Clinical trials, or research studies, help us learn more about potential new drugs and medical devices. They answer questions about safety, effectiveness, the best dose or treatment schedule, potential side effects, and more.
Development of a new drug begins long before it is ever tested in humans. When researchers discover or develop a compound with potential medical benefit, they begin an extensive process of pre-clinical laboratory research, often involving years of experiments in animals and human cells. Researchers send their data to the Food and Drug Administration (FDA), and if the results appear promising, they receive approval to begin clinical trials in humans.
Clinical trials are carefully designed in sequential steps, and a new drug or device must pass several stages of approval before it can be sold in the consumer market. In fact, only about 12% of potential drugs successfully make it through the clinical trial process.
Human Clinical Trial Phases
Once a potential drug or device is approved for human testing, researchers design a series of clinical trials which are typically conducted in four sequential phases. Each phase is developed as a separate study, with its own parameters, goals, and analysis. After each phase, researchers must submit their results to the FDA for approval to move to the next phase of study. If at any point the investigational product is found to be unsafe or ineffective, clinical trials are stopped.
Phase I
Studies assess the safety of an investigational product by evaluating how it affects trial participants, including how it is absorbed, metabolized, and excreted. They also investigate any side effects that occur as dose levels are increased. Phase I testing is usually conducted on a small number of healthy volunteers who are paid for participating. About 70% of drugs pass this phase and proceed to Phase II.
Phase II
Studies evaluate the effectiveness of a potential drug or device. Most phase II studies are randomized, meaning participants are randomly assigned to receive either the investigational product or an approved treatment or placebo. Randomized studies are usually blinded, which means that neither the participants nor the researchers know who has received the experimental product. This ensures that comparative data about its relative safety and effectiveness is unbiased and accurate. Phase II studies usually enroll up to several hundred participants and can last anywhere from several months to two years. About one-third of drugs successfully complete both Phase I and Phase II studies.
Phase III
Studies evaluate a potential drug or device on a much larger scale to develop a more thorough understanding of its effectiveness, benefits, and potential side effects. Phase III studies involve several hundred to several thousand volunteers and can last several years. 70% to 90% of drugs that enter phase III studies successfully complete this phase of testing. Once phase III is complete, researchers submit the data to the FDA and request marketing approval.
Phase IV
Studies, often called postmarketing surveillance trials, are conducted after a product has been approved for sale. Pharmaceutical and medical device companies have several objectives at this stage: (1) to compare the product with others already in the market; (2) to monitor the product's long-term effectiveness and impact on a patient's quality of life; and (3) to determine the cost-effectiveness of the product relative to other traditional and new therapies. In some cases, phase IV studies can result in the product being taken off the market or having restrictions placed on its use.
Volunteering for Clinical Trials
Without clinical trials, we would not have any of the modern medical devices, medicines, and vaccines we use today, and the success of trials depends on the participation of volunteers. Each year, over 2 million people in the United States participate in clinical trials.
People choose to join clinical trials for different reasons. Some have a medical condition and are trying to find an effective treatment. Others feel a social responsibility to help advance medical care for future generations. One thing they all have in common, however, is a belief in the power of science to change lives and improve our world.
Who Can Participate in a Clinical Trial?
A volunteer must qualify for a clinical trial before they can participate. All studies have unique guidelines about who can participate called eligibility criteria. These criteria can include age, sex, the type and stage of a disease, previous treatment history, other medical conditions, and lifestyle considerations. Eligibility criteria are important for identifying appropriate participants, promoting safety throughout the trial, and ensuring study results are complete and accurate.
Are Clinical Trials Safe?
While there are some risks involved with participating in a clinical trial, there are many safeguards in place to protect the health, privacy, and well-being of participants. All researchers are required to follow ethical guidelines called Good Clinical Practice and adhere to strict HIPAA privacy laws concerning the proper handling and storage of participants' personal information.
Clinical trials must follow a detailed plan, or protocol, that outlines exactly how the research will be conducted and how any side effects or adverse events will be managed. Clinical trial protocols must be reviewed and approved by committees responsible for protecting the rights and safety of all participants. These committees, called Institutional Review Boards (IRBs), continue to regularly review the study's progress to ensure there are no unnecessary or excessive risks to participants.
What are the Possible Benefits of Joining a Clinical Trial?
Clinical trials allow participants to play an active role in their health care.
Participants can gain access to investigational treatments before they are available to the general public.
Participants may have access to free healthcare and close medical monitoring during their time in a clinical trial.
Participants can feel good about contributing to scientific research and medical advances that may benefit millions of others in the future.
What are the Possible Risks of Joining a Clinical Trial?
There may be unpleasant, serious, or even life-threatening side effects from an investigational product.
An investigational product may not be effective.
Study-related tests and procedures may be uncomfortable.
The study may require significant time and effort, including multiple trips to the study site, at-home monitoring, hospital stays, or complex dosage requirements.
Should You Participate in a Clinical Trial?
Choosing to participate in a clinical trial is a personal decision that you are entitled to make freely, without influence or coercion. You should take time to learn as much as possible about the study and discuss it with your healthcare team and loved ones. Being properly informed about your rights and responsibilities as a participant is the best way to ensure that you are making the right decision for you.
Understanding Informed Consent
You have a legal right to completely understand a clinical trial before you decide if you want to participate. This is called giving your informed consent. Informed consent is an ethical and a legal process of communication between the study team and a clinical trial volunteer.
When you give your informed consent, you are acknowledging that you understand and accept all aspects of the research study, including:
The purpose of the study
The duration of the study
All the risks, side effects, or discomforts that might be reasonably expected
Any benefits that can be reasonably expected
What will happen in the study and whether any procedures, drugs, or devices are different than those that are used in standard medical treatment
All options available to you and how they are better or worse than being in a clinical trial
It is the responsibility of the research staff to help you understand the information they provide you and to give you enough time to ask any additional questions you may have. In some instances, this may not be possible to accomplish in a single visit. If English is not your first language, inform the researcher that you are not comfortable speaking about a clinical trial in English. Documents that explain every aspect of the study in your preferred language should be available.
Take Time to Understand
A WCG CenterWatch survey of 672 study volunteers offers insight into the informed consent process and whether or not it is working to help volunteers understand their roles and responsibilities. Some key takeaways from the study are:
Nearly 98% of volunteers said they received the informed consent form and 90% said they read the form completely.
The vast majority of volunteers said they understood the expectations of the study, including additional risks and their ability to withdraw at any time.
More than three-quarters understood that they could contact someone outside the study if they had additional questions about their rights during the trial.
More than half were unaware that neither their doctor nor they would know which medication they would receive during the study; more than two-thirds understood that they could receive a placebo.
Nine out of ten volunteers said that the information received prior to the trial matched their actual experience during the trial.
Approximately 75% of the volunteers indicated that the main reason for participating in a study was to help themselves or others and to advance science.
What Questions Should You Ask?
It is your responsibility to ask questions if there is something you do not understand. If you do not understand any part of the process, ask the researcher to repeat the information or to explain it in another way, using everyday words.
Questions to ask about the clinical trial:
What is the main purpose of the study?
What are the chances that this drug will work?
What kinds of risks are involved?
How much of my time will this take?
Does the study involve a placebo or a treatment already on the market?
About your care:
What kinds of tests will be done? Will they hurt? If so, for how long?
How will the tests in the study compare to tests I would have outside the study?
Will I be able to continue to see my own doctor during the study?
Will I be able to continue to take my regular medications during the study?
If I have side effects, can they be treated during the study?
About personal matters:
Who will review information collected about me during the trial?
What happens if I decide to quit the study?
Can the investigator take me out of the study even if I want to continue?
About compensation and costs:
Do I have to pay for any part of the study? If so, will insurance cover these costs?
Your Rights as a Clinical Trial Participant
If you have given informed consent to participate in a clinical trial, or if you have given consent on behalf of another person, you are entitled to the following rights:
To be told the purpose of the clinical trial
To be told about all the risks, side effects, or discomforts that might be reasonably expected
To be told of any benefits that can be reasonably expected
To be told what will happen in the study and whether any procedures, drugs, or devices are different than those that are used in standard medical treatment
To be told about all options available to you and how they are better or worse than being in a clinical trial
To be allowed to ask any questions about the trial prior to consenting and/or at any time during the course of the trial
To be allowed ample time, without pressure, to decide whether or not to consent to participate
To refuse to participate, for any reason, before or after the trial has started
To receive a signed and dated copy of the Informed Consent Form
To be informed of any medical treatments available if complications occur during the trial
Who Funds Clinical Trials?
Funding for clinical research comes from federal government agencies including the National Institutes of Health, the Department of Defense, and the Department of Veterans Affairs, and private industry such as pharmaceutical and biotech companies, medical institutions, and foundations.
Additional Resources
Navigating the healthcare world is a complex task for patients and caregivers. WCG offers additional informational resources for patients and their families. Below are several links that may be helpful.