It is a common misconception that receiving treatment in clinical trials is the same as receiving treatment as a patient. The hard reality about a clinical trial is that it is designed to answer a scientific question, not to provide medical treatment. Someone thinking about participating in a clinical trial needs to understand the difference between research and medical treatment. When you’re a research subject, you often feel like a patient. You usually make visits to a doctor’s office where you’re examined by a doctor, undergo lab tests and receive a medication. In many ways participating in a clinical trial seems just like visiting with your doctor to receive medical care. But your doctor’s primary goal is to help you feel better. The principal investigator’s primary goal is to see how you will react to a new drug in order to determine whether that drug will be medically useful.
This truth doesn’t change the fact that many people feel better while on an investigational drug. Many investigational products prove to be far superior to the older drugs they will one day replace. Drugs given in clinical trials have not only improved, but have also saved thousands of lives.
Patients in clinical trials are treated with drugs for everything from ulcers to strokes years before the FDA approves them. Even people with common illnesses, such as sinusitis or sore throat, are often very motivated to enroll in a clinical trial when other drugs have failed to relieve their suffering. People with AIDS and certain cancers are particularly anxious to sign up for a trial because it gives them access to investigational drugs that may offer their only hope of survival. About 95% of children with leukemia are in clinical trials.
The kinds of benefits people may receive depend not only on the specific study in which they participate, but also on which part of the study they are randomized into. Subjects who get randomized into the control group will, at best, get a standard treatment that is already available at pharmacies and drug stores. But they may also get free screenings and exams, the camaraderie of people dealing with the same medical condition, the opportunity to be an active player in their own health care and the knowledge that they’re helping to answer questions that can improve the health care of future generations.
A surprising number of people participate in clinical trials even if they personally have little, if anything, to gain by doing so. Some volunteers get involved because they want to contribute to the advancement of medical knowledge or to help people suffering from an illness. A few do it out of simple curiosity or because they believe study volunteers get better medical care. An altruistic spirit offers no special protections or guarantees. Altruism – unless it’s balanced with a healthy dose of skepticism – can leave people vulnerable. Smart patients ask questions and get second and third opinions even if they expect little or no medical gain for themselves.
People who participate in clinical trials often learn a great deal more about their illness and about other conditions (including underlying heart disease and diabetes) they may not have known about. Study-related x-rays, lab tests and physical exams have picked up unsuspected cases of many types of cancers early enough to be successfully treated by specialists. For some participants, the best end result of a clinical trial is that they start taking better care of their own health.
Another common benefit of volunteering for clinical trials is that participants get to meet research professionals who can help introduce them to other patients suffering from similar illnesses. Volunteers also may meet scientists and professionals who can help them better understand their illness and can tell them about new treatment options under development. The many people whom you meet in a clinical trial can greatly enrich your knowledge.
For individuals diagnosed with a severe and possibly life-threatening illness, the greatest benefit of clinical trials is that they offer hope. At its best, a clinical trial is an enlargement of – not a substitution for – a patient’s regular medical care team and support circle.
Some people participate in clinical trials because they don’t have health insurance and need help covering medical treatment costs. Drugs for cancer and AIDS can run upwards of $1,000 a month. Volunteers in clinical trials almost always get free medication, as well as physical exams and other medical services like blood tests and EKGs (a tracing of the heart’s electrical activity) that help researchers monitor the drug’s effects. Often, they also get treated at no charge for other minor illnesses that happen to develop during the clinical trial. The free drugs and medical care are primarily provided to ensure compliance with the study protocol and to help the volunteer remain in the study.
A number of study volunteers participate primarily to earn extra money. Payment is most often used as an incentive to recruit healthy volunteers who derive no direct benefit from the research, such as in most phase I studies. Depending on the trial, testing phase and the company sponsoring the research, this can be a significant amount – from $100 to more than $1,500.
There are even some people who make a profession out of being a clinical trial volunteer. They may only earn several thousand dollars a year, but their participation doesn’t involve hard labor and it doesn’t require much mental work. Professional volunteers feel that they are treated well and that they are needed. But along with the common risks in clinical trials, professional volunteers also face another risk: The long-term, cumulative effect of consuming investigational drugs. Professional patients tend to be young and to feel invincible.
The volunteer compensation on most clinical trials primarily covers the costs of participation. These costs might include time, transportation, babysitter and lunch. Some studies simply hand out money to pay for parking. For other types of trials, a flat fee of between $25 and $50 per visit to the study site is pretty typical. But payments can vary considerably from city to city and from study to study. Research institutions may also have their own unique payment policy. Some institutions limit how much a person can earn during a given time period.
Other factors can influence the amount of compensation that a volunteer will receive. Clinical trials competing for volunteers, requiring numerous procedures and visits, or involving some discomfort – such as wearing a 24-hour blood pressure monitoring device or involving an invasive procedure – often pay more. Compensation would be higher for a phase III vaccine trial requiring a five-night inpatient stay, for example.
In Florida, a recent sinusitis study involving four visits, x-rays, CAT scans and tubes up the nose was paying $500 for participants whose sinus passages were sufficiently blocked. A two-month study of an investigational medication for GERD (gastroesophageal reflux disease) was paying $1,700. But it involved having an endoscopy – an inspection of the digestive tract using a tube-like viewing instrument fed through the mouth – on three different visits. By comparison, a recent clinical trial that involved taking several pills for a week paid each volunteer $150.
Typically, the research center writes each volunteer a check as the study progresses – usually on a per-visit basis. A small bonus may also be paid to volunteers who complete the entire study. In some cases, study doctors may dispense approved medication samples and provide additional care free of charge after the trial to show their appreciation to study volunteers.
Most people who participate in a clinical trial have a positive experience. In exit interviews with volunteers, the majority report that they received high quality care, high levels of professionalism and that they would participate again.
The reason people initially enroll in a clinical trial is not always the same reason they remain in a clinical trial. The experience is an ever-changing one and, unfortunately, the changes aren’t always for the better. When that happens, the temptation to drop out of the study can be very strong. Waning interest in a clinical trial – or sudden, mixed feelings about the whole ordeal – is understandable and completely natural. These feelings should not be disregarded. There may be good reasons to drop out of a clinical trial. There may also be good reasons to stick it out.
No more than one third of all people who come in for a screening end up completing a clinical trial. The reasons for leaving a clinical trial are as varied as the number of study volunteers. Some participants never pass the eligibility criteria. Others drop out because the drug isn’t helping them or the side effects are too unpleasant. Some volunteers get too busy to make visits to the research center or they grow tired of the study procedures and having to complete a detailed diary. Some volunteers may move out of the area. Some simply don’t like the location of the research center or they don’t like the study staff. Some volunteers find another clinical trial.
When you have conflicting and ambivalent feelings, you might begin by talking with the investigator or study coordinator at the research center to find out if other study volunteers are feeling the same way. You may also want to speak with your specialist, primary care physician or nurse. Dropping out of a study – at any point and for any reason – is always an option. But it should not be a decision based solely on a bad mood or misinformation. The mood will pass and answers to questions and problems may be forthcoming.
A clinical trial is a partnership between study staff and study volunteer and it’s based on informed trust. Dropping out on a whim betrays that trust. Study staff deserve the courtesy of being approached later if something feels wrong.
If there are serious problems that can’t be corrected or evidence that the investigator or study staff can no longer be trusted, you should most certainly drop out. You have the right to quit a trial at any time, for any reason – or no reason at all. Researchers may not like it if you drop out of a study for seemingly trivial reasons, like a headache, because investigational drugs must be tested in volunteers who remain in a clinical trial to the end. A research doctor, however, may well make the first move to drop participants from a trial if a drug appears to be endangering their health.
No ethical investigator would ever try to penalize study subjects – however subtly – for making the decision to quit on their own. But study dropouts should be aware that their financial compensation, if offered, will probably be lower than that had they stayed in the experiment until the end.
The reasons people choose to participate in clinical trials are compelling: (1) To gain access to new therapies; (2) To advance science and help others who are trying to cope with illnesses; (3) To earn extra money; and (4) To receive free medical care. But there are many reasons why people choose not to participate.
In fact, only about 2% of the American population get involved in clinical research each year. Among people who suffer from severe, chronic illnesses, only 6% participate. As a result, an increasing number of clinical trials are delayed because too few people are willing – or even knew they had the opportunity – to get involved.
Most people appreciate the value of clinical research and say they are likely to participate in a study. Yet no more than a third of those who identify and qualify for a clinical trial choose to enroll. There are a number of reasons for their reluctance. You may share some of these concerns:
They don’t want a placebo. They want a guarantee that they’ll receive a drug meant to treat their disease, not an inactive pill. For medical conditions for which there is already an effective, FDA-approved drug, such as high blood pressure, this may not be a concern. The investigational drug may be compared to a standard one for the entire study. In other cases, a “crossover” study may be done that rotates study subjects through equal periods on the new drug, the standard one and a placebo. Unfortunately, the best (and sometimes only) way to figure out how well some medications work is to compare people who take them with people who don’t. The problem is that patients receiving a placebo are essentially not being treated. Therefore, they may have increased pain and discomfort. Their condition may even worsen, making it more difficult to treat later on. But, some subjects do improve with a placebo because they believe they are being treated. That is why a placebo component is included in many protocols – to study how effective the investigational drug is, compared with how effective the placebo is.
They worry about side effects and potential risks. Previous testing, on animals and other people, never completely rules out new, unexpected reactions to a drug. Side effects, also called adverse events, can be minor, such as those associated with drugs already on the market. Volunteers are told of new side effects identified during a clinical trial. Serious side effects, also called serious adverse events, such as anaphylactic shock or liver failure, would require immediate investigation and could stop a study. The research center would cover the cost of any ensuing medical bills for study-related illnesses, but the center may not cover all the bills that might pile up during a participant’s recovery.
They’re concerned about losing access to the drug when the trial stops. Very little of a drug is made until a pharmaceutical company has clearance from the FDA to sell it. But volunteers with serious or life-threatening illnesses who have completed a phase III study may be rolled into an “open label” study, allowing study subjects to take the investigational drug, for free, until the FDA approves it.
On rare occasions, a life-saving drug will be so popular among study participants that the pharmaceutical company literally can’t make enough of it and has to divvy up what it can produce by means of a “lottery.” This didn’t quite work out as planned for the AIDS drug AZT. Because half of the subjects requesting the drug from every research site were randomly given a placebo, patients ended up dumping their pills together and sharing from a common supply. That way, they figured, everyone at least had some chance of getting the actual drug. Drugs that effectively treat a serious or life-threatening condition and have the potential to address an unmet need are now put on a “fast track” through the FDA approval process, limiting the wait for the product outside the clinical trial environment.
A standard therapy is already available. Some people would rather not take a chance on a new drug if treatments offering even small benefits are already available. Often it is simply inconvenient to change treatments. And, the small benefits of a standard therapy are better known than those of a novel therapy. Patients who are on a helpful medication run the risk of relapse in their illness because testing a new drug requires that study volunteers withdraw from their current treatments. If study participants become too ill, researchers may shorten the “washout” period, which is the period of time when a study participant cannot take any medication in order to “wash out” any drug effects. But there’s still the possibility that they they’ll receive a placebo. FDA-approved “rescue medications” (Tylenol, for example) might also be used to reduce discomfort.
They’re inconvenient. The requirements to participate in some trials might also be viewed as unreasonably burdensome. Some people can’t be paid enough to endure repetitive blood draws, rectal exams, needles, or even to temporarily quit smoking, drinking beer, or having sex. Some people do not have the time to fill out a diary of their symptoms and experiences several times a day or week. Some potential volunteers cannot make numerous visits to research centers that are far away or travel tens of miles to perform a test procedure.
They can’t afford unexpected costs. Although most of the volunteer’s costs in a clinical trial are paid for, some people choose not to participate because they may have to pay for certain routine care costs while they’re in the study. These costs can include doctor visits, hospital stays and blood tests. Medicare now covers beneficiaries’ healthcare costs while they are in a trial, but only a handful of states require commercial health insurance plans to cover even part of the cost of care during a clinical trial.
In Florida, an enrollee in a phase III antibiotic study was stunned to receive a hospital bill for thousands of dollars simply because of her treatment choice for a severe hand infection. Her insurance company wouldn’t pay because the treatment was “experimental.” And the study sponsor wouldn’t pay because the study medicine is what healed her wound – not what landed her in the hospital.
At the present time, a growing number of health maintenance organizations (HMOs) and other insurers are getting involved in clinical research to offer their patients more treatment options. These are likely to be later phase III and IV trials that are a better fit with their philosophy of covering only treatments that are scientifically proven as both safe and effective. Some health insurers now willingly pay for the routine healthcare costs of patients enrolled in FDA-approved trials for investigational cancer drugs.
Before volunteering for any clinical trial, the first question you need to ask is: “How far am I willing to go?” For patients and their families facing a serious, life-threatening illness, the question is often easy to answer. But for less severe though unpleasant illnesses, the answer is more difficult. Your answer to this question dictates how hard you will push yourself to gather as much information as possible about the clinical trials actively seeking volunteers with your illness. Clinical trials are not only time consuming, but also they require an unprecedented commitment from you to intelligently and carefully pursue appropriate trials and the professionals conducting them, to possibly forego using medications with known benefits and to have potentially uncomfortable procedures performed. And, in the end, you may receive a placebo.
The research center isn’t the only – and may not even be the best – source of information about a particular clinical trial. Research centers recommend specific clinical trials for a variety of reasons – scientific, political and even economic factors are all influences. Some clinical trials bestow professional prestige and monetary rewards, for example, on researchers and research centers. Often these rewards may cloud otherwise sound medical decisions. Some research centers may overly promote clinical trials that are having trouble finding study volunteers.
It’s a good idea to seek second opinions – medical or otherwise. Doctors and health professionals should not discourage you from seeking clinical trials when appropriate and should provide you with the information you need to make an informed decision.
Each person’s experience in a clinical trial is unique. Two people with similar conditions – the same diagnosis, the same stage of disease and complicating factors, receiving the same active drug at the same place and time – will not always react the same way to an investigational drug. The human body responds differently to illnesses and illness-fighting drugs due to many factors. The best that researchers can do is seek to do what is best for most people most of the time based on the best available knowledge.
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Introduction