Ultimate Guide to Clinical Trials

Clinical trials are an important part of the medical research and development pipeline.

Here’s what you need to know about the role they play in advancing treatment and cures for a number of diseases and conditions.

What are Clinical Trials?

By definition, clinical research is medical research that involves people. It is broken into two categories.

Observational studies observe people in natural settings. Researchers put volunteers into groups according the broad characteristics dictated by the study, create a baseline, and then compare changes over a period of time.

Data may be collected through questionnaires, medical exams or tests. After the information is analyzed, it may lead to the other form of clinical research which are clinical trials.

Clinical trials are designed to study people and how they respond to controlled medical, surgical or behavioral interventions.

Clinical trial administrators can test new drugs or medical devices this way and then evaluate the results to determine effectiveness and safety.

This may be used to find new treatments or to improve upon existing treatments, as well as determining if there are any negative or harmful side effects.

Clinical trials are also used to find, diagnose and treat diseases as early as possible. This way, more effective countermeasures can be implemented that have a better chance of mitigating or curing a patient.

While some clinical trials attempt to identify diseases and conditions even before there may be noticeable symptoms, other trials are activated to help people with existing life-threatening or chronic conditions to lead better lives.

Some examples of what clinical trials may encompass can include:

• New drugs not yet approved by the U.S. Food and Drug Administration (FDA)
• New uses for drugs already approved by the FDA
• New ways to give drugs, such as in pill, liquid or intravenous form
• Use of alternative medicines, such as herbs and vitamins
• New tests to find and track disease
• Drugs or procedures that relieve symptoms of diseases and illnesses

Before a clinical trial can proceed, the FDA must review and approve trial protocols.

Laboratory tests and studies are often implemented first, many times on animals, to test a potential therapy’s safety, benefits and outcomes.

If the initial studies can pass muster in this environment, then approval is often granted for testing in humans.

Trial teams include a principal investigator who is in charge of the trial. He or she is an expert in what the clinical trial is all about.

For example, a leading oncologist would be a principal investigator for a clinical trial on cancer treatment or medications.

They are the equivalent of a CEO and will choose the research team, oversee the design of the trial and implement the study.

Other scientists who join the research team are known as investigators.

Because clinical trials can be lengthy and expensive, they must have sponsors before moving forward.

Sometimes these are pharmaceutical companies but many times government agencies or non-profit organizations are sponsors as well.

They will fund the clinical trial after they review and approve the proposed trial format, goals and hoped for outcomes.

An Institutional Review Board (IRB) must also approve the trial as well ¹. The IRB typically consists of five members who are chosen by the health care center where patients will be enrolled in the trial.

Part of the IRB’s oversight is to ensure that the rights and welfare of the participating patients are protected. After the clinical trial starts, the IRB will also review progress of the trial at regular intervals as well.

In many cases, Data and Safety Monitoring Boards (DSMB) also oversee patient safety once the trial has started.

They are comprised of professionals who are experts at administering clinical trials and will also oversee the data and the effectiveness of the trial while it is in progress.

The Benefits and Risks of Clinical Trials

Each clinical trial has different benefits and risks for patients, depending the unique circumstances of each trial and how it is designed. But in general, clinical trials share several of the same potential positives and negatives.

The Benefits ²

• You may have access to the most current care or treatment available for your condition.
• You will be treated by experts
• Researchers will generally provide you with more frequent medical care and health check-ups as part of your treatment.
• The results of your treatment will be monitored and tracked closely.
• You may be able to play a more active role in your own health care.
• You will have the opportunity to help others who may be suffering from the same condition as you.
• You may have better and broader access to support groups and information.
• You may be compensated for your participation.

The Risks/Downsides ³

• There may be unknown or serious side effects from testing out a new treatment.
• The treatment you receive may not be as effective as what you are currently getting or what is currently available on the market.
• You will be monitored more closely which will be more of an imposition for you, especially where more paperwork and more trips to your test side are required.
• You may not be part of the treatment or experimental group that gets the new treatment. Instead, you may be part of the control group, which means you get the standard treatment or a no-treatment placebo.

Clinical trials vs. clinical studies

There are several important differences between clinical trials and clinical studies. There are two main types of clinical studies.

Observational studies do not test new potential treatments. Instead, they are used to develop new ideas about how a disease or a condition might best be treated.

Observational studies are conducted many times after a drug has been approved by the FDA as part of the requirement that a pharmaceutical company continues to monitor the safety and effectiveness of the drug in question.

They often take less time and a patient can be enrolled in more than one observational study at the same time because these types of clinical studies do not involve any changes to a treatment plan.

Researchers observe participants on their current treatment plan and track health outcomes through exams and questionnaires.

Clinical trials are also known as interventional clinical studies in many cases. An interventional study refers specifically to a clinical trial in which researchers are testing a treatment method.

This treatment method can range from testing new drugs, medical devices or lifestyle changes, such as smoking cessation or changing exercise habits.

Participants can receive one or more of the treatments that are interventions, or they can receive a placebo, which has no treatment value and is used as a comparative baseline.

Under these two types of clinical studies, there are many sub-types and they are not always mutually exclusive. For example, a behavioral study could be observational or interventional.

Behavioral studies are designed to identify and understand how factors, such as self-management, mental health and social support are associated with health outcomes.

Researchers can observe how the behavior of people with a certain disease affects their health in an observational study.

They can also conduct an interventional behavioral trial to see if a change in behavior can improve the health of people with the same disease.

Why Clinical Trials are Important

Clinical trials are important and patients choose to participate in them for a number of reasons.

The most obvious of these is that clinical trials are a critical component of advancing treatments and cures for thousands of diseases and conditions.

People choose to participate because their current treatments are not working and they want to explore alternatives.

By being part of a clinical trial, participants may find out about new treatments before they are widely available.

In addition to finding cures and advancements on a global scale, for diseases that run in families, a patient may want to help find a treatment that lessens a condition in their own family.

When patients participate, they also become partners to the scientific community in discoveries that could help thousands of people now and in future generations.

Major breakthroughs are not possible without the assistance of clinical trial participants.

Clinical trials are often long and arduous as well as being expensive. Testing and trials often fail, so the need for people to step up is critical to advancing cures.

In fact, one of the biggest challenges faced by clinical trial administrators is finding enough qualified participants to advance the science.

For example, because there are only around 30,000 people with cystic fibrosis in the United States, there is a limited pool of people to draw upon for a clinical trial.

The FDA requires stringent safety protocols are met and that the efficacy is tested extensively on a large group of patients prior to approval.

This is especially daunting, especially in the treatment of cancer where there are more children in clinical trials than adults.

More than 60% of children with cancer join a clinical trial, and 75% survive for a long time after cancer ⁴.

Less than 5% of adults join a cancer clinical trial and about 50% of adults survive a long time after cancer ⁵.

The Four Phases of Clinical Trials and how They're Defined

The FDA and its corollary agencies in foreign countries require that clinical trials be conducted in a series of phases:

Phase I trials test a potential therapy, procedure or drug for the first time in human beings. In this Phase, the most important goal is to establish that a potential new treatment is safe for humans.

As a result, Phase I trials are typically conducted in very small groups of people, normally anywhere from 20 to 80 people.

Phase I research yields important information on side effects, appropriate dosage levels, and the most effective method of delivery, such as by mouth, injection or some other way.

Phase II trials expand to a larger number of participants that number anywhere from 100 to 300 patients ⁶.

The goal of Phase II is to more comprehensively evaluate a treatment’s safety and effectiveness in a larger sample group.

Phase III trials confirm a therapy’s effectiveness, monitors side effects and compares it against current standard treatments.

This is done in a large group of patients that can number anywhere from 1,000 to 3,000 participants ⁷.

Phase III trials last longer, are usually conducted at multiple centers and evaluate whether a treatment will benefit patients and if the benefits associated with a therapy outweigh the risks.

Phase IV trials are conducted after a treatment has received FDA approval and been brought to market. These trials help further evaluate long-term side effects and potential new uses for other conditions.

What is “Randomization”?

If you participate in a clinical trial, you will hear the term “randomization.” This simply means that administrators are assigning people in the trial into different groups.

Doctors use a computer program to do this because it keeps the research team’s opinions from affecting who gets which treatment.

Phase III clinical trials are typically very large and can take many years.

Through randomization, several thousand volunteers can be enrolled and need to include men, women, and people of all ages and racial and ethnic groups.

This helps doctors learn how the treatment works in many different people.

If a phase III clinical trial shows that the treatment works well for a specific condition, say cancer, doctors might begin using it with people outside of the clinical trial.

If they learn that a certain amount of exercise helps make cancer less likely, they publish a report to share the information with other doctors.

How Long Do Clinical Trials Last?

It varies widely from trial to trial. Sometimes, it will be a matter of months. Other trials could last for years, depending on the nature and scope of what is being studied.

Participants are told how long the study will last before they enroll in a trial and this is one of the important questions you need to make sure you ask.

Take a look at this example of one trial process conducted by the Cystic Fibrosis Foundation to get an idea of what one trial timetable might look like ⁸.

Where Are Clinical Trials Conducted?

Clinical studies can take place in many locations, including hospitals, universities, doctors' offices, and community clinics.

In some cases, clinical trials may take the form of survey that can be completed online.

They may not require a physical visit to an office or medical facility. The locations and the number of onsite locations are always discussed as part of the informed consent process.

Can Volunteers Leave a Clinical Trial After Joining?

Yes. If you find that a clinical trial is not suitable after enrolling, you are free to exit the trial at any time.

To withdraw from a trial, a volunteer should immediately inform the trial coordinator of this decision and will need to follow specific protocols to officially withdraw.

Does it Cost to Participate in a Trial? Can I get Paid to Participate?

It depends. Every trial is different in this regard. Compensation for volunteers will vary based on a number of practical and ethical considerations.

Some trials may reimburse volunteers for expenses related to their participation or even offer some compensation to volunteers for participating.

Those trials that require significant travel or an overnight stay may cover the associated expenses.

This is another item that should be discussed up front as part of the informed consent process.

Regulation of Clinical Trials

The U.S. Food and Drug Administration requires that all clinical trials maintain a strict adherence to established protocols.

This includes participants having a discussion and signing an informed consent document at the beginning of the trial.

The informed consent means that everything about the trial has been explained to you and that you have had all of your questions answered prior to agreeing to participate.

The informed consent form will include information about the specific trial you are considering, including the trial's purpose, how long it will last, and the responsibilities of participants.

It will also cover the potential risks and benefits.

Child under 18 must give their own approval to participate in a trial, but parents or legal guardians will also need to grant permission as well.

This allows children and adolescents to play a decision-making role in their health care.

Informed consent continues through the trial as new information becomes available or changes are made in the trial.

If this happens, you will be asked to sign a new informed consent form.

It is critical to understand that an informed consent is not a contract between you and the administrator.

If you do not feel comfortable with the trial, you can stop participating at any time.

An informed consent form is not a contract. You can stop participating in a clinical trial at any time.

If you decide that a particular trial is not a good fit for you, your decision will not affect the care you receive.

In addition to informed consent, Congress has passed laws to protect study participants.

Today, every clinical investigator is required to monitor and make sure that every participant is safe.

Every clinical trial also follows a careful study plan or protocol that describes what the researchers will do.

The head researcher is responsible for making sure that the protocol is followed.

Each study site must also include an Institutional Review Board that is comprised of doctors, scientists, and lay people who ensure that study participants are not exposed to unnecessary risks.

Many clinical trials are closely supervised by a Data and Safety Monitoring Committee that is made up of experts who periodically look at the results of the study as it is in progress.

Where to Find a Clinical Trial That’s Right for You

For good overview information, consider the following resources:

ClinicalTrials.gov
www.clinicaltrials.gov

U.S. Food and Drug Administration
1-888-463-6332
[email protected]
www.fda.gov

There are also several specific ways to find a clinical trial that is right for you:

• One of the most obvious is to talk to your doctor or your health insurance provider.
• Contact various pharmaceutical companies.
• You can also sign up for a registry that will connect you to possible trials in your immediate geographic area.
• Search the ClinicalTrials.gov database which lists publicly and privately supported clinical trials. The National Library of Medicine at the National Institutes of Health (NIH) maintains the website and has information on trials in all 50 states and several countries.
• Center for Information and Study on Clinical Research Participation (CISCRP). The staff at CISCRP will conduct free clinical trial searches.
• CenterWatch. This organization provides information on clinical trials. It includes a database with thousands of open clinical trials.
• World Health Organization (WHO) International Clinical Trials Registry Platform. The WHO coordinates health matters within the United Nations. This search portal gathers clinical trial information from many countries’ registries.
• EmergingMed Clinical Trial Navigator Service. EmergingMed's online service identifies clinical trial options. These options are based on a person's diagnosis, stage, and treatment history. Upon request, clinical trial specialists provide telephone support.

Cancer.Net also lists several possible places to specifically search for cancer-related clinical trials. They include:

• BreastCancerTrials.org. This service helps users find breast cancer-specific clinical trials. It includes a separate search engine for metastatic breast cancer trials. And its alert service notifies users of recently added clinical trials.
• Melanoma Research Alliance (MRA). MRA's clinical trial finder suggests melanoma clinical trials based on your answers to a series of questions.
• Metastatic Breast Cancer Project (MBCproject). The MBCproject gathers information on metastatic breast cancer.
• Metastatic Prostate Cancer Project (MPCproject). The MPCproject gathers information on advanced and metastatic prostate cancer.
• National Brain Tumor Society Clinical Trial Finder. This database allows people to search for brain tumor-specific clinical trials.
• Pancreatic Cancer Action Network Clinical Trial Finder. This service allows people to search for pancreatic cancer-specific clinical trials.
• SPOHNC Clinical Trial Navigation Service. Support for People with Oral and Head and Neck Cancer (SPOHNC) provides this resource, which helps people find diagnosis-specific clinical trials.
• The Leukemia & Lymphoma Society Clinical Trial Support Center. This service helps people with leukemia, lymphoma, or myeloma. People connect with support specialists by phone, live chat, or email. And the specialists provide a personalized list of relevant clinical trials.
• Us TOO Prostate Cancer Clinical Trial Finder. Us TOO International Prostate Cancer Education & Support Network provides this resource. The service offers information on prostate cancer-specific clinical trials.
• Lazarex Cancer Foundation. This foundation helps people find clinical trials and financial assistance.
• National Cancer Institute (NCI) Clinical Trials. This federal agency provides funding for most U.S. cancer clinical trials. The site lists open and closed cancer clinical trials sponsored or supported by NCI. Find NCI-supported clinical trials with the search tool.
• Targeted Agent and Profiling Utilization Registry (TAPUR) Study. The TAPUR Study is a clinical trial conducted by ASCO. It studies advanced cancer in adults. And it explores whether specific targeted therapies may benefit more patients.

NOTE: Some people who are not eligible to participate in a clinical trial may be able to get experimental drugs or devices through what is known as Expanded Access.

This allows certain patients to gain treatment when they suffer from an immediately life-threatening condition or serious disease ⁹.

Eligibility and Considerations for Participation

After you find or are directed to a clinical study for participation, you should contact the administrator or trial coordinator.

If you pass an initial phone screening, you will be set up with a screening appointment to further see if you qualify.

This will also give you the chance to ask all the questions you may have about participation (see section below).

If your regular doctor did not refer you, then let him or her know that you are thinking about joining a clinical trial to make sure you have approval.

You will also need to make sure your care is coordinated with your primary care physician while you are participating in the trial.

Your screening may depend on a number of factors.

Trials often have targeted participants in mind and inclusion might be based on a number of things, including:

• Age
• Sex
• Genetic profile
• Stage of your condition/disease
• Any other health related issues
• Race
• Family history
• Availability and transportation for appointments
• Medications you are currently taking

The factors that allow someone to participate in a clinical study are called inclusion criteria.

The factors that disqualify someone from participating are called exclusion criteria.

These factors can vary widely from trial to trial, so if you don’t meet criteria for one, you could very well meet the criteria for others.

Important Questions to Ask Before Participating in a Clinical Trial

The following are some questions to ask a research team if you are thinking about participating in a clinical trial.

Because there will be a lot of information that you exchange when meeting with the team, it’s best to write down specific questions you may have ahead of time so that you ensure all of your questions are addressed.

• What treatment or tests will I have?
• What is the expected duration of the clinical trial?
• What are the chances I will get the experimental treatment?
• What are the chances that I will receive a placebo?
• What are the possible risks and side effects that the study treatment may compared to my current treatment? What are the anticipated benefits?
• How will you protect my health while I am in the study?
• Can I take my regular medicines while in the trial?
• What happens if my health problem gets worse during the study?
• How will the study affect my everyday life?
• Where will the study take place?
• Will I have to stay in the hospital?
• Will you provide a way for me to get to the study site if I need it?
• Will being in the study cost me anything? If so, will I be reimbursed?
• Will my insurance cover my costs?
• Will I be compensated to be in the study?
• Who will be in charge of my care while I am in the study?
• Will I be able to see my own doctor?
• How will you keep my doctor informed about my participation in the trial?
• Will you follow up on my health after the end of the study?
• Will you tell me the results of the study?
• Does the study compare standard and experimental treatments?
• If I withdraw, will this affect my normal care?
• What steps ensure my privacy?

What Happens When a Clinical Trial is Over?

After a clinical trial is complete, the research team will compile and analyze information and data collected during the trial.

Based on this information, decisions will be made about the findings and whether or not additional testing or trials are needed ¹⁰.

Next steps can vary based on which phase of testing a trial was in.

After a phase 1 or phase 2 trial, administrators and the sponsor decide whether to continue testing the treatment in the next phase.

They may decide to stop because they don’t feel confident enough that the treatment holds enough promise.

When a phase 3 trial is over, researchers will examine whether the new treatment was more effective or has fewer side effects than the current one that’s used.

If it improves on the status quo, they submit an New Drug Application to the FDA so it can become the new standard of medical practice ¹¹.

If you are a participant, you may be able to access the results of the trial when they are over or when they are published.

You will also probably go through an exit interview so that researchers can continue to improve upon the trial experiences of others.

During these interviews, researchers may ask about your symptoms and side effects over the course of the trial.

They may also compare your responses to interviews that were conducted before and during the trial.

You may also want to know if you can continue the new course of treatment you were given during the trial (if it was effective).

Researchers are not obligated to offer continued access to the treatment they’ve provided, but they are required to inform you about your options before the study even begins.

In many cases, the manufacturer of the treatment may make it available to volunteers after the study, especially when continued testing is likely.

Patients may also be able to purchase the treatment privately afterwards as well.

In some instances, the completion of one study will automatically make you eligible for the next study in the research process.

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