Should I Enter a Clinical Trial?

A Patient Reference Guide for Adults with a Serious or Life-Threatening Illness

Who Should Use This Summary?

This Patient Reference Guide Summary highlights key issues covered in the full Guide, Should I Enter a Clinical Trial?, for adult patients who are thinking about enrolling in a clinical trial and their loved ones. Words that appear in bold are defined in the Glossary at the end. We provide checklists that may be useful during your discussions with physicians and loved ones about whether to enter a trial. A list of web resources shows where you can find information about clinical trials that are open for enrollment and more information about various issues related to clinical trials. The full Guide and Summary take no position on whether one should enter a trial — that is uniquely a persona decision. Our hope is that patients consult the full Guide to support their decision making about enrolling in a trial so they can feel as confident as possible about their decision. We dedicate this Guide to the patients and their loved ones who are facing this important decision and to those who benefit us all by participating in a trial.

You can access the full Guide on the web at www.ecri.org or www.aahp.org. If you cannot access it online or here, please contact the American Association of Health Plans (AAHP) to request a hard copy. We encourage readers to obtain the full-length Patient Reference Guide, which provides more detailed information about participation in clinical trials.

Introduction

The knowledge gained through clinical research — trials that test the use of new drugs and medical devices in humans — is at the core of advances in patient care. The results of clinical trials bring us new diagnostic tests and new treatments that improve our health and prolong our lives. The amount of research being done has increased dramatically the past 10 years as researchers in the public and private sectors strive to develop and bring to the public more new diagnostic tests and treatments than ever. Thus, more patients than ever are needed to participate in trials.

In the press and on television, some institutions conducting clinical trials have come under public fire recently because of some serious adverse events and, rarely, unexpected deaths during trials. Although these situations represent a very small fraction of the current clinical research, they have shaken public trust. Patient safety and adequate explanations to patients about benefits and risks of trials have been key issues. At the heart of clinical research are individuals who, by volunteering to participate in a trial, benefit future patient care by helping researchers learn what works in medicine. Researchers cannot promise patients an immediate personal health benefit from participating in a trial, but patients have described to us other kinds of immediate benefits from trial participation.

As one cancer trial patient summed it up, “Tremendous support and benefit come from being a part of a group of patients who are just like you. You feel tremendous medical team support because the researchers are worried about your specific disease and are devoted to treating your disease. They know more than anyone else about it.” Another patient noted that even though she might not experience an immediate health benefit from the trial, she felt great satisfaction that her children or grandchildren might benefit from the knowledge gained from the trial.

This Summary offers some basic information to consider when deciding to enroll in a clinical trial. Should I Enter a Clinical Trial? A Patient Reference Guide for Adults with a Serious or Life-Threatening Illness provides more detailed information on these topics and other questions important to patients and their families. But the final decision about enrolling in a clinical trial rests with you and your loved ones. Being informed will enable you to make a decision that is right for you.

Among the key issues covered in the full guide are the following:

• How can patients make sure they receive adequate information about the risks of a trial when deciding whether to enroll?
• Where can patients find out about clinical trials that are recruiting patients?
• How can patients find out if they are eligible for the trial?
• Can patients get a treatment under investigation even if they are not eligible for the trial?
•  What are the different types of trials, and why should patients take the time to understand those differences before making a decision?
• How might different trials affect a patient’s quality of life?
• Who should a patient talk to about the trial before deciding to enroll?
• Who shares the responsibility for protecting patients in a clinical trial?
• What are the tangible and intangible costs to patients of being in a trial?
• Who is responsible for treating complications from treatment in a trial?
• What potential conflicts of interest exist among trial sponsors, researchers, and institutions carrying out the trial?
• What are patients’ rights to withdraw from a trial?
• What are researchers’ obligations to patients in trials?

What Is a Clinical Trial?

The very purpose of trials is to gain new knowledge about new treatments that might benefit future patients. But in the trial, the new treatment is still under investigation to see how well it works. Although “new” often implies “better” in our culture, the fact is that until clinical research on a new treatment is complete, we do not know if it is better, the same as, or worse than standard treatments. Sometimes, treatments publicized as “promising” or “breakthrough” do not fulfill their promise. The only way to find out is through well-designed and well-conducted clinical trials.

Is participating in a trial different from receiving treatment outside of a clinical trial?

Yes. From a patient perspective, it is important to understand the main purpose of treatment in a clinical trial is different from the purpose of treatment outside a clinical trial. Treatment in a clinical trial is intended to benefit society and future patients by advancing medical knowledge. It is important to understand that individual patients may or may not benefit from the experimental treatment in a trial; this is why the trial is being conducted — to find out how well it works. However, patients may experience other types of immediate benefits, such as the comfort and support that can come from being part of a group of patients with the same condition being treated and closely monitored by a team of experts — the research doctors.

For patients in trials, there are risks associated with participating because researchers cannot guarantee that a treatment being tested will provide a benefit. In a trial, there is only the hope that it will. The very reason for doing the trial is to find out if the treatment works. Weighting the risks and benefits to make an informed decision about whether to participate can be complicated. In making an informed decision, it is necessary to understand something about the different types of trials, the right questions to ask, and patients’ rights as trial participants.

What are the different types of clinical trials, and what do I need to know about them?

There are four general phases of trials in humans (phases I through IV). Human trials cannot begin until laboratory and/or animal tests on the new treatment under investigation have been completed in “preclinical studies.” The results of each phase must show that there are no serious safety problems and that the experimental treatment holds some promise before it can be tested in the next phase. Each phase typically involves a greater number of patients. Phase I may have as few as 10 or 20 patients. Phase III may have several hundred or thousands of patients. The design of trials also changes as the phases progress. Later phase studies often compare results of the experimental treatment group to the results of standard treatment group (control group) in what are known as controlled trials.

Patient safety, the protection of patients’ rights in clinical trials, and the impact of trial participation on a patient’s quality of life are the main reasons it is worth taking the time to understand something about the different kinds of clinical trials. Different kinds of trials offer different potential benefits and risks; they also require different levels of participation by patients. For example, a trial that is done on an outpatient basis may have a very different impact on a patient’s lifestyle than a trial that requires hospitalization. Some trials may require follow-up tests that are time-consuming and/or invasive, such as a biopsy, and others may just require an office visit and quick exam. Some trials may last less than a year; others may last five years or longer. Factors like these may affect a person’s desire and ability to participate.

Different kinds of trials also have different effects on patient feelings about risk and quality of life. As one cancer patient explained her thinking about entering a trial, “I might not be as willing to enter a drug trial designed to identify the highest tolerable dose in humans as I would to enter a trial designed to find the lowest effective dose of a drug that has already been shown to work at a higher dose. The risks involved and impact of one trial on quality of life could be very different.” The different phases of the trials are as follows:

• Phase I trials assess safety and toxicity of the treatment in a small group of healthy volunteers or patients with the disease of interest. Phase I trials are not designed or intended to be therapeutic. These trials cannot promise individual patients any therapeutic benefit because very little is known at this point about the treatment’s activity in humans. Phase I trials lay the groundwork for the next phases of trials that begin to test efficacy (how well the treatment works). Studies of phase I trials have shown that 3% to 5% of participants benefit from the treatment.
• Phase II trials further test safety and begin to test efficacy, typically in 50 to 300 patients with the condition or disease for which the treatment is intended. Phase II trials may take up to two years.
• Phase III trials study safety and efficacy in a larger group, perhaps thousands of patients, and look for uncommon adverse reactions. This phase may last several years. Phase III trials typically compare the new treatment to standard treatment(S) and perhaps a placebo, if it is ethical to use one (trials for life-threatening diseases rarely use placebos.) Trials that compare treatments are controlled trials and may involve random assignment of patients to different treatment groups.
• Phase IV trials are sometimes done after anew drug or device has received US Food and Drug Administration (FDA) approval and is being used by the general public. Phase IV trials determine longer-term effectiveness and identifies rarer side effects. FDA does not require this phase of trial for all newly approved drugs or devices — it depends on whether FDA believes some questions still need to be answered.

How will I learn about the risks and benefits of participating in a trial?

An eligible patient cannot enroll in a trial until the known benefits, risks, purpose, and plan for the trial have been thoroughly explained and all the patient’s questions have been answered. This is called the consent process. It is also often called informed consent. It is very important to take the time to read and consider all the information provided and to ask questions. That often means taking the consent form home to read it again and discussing it with close family, friends, and advisors. Also, taking a trusted family member or friend along to the consent interview may be helpful so someone else hears the same information and you can discuss it later. It may also help to tape record the consent interview to review the information later — just let the doctor know if you want to do this. If a patient decides to enroll in a trial after the interview, he or she signs a consent form and keeps a copy for future reference. This document contains everything that was explained orally, including the contact information for someone on the research team who can answer questions and respond to emergencies.

Even after a patient enrolls in a trial, he or she can withdraw at any time for any reason. Should you choose to withdraw it is very important to let the researchers know why you are withdrawing so they can collect important data that may affect the way they are conducting the trial. Patient consent is an ongoing process throughout the trial. If important new information is gained about the experimental treatment during the trial, researchers are required to share it with patients and reconfirm their consent to participate. Most patients may believe they understand risks and benefits and feel satisfied with the consent process, but often do not realize there are some things they have not understood.

The checklist provided here may help you determine whether you have received all the information you need for your decision making before signing a consent form.

Read or download complete guide here.