For many patients with multiple myeloma, common treatment regimens are not always effective against their cancer. In such situations, physicians may recommend turning to new combinations of treatments or newly developing treatments through participation in clinical trials.

Taking part in a clinical trial is a huge decision for both patients and their families, and it is one that should be made with careful consideration.

This guide, which will be published as a series of articles over the next couple of weeks, is intended to help clarify the clinical trial process and to answer common questions so that you can decide whether a clinical trial is the right option for you. The guide will explain the different types of clinical trials in this first article, and subsequent articles will address common myths, provide answers from physicians to common questions, describe patients’ clinical trial experiences, and provide resources for finding a clinical trial.

What are clinical trials?

Simply put, clinical trials are research studies that involve people. Often, they are meant to help those who do not respond to standard treatments and are looking for other options.

Clinical trials test new drugs, procedures, treatment combinations, and medical devices to improve the diagnosis of the disease, patients’ responses to treatment, and the quality of life of patients. Trials may also try to find methods to prevent certain cancers.

Even though these clinical trials are exploring “new” treatments and procedures, they are actually the final step in a long process that begins with lab research and animal testing. All treatments and drugs used today are the result of successful clinical trials conducted in the past.

Types of clinical trials

• Treatment trials - test experimental treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
• Quality of Life trials (or Supportive Care trials) - explore ways to improve comfort and the quality of life for individuals with a chronic illness.
• Diagnostic trials - are conducted to find better tests or procedures for diagnosing a particular disease or condition.
• Screening trials - test the best way to detect certain diseases or health conditions.
• Prevention trials - look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicines, vaccines, vitamins, minerals, or lifestyle changes.

Phases of Clinical Trials

In order for a treatment to be officially approved for use, it must pass through at least the first three phases of clinical trials. Each phase corresponds to a stage in the testing of the drug on humans. It is also a good way for patients to tell how well tested the drug is.

The following table summarizes the purpose of each phase and the estimated number of people who take part in each phase.

The phase of the trial is important for patients to consider. Most patients feel more comfortable with a clinical trial in a later phase because more information about the therapy is already known (such as short-term side effects and initial efficacy results). However, physicians may suggest early phase clinical trials to patients who are particularly good candidates for responding favorably to the treatment.

Clinical Trial Terminology

Randomized Trials - Randomization is a process used in some clinical trials to prevent bias. Bias occurs when a trial's results are affected by human choices or other outside factors. Randomization helps ensure that unknown factors do not affect trial results.

If you participate in a randomized trial, you will be assigned by chance to either an investigational group or a control group. Your assignment will be determined by a computer program or table of random numbers.

• If you are assigned to the control group, you will get the most widely accepted treatment (standard treatment) for your cancer.
• If you are assigned to the investigational group, you will get the new treatment being tested.

Comparing these groups to each other often shows which treatment is more effective or has fewer side effects. If you are thinking about joining a randomized clinical trial, you need to understand that you have an equal chance of being assigned to either one of the groups. The doctor does not choose the group for you.

Placebo - In certain randomized trials, there is a chance that the patient is given a placebo, a drug that is designed to look like the medicine being tested but which is actually inactive. This is done to account for a “placebo effect,” which is a perceived psychological effect that does not reflect the efficacy of the actual drug.

Fortunately, for the safety of the patients, placebos are almost never used in cancer treatment trials.

Blinding - "Blind" (or "masked") studies are designed to prevent members of the research team or study participants from influencing the results. This allows scientifically accurate conclusions.

• In single-blind (or "single-masked") studies, only the patient is unaware of what is being administered.
• In a double-blind study, only the pharmacist knows what is being administered; members of the research team are not told which patients are getting which medication, so that their observations will not be biased. If medically necessary, however, it is always possible to find out what the patient is taking.

Clinical Trial Protocols

Clinical trials are meticulously conducted under and observed by doctors, nurses, social workers, and a devoted research staff that includes a head research coordinator, who is your liaison between your medical institution, the United States National Institutes of Health, U.S. Food and Drug Administration, the National Cancer Institute, and the pharmaceutical company or private corporation funding the trial.

The protocol, prepared by the principal investigator (the physician in charge) is a strict guideline that explains what the trial will do, how the study will be carried out, and why each part of the study is important. The protocol includes:

• The reason for conducting the study
• Who can join the study
• How many people are needed for the study
• Any drugs the participants will take, including the dose, and how often
• Potential side effects
• What medical tests the participants will take and how often
• What information will be gathered about the participants.

Research involving people is conducted according to strict scientific and ethical principles. These trials and procedures are all put through a rigorous review and approval process by the Institutional Review Board. The patient’s safety is always top priority.

Informed Consent And Confidentiality

An important part of the clinical trial process is the informed consent. It is easy to be confused about what exactly you are giving consent to, but rest assured - you are only giving consent to participating in the trial and that it is only to your benefit.

Your identity remains safe throughout the process as you are put through a system and given an ID number with which you will be identified (this is useful for confidentiality, but there is no need to worry about not being properly identified in an emergency). Confidentiality and personal details, including the data collected during your trial, are kept safe by the Data Safety Monitoring Board.

There are two parts to the informed consent that a patient should be aware of: the informed consent document and the informed consent process.

The informed consent document is to be read by the patient. Always ask for a copy to keep for yourself in case you want to look it over again or have further questions later. The document informs you of the purpose of the trial, the treatment procedures, risks, benefits, etc. Most importantly, it explains to you your right as a participant and affirms that by signing, you consent to participating in this trial but that you have the right to withdraw from the study at any time.

The informed consent process is simply an ongoing process during which you and your research coordinator or physician will discuss the trial. Its purpose is to inform you about everything you will be doing and receiving. Before signing any document, it is mandatory that your physician or research coordinator explains every aspect of the trial to you. The document should be in written form, but the details of the trial should first be explained to you verbally. Do not hesitate to have things repeated or to ask questions. It takes many people time and multiple explanations to understand everything properly and to feel comfortable with the process.

Be sure to look out for specifics in the documents such as side effects, rules that you should be aware of (i.e. no alcohol, pregnancy, etc.), and cost coverage. Again, if you are ever confused or unsure about any part, feel free to ask a doctor to clarify – it is his or her job. And remember, this is not a binding contract.

Check The Myeloma Beacon in the coming weeks for the other articles in the series that will address common myths about clinical trials, provide answers from physicians to common questions, describe patients’ clinical trial experiences, and provide resources for finding a clinical trial.