People choose to participate in clinical research for a variety of reasons. Some enjoy the opportunity to further science; others desire early access to new, still experimental medications; some use clinical research to gain access to highly sought after physicians or specialists; or to obtain medical care not covered by their insurance plans. Others simply enjoy the camaraderie, education and close medical attention afforded by frequent visits to the site where the research is being conducted. Patients may be paid for their participation in studies.
Should you volunteer?
Clinical research is not for everyone. Some people may be hesitant to participate in research due to concerns about the safety of the study medication and how well it may work, their own time constraints and various other concerns. To help you make a more informed decision regarding your own or your child’s participation in clinical research studies, it’s important to understand the process of drug development; U.S. Food and Drug Administration (FDA) requirements for the development and approval of new medications; and federal regulations that protect the rights of clinical research participants.
New drug testing
To ensure that drugs are safe for humans, drug testing is done as follows:
- Drugs are initially developed and evaluated in the laboratory to ensure that each drug possesses the desired characteristics and actions.
- If a drug appears to have the desired properties, it is then tested in animals to determine what, if any, side effects the drug may cause. A wide range of doses are administered to test for side effects, both at the estimated human dose level as well as in large overdoses to determine possible toxic effects.
- The candidate drug is also given to pregnant animals to determine whether it has any adverse effects on the developing fetus. This is to help determine whether the drug would be safe for pregnant women.
- If the candidate drug appears to be safe in test animals, it is then ready to be tested in humans.
Clinical studies on humans
Before an experimental medication is tested in humans, an Investigational New Drug (IND) application must be filed with the FDA. After reviewing all of the laboratory and animal data, the FDA will either approve the IND if they think the drug appears safe enough to be tested in humans, or deny the application if the risks appear unacceptably high. If the IND is approved, the first phase, called a Phase I trial, of advanced drug development begins. This phase usually involves testing the drug in normal adults, followed by adults with the disease targeted by the drug, to determine the safety of the drug at various doses.
Phase I trials are followed by larger Phase II trials in which the effectiveness and safety of the drug is tested over a range of doses. These are generally multi-centered, placebo-controlled, multi-dose, blinded trials. This means that the exact same study is conducted in multiple medical centers across the country. Individual subjects participating in the trial may be on one of several doses of the real medicine or on an inactive placebo (fake). Neither the investigator (research doctor) nor the subject know what the subject is actually getting. The purpose of these studies is to determine scientifically whether the drug is effective compared with a placebo, and if so, what the optimal dose might be. This approach is usually the only way to know for sure if a drug is safe and effective.
Once an optimal dose is determined, even larger multi-center Phase III trials are conducted to establish the safety and effectiveness of long-term treatment (usually up to 12 months). After successful completion of Phase III trials, the pharmaceutical company submits to the FDA a new drug application containing all of the data collected from all of the trials. After thorough evaluation of each piece of data, the FDA acts on the application, approving the new drug only if safety, efficacy and drug stability are proven. The whole process, from the pre-clinical laboratory stage to final approval, takes about 10 years.
Frequently, after a drug is FDA-approved and is marketed, research will be done to determine the best way to use the new medication. These are called post-marketing, or Phase IV, trials. Typical examples of a Phase IV trial would include comparisons between two drugs on the market, or comparisons between two different time/dose schedules for taking a single drug.
Who watches out for the patients?
All research involving human subjects must be reviewed and approved by an Institutional Review Board (IRB). The IRB reviews the research protocol, the informed consent form (the document explaining the study, including risks and benefits, to the potential study subjects), known information about the drug (including reports of unexpected adverse events), and any potential advertising planned for recruitment of subjects.
The job of the IRB is to ensure that the protocol and recruitment techniques are ethical, the potential subjects are fully informed about the procedures, risks, benefits and alternative treatments available before they agree to participate in the study, and that the subjects are not placed at unacceptable risk. People interested in becoming a part of such a research study should first read the informed consent document carefully, and then ask the study personnel any additional questions before agreeing to participate.
Most research protocols have built in safety monitoring for subjects. These may include blood or urine tests, x-rays, electrocardiograms (which monitor heart activity), and other tests. Many protocols also have automatic “kick out” criteria, instructing investigators to withdraw a subject from the study if the disease being studied worsens significantly. These safeguards help to prevent research participants from experiencing increases in their disease symptoms as a result of receiving a placebo or ineffective dose of the study drug.
Research participants should not agree to take part in a study unless they intend to complete it. However, subjects do have the right to drop out of a study at any time. Typical reasons for dropping out include unacceptable side effects from the drug, worsening of a subject’s medical condition, or changes in work schedules that make it difficult to attend the clinic according to the study schedule.
The study doctors (investigators) may also withdraw someone from a study if they feel that it is not in the study subject’s best medical interest to remain in the study. This usually happens if the subject’s medical condition is getting worse, or if new information about serious adverse effects becomes known. The IRB also has the power to terminate a study if they determine that the study procedures or medications pose too much of a risk for subjects. The pharmaceutical company may terminate a study if they discover that the investigational drug is not appropriate for further development. This usually occurs as a result of the drug being too toxic or ineffective.
How do I decide which study to take part in?
Most research centers do several studies at a time, so you may be eligible for more than one study. Try to find a good match between your own needs and the needs of the study. Ask not only whether you fit the study inclusion/exclusion criteria, but also whether the study meets your medical and scheduling needs.
For instance, if you are interested in participating in an asthma study, but you know that your nasal allergies will flare up during the study, you’d probably want to choose a study that allows you to take your nasal medications. If you are particularly concerned about safety issues, a Phase III or post-marketing Phase IV trial may be more desirable for you than an earlier Phase I or II trial, since more is known about a drug’s side effects by that time. Or, if you have a very tight schedule, a study with short visits would work better than one with several long visits. Most research subjects seem to enjoy participating in studies, and many choose to participate in additional studies after finishing a protocol.
If you are interested in participating in research studies, contact Allergy & Asthma Clinic of Central Texas for information on clinical trials taking place in your area.
Your allergist/immunologist can provide you with more information on clinical research trials.
The content of this article is for informational purposes only. It is not intended to replace evaluation by a physician. If you have questions or medical concerns, please contact your allergist/immunologist