“I have a friend with leukemia who went on a clinical trial and now he’s cured,” said Joe, one of the patients I have advocated for. “I would like to be in a clinical trial too,” he added.
There are an almost infinite number of clinical trials–and not all of them yield miraculous results. So when do you know if you should be looking for a clinical trial for a given disease–and what questions should you ask if you are recruited to be in one?
When You Will Want to Consider Enrolling in a Clinical Trial
According to my informal poll of several physicians and epidemiologists with extensive experience in designing and running clinical trials, there is really only one reason to enroll in a clinical trial: if it offers you access to treatment that is potentially better than what you might otherwise receive.
If your doctor tells you that there are other options–that there are ten approved, effective medications that they have confidence in and can prescribe that are on the shelf and available right now — then opting for “standard of care” is a reasonable course of action.
But most people who are recruited for a clinical trial decide to participate because options are limited or there simply are no other options. In that situation, according to Dr. Bob Arbeit, an adjunct professor of medicine at Tufts Medical Center who has spent his career analyzing clinical trials. “If your options are limited, for whatever reason, a clinical trial that offers access to a promising but not yet proven treatment may well be an excellent alternative.”
And it could turn out to be of real benefit to you — just like it did for Joe’s friend.
It is under these circumstances that your doctor may suggest that you consider a clinical trial.
What Questions Should you Ask Before You Enroll?
The following is a list of what I consider to be the first questions to ask your doctor when considering enrolling in a trial. Of course, there are many other important questions, and there is an excellent list at clinicaltrials.gov; consider asking them all.
- Why are you suggesting that I consider a clinical trial?
- What is the standard of care? Why would that not be the best option for me?
- If I say “no” to the trial, do you have any treatment to offer me that you have confidence in or good experience with?
- What do you know about the medication being used in the trial? Is it safe? Is it well tolerated? Is it effective?
- How fast can I be enrolled in the trial? This can be a critical question if your disease is progressing quickly and there are other options available to you. Clinical trials are by definition slow. Enrollment can be especially slow: for example, you may be told that you will start the trial a certain day–but for reasons beyond the investigators’ control, it could be many weeks later. There are almost always some exams and tests required to be sure you are appropriate for the trial. Typically, the time to starting on the study treatment is reasonable, but you should know what to expect and be sure you are comfortable with that.
- Ask what the goal of the trial is. This is also known as the “clinical endpoint.” If, for example, if this is a trial of a cancer therapy, the clinical endpoint might be a decrease in the size of a tumor; and you will want to know how that is defined.
- What other trials might I be eligible for? You can check this out yourself on clinicaltrials.gov.
- Who is running the trial? Sometimes this can be quickly ascertained by checking clinicaltrials.gov. You will want to be sure that the doctor recruiting you for the trial is not the same one as the doctor running it—they should be (and are generally are) separate. If they are not– this can potentially create a conflict of interest (particularly if that doctor may have a financial stake in it) and may put you in an awkward position should you decide to withdraw.
The Consent Process
If you agree to consider the trial, you will meet with a clinical trial coordinator who will go over the study with you in detail. Importantly, they will share with you–and ask you to sign–an often very lengthy document known as a “consent form.” The consent form will describe what the trial is offering for your medical condition, what your other options are, why the new therapy proposed in the trial may help, what visits you will have to make, what procedure(s) might be done and what side effects you might experience.
According to Dr. Arbeit, “It is a lot to absorb all at once. There is almost always the opportunity for you to take the consent form home and think about it. You can also go over it with family or a close friend. I really recommend that: take the time to be sure you understand as much as possible of what you are being told. And if you have questions–go back and ask them. Every good investigator welcomes the opportunity to address your questions so you feel comfortable about enrolling in the trial.”
The Advantages and Disadvantages of Being in a Clinical Trial:
There are definite advantages to participating in a clinical trial. The most important one is that there will likely be more people involved in your care: more people asking you questions, doing exams and tests and thinking about the results. That is because the purpose of a clinical trial is to learn as much as possible about the new treatment.
But the potential disadvantages relate to the fact that the trial is testing a new treatment. It hasn’t yet been proven to be effective or reasonably well-tolerated. These disadvantages include:
- More visits
- More tests
- More blood draws
- Cost: you should ask if there is any cost. In general, the medication is free, but if you develop side effects and require treatment and/or hospitalization, who covers the cost of that–you or the trial?
- If it is a randomized trial, there may be only a 50-50 chance of getting the new therapy (i.e., there is a possibility of being randomized to the control — the group that gets no therapy or the standard of care, if there is one);
- There may be side effects; and there is the potential that some of those may be irreversible;
- There is the possibility that you will get no benefit from the trial.
What is a Clinical Trial?
The simplest clinical trials compare a proposed therapy to current best standard therapy or no therapy (control group). The goal of every trial is to show a clinical response better than than the standard of care or at least equal to the standard of care, meaning to the therapies that are currently available.
But the central idea of a clinical trial is that it shouldn’t happen unless there is some evidence to suggest that the proposed therapy is going to be effective–possibly better, or at least as good as what is out there.
What are the Phases of a clinical trial?
If you are enrolling in a trial, it’s important to know what phase of the trial you are signing on for. There are three of these:
- Phase I: Generally involves persons without the disease; this phase of a clinical trial is done to establish whether or not a medication may be taken safely, and what the side effects are. You enroll in this sort of study for the benefit of humanity. Angels, priests and nuns enroll in this sort of study–since there will be no benefit to them, and it is carried out primarily to get an idea of the toxicities (side effects) of the medications in a patient who does NOT have the disease. Generally, the study will start at a low dose then gradually increase (escalate) the dose.
- Phase II: this involves giving the medication to persons with the disease to find out what dose has the greatest efficacy and how much drug can be given to persons with the disease without unacceptable toxicity. The study will start at a lower dose and will try not to go to a toxic dose but still get the desired clinical response.
- Phase III: Uses the dose that has been determined to be safe and likely effective in the Phase II trial and tests it against the existing standard of care. These trials involve large numbers of patients with the disease. Generally half of the patients will get the new medication and the other half whatever medication is the standard of care (or no medication–a “control group”). This phase is known as the “pivotal” trial: a trial in the population for whom the intervention is intended at the intended dose. After Phase III, pharmaceutical companies can get FDA approval and market the medication. Sometimes companies are given approval after Phase II if there is “severe need”’ This is called “conditional approval”. It is sometimes also possible to get a new drug while the regulatory process is underway; this is called “compassionate use.” Phase III trials generally cost about 50 million dollars, which explains, in part, the high price tag of new medications.
You can google any clinical trial that you are considering enrolling in at clinicaltrials.gov: this will tell you whether or not you are eligible to participate (the inclusion and exclusion criteria) and the goal of the study (clinical endpoints).
Other concerns: Safety
In early (Phase II) trials, everyone may get the same new treatment, but in later, larger trials, there may be a random chance to get either the new treatment or a “control” treatment. That “control” alternative may be the available standard of care or, if there is no standard of care or the disease is not serious, it may be a “placebo” like a sugar pill. In such studies, neither you nor the study team taking care of you will know what you are receiving. But in that case, there is often a special group of outside doctors called the Data Safety Monitoring Board (DSMB) looking at all the information, including who is getting what treatment and how patients are doing both in terms of their disease and side effects. If there is an unexpected problem, they can tell the doctors running the trial and even recommend that the trial be stopped. In short, the DSMB follows the progress of the trial to see if there are toxicities and if the drug is working; if they find serious side effects or lack of efficacy, the trial will be halted.
Joining and Staying in a Trial is Always Your Decision
Remember that participation in a trial is always and at all times your choice. You can decide not to participate even if you are eligible. You can start the study treatment and you can stop at any time for any reason–maybe the side effects are too bothersome, maybe your problem is getting worse, not better. Or maybe you simply change your mind.
The Takeaway
The bottom line: just because you have a friend who benefited from a clinical trial does not mean that you will. Make sure that what you sign up for has a chance to benefit you — and will not lead to excessive toxicity. Each patient has to carefully weigh the pros and cons and make that decision. The best approach is to ask a lot of questions and maintain a healthy skepticism.
**All patient names and identifying details have been changed to protect client confidentiality. The suggestions given here are not intended as a substitute for the medical advice of your physician.
Photo credit: photo by thisisengineering, Raeng, from Unsplash.
