Introduction to Clinical Trials

Learning Objectives

• Identify types of study designs

• Define clinical trials

• Understand requirements for clinical trial

• Explain fundamental rules of clinical trials

• Understand the ethical considerations/requirements

• Describe the process of clinical trial

3

© 2017 USP
 Study Designs

• Cross-sectional surveys
• Case control studies
• Cohort studies
• Community intervention studies
• Randomized control clinical trials

© 2017 USP
 Clinical Trial

Any form of planned experiment that involves human participants that is

designed to elucidate the most appropriate therapy of future patients with
a given medical condition.

© 2017 USP
 Fundamental Rules in Clinical Trials

• Responsibilities, not rights,

should be the first concern of
clinical trials

• Only the Investigator may

remove a research participant
from a clinical trial

• Only the Sponsor may stop a

clinical trial

• Never assign responsibility to a

party who cannot fulfil it
6

© 2017 USP
 Clinical Trial Requirements

Laws &
Regulations

Ethical GCP
Standards Study
Protocol

© 2017 USP
 Ethical Dilemmas

• Clinical trial: Scientific experiment aimed to produce knowledge that

can help improve the care of future patients

• Ethics of clinical medicine: Therapeutic beneficence and therapeutic

non-maleficence

© 2017 USP
 Ethical Considerations

Ethical Principles Clinical Trials

• Respect for person • Informed consent

• Beneficence/Non- • Direct benefit/ Minimal risk

maleficence

• Pre-trial fair selection/ Post-

• Justice trial availability of products

© 2017 USP
 Ethical Requirements for Clinical trials
• Scientific or social value

• Scientific validity

• Fair participant selection

• Respect for participants

• Informed consent

• Favorable risk-benefit ratio

• Independent review 10

© 2017 USP
 Ethical Requirements: Social or Scientific
Value
Clinical trials should:

• Improve health and well-being

• Add knowledge

• Do not expose participants to risks of valueless research, i.e.,

– Non-generalizable studies
– Non-disseminated research

11

© 2017 USP
 Ethical Requirements: Scientific Validity

Clinical trials should:

• Follow rigorous methodology

• Provide reliable and valid data
• Have an adverse events reporting system
• Be monitored by DSMBs
• Provide true and accurate knowledge

N.B. Scientifically unsound studies are unethical

12

© 2017 USP
 Ethical Requirements: Fair Participant
Selection

Clinical trials should:

• Consider scientific objective in selection of participants

• Not exclude participants without scientific reason

– High risk could be a legitimate reason for exclusion

13

© 2017 USP
 Ethical Requirements: Respect for
Participants

Clinical trials should:

• Respect participant’s decision

• Permit refusal/withdrawal without repercussions
• Respect privacy
• Protect confidentiality
• Monitor and promote participant’s welfare
• Inform research outcomes

14

© 2017 USP
 Ethical Requirements: Informed Consent

Clinical trial should:

• Disclose information, such as
o Research purpose and duration of participation
o Risks/Benefits
o Confidentiality
o Compensation
o Voluntariness and right to withdraw
o Contact address

• Ensure voluntary decision

• Consider competency and understanding
• Have signed informed consent (IC)

15

© 2017 USP
 Ethical Requirements: Favorable Risk-
Benefit Ratio

Clinical trials should:

• Consider ratio to both participants and society

• Identify, assess, and minimize risks (physical, psychological, social,

and economic)

• Enhance benefits (physical, psychological, social, and economic) not

from payment, but from research.

16

© 2017 USP
 Ethical Requirements: Favorable Risk-
Benefit Ratio

• Potential benefits outweigh risks to participant → proceed

• Potential risks outweigh benefits to participant 

▪ Consider ways to minimize

▪ Evaluate risk against social benefit or knowledge gained

17

© 2017 USP
 Deciding Risk-Benefit

Initiate and Continue a Trial

Only if anticipated BENEFIT justifies RISK

18

© 2017 USP
 Ethical Requirements: Independent
Review

Clinical trials should:

• Be reviewed by an independent ethics committee/regulatory authority

that will consider –

 Investigator’s conflict of interest

 Rights of participants
 Protection of participants from harm

19

© 2017 USP
 Ethical Conduct of Clinical Trial

• Clinical Trial (CT) does not end with the formulation of a study design and a
signature on the IC form

• Protection of participants’ rights, interests and safety must continue

throughout study duration

• Participant safety monitoring is responsibility of all stakeholders –

 Sponsor
 Clinical monitor(s)
 Investigators/research staff
 EC/IRB/regulatory body
 DSMB

20
• CT also cares for credibility of data © 2017 USP
 Process of Clinical Trial – 1

1. Develop a trial protocol

• Designed by Sponsor, in consultation with Clinical investigators.

• Considers concepts of risk identification, study design, statistical

methodology

• Considers local laws/regulations pertaining to designing, initiating,

and conducting the study

21

© 2017 USP
 Process of Clinical Trial – 2

2. Define responsibilities, records, and methods to be used for study-

related activities:

• Prepared by all stakeholders

 Sponsor’s SOP
– Develops and updates protocol, IB, CRFs, etc.
– Supplies procurement, shipping, handling, IP supplies
– Reviews adverse event reports, conducts data analysis
– Standardizes activities of clinical investigators
– Monitors, documents, audits

22

© 2017 USP
 Process of Clinical Trial – 2

➢ Investigator’s SOP
– Communicates with the IEC/IRB
– Obtains and updates informed consent
– Reports adverse events; preparing and
– Maintains adequate records
– Administers, accounts for and disposes IP

➢ IRB’s SOP
– Determines membership requirements
– Conducts initial and continuing review
– Communicates with investigator and institution
– Minimizes or eliminates conflicts of interest
23

© 2017 USP
 Process of Clinical Trial – 2

 Regulator’s SOP

– Reviews applications/safety reports

– Conducts GCP inspections (where applicable)
– Communicates findings to inspected parties
– Establishes infrastructure for due process
– Imposes sanctions on parties who violate local law or regulations

24

© 2017 USP
 Process of Clinical Trial – 3

3. Develops support systems and tools, such as:

• Trial-related information documents (IB, CRF, checklists, study flow

sheets, drug accountability logs)
• Computer hardware and software
• Electronic patient diaries
• Other specialized equipment

25

© 2017 USP
26
Process of Clinical Trial – 4

4. Selects trial sites, investigator/study personnel

• Sponsor should select clinical investigators who:
 Are qualified
 Have sufficient resources
 Employ appropriately trained staff
 Are knowledgeable about national settings and circumstances of site and study
population

• Clinical investigators should:

 Select appropriate site
 Recruit appropriate personnel

26

© 2017 USP
 Process of Clinical Trial – 5,6

5. Approval by IRB and Regulatory Authority

• Should be approved prior to patient enrollment
• Investigator should obtain approval
• Investigator should provide copy of approval to sponsor
• Reviewed by regulatory body for appropriate use of IP and to ensure
appropriate study design
• Sponsor should register CT

6. Participant Employment
• Eligible participants should be enrolled
• IC should be obtained and documented
27

© 2017 USP
28
Process of Clinical Trial – 7,8,9

7. Accountability for investigational products

• Quality, use, handling, and storage of IP should be assured

8. Conducting trial
• Should be conducted according to approved protocol and applicable
regulatory requirements

9. Safety management reporting

• Investigator is responsible for safety of participants
• Sponsor is responsible for reporting safety to regulatory body and other
investigators 28

© 2017 USP
 Process of Clinical Trial – 10,11

10. Monitoring trial

• Sponsor should perform site monitoring through clinical monitor/CRO

11. Managing data

• Sponsor is responsible for developing appropriate data management
systems (collecting, handling, manipulating, analysing, and
storing/archiving data from start to completion of study)
• Sponsor and investigator share responsibility for implementing such
systems

29

© 2017 USP
30
Process of Clinical Trial – 12,13

12. Quality assurance

• QA verifies through systematic, independent audits
• QA audits may be performed during trial and/or upon completion

13. Reporting the trial

• Report should be complete, timely, well-organized, free from
ambiguity, and easy to review

30

© 2017 USP
 Summary

• CTs are investigations that test how well new medical approaches work
in people.

• Responsibilities, not rights, should be the first concern of CTs.

• CT requires protocols prepared as per regulations, GCP and ethical

standards

• Three basic ethics principles should be considered in CTs

• CTs require ethical considerations
• Ethical conduct is a continuous process in CTs
31
• Clinical trial should follow a process. © 2017 USP