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From Chapter 2: What Is a Clinical Trial?

Modern Medicine
     We now live in an era of evidence-based medicine. Evidence of success, usually collected in clinical trials, is now expected before a treatment is adopted as safe and effective. We use such evidence to understand the risks and benefits of medical treatments, and to make sound decisions about what treatments are best.
     Clinical trials define the gold standard of care—the best treatment available. Medical science advances through clinical trials, even if progress is slow at times. Remember, it took more than 40 years for Dr. Lind’s breakthrough results to become widely accepted. No area of medicine is more in need of advances than cancer care, and hundreds of novel treatments are currently being evaluated in cancer clinical trials.

The Key Ingredients of a Clinical Trial
     Although clinical trials have grown large, complex, expensive, and tightly regulated, the principles of a sound experiment are universal. The basic ingredients from Lind’s eighteenth-century clinical trial remain the same in twenty-first century clinical trials:

• All trials begin with a hypothesis—an idea or a new theory—about what the researcher thinks will happen. For example, Dr. Lind’s hypothesis was that lemons and oranges might cure scurvy. The rest of the trial is all about testing the hypothesis. You prove it to be right, wrong, partially right, or partially wrong. Hypotheses can be as simple as this: the new drug ABC-123 will shrink cancer tumors (most new drugs begin with a boring name that resembles a license plate number!). Hypotheses can also be more complex: new drug ABC-123 will shrink tumors; it will also produce acceptable side effects up to a certain dose, above which the side effects will become unbearable, but it might work really well against some incurable cancers at a dose just shy of unbearable. You get the idea.

• The trial is designed and carried out to test the hypothesis. This is the experiment, the core of the trial (Dr. Lind used six groups of volunteers to test his hypothesis). The experiment, of course, has many parts, which we will explain in detail.

• The results—what everyone is after. Did it work? How well? A little? For which people? Can the results be duplicated with a larger group? Will it lead to a new approved medication or treatment, and, most importantly, did it or will it help you? At the outset, no one knows what the end results will be. That’s why it’s called a trial.

     Even the most complex clinical trials are made up of simple parts and are fairly easy to understand, at least for those conducting them. Dr. Lind had a hypothesis that lemons and oranges would help sailors overcome scurvy. He gave lemons and oranges to some sailors and something else to others in order to find out if he was right (the experiment), and he learned that he was right (the result). Hypothesis. Experiment. Results. That’s it “in a nutshell.”
     To understand what you are getting into if you’re considering a clinical trial, you will need to understand the first two of these ingredients, hypothesis and experiment. Of course, you’ll also want to know the third as soon as possible. It would certainly be nice to know what will happen before you even consider the trial. After all, why would you want to take a drug that may or may not work?
     While you cannot know the results of a clinical trial that has not been completed, it’s important to thoroughly understand why the trial is being conducted (the hypothesis) and how it’s going to be conducted (the experiment). You’ll also want to know how the clinical trial might benefit you: what is the expected—or hoped for—result. We will help you learn to ask the right questions of the right people to get these answers more quickly.

Clinical Trials Versus Standard Care
     You may be thinking, “Why would I want to try a treatment that might or might not help me?” You may be right. If there is an effective standard treatment that works for you, there is no reason for you to enter into a trial. Here are some explanations that might help.
     In many ways, clinical trials and standard care for cancer are similar. Both require you to visit doctors and nurses, take medications, have blood tests, body and possibly brain scans, have regular physical exams, have needles inserted in tender places, and undergo many other procedures and indignities. For those of you who are just beginning cancer treatment, there will be a great many unknowns, in both experimental and standard treatments. After all, you have not done this before. You will encounter a lot of new information, face new treatments and unfamiliar tests, and have unexpected experiences. You could look at it as a new adventure in your life, although not an adventure you ever wished for!
Whoever came up with the term standard treatment didn’t consider that although it may be standard procedure for your doctor, nothing could be further from what you might consider standard. The whole process can be frightening.
     Treatment for cancer—whether standard or experimental—usually involves side effects, expenses, testing, and a lot of your time. Standard treatments become standard when they are shown, in large clinical trials, to be better than the previously accepted standard. By better we mean that the entire group of patients who received the standard treatment generally fared better than the entire group of patients who received the treatment it replaced. This does not mean that every patient benefitted equally, and some people may not have benefitted at all. Standard treatments may involve a fair amount of uncertainty as to your personal outcome.
     Even when you are beginning a treatment that is considered standard for your type of cancer, you will likely hear that there is a certain chance that you will benefit from it, often expressed as a percentage of people who remain cancer-free or whose cancers are under control a number of years after treatment. Hopefully, the chances of success are high, but they are almost never 100 percent, and often they are disappointingly low.
     New treatments are needed because we don’t yet have perfect cancer treatments. So, although there are more unknowns when you consider experimental therapy, they are often similar to those that you face when you receive standard therapy. It will be important for you to understand both options in order to make the right or best choice for you.

The Eligibility Checklist Process
     Despite the similarities, clinical trials are certainly not the same as regular cancer care. Trials are much more carefully regimented. Even before you get started, you will have to qualify to be in the trial. The doctor or study nurse has a long checklist of eligibility criteria. You may or may not be shown this list, but it’s always part of any clinical trial.
     This checklist—often 20 to 40 items long—lists all the criteria you will have to meet in order to qualify for a clinical trial that might or might not work for you. Thank goodness we are not subjected to such checklists in most of what we do in everyday life! We’d never get anything done.
     While the checklist may seem like the “Great Wall of China” standing between you and your hope of joining a study, it is there to protect you, and to make sure that the study is carried out properly. Many of the criteria focus on ensuring that you are healthy enough or—in some cases—unhealthy enough to receive the proposed treatment. The criteria will likely include:
• Kidney function
• Liver function
• Heart function
• Blood counts

     Other parts of the checklist are designed to make sure that all participants in the trial are similar enough that the experiment and results will be valid. It would be difficult to know how well a drug performed in advanced prostate cancer, for example, if the study participants had many different kinds of cancer in all stages. So each trial defines the patient population for which it is designed. You will not know if you meet the trial’s criteria until the qualification process—also called the screening—is completed.
     The rigid nature of a clinical trial does not end with your being admitted into the study. Once treatment starts, your care will follow a tightly scripted plan. The schedule of every blood test, scan, dose of medication, and doctor visit is dictated by the clinical trial protocol—it includes dates, times, places, and procedures. This can also be the case with standard cancer therapy, but although regular cancer therapy is thorough it can be relatively flexible. Clinical trial therapy is closely controlled and monitored, because skipping a test or not taking a medication as prescribed could affect the overall trial outcome.

Informed Consent
     As discussed in detail in Chapter 7, clinical trials are tightly regulated and overseen by an independent oversight committee. One of the committee’s responsibilities is to make sure that all participants are thoroughly informed about the trial they are considering. Participation in a trial will begin with the reading of a detailed, and often exhaustive, consent form.
You need to read the consent form and understand it—even if it seems long and boring. While the concept of informed consent is not unique to clinical trials, in routine care it often consists of nothing more than a conversation between a doctor and a patient. Not so for clinical trials. You get at least one conversation, sometimes two (doctor and nurse or study coordinator), and a volume of questions and statements in fine print. You not only have to read it, but also sign it.