A phase 1 clinical trial is typically a first-in-human study of an experimental therapy, and its historical purpose was to evaluate the safety and identify potential side effects of that investigational treatment, as well as determine an appropriate dosage for use.1 The American Society of Clinical Oncology (ASCO) states that phase 1 trials are critical to translating basic research findings into treatments for patients.2

Many modern phase 1 trials are now including efficacy reporting of the experimental therapy — particularly response rate — as one of the endpoints.3 In addition, some phase 1 trials include a phase 2 extension trial as well, which provides preliminary information on the therapy’s efficacy.1,3

Both phase 1 and phase 2 trials are usually (but not always) required before a therapy moves to phase 3. Phase 3 is used to gather information about the therapy’s safety and efficacy in a large population in the pursuit of US Food and Drug Administration (FDA) approval.1 Some treatments receive FDA approval without a phase 3 trial.3

Most phase 1 trials are small and enroll approximately 20 to 80 patients.1 Because the efficacy and safety of the experimental therapy is typically unknown, there are important risks and benefits that patients should consider before enrolling in a phase 1 trial. In addition, many therapies that enter phase 1 trials ultimately do not receive FDA approval (the likelihood of approval for oncology drugs tested in phase 1 trials is 6.7%).4

Risks and Benefits

There are several potential risks for patients who participate in phase 1 trials. A key risk is the threat of developing an adverse event, which may or may not be permanent, and an associated danger is the risk of death attributed to the experimental therapy.5 The rates of treatment-associated deaths are low at approximately 0.5%, but it is nonetheless possible.6,7 In addition, the experimental treatment may not be effective or found to be not as effective as standard treatments.8

Patients should also be aware that phase 1 clinical trials require a commitment to an intense clinical schedule, which includes multiple visits to the clinic and may also require biopsies or other procedures.8 This commitment may also result in out-of-pocket costs for patients.9

Although Medicare and most private insurance companies often reimburse direct medical expenses associated with a clinical trial, and drug company-sponsored studies often pay for all direct medical expenses, patients are still responsible for indirect costs.10 One study estimated that the median indirect out-of-pocket cost was $985 per month, and the highest costs appeared to be carried by patients with lower incomes or who were unemployed or not working outside the home.9 Out-of-pocket costs include travel costs such as for gas or public transportation, loss of work income, and cost of child care.

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The major benefit of participating in a phase 1 trial is the potential that the experimental therapy will shrink or stabilize the cancer.2 Overall, it is estimated that approximately 7% to 11% of patients experience tumor shrinkage in phase 1 trials, with up to 34% to 48% experiencing at least stabilization of their cancer.6,7 The actual response rate varies between trials. This may be particularly important to some patients, as most patients enrolled in phase 1 trials have metastatic disease that has already progressed after the receipt of other treatments.1 In addition, other potential benefits include access to new treatments and helping advance scientific research.

However, some experts caution that phase 1 trials offer little benefit to most patients, as the risks are typically more pronounced than the benefits in this early phase of experimentation.3,10 There is some debate on the ethics of phase 1 trials, and patients should be aware of all potential risks before agreeing to participate.