Clinical research,

Pharmacoepidemiology,
and Pharmacovigilance
PP 007
Semester 10 general
pharm D
Dr/ Mona Ali Saber
Clinical Pharmacy department
Faculty of Pharmacy
Minia University
 Course Contents

CLINICAL RESEARCH PHARMACOVIGILANCE ADRS REPORTING ARTIFICIAL REFERENCES

SYSTEMS INTELLIGENCE IN
CLINICAL TRIALS
What is a clinical
research

• A systematic observational and

experimental biomedical studies
performed in human subjects to test new
drugs or combination of drugs or devices
or biologics for its safety and therapeutic
uses or new approaches to surgery or
radiotherapy or procedures to improve
the diagnosis of disease and the Quality
life of the patient.
 Purpose of research

• Intended to increase knowledge about

how well a diagnostic test or treatment
works in a particular patient
population.
• To test hypothesis formulated from
observations and or intuition.
• Ultimately to understand better one's
world and make "Sense of it".
Ethical principles in clinical research
• 3 ethical principles guide clinical research:
Importance of clinical research
• New techniques for screening and diagnosing a disease.

• New drugs to market.

• New methods for surgery.

• New approach for radiation therapy.

• New combination of standard treatments.

• New techniques, such as Gene therapy.

 Types of clinical research
• Observational Studies
Observational studies are studies that aim
to identify and analyze patterns in medical data
or in biological samples, such as tissue or blood
provided by study participants.

• Clinical Trials
Clinical trials, which are also called interventional
studies, test the safety and effectiveness of medical interventions such as
medications, procedures
and tools in living people.
 Participation is always completely voluntary, and
participants can leave a study at any time for any
reason.

Clinical research studies need people of every age,

Participants in health status, race, gender, ethnicity and cultural
Clinical background to participate.

Research This will increase the chances that scientists and

clinicians will develop treatments and procedures
that are likely to be safe and work well in all people.

Potential volunteers are carefully screened to ensure

that they meet all of the requirements for any study
before they begin.
 Within the two main kinds of clinical research,
there are many types of studies. They vary based
Types of Research
on the study goals, participants and other factors.

• Biospecimen studies:

A biorepository is a facility that collects, catalogs

and stores specimens of biological material such
Studies

as blood, tissue, or cells to be used for laboratory

studies. A person’s medical information and/or
written consent to use the samples in research
may go along with the samples to be studied.
 2. Healthy Volunteers studies:
People with no known major health issues — also called
clinical research volunteers — also are needed for some
Types of Research
studies.
For new medications, it is safer and easier to start with
healthy individuals. These studies help researchers define
what is normal for such patients compared with those who
have certain illnesses or conditions.
Studies

3. Surveys:
Surveys are commonly used to study health behaviors,
practices and opinions.
 • There are several steps in place to make sure clinical
research is safe.
• First, it is regulated by the government. In addition, the
Is It Safe to institutional review board (IRB) and Human Subjects
Research Protection Program at each study location have
Participate in many safeguards built in to each study to protect the safety
and privacy of participants.
Clinical • Clinical researchers are required by law to follow the safety
rules outlined by each study’s protocol. A protocol is a
Research? detailed plan of what researchers will do in during the
study.
• In the U.S., every study site’s IRB — which is made up of
both medical experts and members of the general public —
must approve all clinical research. IRB members also
review plans for all clinical studies. And, they make sure
that research participants are protected from as much risk as
possible.
 Is It Safe to
Participate in • Many clinical research studies are also supervised by a data
Clinical and safety monitoring committee. This is a group made up
of experts in the area being studied. These biomedical
Research? professionals regularly monitor clinical studies as they
progress. If they discover or suspect any problems with a
study, they immediately stop the trial.
Key Elements of a Clinical Research
Protocol and Informed Consent
A Clinical Research Protocol is a
formal design of an experiment. It is
the plan submitted to an
Institutional Review Board for review
and to an agency for research
support.
The protocol includes a description
of the research design to be
employed, the eligibility
requirements for prospective
subjects and controls, the treatment
regimen(s), and the proposed
methods of analysis that will be
performed on the collected data.
A Clinical Research Protocol should
include the following:

1 2 3 4
1. Protocol title and 2. Name, address and 3. Site(s) where the 4. Sponsor of the
date phone number of the study will be study
principal investigator performed
and coinvestigators, if
applicable
A Clinical Research Protocol should
include the following:
• 5. Introduction: Background-Rational-Literature Review:
• Describe the background, including human subjects or animal research studies,
results and references that are revelant to the design and conduct of the study.
• Where new techniques or procedures are to be used, a description of preliminary
or early work should be provided.
• If a FDA Investigational New Drug (IND) is to be used, animal data on the drug
should be included.
• If a study is one for which a Clinical Investigator’s Brochure (CIB) is provided,
one copy of the CIB must be submitted to the IRB when the protocol is submitted
for review. A summary of the relevant features of the CIB should be included in
the protocol.
A Clinical Research Protocol should
include the following:
• 6. Research Objectives and Hypothesis: State the precise objectives
of the study in the form of a hypothesis. The protocol should be
designed to answer the questions posed by the objectives.
A Clinical Research Protocol should
include the following:
• 7. Study Design and Research Methods:
7.1. Study Design:
 Describe the involvement of human subjects including initial evaluation
procedures and screening tests, phases, procedures, and sequence of the study as
much as possible.
 Describe alternatives to experimental therapy, if they exist.
 Give detailed procedures for the treatment and dose adjustments. Describe the
randomization procedure, if applicable.
 Address the experience of the investigators if procedures are to be performed for
which the investigators have not been specifically credentialed.
A Clinical Research Protocol should
include the following:
This section should also include some or all of the following:
§ Primary and secondary endpoints
§ Design of the study (double-blind, placebo controlled, etc.)
§ Measures taken to minimize bias (randomization, blinding)
§ Study treatments or interventions
§ Expected duration of subject participation (what is done and when)
§ Stopping rules or discontinuation criteria
A Clinical Research Protocol should
include the following:
 Selection and Withdrawal of Subjects:
• Selection (Insert justification for use of special or vulnerable subject populations, if applicable)
• Inclusion Criteria
• Exclusions Criteria
• Withdrawal Criteria:
 describe the types, frequency, duration of tests, admissions, outpatient visits and procedures that a research
participant should expect during the protocol.
 Define stop points and criteria for withdrawing subjects from the study.
 In studies done with therapeutic intent, the protocol should clarify what the off-study criteria for
“deterioration” or “inadequate control” are.
 The protocol should also clearly state that voluntary withdrawal from the protocol is always an option for the
research participant.
A Clinical Research Protocol should
include the following:
Human Subject Protections: Provisions for the protection of the
subject’s privacy and confidentiality
Rationale for Subject Selection:
State the rationale for research subject selection based on a review of
gender/ethnic/race categories at risk for the disease/condition being
studied.
 Include justification for exclusions, if any.
If the protocol involves subject enrollment at multiple sites, describe
plans for ensuring appropriate IRB review and approval at each site.
A Clinical Research Protocol should
include the following:
 Evaluation of Benefits, Risks and Discomforts:
 Describe the potential benefits to subjects or to others that may reasonably be expected from the research.
 Describe any potential risks (physical, psychological, social, legal or other) and assess their likelihood.
 Describe provisions for managing subject adverse reactions.
 Where appropriate, describe alternative treatments and procedures that might be advantageous to the subjects.
 Describe the procedures for protecting against or minimizing any potential risks, such as violations of confidentiality, and assess
their likely effectiveness.
 Where appropriate, describe the risks associated with the collection, storage, and future use of samples or data.
 Where appropriate, discuss provisions for ensuring necessary medical or professional intervention in the event of adverse effects to
the subjects.
 Also where appropriate, describe the provisions for monitoring the data collected to ensure the safety of subjects.
 Discuss why the risks to subjects are reasonable in relation to the anticipated benefits and in relation to the importance of the
knowledge that may reasonably be expected to result.
A Clinical Research Protocol should
include the following:
Informed Consent and Assent Processes and Documents:
Describe the consent procedures to be followed, including the circumstances in which
consent will be sought and obtained, who will seek it, the nature of the information to be
provided to prospective subjects, and the method of documenting consent.
Children are not legally empowered to give consent, but depending on their age, they may
have the ability to give assent. Every protocol involving children should include a
discussion of how assent will be obtained.
 Documentation of informed consent (who will obtain informed consent,
provision for a witness as needed, signatures of the subject or the subject’s representative,
signature of investigator, signature of person obtaining consent, signature of witness, use of
short form if needed, providing the subject a copy of the informed consent information).
A Clinical Research Protocol should
include the following:
7.2. Compensation: if applicable, specify what compensation clinical
research subjects will receive. Compensation may be provided for
their time and inconvenience, and for their travel and escort needs
while participating in the protocol.
7.3. Efficacy Assessment: Ensuring optimal efficacy is an important
facet of patient safety during the conduct of a clinical trial, if , by
“safety,” we mean the anticipation, prevention and assessment of any
event that can have an unfavorable impact of the enrolled patients.
 7.4. Safety Assessment, including recording adverse events
A Clinical Research Protocol should
include the following:
7.5.Statistical Analysis:

Explain the precise outcomes to be measures and analyzed.

Have a data collection tool that you will use for the statistical analysis.

Describe how these results will be measured and statistically analyzed.

Describe methods used to estimate the required number of subjects.

Describe power calculations if the study involves comparisons.

A Clinical Research Protocol should
include the following:
This section should also include some or all of the following:
§ Statistical methods including interim analysis if appropriate
§ Number of subjects to be enrolled
§ Rationale for choice of sample size (power calculation and clinical justification)
§ Level of significance to be used
§ Criteria for terminating the study
§ Procedures for reporting deviations from the original plan
§ Selection of subjects for inclusion in the analysis
A Clinical Research Protocol should
include the following:
• 8. Anticipated Results and Potential Difficulties
• 9. Discussion of Next Steps
• 10.Appendices:
Supplemental material of documents such as flow diagrams or work-up
tables may be added to the protocol. A properly constructed flow diagram can
greatly clarify complex interactions.
• 11. References:
References should be used for any point that can be attributed to a specific
source. They should be sequentially numbered throughout the protocol.
Thank you for
your listening