Clinically Speaking

Risks and Rewards — More than 140,000 trials in the U.S. were searchable on clinicaltrials.gov at press time. Many of them may benefit future patients. Credit: XUBINGRUO/ISTOCK/GETTY IMAGES PLUS

While COVID-19 treatments and vaccines were being developed in 2020, clinical trials made more national news than ever before. How a new drug gets to your pharmacy is a complex regulatory process but also a humanitarian act that can save lives and change the world for the better. Here’s what you need to know — and why you should consider participating for the greater good.

What is a clinical trial?

Any new medication must be approved by the FDA before it can be put on the U.S. market, and that requires the gathering of data in a clinical trial. The new drug (or device, or other intervention) is carefully tested on a group of volunteers to find out if and how well it can prevent, detect or treat a disease or condition.

Clinical trials run the gamut from testing the effects of simple lifestyle changes, like taking a baby aspirin once a day, to testing potentially lifesaving treatments for patients with advanced cancer. In the United States, hundreds of skin cancer clinical trials are happening at any given time.

How do clinical trials for treatments work?

Before a treatment, such as a new immunotherapy drug, can be given to anyone in a clinical trial, it must go through “preclinical trials.” These tests are done in a lab, in cells and in animals (yes, it’s controversial; see box below), and they establish how the drug could work and make sure that it will not cause serious harm.

Once it passes preclinical trials, the drug can move into clinical trials. Clinical trials are conducted through several phases. In a phase 1 trial, a small number of patients are given the treatment and are closely watched to establish its correct dose and overall safety. In a phase 2 trial, a larger group of people are given the treatment to gather preliminary data on how well it works (its efficacy) while still carefully watching for any safety concerns and side effects.

Phase 3 trials are where a drug is really put to the test. These trials typically involve hundreds or even thousands of volunteers who are followed for months or years, and are usually designed to test the treatment in a diverse group of people while comparing it to the current “standard of care.”

Though not always possible, the gold standard for a phase 3 trial of a new cancer drug is a randomized, controlled, double-blind study. We break down what these and other key terms mean in the box, below.

Phase 4 trials, or “post-marketing studies,” happen after the FDA approves the drug and are used to provide additional information on the safety, effectiveness and best uses of the drug.

Why should I consider joining a clinical trial? 

Your doctor may bring up joining a clinical trial if your cancer is at an advanced stage, or if previous treatments have failed, and there is a chance that an experimental treatment will be lifesaving.

While there may be risks or side effects to the treatment, getting involved in a clinical trial could help save many lives, yours included, and future generations will benefit from the research. Even finding out that a drug doesn’t work is an extremely important part of medical research.

What should I expect if I participate?

Remember, you are a volunteer, but you agree to follow the investigator’s guidelines when you join a clinical trial. It’s important to understand both the risks and the potential benefits of joining. If your doctor brings up clinical trials with you, here are some questions you may want to ask:

• What kind and phase of clinical trial is it?
• Are there any results from this or previous trial phases?
• Would I have to travel to get the treatment?
• How long will the trial last?
• What are the risks of joining the trial?
• What side effects have already been reported from the treatment?

What if a trial isn’t about a new drug?

When a clinical trial is investigating something other than a new cancer drug, it might look a little different. A clinical trial looking at an injected treatment that could help scar tissue heal, for example, doesn’t necessarily have a standard of care to compare it to. Patients in the control arm of this study might receive a placebo, though the study would probably still be blinded, so neither patient nor physician would know whether it is the placebo or treatment in the syringe. Some trials may not require you to ingest or receive anything at all. One ongoing observational trial on clinicaltrials.gov asks patients who have had surgery for a skin cancer on their face to fill out an online survey one year after their surgery to evaluate patient satisfaction with any scars and overall appearance.

Other trials might look at preventive measures. These trials may test how well a new intervention performs compared to a standard of care or a placebo but should never purposely expose you to things that might cause you harm. For example, another ongoing study is examining if administering photodynamic therapy (a treatment that destroys cancerous or pre- cancerous cells using a photosensitizing topical drug and a strong light) to organ transplant patients reduces the number of nonmelanoma skin cancers they develop over time.

For this study and the patient satisfaction survey, the trials are asking questions about specific populations, and you would have to belong to that population — often defined by age, sex, race, ethnicity, geographic location or disease status — in order to join. Every study will have slightly different eligibility requirements, depending on what the study is asking.

And you don’t have to have (or have had) cancer to join a clinical trial. Some trials, treatment trials included, require healthy volunteers. If you have a family history of skin cancer and want to find new ways to reduce your own risk, you may be interested in a prevention trial. Some prevention trials may be actively seeking people with certain risk factors as they test interventions that help the most susceptible groups.

Whatever the setup of the clinical trial might be, you are helping to advance medical and scientific research and doing a tremendous service to humanity by participating. You can find more about clinical trials, and even search for ones you may want to join, on clinicaltrials.gov.

Glossary of Clinical Trial Terms

Randomized: The patients enrolled in the study will be sorted equally into groups (often two, sometimes more) at random. Randomizing who is in which group helps ensure that there are no systemic differences between the groups and eliminates a potential source of bias.

Controlled: The groups that patients are being separated into are often referred to as the “treatment” arm(s) and the “control” arm. Those in a treatment arm receive the experimental treatment, while those in the control arm do not. The control group may receive a placebo. In a cancer trial, the control group will get the current standard of care, to compare the new treatment with what is already available.

Double-blind: This means that none of the patients, doctors or researchers conducting the study know who has been randomly sorted into each arm of the study. Double-blind studies are not always feasible. For example, doctors investigating if patients prefer postoperative phone calls or emails after Mohs surgery will know which patients they are calling and which they are emailing.

Placebo: This is what we call what patients in the control group receive. It is a “blank” pill, for example, that has no therapeutic benefit but allows the study to be double-blind and to eliminate bias. If a trial is testing a topical medication that has active as well as inactive ingredients in its preparation, participants in the control group get what is called the “vehicle,” that is, all of the ingredients that make topical delivery of the medication possible, without the active medical ingredient.

Standard of care: This is the current best practice treatment for a specific disease. The treatment is already FDA approved and usually widely used by health-care professionals.

Emergency Use Authorization (EUA): In special circumstances (as seen during the pandemic), the FDA can issue an EUA to allow an intervention, such as a drug or vaccine, to be used before it has gone through the full scope of the testing and approval processes. The circumstances have to be serious or life-threatening, and there cannot be another adequate option already FDA approved.