Clinical Research Trials: The Basics

James Metz, MD and Carolyn Vachani, RN, MSN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 20, 2014

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There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials may be performed on an international level (at institutions around the world), national level (trials run at multiple institutions around the country), or at a single institution. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. This article will help you understand the basics of clinical trials and their importance in the field of oncology.

Oversight of Trials and Informed Consent

An Institutional Review Board (IRB), which is composed of physicians, researchers, and even people not involved in medicine, must review and approve any clinical trial before it can begin. The IRB decides if the study is reasonable, appropriately designed, and safe for the patient population. Once the study is underway, the IRB continues to monitor for safety, adherence to the study protocol and any changes or findings that may affect the participants.

Anyone considering joining a clinical research trial must be fully informed about the trial details, benefits, and risks; explanation of these takes place during an interactive process known as informed consent. It is the responsibility of the study team and physician to explain the trial, in language that the participant/family members can understand, allowing them to make an educated decision about whether or not to participate in the trial. Once the study team has explained the study and the participant's questions have been answered, the participant must sign an informed consent document in order to participate in a trial. This document is designed to explain the trial in clear language, present risks and benefits, alternatives to treatment and explain the participant's right to choose not to participate. The participant may choose to think about his or her options or review the consent with family members and friends before making their decision- this is not a decision to make hastily.

Why Participate?

There are several reasons to consider participation in a clinical trial. Often, through participation in a clinical trial, patients have access to unique treatments that would not otherwise be available. In addition, clinical trials are important because they allow the field of oncology to advance, finding safer and more effective treatments. Today's successful treatments are a result of their effectiveness determined in clinical trials. Unfortunately, only about 3-5% of adult cancer patients participate in clinical trials, leaving many research questions unanswered. This may be due to misunderstandings about trials (from both patient and healthcare provider perspectives), patient fears, providers not recommending a trial or not having access to trials in their treatment center. Clinical trials are time consuming and expensive to run, making it not feasible for all practices to offer them. In some cases, patients may need to inquire about clinical trial options in order to learn about them.

Phases of Clinical Trials

There are different types of oncology clinical trials, including treatment, diagnostic, prevention, screening and supportive care. These address all the steps involved in cancer care, looking to find the best intervention for each step that will result in the best outcomes. Clinical trials are performed in the following phases, typically in this order, with each phase designed to answer specific questions:

Phase I clinical trials:

  • Attempt to determine the dose of a drug (or other treatment) that is safe and any potential side effects that the drug may cause.
  • Typically include a small number of patients, often with advanced disease that is resistant to standard treatments.
  • Typically involve a new or novel type of treatment.
  • These studies often use a dose escalation format. In dose escalation, the first group of patients receives a certain dose, and if it appears safe and well tolerated, the second group of patients receives a higher dose. The dose is increased for each group of patients until the maximum tolerated dose, or the highest dose that is deemed safe and tolerable, is reached.

Phase II clinical trials:

  • Typically include a larger number of patients and look to evaluate whether a treatment is effective (i.e. controls or kills cancer cells) and continues to look at the safety and tolerability of the treatment.
  • Typically patients with a tumor for which there is not an effective therapy available are included in phase II trials of single agents (1 medication or therapy). Perhaps their cancer is no longer responding to available therapies or the type of cancer does not have any effective treatments available.
  • Combination regimens (multiple drugs or treatments given together) may also be evaluated in phase II trials, with the goal of ensuring that the treatment is feasible, safe, and promising enough before expanding to the next phase (and therefore a larger group of patients).

Phase III clinical trials:

  • Designed to compare an experimental treatment to an accepted standard of care and evaluate endpoints such as survival and symptom control.
  • These trials are typically randomized, controlled trials, performed in multi-institutional settings, including university and community medical centers, and involving hundreds to thousands of patients.

Phase IV clinical trials:

  • Often called post-marketing studies. These trials are done once the drug has received FDA approval and is being used in practice, with the goal of further assessing safety and effectiveness.

Can Anyone Participate in a Trial?

Every trial is "governed" by a protocol. The protocol is written before the trial starts and approved by the IRB. It details what the goals of the trial are, which patients and how many will be included, what treatments they will receive, how they will be monitored, when to stop treating a participant, etc. This document is very detailed and is the guidebook that the study team will follow. The protocol specifically states the criteria a person must meet to be eligible to participate. If the patient does not meet these strict criteria, they will not be able to participate.

Randomization

Phase II and III trials are often performed using a technique called randomization. If the patient chooses to participate in a randomized trial, a computer chooses the treatment they will receive randomly. The study team, physician and patient have no control over this decision and, in many trials, do not know which treatment the patient will be receiving (this is called blinding). This is done to make a fair comparison of treatments, leaving out the chance that the results are affected by "bias". Bias occurs when human choices affect a result; perhaps choosing a particular group of patients for one treatment option over another based on preconceived beliefs that this option is best for that group.

The treatment groups may be referred to as control and treatment groups (or arms). The control group typically receives what is considered the standard treatment for that type of cancer. The treatment group receives the experimental treatment being studied. Oncology clinical trials rarely use a placebo and when they do this will be clearly described in the informed consent process and spelled out in the consent that is signed. The study team can explain the design of the particular trial you are interested in and how it will be carried out.

Once the Trial Begins

Once you are enrolled in a clinical trial, you will receive guidance from the study team as to any testing that needs to be done or anything you should report to them- including side effects, health issues that may arise or other concerns. You should know the name of the trial in which you are participating and keep a copy of your consent form handy if should you need to call your oncology office after-hours or go to an emergency room. If you have concerns while on the trial, they should be brought to the attention of the study team. If, for any reason, you do not want to participate in the trial any longer, it is your right to withdrawal from the study.

Conclusion

Clinical research trials are extremely important in expanding treatment options in all cancers. The treatments that are available today are due to the participation of prior patients in clinical research trials. We are constantly trying to identify better treatments to cure cancer. There are also studies to identify less toxic treatments or agents, which can protect the normal tissues and minimize side effects of treatment. Clinical research trials are very rewarding for both the patient and the physician. The patient may benefit from new treatment options and help future cancer patients in their fight against this disease.



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