What you need to know before becoming a human subject in a clinical trial - Public Citizen (2023)

health card, March 2013

Every day, hundreds, if not thousands, of patients are recruited to participate in clinical trials in hospitals, clinics, and doctor's offices across the United States. These trials test new experimental drugs, medical devices, and other interventions for a wide range of diseases and disorders, including cancer, heart disease, depression, asthma, infections, diabetes, and high blood pressure, to name a few.

Before enrolling an individual in a clinical trial, federal regulations require investigators conducting the study to first obtain informed consent from the individual. The process of obtaining informed consent includes informing potential participants about, among other things, clinical trial procedures, their risks and benefits, and alternatives to study participation that may be beneficial to the participants.

To help readers make informed decisions about participating in clinical trials, this invited article explains the fundamental difference between clinical care and research and provides guidance on important issues to consider before participating in a clinical trial.

Clinical care versus clinical research

When physicians invite their own patients to participate in clinical trials, patients can assume that participation in a trial is simply part of clinical care and is in their best interests. However, participating in research and treating a condition are not the same. It is important to understand the fundamental differences between clinical care and clinical trials research, between a patient and a human subject, and between a physician and a researcher.

In clinical care, the physician's sole responsibility is to act in the best interests of the individual patient. Clinical treatment recommendations and decisions are individually tailored and based solely on each patient's unique characteristics, health needs and desires. The sole purpose of clinical care is to benefit the patient.

In contrast, the interventions that a human subject receives as part of a clinical trial are mandated by a research protocol. This protocol generally prescribes the medical interventions that the subject will receive, such as the type, dose, and frequency of medications, and the type and frequency of medical tests and procedures, without regard to individual patient needs or personalized patient recommendations. Physician.

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Furthermore, the primary goal of clinical research is not benefit to the individual subject, but to answer a scientific question or to test a medical hypothesis, and ultimately to generate new medical knowledge that may benefit future patients. Therefore, in the context of a clinical trial, the interests of the individual subject are subordinate to the goals of the investigation.

Some bioethicists have concluded that the only way to effectively minimize the potential for patients to confuse medical research with clinical care is to prohibit physicians from enrolling their own patients in clinical trials in which those physicians are involved are researchers too. Since this ban has not been enacted, it is very important that patients understand the difference between clinical care and research so that they can make informed decisions about whether or not to participate in clinical trials.

important questions

Before a patient agrees to participate in a clinical trial, they should ensure they receive and understand the answers to the following key questions:

What is the purpose and phase of the clinical investigation?

The purpose of a research study indicates why the clinical study is being conducted. In general, purpose is defined by the sophistication of the experimental intervention to be tested. For example, clinical trials of experimental new drugs are generally divided into three phases, referred to as phase 1, 2, or 3.

Phase 1 clinical trials are studies that test a new drug in humans for the first time. In these studies, a small number of people are exposed to a single dose of a new drug and data is collected on short-term toxicity, metabolism, and excretion of the drug (how the drug is absorbed, broken down, and eliminated from the body). . Phase 1 trials generally involve healthy adult subjects, but those testing specific types of drugs include patients with specific diseases. (For example, phase 1 clinical trials of new cancer chemotherapy drugs often involve patients with advanced cancer.)

In Phase 1 trials, there is no human study data to suggest the drug is safe or effective in the patients for whom it is being developed. The primary goal of a phase 1 trial is to find the highest dose of the drug that does not produce unacceptable toxicity. Data from these studies will be used to guide dosing in the subsequent Phase 2 and
Phase 3 Studies.

Phase 2 clinical drug trials are designed to collect preliminary data on the effectiveness of a new drug in patients with a specific disease or condition, as well as additional information on toxicity and metabolism. These studies generally involve relatively small numbers of subjects (approximately 40 to 200) and involve exposure to multiple doses of the study drug. In some phase 2 trials, all subjects will receive the new investigational drug and there will be no control group. In other phase 2 trials, a group of subjects receiving the investigational drug is compared to a control group of similar subjects receiving a different intervention, e.g. B. an inactive substance (placebo) or another drug that is used in the treatment of Alzheimer's disease. disease interest

When phase 2 trials begin, investigators often have little or no information about whether the new investigational drug is appropriate for treating the intended patient population and minimal information about the drug's short-term toxicity.

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For most new drugs, phase 3 clinical trials are the final stage of testing before the Food and Drug Administration (FDA) considers the drug for approval. These studies, which usually involve several hundred or thousands of people, gather more information about the drug's safety and effectiveness by testing the drug in different populations, at different doses, and sometimes in combination with other drugs. For these trials, there is generally limited evidence from previous phase 2 or 3 trials that suggests the drug may offer some benefit to the intended patient population, but that benefit has yet to be demonstrated.

After a drug has been approved by the FDA and is no longer considered experimental for its FDA-approved indication, phase 4 clinical trials are sometimes conducted. These trials, conducted after a drug has been approved, may be considered by the FDA as a condition for the drug requires approval. Approval or can be done voluntarily by the pharmaceutical entrepreneur. They may be similar in design to Phase 3 trials, or they may have only one arm in which all study participants receive the specific drug being tested. The purpose of these studies is to gather more information about the safety, effectiveness, or optimal use of a drug in a real-world setting.

Studies of non-drug interventions such as medical devices or social and behavioral interventions do not fit neatly into the same four phases of clinical trials used to develop new drugs. However, studies of these other interventions generally follow a developmental path from early-stage studies, where little is known about the safety and efficacy of the intervention, to late-stage studies, where more is known. Therefore, before enrolling in a clinical trial, it is important to know where the trial fits into the development schedule.

What will the clinical study consist of and how will it differ from usual treatment?

Patients considering participation in a clinical trial should be given a detailed description of any procedures and procedures that will be required of them and should be informed of the expected length of their participation in the trial. The study description should identify any procedures that are considered experimental. Ultimately, in order to make a fully informed decision about enrollment in a study, patients must make a clear assessment of how the interventions and procedures in the clinical study compare to the treatments and procedures they would undergo in routine clinical practice .

Most clinical trials have three phases. The first step involves screening to confirm that an individual meets the criteria for inclusion in the study. This evaluation may include evaluation of medical history, physical examination, blood work or tests, biopsy, or imaging studies such as X-rays, ultrasound, CT scans, or MRIs. In some cases, the subject would undergo the same procedures and tests as part of routine clinical care, and in other cases, the tests are only part of the investigation.

The second step of a study is to obtain the interventions to be tested from the primary study. In studies comparing different interventions, e.g. eg, when a new investigational drug for high blood pressure (high blood pressure) is compared to an FDA-approved standard antihypertensive drug or a placebo, subjects are often randomized to one of the two interventions. To minimize the possibility of study bias, many clinical studies use double-blinding, in which neither the subject nor the investigator, who is often the subject's physician, knows what intervention the subject is receiving. During this phase of a study, participants may undergo additional tests, blood tests, biopsies, or imaging studies, which may or may not be routinely performed when not participating in the research.

The third phase of a study is a follow-up phase, after study interventions are discontinued and subjects are followed for periods ranging from a few hours to many years. During this phase, information about the clinical status of the subjects will be collected on a regular basis to see how each patient's disease or disorder has responded to the primary study interventions being tested. Again, subjects may be required to undergo additional tests and procedures, which may or may not be routinely performed when not enrolled in the research.

What are the risks of the research?

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Essentially, all clinical trials involve the risk of harm or discomfort to subjects. Researchers often downplay the risks of a clinical trial.

There are many potential sources of research risk, including side effects resulting from:

  • the investigational drug, medical device, or other study intervention (e.g., the investigational drug may cause stroke, heart attack, liver damage, or kidney disease);
  • other procedures that the subjects undergo for the purpose of the investigation, such as complementary imaging tests, blood tests or biopsies; Y
  • poor treatment or no treatment for a potentially serious condition when subjects are assigned to the control group and receive a placebo or non-standard treatment regimen.

Women of childbearing potential need to be aware of the risks that research poses to an embryo or fetus. These can include the risk of birth defects, preterm labor, and stillbirth.

Some studies also include washout periods, during which all subjects are weaned off some or all drugs used to treat the disease of interest for a period of days or weeks before being randomized to receive one of the specified study interventions being tested. These washout periods are particularly common in tests for diseases such as high blood pressure and mental disorders. Washout periods can expose people to adverse events related to inappropriate treatment of their underlying disease or disorder. For example, a person with severe hypertension without blood pressure medication during a washout period may have a stroke or other cardiovascular event due to inadequate blood pressure control. Likewise, without antipsychotic medication, a person with schizophrenia may experience a severe psychotic episode.

Assessing the risks posed by a clinical trial requires considering the various interventions and procedures that are unique to research participation, and assessing the likelihood and severity of adverse events that may result from these interventions. The likelihood of a particular adverse event can range from extremely rare to very likely. Similarly, the severity of a particular adverse event can range from mild (e.g., slightly dry mouth) to extremely serious, life-threatening, or even fatal.

Due to limited prior testing of a particular new investigational drug or medical device, the exact likelihood of a particular adverse event is often unknown. In addition, potential subjects must recognize that a given treatment or research intervention may have unforeseeable risks. The likelihood that a clinical trial will involve such unforeseeable risks is higher in early phase trials (ie, Phase 1 and early Phase 2 trials) due to the limited safety knowledge at these points. For example, last year a phase 2 clinical trial testing an investigational drug against hepatitis C infection resulted in unexpected severe heart failure and death in some people. Because of these unforeseen side effects, the manufacturer ended the drug development program.

What are the alternatives to not participating in the clinical study?

Patients considering participation in a clinical trial should be informed of appropriate alternative procedures or treatment regimens that may benefit them. Standard and state-of-the-art treatments are available for many diseases and disorders. Patients must be informed about these treatments.

Some clinical trials compare different FDA-approved drugs or FDA-approved drug combinations to treat a specific disease. This is particularly common in clinical trials testing new cancer treatment regimens. Many patients choose to enter such clinical trials in hopes of being randomly assigned to the study group receiving the "newer" drug or regimen being tested. For such trials, patients should ask the researchers or their own physicians if they can receive any of the tested drugs or drug combinations without enrolling in the clinical trial.

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Finally, for some patients considering participation in clinical trials of interventions for advanced and terminal diseases, palliative supportive care may be an alternative that may be beneficial to patients.

What are the benefits, if any, of participating in the research?

The potential benefit to individuals that may result from participation in clinical trials varies widely between trials. Researchers often exaggerate the potential benefits of the research and subjects have unreasonable expectations of them.

For some studies, particularly phase 1 studies in healthy volunteers (which are usually paid to participate), there is no medical benefit. For patients with a specific disease or disorder being studied, the potential benefit in early-stage trials is less. In fact, subjects in early-stage trials typically experience harm rather than clinically significant benefit.

The prospect of benefit for individual subjects in phase 3 trials is greater than in earlier phase trials, but the magnitude of the benefit is unknown and may be minimal compared to routine off-trial health care. In fact, the purpose of such studies is to determine what, if any, benefit the experimental interventions provide for the treatment of the disease or disorder of interest.

Ideally, if the study is well designed and conducted, researchers will gain important new insights that will benefit future patients.

What rights do you have as a test subject?

Potential subjects must be informed that participation in the research is entirely voluntary and that refusing to participate will not result in penalties or forfeiture of any benefits to which they are entitled. For example, patients who are invited to participate in a clinical trial cannot be threatened with the loss of healthcare benefits if they choose not to participate in the research.

Additionally, patients who enroll in clinical trials are free to discontinue their participation at any time without penalty or loss of benefit. In addition, while investigators may recommend that individuals who wish to withdraw from the study undergo certain tests and procedures to ensure safe and orderly exit from a study, individuals are not required to follow these recommendations.

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Participants also have the right to be informed of any new information or discoveries about the drug or device that develop during the study that may relate to participants' willingness to continue participating. For example, if researchers determine during a clinical trial that a new investigational drug carries a risk of severe liver failure, subjects should be promptly informed of this new risk information so that they can reassess it if necessary.

Tips for Readers

Before signing up for a clinical trial, you should discuss each of the above questions in detail with the researchers. You should request a copy of the consent form for the study and ideally, if time permits, go home and take the time to discuss the proposed study with family, friends or your GP. Please consider carefully whether participating in the survey is right for you. You may also wish to conduct independent online research to learn more about proposed research interventions as well as currently available treatment options for your disease or condition. Only after you are comfortable with understanding the research and have considered all of your options should you decide if participating in a clinical trial is right for you.


1. History and Myths of Clinical Trials with Quincy Byrdsong
(Black Women In Clinical Research)
2. Clinical Data science Information Session
(Sollers College)
3. Clinical Trials 101
(Surviving Breast Cancer)
4. Lessons from the First Clinical Trial to Reverse Cognitive Decline
(Apollo Health)
5. Michael Carome presents at the HHS Public Meeting (August 28, 2013)
(U.S. Department of Health and Human Services)
6. Jazz, Blues, and Improvisation – the Changing Rhythm of Ethical Clinical Research
(U.S. Department of Health and Human Services)
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