# Presentation: 097206

## Clinical Trials

- The Way We Make Progress Against Disease

**Notes:**
Whether you have <insert condition>, are a friend or family member of someone with <insert condition>, or someone who works with people with people who have <insert condition>, this presentation will help answer some of the most important questions you may have about clinical trials.  

The presentation will include a discussion about: 
 Why clinical trials are important		
 How clinical trials work
 How clinical trials advance patient care
 How participants are protected 		
 Some of the barriers to participating in clinical trials

And finally, I’ll talk about ways you can find clinical trials in your community.		

## What Are Clinical Trials?

- Research studies involving people
- Try to answer scientific questions and find better ways to prevent, diagnose, or treat disease

**Notes:**
Clinical trials are research studies involving people. Clinical trials are the final step in a long research process that includes preliminary laboratory research and animal testing.

Clinical trials try to answer specific scientific questions to find better ways to prevent, detect, or treat diseases, or to improve care for people with diseases. 

In cancer research, for example, a clinical trial is designed to show how a certain anticancer approach—for instance, a promising drug, a new surgical procedure, a new diagnostic test, or a possible way to prevent cancer—affects the people who receive it.

## Why Are Clinical Trials Important?

- Why Are Clinical Trials Important?

- Clinical trials translate results of
-    basic scientific research into better ways to prevent, diagnose, or treat disease
- The more people take part, the faster we can:
-    - Answer critical research questions
-    - Find better treatments and ways to prevent disease

**Notes:**
It is important to understand what clinical trials do to fight disease:
         Clinical trials translate results of basic scientific research into better ways to prevent, diagnose, or treat disease.
         Clinical trials contribute to knowledge and progress against disease. Many of today’s most effective treatments are based on previous study results. Because of progress made through clinical trials, many people treated for various diseases are now living longer.
         The more people that participate in clinical trials, the faster we can answer the critical research questions that will lead us to better treatment and prevention options for a range of diseases. 

## Do Many People Take Part in Clinical Trials?

- Few people participate

**Notes:**
We know that few people in the U.S. participate in clinical trials.  

According to the National Cancer Institute, for example, fewer than 5 percent of adult cancer patients in the U.S. participate in clinical trials.

We’ll talk more later about why so few participate.

## What Are the Different Types of Clinical Trials?

- Treatment
- Prevention
- Early detection/screening
- Diagnostic
- Quality of life/supportive care

**Notes:**
There are at least 5 types of clinical trials:

1. Treatment trials seek to find out: 
         What new treatment approaches can help people who have a disease
         What is the most effective treatment for people with that disease

2. Prevention trials seek to find out what approaches can prevent a disease from developing in people who have never had it

3. Early-detection/screening trials seek to discover new ways of finding a disease in people before they have any symptoms

4. Diagnostic trials seek to find out how new tests or procedures can better identify a disease in people when we think it is there

5. Quality-of-life/supportive care trials seek to find out what kinds of new approaches can improve the comfort and quality of life of people with a disease

## Treatment Trials

- What new treatments can help people with a particular disease?
- What is the most effective treatment for people with that disease?

**Notes:**
Most clinical trials are treatment trials. These clinical trials involve people who have a disease. 

These studies try to answer specific questions about the effectiveness of a new treatment or a new way of using an existing treatment. 

## Clinical Trial Phases

**Phase 1 trials**
- How does the agent affect the human body?
- What dosage is safe?

**Notes:**
Clinical trials take place in phases.

Once laboratory studies (in test tubes and animals) show that a new approach has promise, a phase 1 trial can begin. A phase 1 trial is the first step in testing a new agent (drug or compound) in humans.

In these studies, researchers look for the best way to give people the new agent (for example, by pill or by injection), how often it should be given, and what the safest dose is. These studies also include special laboratory tests such as blood tests and biopsies to evaluate how the new agent is working in the body.

In phase 1 trials, small groups of people with a disease are treated with a certain dose of a new agent that has already been extensively studied in the laboratory. The dose is usually increased group by group in order to find the highest dose that does not cause harmful side effects. This process determines a safe and appropriate dose to use in a phase 2 trial. 

While the primary purpose of  phase 1 trials is to find the safest dose of a new agent, researchers also evaluate whether the new agent benefits patients.

People with a disease who are eligible for phase 1 studies have no known effective treatment options, or they have already tried other treatment options. Many participate in these trials because they want to help others and contribute to research. Phase 1 trials usually have 15 to 30 participants. 

## Clinical Trial Phases

**Phase 2 trials**
- Does the agent or intervention have an effect on the disease?

**Notes:**
Phase 2 trials continue to test the safety of the new agent, and begin to evaluate how well it works against a particular disease. 

In phase 2 trials, the new agent is given to groups of people with the disease in question, using the dosage found to be safe in phase 1 trials. 

If a new agent has demonstrated that it works against the disease and is safe for people in phase 2 trials, it enters a phase 3 trial.

In general, people who take part in phase 2 trials have other treatments, but those treatments have not been effective. Participation in these trials is often restricted based on the previous treatment received. Phase 2 trials usually have less than 100 participants.

## Clinical Trial Phases

**Phase 3 trials**
- Is the new agent or intervention (or new use of a treatment) better than the standard?
- Participants have an equal chance to be assigned to one of two or more groups

**Notes:**
Phase 3 trials focus on learning how a new treatment compares to “standard treatment” (the most widely accepted treatment, based on results of past research).  Researchers want to learn whether the new treatment is better than, the same as, or worse than the standard treatment.

In most cases, trials move into phase 3 testing only after a treatment shows positive results in phase 2 trials. 

In phase 3 trials, participants have an equal chance of being assigned to one of two or more groups (also called “arms”). 

The process of assigning participants to groups is called randomization.

Many people choose to get their first treatment in a phase 3 trial. The type of participant varies, depending on the kind of question being asked about a particular disease.  Phase 3 trials usually have hundreds to thousands of participants, in order to find out if true differences exist in the effectiveness of the treatments being tested. 

## Randomized Trials

**Participants have an equal chance to be assigned to one of two or more groups:**
- One gets the most widely accepted treatment (standard treatment)
- The other gets the new treatment being tested, which researchers hope and have reason to believe will be better than the standard treatment

**Notes:**
Phase 3 trials are randomized clinical trials, and some phase 2 trials may also be randomized.

Randomization is a method used to prevent bias in research. Treatment assignments are generated by a computer, and each participant has an equal chance of being assigned to one of two or more groups, the control group and the treatment group:
 The control group is made up of the people who get the most widely accepted treatment (standard treatment) for the disease
 The investigational group is made up of the people who get the new treatment being tested.

The next slide illustrates how randomization works.

## Randomization

**Notes:**
Explain slide.

## Why is Randomization Important?

- So all groups are as alike as possible
- Provides the best way to prove the effectiveness of a new agent or intervention

**Notes:**
If participants or health care providers choose a particular group based on what they think is best, then one of the groups would likely be very different than the other, making comparison between the groups difficult. 

Randomization eliminates this bias because participants have an equal chance of being assigned to either group and the subgroups are as similar as possible. 

Comparing similar groups of people taking different treatments for the same disease (or class of disease) is a way to ensure that the study results are caused by the treatments rather than by chance or other factors. 

## Treatment Trials

- What new treatments can help
-     people with a particular disease?
- What is the most of effective
-    treatment for people with that
-    disease?

**Notes:**
Most clinical trials are treatment trials. These clinical trials involve people who already have a particular disease.

These studies try to answer specific questions about the effectiveness of a new treatment or a new way of using an existing treatment.

## Treatment Trials

**Placebos are almost never used:**
- Placebos are used only when no standard treatment exists
- Patients are told of this possibility before deciding to take part

**Notes:**
Placebos (treatments, often drugs, designed to look like the medicine being tested but that don’t contain any active ingredient) are almost never used in treatment trials. 

Placebos are used in treatment trials only when we don’t yet have a known approach (standard agent) for a particular disease. 

Patients are told if this is a possibility before they decide whether to take part.

## Prevention Trials

-   Evaluate the effectiveness     of ways to reduce the risk of a particular disease
-   Enroll healthy people at high risk for developing that disease

**Notes:**
Unlike treatment trials, prevention clinical trials are studies involving healthy people who are at high risk for developing a particular disease. These studies try to answer specific questions about and evaluate the effectiveness of ways to reduce the risk of disease. 

## Prevention Trials

**Action studies** (“doing something”)
**Agent studies** (“taking something”)—also called “chemoprevention studies”

**Notes:**
There are two kinds of prevention trials:
         Action studies (“doing something”) focus on finding out whether actions people take, such as exercising more or quitting smoking, can prevent disease. 
         Agent studies (“taking something”) focus on finding out whether taking certain medicines, vitamins, minerals, or food supplements (or a combination of them) may lower the risk of disease. Agent studies are also called “chemoprevention studies.” 

## Chemoprevention Trials

- Phase 3 chemoprevention trials compare a promising new agent with either a:
-    --Standard agent
-    --Placebo

**Notes:**
Chemoprevention trials also go through phases, as outlined earlier for treatment trials. 

However, phase 3 chemoprevention trials compare a promising new agent with either a standard agent or a placebo with two or more groups of people.  

1. One group takes the promising new agent (called the study agent). 

2. The other group takes either:
         A standard agent, already being used for disease prevention 
         A placebo

Placebos are used in prevention trials when we don’t yet have a known approach (standard agent) for prevention. 

## Clinical Trial Protocol

- A recipe or blueprint
- Strict scientific guidelines:
-     --Purpose of study
-     --How many people will participate
-     --Who is eligible to participate
-     --How the study will be carried out
-     --What information will be gathered about participants
-     --Endpoints

**Notes:**
Clinical trials follow strict scientific guidelines. These guidelines clearly state the study’s design and who will be able to participate in the study. 

Every trial has a head person in charge, usually a doctor, who is called the principal investigator. The principal investigator prepares a plan for the study, called a protocol, which acts like a “recipe” for conducting a clinical trial. 

The protocol explains what the trial will do, how the study will be carried out, and why each part of the study is necessary. 

Every doctor or research center that takes part in the trial uses the same protocol. This ensures that participants are treated identically no matter where they are receiving treatment, and that information from all the participating sites can be combined and compared.

## Benefits of Participation

- Possible benefits:
- Patients will receive, at a minimum, the best standard treatment (if one exists)
- If the new treatment or intervention is proven to work, patients may be among the first to benefit
- Patients have a chance to help others and improve patient care

**Notes:**
Making a decision about taking part in a clinical trial is a very personal one. This is a question that only the person with disease in question (or at high risk for that disease) can answer for him or herself.

Some of the possible benefits of participating in a clinical trial are listed here.

## Risks of Participation

- Possible risks:
- New treatments or interventions under study are not always better than, or even as good as, standard care
- Even if a new treatment has benefits, it may not work for every patient
- Health insurance and managed care providers do not always cover clinical trials

**Notes:**
While a clinical trial is a good choice for some people, there are possible risks. People need to consider these as they think about joining a trial. 

Some of the possible risks of participating in a clinical trial are:

New treatments or interventions under study are not always better than, or even as good as, standard care.  New approaches may have unknown side effects or other risks.
Even if a new treatment has benefits, it may not work for every patient
Health insurance and managed care providers do not always cover clinical trials.  Participants may have to deal with the costs of travel, childcare, lost work hours, and meals.

## Patient Protection

- There have, unfortunately, been past abuses in patient protection
- Federal regulations ensure that people are told about the benefits, risks, and purpose of research before they agree to participate

**Notes:**
Although we now have strong safeguards for protecting those who participate in research, these protections have resulted from notorious abuses of human rights in the past.

The first formal statement of protection for individuals in research emerged from the Nuremberg trial in Germany where Nazi scientists and physicians who conducted experiments on World War II concentration camp victims were convicted. The Nuremberg Code outlined broad concepts for the protection of human subjects and forms the basis of today’s international code of ethics for the conduct of research.

In the United States, several controversial research studies alerted us to the critical need for protection for those participating in clinical trials. None of these studies sought to inform the participants about the research or gain their consent for participating. 

         From 1932 to 1972, the infamous Tuskegee Syphilis Study followed poor African American men with syphilis but did not treat them. During the study, the men were offered free medical care and were told that they would be treated for “bad blood.” 
         In the 1960s, two other research studies received major public attention. The first was a series of experiments with mentally retarded children; another involved debilitated elderly participants. 

In response to these tragedies, regulations and policies were developed to ensure that people are told about the benefits, risks, and purpose of research for which they volunteer. 

## How Are Patients’ Rights Protected?

- Informed consent
- Scientific review
- Institutional review boards (IRBs)
- Data safety and monitoring boards (DSMBs)

**Notes:**
Participant rights and safety are protected in four main ways:
Informed consent
Scientific review
Institutional review boards (IRBs)
Data safety and monitoring boards

## How Are Patients’ Rights Protected?

- Informed Consent:
- Purpose
- Procedures
- Potential risks and benefits
- Individual rights

**Notes:**
Participant rights and safety are protected through informed consent.

Informed consent is a process where potential participants learn the purpose and the potential risks and benefits of a study before deciding whether they wish to participate. This process continues throughout the study.

The research team, which is usually made up of doctors and nurses, first explains the trial to potential participants in understandable language. The team explains the trial’s: 
         Purpose
         Procedures 
         Risks and potential benefits
         Participant rights, including the rights to:
 Make an independent decision about participating
 Leave the study at any time without jeopardizing future treatment

This discussion is the beginning of the informed consent process.

After discussing all aspects of the study with a potential participant, the team gives him/her an informed consent form, which includes written details about the information that was discussed. The form also describes the confidentiality of the participant’s records. If a person agrees to take part in the study, he or she signs the form. 

The informed consent process does not end once the form is signed. If new benefits, risks, or side effects are discovered during a study, the researchers must inform study participants. In addition, participants are encouraged to ask questions at any time about what is happening during the study. 

## How Are Patients’ Rights Protected?

- Scientific review
- Institutional review boards (IRBs) are required by federal law for trials that are:
-    --Federally funded
-    --Subject to FDA regulation

**Notes:**
Participant rights and safety are protected through two review panels, which must approve each study protocol before it begins.

Scientific Review
Clinical trials that are sponsored by the National Institute of Dental and Craniofacial Research or any other NIH Institute —whether funded by a grant, run by a cooperative group, or run through a research center—are reviewed through different types of panels that include experts who review the scientific and technical merit of the proposed research. Many other clinical trial sponsors, such as pharmaceutical companies, also seek expert advice on the scientific and technical merit of their trial protocols. 

Institutional Review Boards
IRBs are made up of people who are qualified to evaluate new and ongoing clinical trials on the basis of scientific, legal, and ethical merit. They include medical and dental specialists as well as lay members of the community. The IRB determines whether the risks involved in a study are reasonable with respect to the potential benefits. IRBs also monitor the ongoing progress of the trial—from when it begins to when it ends.

## How Are Patients’ Rights Protected?

- Data and safety monitoring boards:
- Ensure that risks are minimized
- Ensure data integrity
- Stop a trial if safety concerns arise or objectives have been met

**Notes:**
All clinical trials are required to have provisions for data safety and monitoring.  

Many trials, particularly phase 3 trials that take place in many locations, have Data Safety and Monitoring Boards (DSMBs) to help ensure participants’ safety.

DSMBs:
Ensure that any risks associated with participation are minimized to the extent practical and possible
Avoid exposing participants to excessive risk
Ensure the integrity of data
Stop a trial if safety concerns arise or as soon as its objectives have been met

DSMBs are made up of physicians, dentists, statisticians, other scientists, and laypeople who have no affiliation with the institution leading the study. 

## Why Do So Few People Participate in Clinical Trials?

- Sometimes patients:
- Don’t know about clinical trials
- Don’t have access to clinical trials
- May be afraid or suspicious of research
- Can’t afford to participate
- May not want to go against health care provider’s wishes

**Notes:**
Many people do not participate in clinical trials.  Common barriers include:

Lack of awareness
Lack of access
Fear, distrust, or suspicion of research
Financial and personal concerns

## Why Do So Few People Participate in Clinical Trials?

- Health care providers might:
- Lack awareness of appropriate clinical trials
- Be unwilling to “lose control” of a person’s care
- Believe that standard therapy is best
- Be concerned that clinical trials add administrative burdens

**Notes:**
Health care providers might:
 Lack awareness of appropriate clinical trials. Providers are not always aware of available clinical trials. Some may not be aware of the local resources, or some may assume that none would be appropriate for their patients.
 Be unwilling to “lose control” of a person’s care. Most health care providers feel that the relationship they have with their patients is very important. They want what is best for the patient, and if the person must be referred elsewhere to participate in a trial, providers fear they may lose control of the person’s care.
 Believe that standard therapy is best. Many health care providers may not adequately understand how clinical trials are conducted or their importance. Some believe that the treatment in clinical trials is not as good as the standard treatment. They also might be uncomfortable admitting that there is uncertainty about which treatment is best in a phase 3 clinical trial.
 Be concerned that clinical trials add administrative burdens. The length and details of most research protocols may deter providers from participating in clinical trials. The possibility of incurring additional costs and expenses that might be inadequately reimbursed is a deterrent for many. 

## Where to Find Clinical Trial Information

- Where to Find Clinical Trial Information

**Your health care provider**
**National Library of Medicine**
-     www.ClinicalTrials.gov

- 

**Notes:**
You can ask your health care provider about local clinical trials.

You can go to www.ClinicalTrials.gov.  The ClinicalTrials.gov website provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases and conditions. The National Institutes of Health (NIH), through its National Library of Medicine (NLM), has developed this site in collaboration with all NIH Institutes and the Food and Drug Administration (FDA). 
Search by keyword or browse the Mouth and Tooth Diseases page. 

## 				National Institute of Dental and 		Craniofacial Research		NATIONAL INSTITUTES OF HEALTH 				www.nidcr.nih.govAdapted from a slide presentation developed by the National Cancer Institute, for its Cancer Clinical Trials Education Series.