Part 1 of 2
Enrolling in a clinical trial is not something that should be done lightly or without a good deal of thought. While there may be advantages to you, your family and to society, there are likely to be risks as well. People enroll in clinical trials for a variety of reasons. Some are seeking out new treatments for themselves or family members. Others have an interest in a particular disease. Many people find out about clinical trials from their physician. Others are identified through ads in local newspapers, television and radio announcements and posters. Regardless of why you may be considering enrolling in a clinical trail or how you found out about it, you will need some additional information before making a decision.
What Are Clinical Trials?
Clinical trials are studies done in humans that are designed to answer very specific questions. Examples of kinds of issues that clinical trials might examine include the use of a new treatment or a new diagnostic test, the impact of the environment on a disease, or how genetics determine clinical outcomes. When done correctly, clinical trials can add to our understanding of health, disease, diagnosis and treatments. The overwhelming majority of clinical trials are done responsibly. However, this was not always the case. As a result, a series of regulations have been established that define the ways in which studies should be done and provide for both government and institutional oversight.
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All clinical trials done in the United States fall under a complex and sometimes bewildering set of state and federal regulations. The regulations are designed to protect the people who participate in clinical trials. Although they require a bit of interpretation, the regulations are actually well constructed and are based on a series of time-honored principles. The foundations for the regulations lie in two documents produced by the National Institutes of Health: the Nuremberg Code and the Belmont Report. Simply put, the regulations ensure:
- Respect for persons — People have the right of self determination and should enroll in clinical trials of their own free will. Those with diminished capacity should have special protections.
- Beneficence — Clinical trials should be designed to maximize possible benefit and minimize possible harm.
- Justice — People participating should be fairly chosen without undue regard to race, ethnicity, religion, social status or gender.
To make sure that these principles are carried out, the federal government in 1974 mandated the formation of an oversight committee at every institution that conducts clinical trials. The committees, called institutional review boards (IRBs), were given the responsibility of ensuring the protection of people participating in clinical trials. The IRBs must have people from the community serving as full members in addition to experts from the medical profession and other professional staff. The activities of the IRBs are regulated by both the federal and in some cases state governments. In addition to meeting standards set by the government, IRBs can seek to be accredited by well-respected national organizations such as the Association for the Accreditation of Human Research Protection Programs and others.
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Types of Clinical Trials
Most clinical trials fall into one of three general categories:
- An observational study — The study only involves the collection of information without any type of personal testing or sampling
- A non-interventional study — The study could include collecting blood or urine samples, a specific meal plan, an exercise program, or monitoring sleep patterns.
- An interventional study — These are the studies that might require taking a new drug or an old drug for a new indication, undergoing diagnostic testing, or having a surgical procedure.
From the standpoint of risks, interventional studies usually are at the top of the list, with non-interventional and observational studies ranking second and third, respectively.
Observational Clinical Trials:
Observational clinical trials involve the collection of information. There are no study procedures or laboratory tests. No new drugs or diagnostics are involved. Your involvement is usually limited to allowing the collection of:
- Information about your care and your progress while in treatment
- Specimens that are already routinely collected during care. The specimens can have additional tests run on the same samples. Another example is having tissue that was removed during necessary surgery examined for something more than the initial intent.
- Your responses to a series of questions about treatment or living with a particular disease
The major risks of being part of an observational study are risks to privacy. Observational studies can involve the collection of a great deal of information about you and your family.
Non-Interventional Clinical Trials
Non-intervention trials are very similar to observational studies but there is some procedure that is done just for the study. The procedures are usually defined as having very low risks such as the collection of a small blood sample, urine sample and the like. Non-interventional studies also can involve other kinds of noninvasive diagnostics such as ultrasound or MRI. Like in observational studies, a good deal of information is sometimes collected, so privacy can be a concern. The actual study procedures should be of very low risk as well.
Interventional Clinical Trials
Interventional trials are studies that do involve some action performed solely for study purposes. The intervention can include:
- A new drug or biological agent
- A new vaccine
- A new radiology test
- A new surgical or other kind of procedure
Interventional studies usually include some form of risk. The risks may be directly related to the drug or test or procedure. There is also the risk of not receiving the standard drug, test or procedure if you are assigned to the experimental group and the experimental action turns out to be less effective.
Interventional trials involving new drugs are usually conducted in a stepwise fashion (called phases). Each phase has a different purpose and helps answer different questions:
- In Phase I trials, researchers test a new drug or treatment in a small group of people, usually without disease, to test its safety, determine a safe dosage range, and identify side effects.
- In Phase II trials, the study drug or treatment is given to a larger group of people with the disease to see if it is effective and to continue to evaluate it for safety.
- In Phase III trials, the study drug or treatment is given to large groups of people with the disease to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. Phase III trials may also include the use of placebo or a standard drug or treatment for the disease.
- In Phase IV trials, the risks and benefits of the treatment are evaluated after the approval from the U.S. Food and Drug Administration. These are called “post marketing studies,” and they are designed to obtain real-world information of the value of the treatment.
Next month, in Part 2, I will discuss how you can participate in a clinical trial, and what questions you should ask when making the decision.
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Harold J. DeMonaco, M.S. is senior clinical associate in the Decision Support and Quality Management Unit at the Massachusetts General Hospital and is currently a Visiting Scholar at the MIT Sloan School of Management. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals.