Clinical Trials: How they Work; Why Participate

Clinical Trials: The Bridge to Medical Innovation

Most people don't think about the origins of the drug they buy at the local pharmacy or the inspiration behind the medical procedure they undergo at their neighborhood hospital. Yet every pill, every diagnostic image, every surgical procedure–medical treatment in any shape or form–stems from a single source: research. Medical innovations start with the ideas and visions of committed scientists. Successful innovations then evolve over time–not weeks or months, but years–graduating through the different stages of development: basic research, translational research, and clinical research.

"Basic research, done in labs, involves studying how cells work, how they talk to each other, how they know what to do, and what conditions and drugs make their functions more or less efficient. Here, scientists first test new treatments in animals to find out if they might be helpful or harmful to people," explains Henry M. Spotnitz, MD, George H. Humphreys II Professor of Surgery at Columbia University College of Physicians & Surgeons and Vice Chairman for Research and Information Systems at the Department of Surgery.

Translational research bridges scientific discovery to clinical delivery—whether by bringing tools out of the laboratory and delivering them to the patient, or by taking techniques and findings from the clinical setting back to the laboratory for evidenced-based practice. "The process of identifying drugs, devices, or treatments that should be developed, funding and conducting the development, and putting the therapy in the hands of clinical investigators is the essence of translational research," Dr. Spotnitz continues.

Clinical trials, also known as clinical research, are the furthest progression from the basic research lab. In clinical trials, scientists apply their discoveries to humans, testing new drugs, devices, or innovative therapies in selected patients.

What is a Clinical Trial?

Clinical trials are the bridge over which all new medical therapies must pass to become accepted practice—and the bridge is a long one. For patients, clinical trials can typically last for a few weeks or months. For scientists, they can continue on for years before a new therapy may see the light of day.

There are different types of clinical trials: treatment, prevention, diagnostic, screening, and quality of life trials—and the trials are conducted in progressive phases (I-IV). Once a clinical trial reaches the end of the bridge–proving its potential worth as a medical therapy–the Food and Drug Administration (FDA), a government agency, must officially approve the therapy for medical consumers.

For patients, participation in a clinical trial is voluntary. Common reasons for joining a clinical trial include: playing a more active role in your own health care; gaining access to innovative treatments before they become widely available; and helping others by contributing to advancements in medical research.

How Do Clinical Trials Work?

To ensure that no one can influence the results of a study, clinical trials employ a range of specialized testing mechanisms intended to prevent bias and provide reliable results:

  • Prospective Trials—Patients are identified and then followed over time.
  • Randomized Trials—Patients are grouped by chance into (typically) a treatment group and a control group (also called a placebo group). A control group receives either the current standard treatment or a placebo-an inactive pill or liquid. The results of the control group are then compared with those of the treatment group.
  • Cross-over Trials—Patients receive both the treatment and the placebo at different times, with careful monitoring of their responses to both approaches.
  • Double-blinded Trials—Neither the patient nor the researcher knows if the patient is receiving the treatment or the placebo.

In addition, some clinical trials are called open label studies, because both the patient and the researcher know that the patient is receiving the treatment and not the placebo.

By federal regulation, every clinical trial in the United States must be approved and monitored by an Institutional Review Board (IRB), an independent committee of physicians, statisticians, community advocates, and others. The IRB is charged with ensuring that all clinical trials within a given medical institution are ethical and that the rights of the participants in those trials are protected.

Clinical trials retain very specific participation guidelines. Establishing and maintaining these guidelines is a critical part of producing meaningful and reliable results. The factors that allow someone to participate in a clinical trial are called "inclusion criteria," while those that disallow someone are called "exclusion criteria." Typical criteria include age, gender, the type and stage of a disease, previous treatment history, and other medical conditions.

What are the Different Types of Clinical Trials?

  • Treatment Trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy.
  • Prevention Trials look for better ways to prevent a given disease in people who have never had that disease or to prevent a disease from returning. Preventative approaches include medicines, vitamins, vaccines, minerals, and lifestyle changes.
  • 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.
  • Quality of Life Trials (or supportive care trials) explore ways to improve comfort and the quality of life for individuals with a chronic illness.

What are the Phases of Clinical Trials?

Clinical trials are conducted in phases. Each phase of a trial has a different purpose and helps scientists to answer specific questions.

While small, early phase trials may be conducted by individuals or small groups of physicians, larger trials are typically conducted by hospitals, pharmaceutical companies, or device manufacturers. If a therapy successfully passes through phase III trials, the FDA may approve it to be marketed to the public.

Phase I Trials

Researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

Phase II Trials

The study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

Phase III Trials

The study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

Phase IV trials

Post-marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

The Challenges and Rewards

The importance of clinical trials to the advancement of modern medicine cannot be overstated. Clinical trials partner scientists, patients, and industry in a journey that may improve medical treatments and, in some cases, lead to spectacular medical breakthroughs. Dr. Spotnitz emphasizes that the journey is long, costly, and sophisticated, but also represents the core mission of dedicated physician-scientists.

"Clinical research differentiates us from routine practice. It allows us to offer the best-known therapies and diagnostic tests to patients and to achieve superior clinical results," says Dr. Spotnitz. "Today, our potential to help patients is limited primarily by our ability to assimilate this flood of information and imagine innovative ways to apply it. Also, research is heavily dependent on financial support from the government, industry, and philanthropy. Raising money for research is highly competitive and is one of the challenges all scientists face."

As to the rewards of medical research in general, Dr. Spotnitz is quick to answer. "There is nothing more exciting to a dedicated scientist than making a new discovery. To imagine a solution to an important problem, to actually solve the problem, and to use that solution to help patients is an almost unimaginable thrill. The best thing about research is the sense that you are doing something that is important to other human beings, and that makes the journey–and struggles along the way–certainly worth the effort."