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 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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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. 4

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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.

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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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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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

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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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/participants in a clinical trial;

Keeping of records is not

optional, but now represents an

obligation;

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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.

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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CONCLUSIONNowadays, 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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