Lecture Notes : CREDE GCP Beginner GCP Webinar Course

Sections 1 - 4
 Section 1: Clinical Research, Phases and Role Players

In this section we will explore 3 major topics:

● What is clinical research?
● The phases of clinical trials (the “clinical development pathway”)
● Role players in clinical research

Lecture Notes: Section 1

What is clinical research?

Clinical research is a wide area.
In essence, it covers any research activity in humans that is health related.
Here are a few things to consider:
The ​“clinical”​ in clinical research refers to the fact that it involves humans, as opposed to, for
example, animals. The clinical does not necessarily mean clinical activities such as medical
procedures, physical examination or vital signs. It may include those, but it’s wider than that.

GCP therefore applies to any person involved in the research process, whether you are the
one working directly with the participant, or just with their samples, or just with their data and
analysis, and everything in between.

Consider this statement:

​“All clinical trials are clinical research studies, but not all studies are clinical trials”​.
There are a variety of clinical research study designs, such as observation studies,
case-control studies, retrospective reviews, and many others.
One important type of study design is the clinical trial.

What makes a clinical trial different and why is this distinction important?
We’ll discuss this during the webinar (here’s a clue: what is an “intervention”?).

While you think about clinical trials, consider these terms:

- Randomization
the process whereby a participant is allocated by chance to one of the study groups
- Blinding
study team members and the participants don’t know into which group a participant
was allocated until the trial is over
- Bias
when things affect the outcome that shouldn’t, other than the intervention

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Case scenario: avoiding bias

You are an investigator on a clinical trial with a potential new medication for resistant
tuberculosis (MDR TB). You are personally convinced that this new medication is effective.
Perhaps unconsciously, you select participants with less severe disease and a better chance
of survival to go into the experimental arm of the trial, and others with a worse prognosis into
the control arm.
Your colleague sees a participant at a follow-up visit who was allocated to the experimental
arm. The participant complains of a mild headache. Knowing that the new medication has
previously been reported to cause terrible headaches, your colleague interprets and records
the symptom as severe, or very bad.
Another participant, knowing that she has been allocated to the control arm, thinks that the
nausea she gets after taking her pills is unimportant, and keeps it to herself.

What could go wrong with the results in these cases?

How could you design the study processes for randomization and blinding to prevent bias?

The clinical development pathway

The development pathway describes the process of testing a new intervention (e.g.
experimental drug, vaccine or device).

It classically involves clinical trials in 4 phases:

● Phase 1: “First in Human trials”
Healthy participants
Very small sample size (10-20)
Only looking to exclude major safety issues

● Phase 2: “Proof of Concept trials”

Participants with the disease, but otherwise healthy and uncomplicated
Larger but still small sample size (about 50-100)
Still testing primarily for safety only (not efficacy)
Sometimes additional secondary data is collected for dosing,
pharmacokinetics and & immunology

● Phase 3: “Registration trials”

Participants with the disease, often including further advanced disease or with
co-morbidities
Large sample size (often 1000’s over many sites, often global)
Safety + Efficacy
(for the first time asking “does it work” in addition to “is it safe?”)

AT THIS POINT THE SPONSOR APPLIES FOR REGISTRATION FOR THE PRODUCT TO
BE USED NON- EXPERIMENTALLY e.g. prescribed in clinical practice

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 ● Phase 4: “Post-registration trials”
When the product is being used in a new or different way e.g. new study
population, in new combinations, for extended monitoring, or usability
Sample size & participants would depend on the reason for doing the trial

All pharmaceutical medicines or vaccines on the market need to undergo a version of this
process. This may take years and is a very expensive pathway.
What is the success rate i.e. of every 10 products that enter phase 1 trials, how many end up
successfully on the market?

Role players in clinical research (who does what?)

During the webinar, we will discuss each role player in more detail.
For now, this is a very quick summary:

The ​SPONSOR ​sets up the study, pays for it, appoints the researcher, writes the protocol,
oversees the process, and provides the study infrastructure e.g. database.

The ​RESEARCH TEAM​, led by the Principal Investigator (PI), conducts the study.

MONITORS ​and ​AUDITORS a ​ re appointed by the sponsor to link the sponsor and the
research team and to monitor the conduct of the research by the research team.

An​ ETHICS COMMITTEE​ represents the interests of the research participants and oversees
the rights, safety and well-being of participants by approving and monitoring research
activities and documentation.

SOUTH AFRICAN HEALTH PRODUCTS REGULATORY AUTHORITY (SAHPRA)​ is

responsible for all health products in South Africa, including approval and oversight of those
being tested in humans.

SAHPRA appoints ​INSPECTORS ​to check compliance by the research team and sponsor,
to the protocol and GCP guidelines.

COMMUNITY ADVISORY BOARDS​ represent the community and advise the research team
on community issues, opinions and preferences.

The SOUTH AFRICAN NATIONAL CLINICAL TRIALS REGISTER (SANCTR) is a database,

accessible by the public, that lists all ongoing clinical trials in the country. Registration on
SANCTR is a requirement for clinical trials before they start.

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Consider each of scenarios/questions:
● A researcher from a university gets a funding grant from a funder who is not a
sponsor (they only give the money and don’t perform any other sponsor roles).
Who takes on the sponsor role?
● What is a Clinical Research Organization (CRO)
(hint: they often employ monitors)?
● From whom does a researcher need approval for each of these:
- clinical trial with an investigational product like a new medication or vaccine?
- a non-interventional study e.g. observational study
● Why is it a good idea for all clinical trials to pre-register on a clinical trial register
like SANCTR? (what are we trying to prevent and how are we being transparent?)

“All study material is the copyright of CREDE (Pty) Ltd and may not be
reproduced or used without written permission”

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 Section 2: History, Guidelines and Research Steps

In this section we will explore 3 major topics:

● Some well-known historical incidents where research was not done ethically
● Important guidelines that guide clinical research
● Steps and flow in clinical research studies

Lecture Notes: Section 2

Historical incidents and guidelines

Sadly, there are a number of examples from history that demonstrate what can go wrong
when clinical research is not done properly.
We’ll just look at a few of the classic examples:

The Nuremberg trials and the Nuremberg Code

Thalidomide disaster and the Declaration of Helsinki
Tuskegee Syphilis Study and the Belmont Report

Finally, we’ll end the subsection by summarizing how GCP came about.

The ​Nuremberg Code​ was published in 1947 after the Nuremberg war trials.
Nazi physicians were put on trial after the second world war for medical experiments that
were performed on prisoners in the concentration camps.
The Nuremberg Code was an attempt to prevent these atrocities from recurring and contains
10 items, amongst which the importance of informed consent, the right to withdraw, and
consideration of risk versus benefit.

This link to a NEJM article contains the 10 items and some more detail:
Fifty Years Later: The Significance of the Nuremberg Code

Please see the case scenario on the next page

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Case Scenario:
What is ​Risk versus Benefit​ in clinical research?
What possible risks are there for participants? What are the possible benefits?
Who gets this benefit (e.g. individual versus community)?

Scenario 1:
A clinical trial is planned in participants with tuberculosis (TB) with a new combination of
drugs.
Scenario 2:
A simple non-interventional study is planned by a psychology Masters’ student, who is also a
teacher’s assistant on some undergraduate courses. She will administer a questionnaire to a
sample of university students recording negative life experiences over the previous year.

Thalidomide ​was a drug used in the 1950’s and 1960’s for nausea in pregnancy. However,
even though the drug was used extensively for many years, there were very little data for it’s
safety (certainly nothing like phase 1 to 4 that we have these days) and no testing in
pregnant women. It turns out that Thalidomide in early pregnancy causes serious birth
defects like underdeveloped limbs.

Here’s an excellent article and video from the New York Times:
The Death and Afterlife of Thalidomide

The Thalidomide disaster was a catalyst for the ​Declaration of Helsinki​ - one of our
cornerstone documents.
We have provided you with your copy of the Declaration of Helsinki as part of the resources.
Please read through the principles before the webinar.

Some important points about the declaration:

● It is published by the ​World Medical Association (WMA)
● It’s first version was formulated in 1964, and there have been a number of
subsequent versions, of which the latest is the 2013 version
● In the declaration there are 37 principles, covering all the major ethical points for
clinical research e.g. risk versus benefit, the role of ethics committees, informed
consent, the use of placebos, post-trial access, and a number of others

Please see the case scenario on the next page.

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Case Scenario:
The Declaration of Helsinki recommends against using placebos as controls in clinical trials
under certain conditions. When would it be unethical to use a placebo in participants in a
clinical trial?
It also recommends that sponsors apply “post-trial access”. What does that mean?

A sponsor contracts a site in South Africa to perform a clinical trial on a new

anti-hypertensive (medication for high blood pressure). They design the protocol with 3 study
groups. Participants with uncontrolled high blood pressure will be recruited and randomized
into a group that gets the new experimental drug, or a group that gets standard of care
treatment (the “usual treatment”), or a group that gets placebo (no active treatment).

Any issues here?

The trial ends with a favourable outcome result - the new medication works well. For the 2
years that participants in the experimental arm were on the new fancy medication, they did
very well and their disease was well controlled. They did have some mild and moderate
adverse events (side effects) though.
However, the trial is now over, so the sponsor thanks them and refers them back to their old
clinic to go back onto their old medication they used before.

Does this sound right?

The ​Tuskegee syphilis study​ was a study conducted on poor, black American males with
syphilis from 1932 to 1972 who lived in the small town of Tuskegee in the USA. They were
all already infected with the sexually transmitted disease syphilis.
At the start of the study no treatment for syphilis existed, and the plan was to follow the
participants over their lifetimes to observe the natural history of the disease over time.
Without treatment syphilis worsens over many years, causing debilitating symptoms like
neurological damage, dementia and early death.

Here’s the thing though: a treatment, in the form of penicillin, became available in the 1940s
- but these participants were never given the opportunity to receive that treatment.
In fact, the treatment was actively concealed from them so that the study could continue into
the effects of syphilis - and so that autopsies could later be performed on their bodies. So for
decades they continued to be followed up with their disease as part of the study, while they
could actually have been cured.
When the study was exposed in a headline article in the New York Times, there was an
uproar in the USA. A commission was set up to lay the foundation for legislation and
measures to prevent such incidents.

Here’s a useful video and interview with the journalist who exposed the study in 1972:
The unknowns about the Tuskegee syphilis study

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An important part of the response to the Tuskegee incident was the publication of the
so-called ​Belmont report​.

The Belmont Report is well-known for its 3 ethical principles for clinical research:
1. Respect for persons​ (autonomy or agency) which requires researchers to respect
and protect the rights and decision-making capacity of participants.
2. Beneficence​ means that everything we do is in the best interests of the participant.
Non-malificence​ means we minimize and manage the risks. So we maximize benefits
and minimize risks.
3. Justice ​- the fair and equal distribution of benefits and risks. The communities or
individuals that take on the risk should be the ones benefiting from the research.

Case scenario: ​What do you think about this situation?

A sponsor is eager to do a clinical trial in South Africa on their expensive new drug for
Yellow Mountain Spotted Fever. This illness is common in certain areas of the USA, but is
rare in SA.
Costs will be significantly less if they do it in SA because of the favourable Rand-dollar
exchange rate.

So what about Good Clinical Practice (GCP)?

There are lots of technicalities we could discuss on how GCP came about and how the
guidelines are structured.
However, here is a oversimplified summary:
● In the 1990s the clinical research industry had a problem. Different countries or
regions had their own guidelines and policies for the conduct of studies and trials.
Although there was overlap between the guidelines it was becoming challenging to
perform the same study in different locations, especially global multi-site trials,
because the sponsor needed to comply to each separate regulation
● There was a recognized need for a common or harmonized guideline
● The thinking was: “we need a common rule book - wherever in the world where
research is conducted, everyone uses the same set of rules”
● This initiative was initiated in 1990 with the first meeting of industry representatives
from the USA, European Union and Japan in Brussels, and over the next few years
led to the development of a set of international guidelines
● These guidelines are referred to in shorthand as “ICH GCP”
● ICH​ (follow the link for more information) - in a nutshell - is the organization
responsible for drawing up these guidelines
● The latest version of ICH GCP is 2016, R2

As part of your resource package, you have your own copy of ICH GCP (Topic E6).

Apart from ICH GCP, in South Africa, we also have a SA version,

based on ICH GCP - “SA GCP”

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SA GCP is legally binding in South Africa
The current version is SA GCP 3rd Edition, 2020

We have provided you your copy of SA GCP as part of your resources.

During the webinar, we will discuss some differences between ICH and SA GCP.

Consider each of scenarios/questions:

There is much focus in the SA GCP guidelines on the relevance and appropriateness of
clinical research being conducted in South Africa and local involvement in those studies.

● What studies or clinical trials would be most appropriate for SA?

● How would you ensure that the “control” and accountability of the research is in SA
and not remotely from outside the country?
● Why are a local set of guidelines necessary or useful?

The flow and steps of a clinical research study

These are the typical steps in the life cycle of a study or clinical trial:
1. Formulate the ​research question
2. Prepare a summary ​proposal
3. Find ​funding​ and put together the ​team
4. Write the ​protocol
5. Seek ​approval
6. Conduct​ the study & ​collect​ data
7. Analyse​ the data
8. Prepare the ​study report

During the conduct of the study, a number of processes follow each other (the typical steps
to any research study):
1. Recruitment​ (the process of identifying and approaching potential participants)
2. Informed consent
3. Screening​ (the process of determining whether a potential participant is eligible
according to inclusion and exclusion criteria in the protocol) and ​enrolment
(participant now becomes part of the study)
4. Conduct​ of the study and ​data collection
5. Close-out ​(the last visit on the last participant) and ​data analysis
6. Compile a ​study report

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Case scenario: ​What information are we allowed to gather and what procedures are we
allowed to do on potential participants before they undergo the informed consent?

You are part of a team conducting research into pregnant women.

The best recruitment strategy, you determine, is to go to ante-natal clinics.
You arrange with the sister-in-charge for you to give an introductory talk in the waiting room
where the women are waiting for their appointment, during which you tell them about the
study.
One of the exclusion criteria is being HIV positive.
Consider which of these scenarios is ethically acceptable:

a) In order to avoid doing unnecessary consenting, you ask the sister-in-charge, who is a
friend of yours, if you can page through the clinical records in her office, so that you only
have to approach the women who are HIV negative for the full informed consent

b) After the introductory talk, one of the women comes to you in private. She says she just
wants to check that she understands. “I’m HIV positive” she says, “does this mean I can’t
take part?”. You confirm her understanding.

“All study material is the copyright of CREDE (Pty) Ltd and may not be
reproduced or used without written permission”

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 Lecture Notes Section 3: Investigator Responsibilities

SA GCP section 5 and ICH GCP section 4 discusses the responsibilities of the
Investigator. In this section we will list those responsibilities, and look at some of them in
more detail. In particular, we will be dealing with:
● Delegation and supervision by the Principal Investigator (PI)
● Good Documentation Practice (GDP)
● Accountability of the Investigational Product (IP)
Please refer to:
● SA GCP section 5 (the equivalent is section 4 in ICH GCP)
● Case scenarios and questions within the notes below

The responsibilities of the investigator listed in SA GCP and ICH GCP include:
● Demonstrating that adequate qualifications and agreements are in place
● Providing adequate resources for the study to be conducted
● Medical care of clinical trial participants
● Informed consent
● Care and accountability of the Investigational Product
● Compliance with the protocol and with monitoring and auditing
● Data management and good documentation practice
● Safety reporting
● Providing progress reports and disseminating study results

Delegation and supervision by the PI

First, who is the Principal Investigator (PI)?
SA GCP defines this person as: “…usually, but not limited to, a medical doctor with appropriate
qualifications to undertake the study, who has entered an agreement with a sponsor to conduct
a clinical trial. She/he is the person responsible for the conduct of the clinical trial at the trial
site/s.”

In simple terms, the buck stops with the PI.

There is a research team, with people fulfilling different roles, but there is one PI who is
responsible and accountable for the team and everything it does.

Some terminology:
When I ask you who is the “investigator”, who do you think of?
What is the difference between the PI, a sub-investigator, site investigator, investigator, and
co-investigator?

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GCP has lots to say about the importance of ​delegation & supervision ​by the PI within the team.

Supervision:​ “…individual or party to whom the investigator delegates trial-related duties and
functions …”
Delegation: ​“…should ensure this individual or party is qualified to perform those trial-related
duties and functions and should implement procedures to ensure the integrity of the trial-related
duties and functions performed and any data generated.”

Case scenario: the absent PI

Dr X is the head of the department. He’s a really important person and is super busy.
His name is on the protocol, he gets to go to all the fancy conferences, and of course his name
is on all the papers.
But…you never see him around. He’s just too busy with all his other stuff. If you want to know
what he looks like, you need to go look at his bio picture on the website!
Is that ok?

Not only does the PI need to be involved, we need to be able to demonstrate to a sponsor,
monitor, auditor, inspector and ethics committee that adequate delegation and supervision has
taken place.

Case scenario: demonstrating delegation and supervision

You are the study coordinator and your study is about to be audited. You have been told about
a trend lately for findings such as : “…lack of documented evidence for PI delegation and
supervision…”
What documentation can you provide to the auditor to prove that your PI knows what’s going on
in the study and is adequately involved?

During the webinar, we will look at something called the ​Delegation of Authority Log​.

If you are the PI, before you sign someone onto your log, what would you like to know about
that person?
GCP refers to 3 competencies:
● Education - if you need a qualification to fulfil your role
● Training - protocol training, GCP training, protocol on SOPs etc.
● Experience - relevant to your role and the area of study
Traditionally, the types of skills that the PI and everyone on the team need to have, are divided into:
● Technical skills - skills and techniques
● Humanistic skills - how we work with people, our manner with participants and team
members, ethics etc.

What documentation and evidence can we provide to demonstrate each of these competencies
and skills?

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Data management and Good Documentation Practice
Data management refers to the entire process of collecting data, storing it, working with it,
entering data onto the database and maintaining the data’s accuracy and integrity.
How we work with our data and documentation is very important because research whose data
can’t be trusted is unethical research, don’t you think?

Our “source data” are very important to us. Why?

But what are source data and source documentation?

“Original documents, data, and records (e.g. hospital records, clinical and office charts,
laboratory notes memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing
records, recorded data from automated instruments, copies or transcriptions certified after
verification as being accurate copies… “
SA GCP: Glossary,p.70/ ICH GCP 1.52

Here’s a quick way of thinking about what source is: “​the first place where we record data or
information​.”

We’ll look at some more examples of source data and source documentation during the
webinar, and the difference between source documents and a Case Report Form (CRF).

Definition of CRF: “A printed, optical, or electronic document designed to record all the protocol
required information to be reported to the sponsor on each trial participant”.
SA GCP Glossary,p.66/ ICH GCP 1.11

GCP has some guidance on how we work with our source documentation, the so-called ALCOA
CCEA principles.

A - Attributable: we are able to link an entry in the source to a person (who made the entry)

L - Legible: needs to be readable and clear

C - Contemporaneous : made in real time

O - Original : not a copy, true source (first entry)

A - Accurate: a true reflection of the data collected

C- Complete: no open spaces or left out information

C- Consistent: tells a story that makes sense

E- Enduring:lasts as long as it needs to

A- Available: easily retrievable to work with and review

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Case scenario: following data principles
You are part of the study management team. The study is recording stressful life events and
investigating a hypothetical link to biochemical and hormonal markers. Team members will go
out to participants’ homes, and administer standardised questionnaires. We will draw blood from
participants and the specimens are then transported to the research laboratory for processing.
Your role is to set up the documentation and data management system.
Consider this:
- where and how will you store participant folders?
- how will you transport them, how will you know which team member has taken which folders?
- how will you maintain confidentiality?

In practice how will you do the following?

- how will you know which team member made each entry (attribution)?
- how could you design your source to promote legibility and completion of documents at the
time of data collection?
- let’s say you need to make copies of the ID document. What process will you follow to show
that the copies are true reflections of the original?
- what else?

We also need to think about the correct procedure for correcting our errors, things like the
format of dates, and other best practices. More about this on the webinar.

Accountability of the Investigational Product

Put simplistically, the Investigational Product (IP) is the experimental medicine, vaccine or
device that we are testing.
One of the responsibilities of the PI, is accountability of the IP.
To fulfil this responsibility, the PI often delegates this responsibility to a pharmacist on a clinical
trial.
Some of these roles include:
● Stock control e.g. knowing exactly how much medication we have received, used,
discarded or returned
● Accountability e.g. logs to demonstrate how much product we dispensed to each
participant and on what date
● Storage - temperature control, temperature logs, fridges, back up plans for power cuts
etc.

“All study material is the copyright of CREDE (Pty) Ltd and may not be
reproduced or used without written permission”

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 Section 4: Informed Consent and Safety Reporting

Continuing with the discussion of the responsibilities of the investigator, this section examines 2
of those that are very important:
● Informed consent (IC)
● Safety reporting and adverse events
Please refer to:
● Lecture notes below
● SA GCP sections 2.5, 5.9

Informed Consent
Informed consent (IC) is a core responsibility of the research team.
Even if you're not the one taking the actual consent, whatever your role you do fulfil, must be
covered by consent in some way.
Here are some things to consider about informed consent in clinical research:
● It is never implicit (in other words just implied) - it is explicit and obvious
● It is not just verbal - it is always written
An audit trail is essential when it comes to IC - both the actual signed document, but also good
notes in the source documentation around the process.

There are 5 categories of issues to consider:

1. Information ​shared with the participant
2. Facilitating ​understanding ​by the participant
3. Competency ​to give consent
4. Procedural ​issues e.g. where to sign, what to do in the case of an illiterate participant
5. Factors that can influence our participant’s ability to make a proper choice: ​“coercion”
(something bad will happen to you if you don’t take part) ​vs ​“undue influence” (an offer
they can’t refuse)

Please see case scenarios on the next page

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Case scenario (1-6):
You have been delegated to take informed consent from a study involving children, adolescents
and adults. The study is a clinical trial testing a new combination of drugs to treat TB.

Scenario 1:​ you are taking consent from a 16yr old potential participant. Her mother
accompanies her to the site. Who signs the consent? What is assent?
Scenario 2:​ your adult participant speaks Xhosa at home. Your printer is broken, so you couldn’t
print the Xhosa consent forms. But you have the English version, and that’s ok because
everyone speaks some English, don't they?
Scenario 3: ​Your participant is 8 years old. Her parents aren’t around any more, and she’s
grown up in the household of her grandma. Can grandma sign consent?
Scenario 4: ​your participant can’t read or write. What do we do now?
Scenario 5:​ your potential participant walks into the consent session and says to you: “whatever,
you don’t need to talk to me, as long as I get my money by the end of the visit today I’m happy,
where do I sign?”
Scenario 6:​ Your adult participant has TB and needs life-saving treatment. You inform her that
she has a choice not to take part, but do point out to her that the local clinic is under-staffed and
doesn’t have medication in stock, and so she would probably not get proper treatment there.

We’ll discuss some of these issues on the webinar.

For now, consider these highlights:
● There are some things we have to discuss with our participants. There’s a list of these
required items in GCP (see page 25 of SA GCP).
● GCP requires us to facilitate understanding through ample time, opportunity, by using
simplified language and the preferred language of the participant.
● Legal age for consent in South Africa is 18 in clinical research. Even if someone is above
the age of 18 some things might make them unable to give legal consent e.g. intoxicated,
in a coma (what else?).
● When the participant is unable to give legal consent, he or she must still give assent, and
someone else gives consent on their behalf.
● On the consent form (called the “ICF”), there must be a written name, date and signature
of the person giving consent/ assent, as well as the person taking the consent.
● When our participant is illiterate (can’t read or write) GCP requires the use of an impartial
witness and a thumbprint.
● When money or an equivalent is given to a potential participant (or any other benefit) the
value must be appropriate so that it isn’t an undue influence (an offer they can’t refuse).

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The TIE principle determines an appropriate value of participant reimbursement, and is based
on:

T- ​Time ​spent by the participant on site e.g. a short hour long visit versus the entire day
I- ​Inconvenience s​ uffered by a participant e.g. consider the difference between a simple
questionnaire and an invasive procedure
E- ​Expenses ​e.g. transport money, money for food

For clinical trials in SA, SAHPRA has a guideline for the minimum amount that should be given
to participants per study visit.
Do you know what that amount is?

Is this difference in terminology important: payment, incentive and reimbursement?

Safety reporting
In clinical trials, reporting of adverse events becomes critically important.
Why? Well, obviously for the health safety of our participant, but also because this becomes
important data on the safety profile of our intervention, doesn’t it?
The sponsor and the PI (and therefore the entire research team) need to put systems in place to
detect, manage and report adverse events.

What is an adverse event (AE)? Here’s the definition from SA GCP:

“An untoward medical occurrence in a clinical investigation participant administered a product
which does not necessarily have a causal relationship to the product”

Untoward: “unintended and unfavourable” (we didn’t set out for this to happen and it’s not a nice
thing)
Medical occurrence: any health related event e.g. symptom, physical sign, abnormal lab result
Causal relationship: one thing causes another, i.e. the AE is caused by the intervention

Case scenario: adverse event

Your participant in a preventative vaccine trial received her experimental vaccine 2 days ago.
She is a passenger in a car accident, breaks her femur (thigh-bone) and is admitted to hospital
for surgery. This is obviously not related to the vaccine, so we don’t need to report this, do we?
If this were not a car accident and something benign like an ingrown toenail, would the situation
be any different?
Is there something else we need to do in this case or can we just record the AE in our source
and in the database?

CREDE GCP Beginner Webinar lecture notes Page 3 of 4

Some adverse events (AEs) are “special” because they are “serious”.
That’s why we call them “Serious Adverse Events” (SAEs).

What makes an AE a SAE? GCP mentions 6 things:

1. Death
2. Life-threatening
3. Hospitalization or prolongation of hospitalization
4. Significant disability or incapacity
5. Birth defect or congenital abnormality
6. Any other serious medical event

What do we need to do differently for SAEs than non-serious AEs? (hint: what is “expedited
reporting” and what is an SAE report?)
According to SA GCP, we need to report the SAE urgently, at least within the time frame
specified in the protocol (which is often in the vicinity of 1 day).

Some SAEs are even more special, and we call them “SUSARs”
What does SUSAR stand for?

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CREDE GCP Beginner Webinar lecture notes Page 4 of 4