Volunteers who participate in clinical trials help advance medical knowledge but also risk subjecting themselves to uncomfortable conditions and serious side effects. Before agreeing to participate, potential participants should understand the clinical trial process, the benefits and risks, how they are protected and what their responsibilities are before, during and after the trial.
Clinical trials are the frontlines of the war the healthcare industry wages against disease and debilitating medical conditions. Researchers test new drugs, devices, vaccines and therapies on volunteers in clinical trials before the treatments are approved for use in the general population. New treatments aren’t always better treatments though, and many new treatments produce ineffective or dangerous results in clinical trials.
The Food and Drug Administration (FDA) requires evidence of safety, effectiveness and proof that benefits outweigh risks before approving a drug. The only way to provide that evidence is through clinical trials.
Clinical trials vary depending on the disease or condition being studied and the population being treated. However, they all have a protocol or action plan that describes the study’s purpose, process and rules. Some studies require participants with a certain disease or condition while others require healthy volunteers.
Doctors, therapists, scholars and administrators conduct clinical trials at hospitals, clinics, universities, medical centers and other research institutions around the globe. Pharmaceutical companies fund most clinical trials, because the industry has the most money to support the overwhelming cost of developing drugs. But, some trials are funded by nonprofit organizations, academic centers and government organizations like the National Institutes of Health, U.S. Department of Defense and Veterans Affairs.
Clinical trials are essential to the drug development process, and they should include a variety of demographics – like age, race, and gender – to be sure that the treatments work on all populations.
There are many things that participants should know before participating in a trial, and many questions they should ask to be sure that participation is right for them. There are also many measures built into the clinical trial process to protect participants as they weigh the benefits and risks of participating. Participants should learn the clinical trial lingo (described below) and understand what happens after a trial is complete.
The Drug Approval Process
The process required to obtain drug approval is extensive.
The first step of the approval process involves animal testing. Researchers must study potential treatments on laboratory animals before they can be tested in humans. If animal tests provide evidence of potential safe use in humans, drug developers must submit an Investigational New Drug Application to the FDA’s Center for Drug Evaluation and Research (CDER).
The application must include all information available about the drug. Once approved, researchers can begin clinical trials in humans. The goals of a clinical trial are to determine the safety of a drug in and to find out if a drug results in a health benefit.
During development, the drug is usually under patent protection, which gives the developer the sole right to sell the drug once approved. When the patent expires, other drug manufacturers can submit applications to the FDA to sell generic versions of the drug.
If clinical trials provide sufficient evidence of safety and efficacy, and if the benefits of the drug outweigh the risks, the developer can submit a New Drug Application. The New Drug Application contains clinical trial results and data included in the investigational application submitted earlier in the drug approval process. The CDER will make a decision to approve or deny based on all of the available data.
Process to Participate
The process for participation usually begins when a prospective participant sees an advertisement for a clinical trial, is recommended for a trial by a medical professional, searches for a trial on a pharmaceutical company website or searches the government database ClinicalTrials.gov.
Researchers usually need both patient volunteers – those who suffer from the illness a drug is meant to treat – and healthy volunteers. Participants are called volunteers because their involvement must be voluntary, although compensation is available for some trials. If there isn’t a clinical trial available for a patient volunteer, he or she may choose to be put on a waiting list until a trial for that condition becomes available. Sometimes the wait takes years.
Before gaining acceptance into a clinical trial, participants undergo a thorough screening process to ensure they meet the necessary criteria for participation. The screening process can take 3-4 weeks to complete. Information examined during the process usually includes medical history, laboratory results and risk factors. The researchers must determine if the participant is the right person for the study, but participants should also determine if the study is right for them.
Things to Know Before Participating
Before agreeing to partake in a clinical trial, there are many things participants should know.
Participants should be fully aware of all of the information provided in the research protocol, which typically includes:
- The purpose of the study
- The criteria for participation
- The study’s schedule
- The study’s length
- The information about the participant being studied
Participants should also understand how treatments used during the trial will affect any current treatments they are taking. They should always consult their personal physicians before agreeing to participate in a clinical trial. Most participants work with their health care providers and the trial’s research team collaboratively. Some patient volunteers may benefit from a drug being studied, but the research team does not provide complete health care.
The amount of information that participants require to make an educated decision about participation varies based on the type of clinical trial and the individual making the decision. Some questions participants should ask researchers include:
- What type of treatment will be involved in the study?
- What evidence is there that the new treatment could be effective?
- What other tests have been done involving this treatment?
- How do the test treatment’s risks compare with those of alternative treatments?
- What are the responsibilities for participation?
- What safety measures are in place?
- What happens if an injury occurs?
- What follow-up or long-term care is available?
- Can treatment be continued after the study if it is effective?
- Who is funding the study?
- Will results of the study be provided afterward?
Patients should understand what their options are if they were to become sick or their condition were to worsen during a clinical trial.
Clinical Trial Lingo
It’s important for participants and prospective participants to understand certain terms and phrases associated with clinical trials.
All clinical trials are conducted in phases:
- Phase I trials: involve a relatively small group of 20-80 people in order to evaluate safety and identify side effects of a new drug or treatment for the first time.
- Phase II trials: involve a bigger group of 100-300 people in order further evaluate a drug’s safety and effectiveness.
- Phase III trials: involve even more people, usually between 1,000-3,000, to confirm effectiveness, monitor side effects and compare with typical treatments.
- Phase IV trials: also referred to as post-market monitoring, occurs after the FDA approves the drug or treatment and the organization monitors its use among the public.
A control group is a group of participants, usually half of all participants, that receives either no treatment or a standard treatment. Researchers compare a control group with a group receiving the experimental treatment in order to determine differences between the two groups.
A placebo is a drug or treatment that is harmless. It is given to the control group in a study without their knowledge. Usually, it is not used if a participant has an illness or condition that would be made worse if he or she went without some kind of treatment.
In order to further reduce bias, researchers conduct blind studies. In single blind studies, patients are not told which treatment they are given. In double-blind studies, neither the research team nor the participants know who is receiving which treatment. Typically, a third party, such as a pharmacist, will know who receives what treatment.
Randomization occurs when different treatments, including placebos, are assigned to participants at random without the knowledge of researchers or participants in order to reduce bias.
Once participants understand the study and understand the lingo used in clinical trials, they should evaluate the benefits and risks of participating.
Benefits and Risks
All clinical trials involve risks. Participants should consider the chance of harm occurring and the degree of harm that could occur. Participants should only partake in trials if the benefits of an experimental treatment outweigh the risks.
Potential risks to participating in clinical trials include:
- Trials may take more time than standard treatments
- Testing procedures may be unpleasant, like taking blood tests
- Treatment could result in minor side effects, like nausea and headaches
- Treatment could result in serious or life-threatening side effects
Potential benefits to participating in clinical trials include:
- The ability to help discover new treatments
- Quicker access to potentially helpful treatments
- Regular medical attention
- The ability to help others
- Financial compensation
Compensation for Participation
The use of financial compensation for participation in clinical trials raises several ethical issues, particularly involving vulnerable populations.
Children and mentally-challenged populations may not be able to make decisions for themselves, and their guardians may be in charge of their finances which creates conflicts of interest. Lower-income and illiterate populations may have trouble understanding risks, and they may be more likely to take risks for money.
Still, compensation for participation is common. Sponsors usually pay to increase participation or pay for injuries. The amount of compensation depends on a variety of factors considered by researchers. Some trials compensate based on the supply and demand of eligible participants, and some pay for reimbursement of travel costs or wages lost. Compensation can also be used to reward for helping advance medical knowledge
As with all aspects of clinical trials, the amount of money compensated varies from trial to trial.
- Some participants are paid around $50 just for going through the screening process, even if they aren’t accepted for a trial.
- Some three-day trials pay between $500-$700.
- An antidepressant trial in Nebraska paid participants around $2,000 per week, but the risk of side effects was high.
- Volunteers for a study researching Malaria vaccines in Seattle received between $2,000 to $4,000.
- There are reports of young adults regularly participating in clinical trials, making more than $20,000 to pay their way through college.
However, not all clinical trials pay for participation. Typically, early-phase trials pay the most often and the highest amounts because the risks are greatest early in a drug’s development. In order to protect participants from being taken advantage of, certain requirements are built into the participation process.
The history of clinical trials and human experimentation isn’t pretty. The human experiments on Jews in concentration camps during the Holocaust and the experiments on African-American men during the Tuskegee Study led to the establishment of Institutional Reviews Boards (IRB) to protect study participants.
During the Holocaust, Nazis experimented on Jews (and other Nazi enemies) to test the limits of the human body. During the Tuskegee Study, the U.S. Public Health Service and the Tuskegee Institute allowed participants with Syphilis to go untreated to study the disease’s progression to help develop treatments. In both cases, participants either participated against their will or were misled.
IRBs are independent committees that review, monitor and approve all experiments involving humans. IRBs that approve clinical trials usually include physicians, statisticians and community members. In order to receive IRB approval, trials must be ethical, protect the rights and welfare of participants and make sure risks are reasonable compared to potential benefits.
The FDA offers additional protections. In order to monitor clinical trials, the FDA’s bioresearch monitoring (BIMO) program is supposed to conduct on-site inspections. Other organizations, such as the Office of Human Subjects Research Protection, can help ensure participants are protected during trials.
One of the most important tools for participant protection is the informed consent process. During this process, participants receive information necessary for them to make educated decisions. The informed consent document includes risks, potential benefits and alternate treatment options. The process also involves question-and-answer sessions and activities that measure participant understanding. It also ensures participants act voluntarily and know they can quit participation at any time.
Once the screening process is complete and the informed consent form is signed, the clinical trial begins.
Responsibilities During a Clinical Trial
Every trial is different, but many trials require reporting to a research center multiples times a day, week or month for blood draws and physical examinations. Some trials require participants to keep records of their nutritional intake, exercise levels or lifestyle habits. Depending on the length and type of the trial, participants may be required to stay overnight for around-the-clock observation. Trials can be as short as a weekend or as long as a multiple years.
While the researchers examine participants for health benefits and side effects of the treatment being studied, they must keep the participant’s safety at the forefront of their concern. If a patient volunteer is in a control or placebo group, he or she could suffer from receiving no treatment for a disease. Of course, all volunteers are subject to negative side effects that could develop during a trial. Many participants are forced to quit due to negative side effects or disturbing lab results. Volunteers can always quit a trial at any time, even if they just don’t feel like participating any longer.
What Happens After the Trial Ends
At the end of a clinical trial, researchers examine data and information collected during the study to try to develop conclusions. After a phase I or phase II trial, the researchers decide if the treatment was effective enough to move on to the next phase or if they should discontinue because of concerns about safety or effectiveness. After a phase III trial, researchers determine if the drug is ready to apply for FDA approval.
Sometimes, researchers will try to get clinical trial results published in academic or medical journals. Media organizations may also cover the results of major studies, but patient data should always be anonymous. If the FDA approves a treatment, it can become a standard treatment for the population it is meant to treat.
Even after a trial is complete or a participant quits, participants may still have to visit research labs. Researchers can still collect data to analyze possible withdrawal systems after participants stop a treatment.
If a participant is planning on participating in a future trial or resuming other medications, they usually must wait for all of the trial medication to leave their system before beginning a new one.