Clinical Trials: Types and Design Experimental Study- RCT and Non RCT, Observation Study: Cohort, Case Control, Cross sectional Clinical Trial Study Team Roles and responsibilities of Clinical Trial Personnel: Investigator, Study Coordinator, Sponsor, Contract Research Organization and its management.

1. ROLES & RESPONSIBILITIES OF
CLINICAL TRIAL PERSONNEL
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Presented BY
Ramavath Aruna
B. Pharm
170117887007
Dept. of Pharmacology
G. Pulla Reddy College of
Pharmacy

2. DEFINITION OF CLINICAL TRIAL
 Clinical trials are scientific research investigations in which people volunteer
to test new treatments, interventions or tests as a means to prevent, detect,
treat or manage various diseases or medical conditions.
 According to World Health Organization (WHO) clinical trial is may be
defined as
‘any research study that prospectively assigns human participants or
groups of humans to one or more health-related interventions to evaluate the
effects on health outcomes’.
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3. PHASES INVOLVED IN CLINICAL TRIALS
 PHASE 1
 PHASE 2
 PHASE 3
 PHASE 4
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4. TYPES OF CLINICAL STUDIES
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5. RANDOMIZATION
The volunteers are randomly allotted by different groups. One group receives
investigational new drug treatment while the other group is administered either the
standard drug or a placebo.
BLINDING (sometimes called masking)
Keeping people unaware of treatment group assignment after randomization.
Single blind – Here, volunteers are unaware of the treatment given to them.
Double blind – In this design, both the volunteer and the physician are unaware of
the drug treatment.

6. PLACEBO EFFECT
 It has been shown that if you think and believe you are going to get
better, you are more likely to do so.
 If you take something you believe to be an effective medicine, your
symptoms may improve.
 Reassurance from a doctor or other health care professional also helps
some people to feel better. This is known as the ‘placebo effect.’
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7.  CROSS OVER – over time, each participant
receives (or does not receive) an intervention in a
random sequence

8. CLUSTER – pre-existing groups of participants (e.g., villages, schools)
are randomly selected to receive (or not receive) an intervention.
FACTORIAL – each participant is randomly assigned to a group that
receives a particular combination of interventions or non-interventions (e.g.,
group 1 receives vitamin X and vitamin Y, group 2 receives vitamin X and
placebo Y, group 3 receives placebo X and vitamin Y, and group 4 receives
placebo X and placebo Y).

10. RTC
 It eliminates bias in treatment
assignment, specifically
selection bias and confounding
 "It facilitates blinding
(masking) of the identity of
treatments from investigators,
participants, and assessors."
 "It permits the use of
probability theory to express
the likelihood that any
difference in outcome between
treatment groups.
 Time and Costs
 Logistics
 Applicability
 Ethical limitations
 Contamination of intervention
group
 Problems with blinding
ADVANTAGES DIS-ADVANTAGES

11. A clinical trial in which the participants are not assigned by chance to
different treatment groups.
Participants may choose which group they want to be in, or they may
be assigned to the groups by the researchers.
Uses natural groups or assigns participants to groups using a non-
random procedure
•The investigator controls the exposure of groups to the intervention
•Prospective
•Confounders exist due to non-randomization
NON- RANDOMISED CLINICAL TRIAL

12. Concurrent controls: Treatment and control group participants are matched at
the group level based on demographic and other characteristics, and receive
different treatment conditions at the same time.
Historical controls: Investigators compare outcomes among a group of
participants who are receiving a new treatment (experimental group) with
outcomes among participants who received standard treatment in a previous
period (control group).
TYPES OF CONTROLS THAT CAN BE USED IN
NON-RANDOMISED CLINICAL TRIALS
ADVANTAGES
 Easier to select patient.
 Prefer to select the control group by means of matching key characteristics.
DISADVANTAGES
 Potential bias that the study groups are not strictly comparable.

13. DIFF B/W COHORT STUDY & CASE CONTROL STUDY
Case control studies Cohort studies
Proceeds from effect to cause Proceeds from cause to effect
Starts with the disease Starts with people exposed to the risk factors
Tests whether the suspected cause occurs more
frequently in those with disease than those
without disease
Tests whether disease occurs more frequently
in those exposed than in those not exposed
Usually the 1st approach to the testing of
hypothesis, but also useful for exploratory
studies
Reserved from the testing of precisely
formulated hypothesis
Involves fewer study subjects Involves large number of subjects
Yields results relatively quickly Long follow-up, delayed results
Suitable for study of rare diseases Inappropriate when disease or exposure under
investigation is rare
Generally, yields only estimate of relative risk
(odds ratio)
Yields incidence rates, relative risk, attributable
risk
Cannot yield info about disease other than that
under study
Can give information about more than one
disease outcome
Relatively inexpensive Expensive

14. PERSONS INVOLVED IN CLINICAL TRIAL
Appropriately qualified and trained personnel are required to ensure the
satisfactory conduct of research studies at a site. This may include staff
directly involved in the conduct of the research such as:
 Principal Investigator (PI)
 Study coordinators
 Sponsor
 Control research organization & its management.
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15. INVESTIGATOR
Good Clinical Practice (GCP) guidelines:
Study Protocol and applicable regulatory requirements, it is essential that
all staff involved are aware of their roles and responsibilities and that they
are appropriate for the duties delegated to them by the PI.
International conference of Harmonization GCP (ICH GCP)
guidelines:
define an investigator as “A person responsible for the conduct of the
clinical trial at a trial site”. The investigator is responsible for protecting
the integrity, health and welfare of the research subjects.
The investigator must be:
Qualified by education, training and experience & should be Thoroughly
familiar with the study protocol and any investigational product(s)
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16. INVESTIGATOR ROLES
 Good Clinical Practice (GCP) in FDA‐regulated research is not the same as
GCP in caring for patients.
For example,
 FDA regulations have very specific requirements for following the protocol
 Recordkeeping &
 Drug accountability
Regulations are designed to:
 -Ensure the quality and integrity of data collected in clinical trials
 -Ensure that the rights, safety and welfare of research participants are protected
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17. THE RESPONSIBILITIES OF A PI
The responsibilities of a PI are summarised in Appendix A and include:
 Ensuring the welfare and medical care of study subjects
 Obtaining approval of and continued communication with regulatory bodies
 Conduct of the study in compliance with the protocol and required governance
regulations and guidelines
 As well as local policies/procedures
 Administration
 Management
 Storage of investigational product
 Safety reporting
 The accurate and timely completion
of study data
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18. RECORD KEEPING AND RETENTION
 Maintaining adequate records of the disposition of the drug
 Accurate case histories that record all observations &
 Other data pertinent to the investigation on each individual administered of the
investigational drug or employed as a control in the investigation.
An investigator is required to maintain investigation records for:
 2 years following the data a marketing application is approved for the drug for
the indication for which it is being investigated
 2 years after the investigation is discontinued and FDA is notified if no
application is to be filed or if the application has not approved for such
indication.
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19. INVESTIGATOR REPORTS (PSPIFF)
 Progress reports
 Safety reports
 Promptly report any adverse event that may reasonably be regarded as caused
by, or probably caused by, the drug (err on the side of reporting)
 Immediately report any adverse event that is alarming (e.g. an unexpected
event that is serious or life‐threatening)
 Final report
 Financial disclosure
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20. ROLES & RESPONSIBILITIES OF STUDY
COORDINATOR
 A clinical research coordinator (CRC) is responsible for conducting CTs at CT
sites according to the protocol, ICH-GCP and other regulatory requirements.
 The role of a SC in CT is very important.
 Every CT site may have 1 or more SC depending on the workload at trial site.
 CT at site level can be roughly divided into 3 stages. They are:
1) Before the start of the clinical trial
2) During the conduct of the clinical trial
3) After close out of the clinical trial
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21. 1) BEFORE THE START OF THE CLINICAL TRIAL:
 The SC has to collect & complete feasibility questionnaires received form
different CRO’s and Sponsor’s.
 CRC’s should collect all the information from the PI, & send back to the
respective people.
 After selecting CT sites they conduct Investigator meetings, which have to be
attended by the SC along with the PI. Investigator meetings are conducted
either at national level or international level.
 Before start of the trial CRC’s are usually busy with submitting all study
documents to the ethics committee & it normally include the study protocol,
investigator brochure and informed consent forms with translation certificates.
 If any amendments are available they need to be submitted to the ethics
committee.
 After obtaining approval from the ethics committee the CT can be initiated at
the site level.
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22. 2) DURING THE CONDUCT OF CLINICAL TRIAL:
 By the time a CT, is initiated at a site the CRC & must have a good
understanding of the study protocol and must know well about inclusion and
exclusion criteria.
 During the screening time, the SC has to obtain informed consent from the
subject in if delegated to do so by the PI.
 SC have to collect subjects from previous medical records & according to
study protocol he/she has to conduct subjects scheduled visits.
 Before randomization visit of the subject the CRC must check inclusion and
exclusion criteria thoroughly, and only then eligible subjects must be enrolled
into the study.
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23. CONT…
 After completion of all visit procedures coordinators have to enter data in case
report forms (CRF).
 CRF’s are 2 types, one is paper CRF and another one is electronic (eCRF).
 All details have to be entered in these online data collection tools based on
source documentation available.
 During monitoring, sponsor representatives & credit rating agency (CRA’s) cross
verify both the source documents & the data filled by the CRC in the case report
forms.
 During the monitoring visit the CRA’s also verify Encumbrance Certificate (EC)
notifications and Investigator Site Files (ISF).

24. CONT….
 To keep all these documents up to date, it is the responsibility of the clinical
study coordinator. SC also has to maintain site SOP’s, EC sops and EC
members list.
 Whenever study subjects come for next schedule visit, study drug
accountability has to be calculated by the CRC.
 IP (Investigational product) is the major part in clinical trial and SC have to
store the same in proper condition and maintain required temperature logs.
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25. 3) AFTER CLOSE OUT OF CLINICAL TRIAL:
 Before a CT is closed at the site, SC have to check all documents and all the
documents have to be updated.
 On the day of close out CRA will verify all documents.
 After verification of all documents by the CRA, CRC will assist in archiving
the documents at site.
 Site has to maintain all study related records for 15 to 20 years.
 As you can see a CRC plays a vital role in managing a CT at the site level and
acts as a link between the sponsor and the Investigator Site.
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26. SPONSORS
 A sponsor is defined as “a person who takes responsibility for and initiates a
clinical investigation” is called sponsors.
 The sponsor may be an individual or a pharmaceutical company that initiates a
clinical trial for one of its products.
 The regulatory responsibilities of sponsors are found primarily in 21 CRF 312,
subpart D (Responsibilities of Sponsors and Investigators).
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27. SPONSORS ARE RESPONSIBLE FOR:
 Selecting qualified investigators.
 Providing the investigators with the information they need to conduct an
investigation properly.
 Ensuring that the investigation is conducted in accordance with the general
investigational plan and protocols contained in the IND.
 Maintaining an effective IND with respect to the investigations.
 Ensuring that the FDA and all participating investigators are promptly
informed of significant new adverse effects or risks with respect to the drug.
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28. CONTRACT RESEARCH ORGANISATIONS (CRO)
Definition :
 A person or an organization (commercial, academic, or other) contracted by
the sponsor to perform one or more of a sponsor’s trial-related duties &
functions.
 A CRO is a service organization which provides support to the
pharmaceutical industry.
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29. ROLE OF CRO’S IN CLINICAL TRIALS
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30. RESPONSIBILITIES OF CRO
 Implement systems and procedures for conduct of & assessment of safety in
clinical trials,
 Conduct CTs in accordance with the applicable regulations & guidelines,
 Abide by contract signed with the sponsor,
 Communicate concerns to the sponsor in a timely manner &
 To maintain accurate records.
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31. CONT…

32. OVERVIEW OF CLINICAL TRIAL
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33. THANK
YOU
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