What Is a Phase 1 Clinical Trial? What to Know, Risks and Benefits

The Importance of Clinical Trials

Progress in cancer treatment is made possible by the crucial contributions of scientific and clinical research. Phase 1 clinical trials are a critical stage in this process because they are where the safety and effectiveness of new treatments are first assessed. This article examines in detail what a phase 1 clinical trial is, the potential risks and benefits of participation, and what patients should expect. This information can help healthcare professionals and potential participants better understand the importance of phase 1 trials and why this type of study is needed.

What Is a Phase 1 Trial? Its Purpose and Importance

A phase 1 clinical trial is a study in which a treatment is tested in humans for the first time.

Historically, the main aims of these trials have been to assess the safety of the new treatment, identify potential side effects and determine an appropriate dose.

Phase 1 trials are a critical step in translating findings from laboratory and animal studies into treatments for patients.

Phase 1 and phase 2 trials are generally prerequisites for moving a treatment into a larger phase 3 trial. Phase 3 trials are conducted in large patient populations to collect comprehensive safety and effectiveness data with the aim of obtaining US Food and Drug Administration (FDA) approval. However, some treatments can receive FDA approval without a phase 3 trial.

What Is the Status of Phase I Trials in Turkey?

As of September 2023, Turkey had 26 registered phase 1 clinical trials, 16 of them in cancer. By comparison, the number of registered phase 3 clinical trials in Turkey was 649.

Phase 1 clinical trials are generally conducted in countries with advanced biotechnology and healthcare sectors. They require sophisticated laboratory equipment, specialist knowledge and experience. Regulatory frameworks are also needed to ensure that these trials are conducted ethically and safely.

How Many Patients Are Enrolled in a Phase 1 Trial?

Many phase 1 trials typically enroll between 20 and 80 patients. Because the effectiveness and safety of the experimental therapy are largely uncertain, patients must consider important risks and advantages before joining a phase 1 trial.

Many therapies evaluated in phase 1 trials never receive FDA approval. Oncology drugs tested in phase 1 trials have only a 6.7% chance of approval.

Risks and Benefits of Phase 1 Trials

Patients participating in phase 1 trials face several potential risks. A prominent risk is an adverse event (side effect) that may be temporary or permanent; the experimental therapy may also carry a risk of death. Although deaths due to experimental treatment occur at a very low rate, around 0.5%, they remain a possibility. In addition, the experimental treatment may not work or may be less effective than current standard treatments.

Another important point for patients is that phase 1 clinical trials involve an intensive schedule with frequent clinic visits, which may include procedures such as biopsies. This commitment can create additional costs for patients.

In Turkey, clinical trials are generally funded by the sponsoring pharmaceutical company. The sponsor must cover the costs of all products, equipment and materials used in the trial. Volunteers or social security institutions cannot be required to pay these costs. If the sponsor has no representative in Turkey, it submits the clinical trial application through a contract research organization (CRO) based in Turkey.

Potential Benefits: Tumor Shrinkage and Contributions to Science

The main advantage of joining a phase 1 trial is the possibility that the experimental therapy may shrink or stop the cancer. Overall, it is estimated that 7% to 11% of patients in phase 1 trials experience tumor shrinkage, while 34% to 48% achieve at least stable disease. Actual response rates vary between trials. This can be crucial for some patients, since many participants in phase 1 trials have advanced metastatic disease that has not responded to other treatments. Other potential advantages include access to new treatments and the opportunity to contribute to scientific progress.

However, some experts point out that phase 1 trials provide minimal benefit to most patients because the risks at this stage generally outweigh the potential benefits. The ethics of phase 1 trials are debated, and patients must understand all possible risks before deciding to participate.

What Should You Expect From a Phase 1 Clinical Trial?

After patients and healthcare professionals discuss participation in a phase 1 trial and reach a decision, the research team assesses the patient to determine whether they meet the eligibility criteria. The team explains the details of the trial, what is being studied and what is expected of the patient. Patients may ask questions about anything they wish to know. Those who still want to participate are then asked to sign a consent form confirming that they have been informed of the potential risks and benefits and that their questions have been answered.

Patients may wish to ask about the treatment and/or tests involved, how the experimental therapy compares with standard treatments, possible side effects, the trial's duration, the time commitment required and who will be responsible for their medical care.

After consent is obtained, patients are screened to determine whether they meet the trial's eligibility criteria. Inclusion criteria vary between trials and may involve factors such as age, disease stage, family history or genetic profile. Exclusion criteria, on the other hand, generally restrict participation because of current or past health conditions other than cancer, or certain medications taken previously.

Patients who meet the eligibility criteria undergo baseline testing, which may include laboratory analyses or molecular tests. Once testing is complete, patients begin the designated experimental treatment.

During treatment, additional tests may monitor specific side effects and, in some cases, treatment effectiveness, requiring follow-up visits to the research center. The team regularly assesses patients for possible side effects.

If a side effect occurs, it is managed according to current standards of care. This does not necessarily mean that the patient must stop experimental treatment or leave the study; the decision depends on the nature and severity of the side effect.

Patients may continue experimental treatment for as long as they benefit from it. Many phase 1 trials last approximately 2 years. If a patient's condition worsens during the trial, they generally stop the experimental treatment. They may then join another clinical trial, switch to a standard treatment or choose palliative care .