Patient safety is and should be the number one priority in clinical research. Human participants in a clinical trial are necessary in order to improve and develop new therapies for certain conditions and advance the understanding of how a condition can be treated. Such medical advancements wouldn’t be possible without human subjects as participants. However, even though we all know the importance of clinical trials in the advancement of medicine, most people still have some misconceptions regarding this topic. The feeling of being treated as a ‘’guinea pig’’ and fear of potential risks and side effects are still common among patients who suffer from a certain condition. Such misinformation and misconceptions regarding clinical trials can unnecessarily prevent patients from finding a potential cure or relief, and can also decrease the number of enrolled patients in studies. In order to clarify these misunderstandings, we’ve decided to tell you everything there is to know about patient safety in clinical trials. We hope that with this information we can help you to better understand patient safety in clinical trials so that you gain more insight and start considering clinical trials as valid options that can help you improve any condition.

1. Guideline on
Patient Safety and Well-Being In
Clinical Trials

2. Introduction
Patient safety is and should be the number one priority in clinical research.
Human participants in a clinical trial are necessary in order to improve and
develop new therapies for certain conditions and advance the understanding
of how a condition can be treated. Such medical advancements wouldn’t be
possible without human subjects as participants. However, even though we all
know the importance of clinical trials in the advancement of medicine, most
people still have some misconceptions regarding this topic.
The feeling of being treated as a ‘’guinea pig’’ and fear of potential risks and
side effects are still common among patients who suffer from a certain
condition. Such misinformation and misconceptions regarding clinical trials can
unnecessarily prevent patients from finding a potential cure or relief, and can
also decrease the number of enrolled patients in studies.
In order to clarify these misunderstandings, we’ve decided to tell you
everything there is to know about patient safety in clinical trials. We hope that
with this information we can help you to better understand patient safety in
clinical trials so that you gain more insight and start considering clinical trials as
valid options that can help you improve any condition.
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3. Phase I Trials and Patient Safety
When people refer to clinical trial participants, they
refer to them as ‘’guinea pigs’’. This term is mostly
used for people who are actually healthy volunteers
that join clinical trials for a compensation. Even
though patient safety is always a priority in all
phases of clinical trials, Phase I studies have an
even greater supervision and safety measures for
patients.
The main goal of a Phase I study is to determine
the maximum tolerated dosage of a new
treatment or IP (investigational product),
before showing any intolerable side effects.
For this reason, Phase I trials require
healthy volunteers who will be closely
monitored in order to minimize any
potential risks. The enrollment of
participants in Phase I trials has no space
for errors, and the participants have to be
100% healthy. Further on we’ll see the
importance of PIs regarding this selection
of participants.
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PI Oversight and Patient Safety
When we’re talking about patient safety, the
first and most important topic of interest is
the PI oversight. The PI or the principal
investigator is a doctor with a medical
license that possesses the necessary
education, knowledge, and means to
oversee patients’ safety and well-being. PI
oversight is important for the whole study
in general, but especially when it comes to
patient care. With the proper PI oversight,
patients should be able to feel safe and
taken care of in case of any adverse events.
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PI Oversight and Patient Safety
PI oversight is especially important in Phase I
studies. As we’ve mentioned before, Phase I
trials require exceptionally healthy individuals.
However, in some cases, the patient might be
perfectly healthy on paper, but in reality, he or
she might be on the border of a condition
(higher BMI, borderline hypertension, etc.). In
this case, even though the patient might not be
diagnosed with a condition, the PI should be
the one who decides if this patient is eligible to
enter the study. This is sort of a ‘’gray area’’ in
Phase I studies.
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If the site enrolls a patient who is otherwise
healthy, but his BMI is on the border, and later that
patient develops complications related to the study
drug, then the PI will be responsible for everything
that goes wrong. If a patient looks good on paper,
and all of his/her lab values are good, that doesn’t
mean that the patient should be enrolled without a
physical examination from the PI. Unfortunately,
many PIs are sometimes busy, so the coordinators
are doing their jobs. However, coordinators are not
required to be MDs or have a medical license, so
they’re not the right person to examine patients
and determine if they’re fit to enroll the study. For
this reason, PI oversight should be extremely
important in all studies, especially Phase I.

6. Training the study staff;
Supervising the conducting
of the study
Delegating study tasks only
when appropriate;
Proper oversight of all
other third parties
involvement;
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FDA expectations from the
PI
Study Oversight
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FDA expectations from the
PI
Protecting the
Rights, Welfare,
and Safety of
Subjects
Avoid/prevent the
exposure of subjects to
unnecessary risks;
Facilitate and provide medical
care for any adverse events
that a subject might
experience during study
participation;
Provide medical care for
other non-study-related
medical problems that
might arise throughout
the duration of the study;
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8. Protecting Patient
Safety, Rights, and
Well-Being
Protocol Approval Informed Consent
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All clinical trials conducted in the U.S. have to be monitored and approved by an IRB (institutional review
board). An IRB is basically an independent board of physicians and other appropriate parties whose main
task is to ensure that a certain clinical trial is conducted in an ethical way. Even if a study is conducted
outside of the U.S., all countries have the same or similar guidelines and review boards.
An IRB is there to
monitor the whole
trial, ensure that the
risks to patients are
minimized as much
as possible, and that
the ratio between
risks and benefits is
valid.
This study protocol has to
contain all the details
regarding the way in which
researchers will conduct the
study. Once this protocol is
approved by the IRB,
researchers are obliged to
follow it. In case of any
protocol changes, the site is
obliged to report this case
to the IRB.
The informed consent is
another thing that has to be
approved by the IRB before
giving to the patients to
sign. In this case, the IRB
will check if the informed
consent contains everything
that the patients need to
know, including all potential
side effects and benefits
from the study.
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9. Following Patient Safety Throughout the Trial
In all phases of research, patients have to be
followed and monitored regularly and closely. In
order to determine their health and well-being,
they will be required to regularly come for visits in
order to check their lab results, ECG, vitals, the
possibility of any adverse events, etc. These tests
should be performed by the PI or by another
person who possesses a medical license and is
educated in such procedures.
Tests such as lab results should be read and
checked by the PI or an MD who’s trained to
read these results. A person without a
medical background can only see the more
serious ‘’flagged’’ results that are
automatically printed out. However, many
times there are some subtle increases or
decreases in lab values that a trained
physician will know how to recognize. Such
subtle changes can actually be serious and
harm a certain patient.
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Common Ethical Dilemmas
In the U.S., studies containing a placebo control group are not allowed for progressive and life-
threatening diseases such as cancer. In these cases, the control group will receive the
standard/mainstream treatment while the other group will receive the new IP (investigational product)
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In the early years, researchers
used to perform cancer studies
with placebo control groups in
the undeveloped places such as
Africa and India because there
they still didn’t have conventional
treatments for cancer. And this
practice was highly unethical!
However, nowadays these
countries have access to
conventional therapies, so this
practice is no longer allowed.
Another famous example of
unethical behavior in clinical
trials is the experiment that
occurred in the past in
Tuskegee, Alabama, U.S. In
this experiment, 400 African-
American men were denied
syphilis treatment in order
for the researchers to be
able to see how this disease
progresses.
Example #1 Example #2

11. Common Ethical Dilemmas
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After many other similar cases of abuse and unethical research behavior, many guidelines were
introduced in order to increase and ensure patient safety. Some of these guidelines that have the
greatest contribution to patient safety are:
FDA must be
informed before
a clinical trial is
started;
FDA is allowed to
inspect all records
related to clinical
research;
Drug approval will
be based not only
on efficacy but
also on safety;
Complete
authority over
‘’Investigational
New Drugs’’ (IND);
FDA has the
absolute power
to stop/dismiss
clinical trials if
necessary;
Kefauver-Harris Drug Amendments Act in 1962
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12. Common Ethical Dilemmas
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IND Regulations of 1963
Current
framework of
clinical research
was created;
Investigators to be
properly qualified,
possess the required
scientific training, and
have experience in
their therapeutic area;
All trials have to
be controlled;
Informed Consent
forms are required
to be given to all
human
subjects/participant
s in a clinical trial;
Keeping of records
is not optional, but
now represents an
obligation;
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13. Common Ethical Dilemmas
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Even though nowadays we have all these guidelines that ensure a higher level of patient safety,
there are many so-called ‘’gray areas’’ in clinical research that depend mostly on ethics and PI
oversight and opinion.
‘’GRAY AREA’’ EXAMPLE
For example, let’s say we have a patient with Alzheimer’s Disease who came to participate in a
clinical trial with a placebo control group. In this case, the IP (investigational product) is supposed
to work by slowing down or stopping the progress of the disease. However, the patient has been
placed in the placebo group. If this study goes on for 1 year, then the patient who’s given a
placebo will continue to lose his/her mental health, while patients who receive the IP will
successfully stop the progress of Alzheimer.

14. Common Ethical Dilemmas
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‘’GRAY AREA’’ EXAMPLE EXPLAINED
If you think about this case, it seems unethical that the patient has wasted a year receiving
placebos while his mental health was constantly worsening. However, since Alzheimer’s is not a
life threatening disease, trials with placebo groups are allowed in this case.
From an ethical point, this seems wrong. However, patients are informed and aware that they will
be randomized in one of the two groups - placebo or IP.
Clinical research would be impossible without these ‘’GRAY AREAS’’!

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CONCLUSION
Nowadays, the safety of patients in clinical trials is on a much higher level than it was in the past. It’s a general rule that
patients are informed in details about every detail of the trial so that they can make their own conclusion and decide if they
want to participate. Today, there are many safeguards when it comes to patient safety, such as the IRB, FDA, informed
consent forms, PI and other MDs oversight, CRAs (monitors), IRB approved protocols, etc. All of these safeguards are there to
put patient safety first!
If you’re a patient looking for information on clinical trials and patient safety, we hope we’ve managed to answer your
questions. And for all the sponsors, PIs, site owners, and coordinators - we hope that you can use this as a cautionary
warning and a guide to help you increase patient safety in your studies! The safety of patients should always be ranked the
highest, and this is your responsibility to provide, respect, and follow!
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