Understanding Clinical Trials
As a breast cancer patient, it is important to know about clinical trials. Not only are clinical trials a critical part of the development of treatments, but your participation in them help researchers, patients and advocates learn more about diseases. Below, we provide you with important information you should know.
What are clinical trials?
A clinical trial is a type of medical research study that determines whether an intervention – a new drug, medical device or diagnostic tool – is safe and/or effective. The investigators leading a clinical trial develop a protocol – a detailed document that describes how the study will be performed. A clinical trial recruits volunteer study participants to test the intervention. Clinical trials are conducted by government agencies, universities, hospitals, and drug companies.
It takes an average of seven years for a promising intervention to progress through the steps of clinical testing. First, the protocol must be approved by the institutional review board (IRB), and by the Food and Drug Administration (FDA). Following this initial approval, the intervention progresses through a rigorous series of clinical studies. Some interventions that are being tested never complete the testing series. Others complete all of the testing, but they are not approved because they are either not safe or because they are not effective, or both.
What are the different types of clinical trials?
Clinical trials are categorized into four phases or types.
Phase I: Phase I clinical trials are the first time the drug is used by people. For these clinical trials, a small group of healthy volunteers are given the drug to determine the dose range that is tolerated for a single dose or for multiple doses. These studies are also performed to learn if the drug has any side effects.
Phase II: If the phase I studies have demonstrated that the new drug is safe, phase II clinical trials are conducted on patients with the disease or condition to be treated, diagnosed or prevented. Phase II studies are performed to determine if the new drug is safe and effective at treating the disease. Phase II trials may also be performed to determine if drugs that are already on the market can be used for another purpose.
Phase III: Phase III clinical trials are done as a final step to gain regulatory approval to market the drug. In phase III trials, the drug is given to a large group of patients with the disease. For comparison, some of the study participants are given standard treatment, placebo or both.
Phase IV: Phase IV trials, sometimes referred to as post-marketing surveillance, are performed after the drug is available and in use to the general public to provide additional details about the drug’s safety. This may include side effects not observed in the earlier clinical trials. Evaluations may include different formulations, dosages, durations of treatment, and interactions of different medicines. Evaluations may also include new age groups, races and other types of patients. If new side effects are identified that are serious, the use of the drug may be limited or restricted. In some cases, the intervention may be removed from the market.
Why are clinical trials important?
Today, people are living longer in part because of the results of clinical trials. Imagine for a minute – aspirin and other common medications and medical devices went through clinical trials before they were approved for public use. Clinical trials also help us learn more about diseases and other health conditions. This includes learning how the condition develops, if there are certain characteristics that make us more likely to get a disease, and which treatment would be better for treating us.
Who should participate in a clinical trial?
For each clinical trial, the accompanying study protocol describes who can and cannot join the study. These enrollment characteristics may include age, gender, medical history, previous treatment, current health status, and the particular type or stage of cancer.
After you have signed an informed consent form, which indicates that have agreed to participate in the clinical trial, a doctor or nurse will assess your medical history, perform a physical exam and perform laboratory tests to determine whether you meet the eligibility criteria. Do not feel discouraged if you cannot join a specific clinical trial. The research team’s top priority is to ensure that the study is right and safe for all of the patients. So if you are not selected, you can try to join another clinical trial.
How are clinical trials conducted?
Clinical trials follow the set of rules that are described in the protocol. After the protocol has been approved by the IRB and the FDA, the research team begins recruiting study subjects. Upon receipt of the signed informed consent from each study subject, these individuals are then treated and cared for as detailed in the protocol.
Who conducts clinical trials?
Clinical trials are led by a principal investigator, who is usually a medical doctor. The clinical trial team may include doctors, nurses, study coordinators, social workers and other health care professionals.
Who sponsors clinical trials?
The money to perform clinical trials is commonly provided by pharmaceutical companies who have produced a drug or medical device. Academic medical centers, federal agencies, and hospitals may also provide funds for clinical trials.
How long are clinical trials?
It takes an average of 7 years from the beginning of clinical testing of the investigational drug to market approval. The average length of time for each phase is as follows: 21.6 months for phase I, 25.7 months for phase II and 30.5 months for phase III.
Where are clinical trials conducted?
Clinical trials can take place in various locations such as hospitals, universities and community clinics.
What are the benefits of participating in a clinical trial?
Less than 5% of all cancer patients are currently enrolled in a clinical trial. Further, even though cancer mortality is higher among minorities, less than 10% of racial and ethnical minorities are enrolled in clinical trials – with minorities being 60% as likely to enroll in a clinical trial compared to whites. The underrepresentation of minorities in clinical trials means that there are few studies that analyze and report safety and efficacy by race or ethnicity. Therefore, it is difficult to know if minority patients tend to have a specific type or subtype of cancer and if they process certain drugs differently.
As a minority, participating in a clinical trial allows the researchers to conduct a study that is more representative of the general population and to gather racial and ethnic data on the disease and treatments that they are studying. Participating in a clinical trial also allows you to have access to the newest treatments and care that are hopefully more effective than the current standard care. In some cases, you could earn money as a volunteer study participant.
What should I know before I decide to be part of a clinical trial?
When you express interest in learning more about a clinical trial, you will be provided with an informed consent form, which describes the clinical trial. If there is something on the form that you do not understand, the study doctors and nurses are available to answer your questions. Before you decide to be part of a clinical trial, make sure that you understand:
- the purpose of the study
- the tests and procedures that will be used
- the risks and benefits
- the length of the study
- how often you will meet with the clinical trial team
how much of your time is expected
- what are your responsibilities
- what procedures are in place to keep you safe
- how to contact someone if you have an adverse effect
- what procedures are in place to keep your information confidential.
As a clinical trial subject, there are a few additional items to consider:
You are not guaranteed to receive the new treatment being tested. Instead, you may receive the older treatment or you may receive the placebo.
Depending on the type of treatment being studied and your individual health, you may experience unpleasant, and sometimes serious, side effects. Often these side effects are temporary and end when the treatment stops. The researchers will warn participants of all known side effects, but unanticipated problems may arise.
The experimental treatment may not work as well as intended, and in some cases, it may not work as well as standard treatment.
You may be required to devote more of your time and make changes to your daily schedule. For example, you may spend more time traveling to the study site and you may send time in the hospital. You may also spend more time taking treatments.
What is expected of me when I participate in a clinical trial?
As a research participant, you are an important part of the research study. It is important that you understand your role and how it impacts your safety and welfare. Some of your responsibilities include:
- reading the entire informed consent form and asking questions about what you don’t understand about the study
- following all instructions from the research team
telling the research team about what worries you about the study
- following directions for proper use, dosing, and storage of self-administered study medications
- telling the research team if you have any side effects, hospitalizations, missed doses, and pregnancy
- keeping scheduled appointments or if unable to do so, informing the research team as soon as possible
- notifying the research team when your contact information changes (for example, phone number, address)
- informing the research team if you choose to withdraw from the study
Is it safe for me to participate in a clinical trial?
The Food and Drug Administration helps to protect the rights and welfare of research subjects by performing inspections of clinical trial study sites and the research team to ensure that the study is being performed properly, and by verifying the quality and integrity of data from the clinical trial.
The Institutional Review Board also helps to protect the rights and welfare of research subjects by ensuring that the proposed clinical trial follows ethical principles and meets federal regulations for the protection of research participants. The Institutional Review Board protects the rights and welfare of research subjects, by balancing the individual rights of research subjects with increased knowledge gained by society as a whole. The Institutional Review Board approves a proposed clinical trial if:
- informed consent will be obtained
- there are minimal risks to research subjects
- the risks to research subjects are reasonable when compared to the anticipated benefits of the study
- there is a clear plan for monitoring research subjects’ data and safety
- there is a clear plan for maintaining research subjects’ privacy and confidentiality
- there is a clear plan for applying safeguards for vulnerable research subjects
As the study progresses, the research team submits annual progress reports to the Institutional Review Board and alerts them of adverse effects experienced by the research subjects. Thus, the Institutional Review Board is continuously reviewing risk-benefit of the clinical trial and deciding if the study should continue.
How do I enroll in a clinical trial?
You can enroll in a clinical trial by signing the informed consent form. During the informed consent process, the research team will explain to you that your participation is voluntary, and that you can stop participating at any time. The researcher will also explain the study to you and answer any questions that you have. You can take the informed consent form home to think further about whether you would like to participate in the study. If you do decide to participate in the clinical trial, you must sign the informed consent form.
By signing the informed consent form, you are acknowledging that the researcher has provided you with all of the appropriate information so that you are “informed” (educated) about your rights and about all aspects about the study, and that you “consent” (agree) to voluntarily participate as a research subject. A typical informed consent form will include:
- the clinical trial’s purpose, procedures, treatment, length of research subject participation, approximate number of enrolled research subjects
- your right to voluntarily decide if you would like to participate in the study
forseeable discomforts to research subjects
- benefits to research subjects
- alternative treatments or procedures that might be advantageous to research subjects
- plan for maintaining research subjects’ confidentiality and privacy
contact information for the research team
- What happens after a clinical trial is complete?
At the end of each phase of a clinical trial, the data are collected and analyzed to determine if the experimental drug is effective and safe, and if there are any side effects. The data will determine if testing should be stopped or if it is ok to move on to the next phase of the clinical trial. The data are submitted to the Institutional Review Board and the Food and Drug Administration. The researchers may submit the data to science journals for peer-review and publication. The highlights from these studies are sometimes re-written in non-technical language for the general public to easily understand.
If the experimental drug completes all phases of the clinical trial and is shown to be safe and effect, the experimental drug could become the standard treatment.
Talking with your health care provider and clinical trial staff
Clinical trials are led by a principal investigator, who is usually a medical doctor. The team may include doctors, nurses, study coordinators, social workers and other health care professionals. The clinical trial team is available to speak with you about the study and answer your questions. Below are some suggested questions that you can ask your research team:
- What is the purpose of the study?
- Who is going to be in the study?
- Where is the study site?
- How will I know that the treatment is working?
- Who will be in charge of my care?
- Why do researchers believe the new treatment being tested may be effective?
- Has the experimental drug been tested before?
- What kinds of tests and treatments are involved?
- How do the possible risks, side effects, and benefits in the study compare with my current treatment?
- How might this clinical trial affect my daily life?
- How long will the clinical trial last?
- Will hospitalization be required?
- Who will pay for my treatment?
- Will I be reimbursed for other expenses?
- What type of longterm follow up care is part of this study?
- Will I have access to the clinical trial results?
How to interpret a clinical trial study?
Baseline Characteristics: Baseline characteristics are data collected at the beginning of a clinical trial. These include age, gender, weight, blood pressure, and current medications.
Investigation Drug/Experimental Drug: This is the drug that is being tested in the clinical trial.
Sample Size: The sample size refers to the number of research subjects in the clinical trial. When the study protocol is being developed, investigators perform mathematical predictions to determine how many study patients are needed to strengthen the validity of the results. This mathematical calculation is important because even though results from a research study may suggest that the experimental drug is effective, it could be a coincidence. When the same result is observed in many people, it is less likely to be due to coincidence.
Control Group: The control group refers to the group of research subjects who receive either a dummy treatment, an older treatment or no treatment at all. With the control group, investigators are able to specifically determine how likely it is for patients receiving the treatment to get better on their own or on a different treatment.
Study Duration: The study duration refers to the length of time of the research study. It is important that investigations treat “treatment group” patients and “control group” patients during the same time period and observe the two groups of patients side-by-side. In the past, investigators used results of a “control group” that were monitored at an earlier time, perhaps when medical advances were not as good. This made the study non-ideal because it used an unfair comparison. Today, research studies are done on all treatment groups at the same time.
Study Sample: The study sample refers to the group of research participants. The study sample represents a subset of the population who match the eligibility criteria of the study. Investigators often recruit a diverse group of study subjects so that they are representative of the general population.
Trial End Points: Trial end points are the primary results or outcomes that the researchers are measuring. Some examples of trial end points include response rate – how well the cancer shrinks in response to treatment, duration of response – how long before the cancer starts to grow again, disease progression – does the cancer grow despite the treatment, and survival rate – how long do the patients live.
Response: If the cancer completely disappears during treatment, this is a complete response – this is the best case scenario. If it shrinks incompletely, this is a partial response. If the treatment has no effect on the cancer, then the disease is stable. If the cancer disappears and then begins to grow again, this is called a relapse.
Disease Progression: During treatment, if the cancer size increases by 20% or if a secondary cancer develops, this is called disease progression.
Survival: At the end of a clinical trial, the research team continues to follow the research subject results so that they can present 5-year survival or 10-year survival data. These data refer to the percent of research subjects who are alive for 5 or 10 years, respectively, after treatment. Disease-free survival refers to the percent of research subjects who are alive and cancer-free after a specific number of years. Overall survival is the number of research subjects who are alive with or without cancer. Median survival is the length of time when half of the study subjects are still alive.
Adverse Events: An adverse event refers to a change in a research subject’s health status during the clinical trial, and it is an unfavorable or unintended sign, symptom or disease. Some examples of adverse events include convulsions, nausea, hair loss, development of drug dependency or drug abuse, and death.
Statistical Significance: This refers to whether an event or difference occurred by chance alone. In clinical trials, the level of statistical significance depends on the sample size, observations documented in the study, and the size of the differences or number of events that occurred.
Where can I find clinical trial results?
The clinical research team will inform you of where to find the results of the clinical trial. The results from clinical trials are usually published in scientific or medical journals. Some journals require a subscription to access articles. On Google, you may find abstracts – summaries of the articles. You may also see the results of clinical trials published in newspapers such as the New York Times.
Definition of terms used to talk about clinical trials.
- Adverse Events: An adverse event refers to a change in a research subject’s health status during the clinical trial, and it is an unfavorable or unintended sign, symptom or disease.
- Clinical Trial: With the approval of the Food and Drug Administration (FDA) and the institutional review board (IRB), scientists conduct research studies to test new drugs, treatments or devices in volunteer research subjects.
- Confidentiality: This is the assurance that a research subject’s information will be kept in secret and that access to the information will be restricted to only authorized personnel.
- Control Group: This is a group of patients who are similar in demographics as the experimental group of patients. The control group may be healthy individuals who are receiving a placebo or they may be receiving standard therapy.
- Data: Data are a series of observations, measurements and facts about the research subjects that are recorded during the study.
- Disease Progression: If during treatment, the cancer size increases by 20% or if a secondary cancer develops, this is called disease progression.
- Dosage Regimen: The dosage regimen refers to timing for each dose of the medication eg. twice per day, or the quantity of the medication that is given a specific time of dosing 2 tablets every 6 hours.
- Double Blind: This refers to studies where neither the patients nor the physicians know which treatment the patient is receiving.
- Efficacy: Efficacy is the ability of the drug to produce beneficial effects on the duration or course of the disease.
- Exclusion Criteria: Exclusion criteria refer to the factors that determine which individuals cannot participate in a research study. These criteria include age, gender, type and stage of the disease, treatment history and medication conditions.
- Experimental Group: This is a group of patients who are receiving the intervention that is being tested.
- FDA: The Food and Drug Administration (FDA) is an agency that controls and supervises food and drug safety.
- HIPAA: The Health Insurance Portability and Accountability Act of 1996 provides guidelines to safeguard medical information.
- Inclusion Criteria: Inclusion criteria refer to the factors that determine which individuals can participate in a research study. These criteria include age, gender, type and stage of the disease, treatment history and medication conditions.
- Informed Consent: This describes the process by which the researchers provide information about a study to potential study volunteers. If you decide that you would like to be part of a study, you will sign a form to consent or agree to voluntarily participate in the study.
- IRB: An institutional review board (IRB) is an independent committee that ensures that the research study is ethical and that it has minimal risks to the research subjects.
- Investigator: This is a researcher in a clinical study. The principal investigator is the researcher who is responsible for the scientific and technical direction of the clinical trial.
- Peer-review: This is evaluation by experts in the field.
- Phase: This is the type of clinical trial: phase 1, 2, 3 and 4.
- Placebo: This is a substance that has no therapeutic effect that is used as a control for testing new drugs. The placebo is physically indistinguishable from the experimental drug. If a study uses a placebo, the study is described as “placebo-controlled” and the study subjects who receive the placebo are called the “control group.”
- Protocol: A protocol is a map to a research study. It includes details such as eligible characteristics of research subjects, methods, treatment, safety, and risk and benefits.
- Prospective: When a study is described as prospective, it means that the researchers are providing the study subjects with a particular treatment and observing the study subjects over a period of time (usually months or years) to record results or outcomes. Outcomes could include side effects, and improved or worsened health conditions.
- Randomized: In some types of studies, the study patients are randomly assigned by a computer to one of the treatment groups.
- Research: This is a careful and systematic study to answer a question. In science, we perform research to better understand a disease and improve treatments.
- Research Subject: A research subject, study patient or human subject refers to a person who is being observed by researchers to determine the effect and safety of a treatment.
- Response: Response refers to the effect of the treatment on cancer.
- Risk: This is a measure of likelihood of harm to human health or the severity of harm that may occur.
- Risk-Benefit Ratio: This is a comparison of individual subject risk and potential benefits to the individual and to society at large.
- Single-Blind: This refers to studies where the patients do not know whether they are receiving the experimental drug or another drug.
- Sponsor: The sponsor is the organization or person who oversees the clinical trial and is responsible for analyzing the data.
- Statistically Significant: To determine if the outcomes between the various treatment groups did not differ simply because of chance, researchers do a test on the results to see if a p value of 0.05 or less was achieved. If a p value of 0.05 or less was achieved, then the results are statistically significant.
- Study Sample: This refers to the group of research participants who are a “sample” of the general population or a “sample” of the group affected by a particular diseases or condition.
- Study Duration: The study duration refers to the length of the research study.
- Survival: An important data outcome of a clinical trial is the percent of research subjects who are alive 5 years and 10 years after treatment. Disease-free survival refers to the percent of research subjects who are alive and cancer-free after a specific number of years. Overall survival is the number of research subjects who are alive with or without cancer. Median survival is the length of time when half of the study subjects are still alive.