone numbers;
• 5. Fax numbers;
• 6. Electronic mail addresses; 25
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HIPAA18
• 7. Social Security numbers;
• 8. Medical record numbers;
• 9. Health plan beneficiary numbers;
• 10. Account numbers;
• 11. Certificate/license numbers;
• 12. Vehicle identifiers and serial numbers, including license plate
numbers;
• 13. Device identifiers and serial numbers;
• 14. Web Universal Resource Locators (URLs);
• 15. Internet Protocol (IP) address numbers;
• 16. Biometric identifiers, including finger and voice prints;
• 17. Full face photographic images and any comparable images;
and
• 18. Any other unique identifying number, characteristic, or code
(note this does not mean the unique code assigned by the
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Regulations (India Specific)

• Digital Information Security in Healthcare Act ("DISHA“)
• Electronic health data • PHI
1. Name
• Privacy
2. Address
• Confidentiality 3. Date of Birth
• Security 4. Telephone Number
5. Email Address
• Standardization
6. Password
7. Financial information such as bank account or credit card or debit
• Coverage card or other payment instrument details
8. Physical, physiological and mental health condition
• Ownership of data 9. Sexual orientation

• Patient Consent 10. Medical records and history

• Purpose for access to data
• Storing of Digital data
11. Biometric Information
12. Vehicle number
13. Any government number, including Aadhar, Voter’s Identity,
Permanent Account Number (‘PAN’), Passport, Ration Card, Below
Poverty Line (‘BPL’).
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Regulations (India Specific)

• Digital Information Security in Healthcare Act ("DISHA“)

• Ambiguity/Cons
• No clarity about implementation on a large scale

• Use of unidentified data for clinical research requires consent of individuals.

• Discontinued

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Regulations (India Specific)

• Data Protection Framework on Digital Information Privacy, Security &
Confidentiality’ Act
• Ministry of Electronics & Information Technology (MeitY)

• The Digital Personal Data Protection Bill, 2022

• Ayushman Bharat Digital Mission

• Health Data Management Policy
• Health Data Retention Policy (In early stages)

• New Drug and Clinical Trials Rule, 2022

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Regulations (India Specific)

• The Indian Medical Council (Professional Conduct, Etiquette and Ethics) Regulations,
2002
• “every physician shall maintain the medical records pertaining to his / her indoor patients for
a period of 3 years from the date of commencement of the treatment in a standard proforma
laid down by the Medical Council of India”.

• The Clinical Establishments (Registration and Regulation) Draft Rules, 2010

• Medical Records should be retained for 3 to 5 years

• Directorate General of Health Services for Central Government Hospitals in 2014

• Indoor patient medical record: 10 years
• OPD: 3 years

• The Pre-Conception Pre-Natal Diagnostic Techniques (Prohibition of Sex Selection)

Act, 1994,
• Documents : 2 years

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Regulations (India Specific)

• The Personal Data Protection Bill, 2019
• Data can be stored only for as long as it is necessary to satisfy the purpose for
which the data has been recorded by the entity.

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