Clinical Trials

What are clinical trials?
A clinical trial is the investigation of a new medication for the treatment of a disease. The work might be sponsored by a pharmaceutical or biotechnology company, government or a private foundation. The purpose of these studies is to find out whether a medication is safe to use and effective against various diseases or medical conditions. In order to study the medication, several questions need to be answered first. For example, what patient population or disease is the drug meant to treat? What criteria should be used for accepting participants into the study? What general and disease-specific information are the study doctors going to obtain?

Essentially, once these and other important study questions are answered, the study doctors (investigators) are chosen, the regulatory documents are approved and the study is ready to begin.

Why are clinical trials important?
There are several reasons why clinical trials are important. First, the participant may have a positive response to the study medication, and his disease or condition may improve. In addition, participants receive free laboratory and medical testing. More often than not, the study medication is in development because it works differently than other drugs on the market, and therefore, it may present an alternative course of treatment for the patient.

Second, participation in a clinical trial helps manufacturers make informed decisions about whether to pursue getting a particular drug approved by the Food & Drug Administration (FDA).  In the best-case scenarios, these data can help get a new medication approved by the FDA, and ultimately continue the industry's efforts in developing medications that are safer, more effective, and work faster than any before them.

How are a participants' rights safely protected?
The FDA is the governing agency that develops the policies and guidelines for all clinical research, regardless of manufacturer, study phase or drug type. There are also independent Institutional Review Boards (IRB) that review and approve all study-related documents, such as protocols, Informed Consent forms, physician credentials and eligibility, and patient recruitment materials, such as print advertisements and public service announcements. (See "Protocol" and "Informed Consent" Form in the "Common Terms Used in Clinical Trials" section.)

What are the phases of the clinical trial process?
There are three primary phases an investigational drug has to go through before it can be approved by the FDA, and a fourth phase that an approved drug may enter.

Phase I
In this phase of a clinical trial, the sponsor wants to determine the maximum tolerated dose for the medication. Mode of action (how the drug exerts its effects), safety and side effects - these are some of the main issues that are of the utmost concern to drug makers at this stage of the clinical trial process. It is important to note that in Phase I studies, the overall safety of the medication in patients has not been established. Efficacy in Phase I, if observed, must be considered anecdotal until confirmed in more advanced studies.

Phase II
A drug reaches Phase II only when the FDA has reviewed the Phase I data and concludes that the drug is safe for patients, and that its clinical activity may be beneficial against a particular disease or condition. At this point, a larger group of patients are enrolled and condition- or disease-specific rating scales are used to record data. The goals are to continue safety assessment and to determine doasge for pivotal, Phase III efficacy trials.

Phase III
This is an important turning point for drug development. The medication has already passed the rigorous testing and review process required by the FDA, and now it is ready to be studied in an even larger patient population, with even more advanced rating scales and clinical measures. In recent years, there has been a growing industry trend to not only measure clinical effectiveness at this phase, but also measure "real world" results. For example, if patients show clinical improvement after entering the study, how are their activities of daily living improving (e.g., patients can work in the garden more often or attend their child's games on a regular basis)? Most medications that reach Phase III will at least be considered for approval by an FDA advisory board.

Phase IV
At this phase in development, the drug has already been granted FDA approval. Phase IV studies are often performed to either identify an additional use for an already approved drug, or to gather additional safety information from a larger group of patients. In some cases, Phase IV studies are implemented to establish effectiveness in a subgroup of patients, for example, patients over age 65.

What happens after a study is complete?
After a study is complete, the FDA decides whether to continue or halt the drug's development. If it remains in development, the sponsor may build in a compassionate use extension for the study. This means that eligible patients may receive the study drug for a predefined amount of time without having to undergo any typical study procedures, such as blood tests or clinical ratings. This usually occurs in later studies, such as Phase III and Phase IV (post-marketing surveillance).

In some cases, a study doctor may dispense approved medication samples and provide additional consultation free of charge. These are just a few of the ways he or she might show appreciation for a patients involvement in a study.

What are some questions I may want to ask my study doctor?

• How long does the average trial last?
• What if I am on other medication(s) from my regular doctor?
• What are the risks involved?
• What if I am harmed?
• Are there any tests requiring painful shots or blood samples?
• What should I do if I want a friend/parent to join a study?
• Will I be paid?
• Will I be reimbursed for gas?
• What kinds of medical problems would prevent participation in the clinical trial?
• Do I have to talk to my health insurance company before enrolling in a study?
• What if I miss a dose?
• Can I drop out at any time?
• Are there placebos involved?

If you decide that a clinical study may be right for you, make a list of questions and discuss them with the study doctor at your initial visit.

Common Terms Used in Clinical Trials (and what they mean):

Baseline  An important study visit when a patient's vital signs and clinical symptoms are documented. The initial batch of study medication is usually dispensed during this visit and the patient's response is compared back to baseline over time.

Clinical Trial Site  The facility where the trial is being conducted. It can be a physician's private practice, a center dedicated solely to clinical research or a hospital setting.

Contract Research Organization (CRO)  A clinical services company involved with various steps in the clinical trial process from study design to trial execution and data management.

Double-blind Trial  Many clinical trials are double-blind in design. This means that neither patients nor investigators/doctors know whether an individual participant is on an active drug or a placebo.

FDA (Food & Drug Administration)  The federal agency responsible for ensuring that drugs, biological products and medical devices are safe and effective for the general public. The FDA reviews and oversees the manufacturing specifications of these products, as well as the execution of clinical trials in which these products are evaluated. The agency also ensures that these products, once made commercially available, are represented in an accurate and informative manner.

Inclusion/Exclusion Criteria  An actual section of a clinical trial protocol that lists specific medications, conditions and relevant medical information that may, or may not, be allowable during a trial. Age, blood pressure and previously taken medications are a few examples of patient-specific information that would be compared to the inclusion/exclusion criteria of a protocol to determine eligibility.

Informed Consent Form  A document created by the drug manufacturer (with the FDA's guidance) that outlines a patient's rights during participation in a clinical trial. It also discusses the potential risks and benefits associated with participation, including all available data on previous studies. An informed consent form must be signed by the patient or authorized caregiver before entrance into a study.

Institutional Review Board (IRB)   An independent committee, comprised of individuals with diverse medical and non-medical backgrounds, which reviews and approves all study-related documents. An IRB approves protocols, informed consent forms, physician credentials and eligibility, and patient recruitment materials, such as print advertisements and public service announcements. IRBs work closely with the Food & Drug Administration to ensure that patient safety is the number one priority in a clinical trial.

Open-label Trial   Later-phase studies (Phases III-IV) often have an open-label design, meaning that all patients receive active study medication - no placebo is dispensed.

Placebo  A substance containing no active ingredients and having no pharmacological effects. Clinical trials often compare an investigational medication to a placebo in order to differentiate patient response.

Principal Investigator (PI)  The lead doctor in charge of the execution of a clinical trial. As part of the site selection process, the PI's academic credentials and area(s) of expertise are evaluated.

Protocol  A set of guidelines that must be followed during a clinical trial. It includes information on patient eligibility, data to be collected during patient visits, and included and excluded medical conditions and medications, to name a few.

Randomization  The assignment of individuals to treatment groups in such a way that each individual in a clinical trial has an equal chance to be assigned to each treatment group. (Also see Double-blind Trial).

Study Coordinator  A key member of the clinical team who works directly for the principal investigator. Responsibilities usually include maintaining accurate patient documentation, dispensing medication and general patient correspondence.