Guideline on

Patient Safety and Well-Being In

Clinical Trials
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 wouldnt 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, weve 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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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 well see the
importance of PIs regarding this selection
of participants.
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PI Oversight and Patient

Safety
When were 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 weve 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.
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 doesnt
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 theyre not the right person to examine patients
and determine if theyre fit to enroll the study. For
this reason, PI oversight should be extremely
important in all studies, especially Phase I. 5
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FDA expectations from

the PI
Supervising the conducting
Training the study staff;
of the study

Study Oversight

Proper oversight of all

Delegating study tasks only
other third parties
when appropriate;
involvement;

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FDA expectations from

the PI

Provide medical care for Facilitate and provide medical

other non-study-related Protecting the care for any adverse events
medical problems that
might arise throughout
Rights, Welfare, that a subject might
experience during study
the duration of the study; and Safety of participation;
Subjects

Avoid/prevent the
exposure of subjects to
unnecessary risks;

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www.trialjoin.com IRB and Patient Safety

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.

The informed consent is

An IRB is there to This study protocol has to
another thing that has to be
monitor the whole contain all the details
approved by the IRB before
trial, ensure that the regarding the way in which
giving to the patients to
risks to patients are researchers will conduct
sign. In this case, the IRB
the study. Once this
minimized as much will check if the informed
protocol is approved by the
as possible, and that consent contains everything
IRB, researchers are
the ratio between that the patients need to
obliged to follow it. In case
risks and benefits is know, including all potential
of any protocol changes,
valid. side effects and benefits
the site is obliged to report
from the study.
this case to the IRB.
Protecting Protocol
Patient Safety, Approval Informed
Rights, and Well- Consent 8
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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 whos 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)

In the early years, researchers

used to perform cancer studies
with placebo control groups in
the undeveloped places such as
Example #1 Africa and India because there
they still didnt 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 Example #2
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.
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Common Ethical Dilemmas

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:

Kefauver-Harris Drug Amendments Act in 1962

1 2 3 4 5

Complete FDA has the

FDA must be FDA is allowed to Drug approval will
authority over absolute power
informed before inspect all records be based not only
Investigational to stop/dismiss
a clinical trial is related to clinical on efficacy but
New Drugs (IND); clinical trials if
started; research; also on safety;
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Common Ethical Dilemmas

IND Regulations of 1963

Investigators to be Informed Consent

Current properly qualified, forms are required Keeping of records
framework of possess the required All trials have to be to be given to all is not optional, but
clinical research scientific training, and controlled; human now represents an
was created; have experience in subjects/participant obligation;
their therapeutic s in a clinical trial;
area;

1 2 3 4 5

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Common Ethical Dilemmas

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, lets say we have a patient with Alzheimers 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 whos given a
placebo will continue to lose his/her mental health, while patients who receive the IP will
successfully stop the progress of Alzheimer.

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Common Ethical Dilemmas

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 Alzheimers 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. Its 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 youre a patient looking for information on clinical trials and patient safety, we hope weve 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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