Clinical Trials: Medicine's Method for Answering Questions

What is a Clinical Trial?   

A clinical trial is a research study involving people. This means that people are participants in a highly structured, controlled process designed to answer a specific, medical question. Before a new treatment can be tested on people, it must be tested and evaluated in the laboratory. This type of research uses tissue cultures of cells or animals to test the treatment. This pre-clinical phase gives an indication of how the treatment works and its possible side effects, but it cannot predict how a person might react. The only way to know how it will work in humans is through a clinical trial. Clinical trials typically involve three progressive phases, and can take place in hospitals, universities, doctor's offices or community clinics.    

A list of all the ACC clinical trials currently available from the National Cancer Institute    

Recent History of Clinical Trials       

Starting about 20 years ago, doctors made a radical shift in treatment recommendations for women with breast cancer. Instead of routinely recommending mastectomy (surgical removal of the breast) to their patients, they began to discuss lumpectomy (the removal of the tumor and a small margin of normal tissue) plus radiation therapy. How did these doctors know that the far less invasive lumpectomy would give their patients the same results as a mastectomy? Because the results of clinical trials showed that lumpectomy with follow-up radiation therapy was as effective as mastectomy in treating certain types of breast cancer.


Although not all clinical trials change the practice of medicine in such a dramatic way, clinical trials provide the most scientific evidence to help determine whether experimental treatments are safe and effective, as well as answer difficult medical questions. Additionally, clinical trials may offer many benefits, including possible access to experimental treatments not otherwise available; high-quality care; and the chance to benefit society. However, research shows many people are not aware of clinical trials and mis-perceptions about these studies are common.   

Three Phases

There are three main phases of a clinical trial, each designed to address specific phases of the drug development process. All three require informed consent, which is a process to educate patients about the clinical trial, other treatment options, the risks and benefits of participating in a trial, and their rights as a participant. All federally funded clinical trials and trials conducted under the U.S. Food and Drug Administration's (FDA) authority must be reviewed and approved by an Institutional Review Board (IRB) to ensure participants are treated fairly and ethically throughout the study. Clinical trials follow a course of three phases to assure safety, effectiveness and risk vs. benefit results.

Phase I: Safety

Phase I clinical trials seek to answer the following questions:

  • How much of the drug can be given safely and what are the side effects? Through a process called dose escalation, the first participants will be given a small dose of the drug. If there are no or few side effects, the next group is given a higher dose. This process continues until the doctors determine the highest dose that can be given without severe side effects.
  • What is the best way to give the treatment? In this phase, researchers will strive to answer questions such as, "Should the drug be given by mouth in a pill or intravenously (through a vein)?"
  • What happens to the treatment when it is given? Researchers seek to understand how the drug is processed by the body, the reason why the drug works (called the mode of action), and how the drug is eliminated from the body.

During this phase, doctors are mainly concerned with safety. Typically, many tests are conducted during this phase to monitor a patient's response; however, it is rare that a drug being studied in phase I slows or stops tumor growth. Because little is known about how people will be affected by the treatment, a limited number of patients are included in phase I trials.

Phase II: Effectiveness

Once researchers have determined a dose and have enough information about the treatment to design a well-controlled, scientifically valid clinical trial, they may begin a phase II clinical trial. A phase II trial evaluates the effectiveness, short-term side effects, and risks associated with the experimental treatment in the target group (the people the new treatment is meant to help). This might mean all participants have the same type of cancer, for example.

Information from the phase I trial determines the dose and method of administration of the treatment being tested in phase II. During this phase, doctors are looking for evidence that the new treatment is effective, as well as trying to determine side effects and risks associated with the drug. Because effectiveness of the drug hasn't been determined yet, only a few hundred people are enrolled in each phase II trial. Doctors are looking to answer the following questions in a phase II clinical trial:

  • Does it shrink or slow the growth of the tumor?
  • Does it decrease symptoms?
  • Does it lengthen remission (the temporary or permanent absence of disease)?
  • Does it help people live longer?
  • Does the anti-tumor activity of the drug seen in this small, but disease-specific, population justify further testing?

If the treatment shows an acceptable balance between potential benefit(s) and known risks during phase II testing, it will be further studied in phase III testing.

Phase III: Overall Risk versus Benefit

A phase III clinical trial is the largest clinical trial and usually tests whether the new treatment is better than current, standard therapy. A trial is usually designed to evaluate the experimental treatment compared with the current standard of care. In cancer treatment testing, placebos are used infrequently and only when the standard of care has little effectiveness or is very toxic or when no known effective treatment is available.


A standard phase III trial to confirm effectiveness may be blinded (only the doctor knows if the participant is receiving the experimental or standard treatment) or double-blinded (neither the participant nor the doctor knows if the participant is receiving the experimental or standard treatment), so there will be no bias from the patient or doctor in reporting the results. If a clinical trial is blinded or double-blinded, it is also usually randomized, meaning patients are assigned to different treatment groups by chance to prevent bias. However, many cancer clinical trials, depending upon the type of trial, stage of disease, current standard of care, and mode of action of the drug, are open-label, meaning that patients and doctors know which treatment is being given.


A phase III study usually requires hundreds to thousands of participants and is often performed in multiple locations using the same protocol (a blueprint of a clinical trial outlining the purpose and detailed plan). Use of a protocol ensures that all participants are treated using the same rules. This trial is often termed a “pivotal” trial, as the data obtained is used by the sponsor to determine the drug's overall risk/benefit profile. Depending upon the balance of risk versus benefit, the sponsor of the trial determines whether FDA approval for the drug will be pursued. The data is also used to help create the drug's labeling if approved by the FDA.

FDA Approval

If the sponsor of the phase III clinical trial determines that the experimental treatment is at least as good as existing treatments and the benefit for patients outweighs the risks associated with the drug, it submits an application to the FDA seeking approval to market the drug. The FDA reviews all the information from pre-clinical testing and clinical trial and decides whether to approve the drug. The FDA only approves drugs for the specific group of people and disease studied in the phase III clinical trial. This information can be found in the drug's label and patient information sheet that is given when a prescription is filled. Sometimes, questions arise during the testing process that are important but not crucial to FDA review. Therefore, after FDA approval, doctors may continue to test the treatment in a phase IV clinical trial. Additional trials may also be done to test the drug in people with other diseases or with other stages of a disease.

Patient Generosity and Participation

Most medical advances have occurred because of people who join in clinical trials. Without participants, many questions would remain unanswered and the progress of medicine slowed. Since it is important for a clinical trial to enroll people of different ages, races, ethnicities, and other demographics, a variety of groups advocate for private insurers to cover patient care costs related to clinical trials.


Despite the promise offered by clinical trials, less than 5% of adult cancer patients enroll in them. This lack of participation slows progress in the development of new, more effective therapies. By contrast, more than 60% of children with cancer are enrolled in clinical trials. Approximately three-quarters of children with cancer survive their disease long-term, compared with half of adults. The increased survival rate for children can be directly linked to their higher rate of participation in cancer clinical trials. 

Sponsorship, Costs and Insurance Coverage

Clinical trials are sponsored by government agencies such as the National Institutes of Health (NIH), including the National Cancer Institute (NCI), pharmaceutical companies, individual doctors, health care institutions such as health maintenance organizations (HMOs), and organizations that develop medical devices or equipment. Currently, Medicare provides coverage of routine costs for most cancer clinical trials. Additionally, several states have enacted laws or negotiated agreements for insurers to provide coverage. Any cost to the participant should be explained during the informed consent process.  


One effective mechanism for operating clinical trials is a cooperative group. Cooperative groups are large networks of doctors and other health care professionals from many different institutions that develop and coordinate clinical trials. Cooperative groups are funded by the NCI. Because so many doctors and institutions are involved, the clinical trials sponsored by cooperative groups can enroll more people than a single clinical trial at one hospital. Also, the cooperation makes it easier for people from different parts of the country to enroll in a clinical trial.

The coverage of clinical trial costs differs by state. Medicare covers routine costs related to phase II or phase III trials. Some clinical trials offer payment, while others do not. In some programs, researchers will reimburse for expenses associated with participating in the research, such as transportation, childcare, meals, and accommodations.       

Sources for Clinical Trial Information

The information for this page was obtained primarily from the website which has more information available regarding clinical trials. For details such as questions to ask your doctor, insurance information, stories from patients who participated in clinical trials,  and informed consent forms, you can find out more at the clinical trials section at's website. 


For people interested in locating and possibly enrolling in a clinical trial, you can visit the most definitive list of current clinical trials for ACC which is hosted and updated by the NCI 

For a comprehensive list of medical institutions and cooperatives who conduct and support clinical trials.