What is Phase 1 Clinical Trial?
Phase 1 clinical trial is the first phase of the clinical research process. It involves testing new or experimental drugs on humans for treatment. The aim is to determine the tolerability, safety, best dose, side effects, and pharmacokinetics (PK) of a compound.
Clinical trials are key research tools that are only performed when there is a good reason that a new drug, test, or treatment may improve patients’ lives.
Clinical trials are not directly held. Before these trials, tests and treatments are assessed in pre-clinical research that is not done with people.
Phase 1 trials aim to find the most competent dose for a new or improved drug with the fewest side effects.
The drug is tested on 15 to 30 patients, and Doctors start by giving very low doses of the drug.
The drug may help patients; however, the motive is to test a drug’s safety. If a drug isn’t found safe enough, it is tested in a phase 2 clinical trial.
Phase 1 Clinical Trial – Everything You Need to Know About It
Phase 1 clinical trials are designed primarily to accumulate short-term safety and pharmacological data. These studies are the first to involve people. However, the number of patients involved is small, and they receive a very low amount of doses.
The purpose of phase 1 studies is to find the highest dose of the new treatment without causing any severe side effects. The treatment is first tested in the lab and on animals.
- Phase 1 trial is the first phase of clinical trials overseen by the Center for Drug Evaluation and Research (CDER).
- It begins after the research and development of a new drug. The aim is to test the safety of a new drug by establishing its side effects.
- The few people get involved in this trial process where they start with a smaller amount of dose and are observed.
- If side effects are rare, the next few participants of the trial get a higher dose.
- The process is continued until the doctors find a dose that works at an acceptable level.
- Approximately 70% of drugs that are submitted for phase 1 clinical trial make it to phase 2.
- Phase 1 clinical trials often carry the most potential risk. However, patients who have tried all other treatment options and are suffering from life-threatening illnesses choose to join such trials. Also, it has been noticed that these studies do help some patients.
- Clinical trials, especially phase 1 trial, is expensive. It can cost approximately between $1.5 million to $6.5 million.
Phase 1 Clinical Trial – The Process
Phase 1 clinical trial requires a small group of 20–100 healthy volunteers will be recruited. These trials are often administered by contract research organizations (CROs) that conduct studies on behalf of the research investigators or pharmaceutical companies.
The clinical trials ate often conducted in a clinic where the subject who receives the drug is closely examined.
Phase 1 trials normally study dose escalation to find the best and safest dose. It is a long and grueling process that enables vital information about the effects of the drug.
This information is used to facilitate the design of scientifically valid and well-controlled phase 2 studies.
Phase 2 clinical trial process focuses on the drug’s effectiveness, and Phase 3 compares the treatment of new drugs to the current treatment available for a medical problem. Phase 4 tests the effects of the drug on the population after being approved by the FDA.
Phase 1 Trial Designs
Phase 1 clinical trials are further divided into different trial designs. Let us learn about it.
- Single Ascending Dose
In single ascending dose trials, a small group of subjects, usually three, receive a single dose of the drug. They are then observed and closely monitored.
If they do not exhibit any adverse effects, the compound is deemed to be well tolerated, and the dose is escalated. It occurs within the same group, or a new group of subjects is then given a higher dose.
Dose escalation is continued until the maximum dose has been attained or intolerable side effects become apparent. When unacceptable toxicity is observed after being experienced in one-third of participants, the dose escalation is terminated. The previous amount of dose is then declared as the maximally tolerated dose.
- Multiple Ascending Dose
Multiple Ascending Dose studies are conducted to elucidate the pharmacokinetics and pharmacodynamics of the compound. Looking at tolerability and safety, a group of patients receives dose levels, and dosing intervals are selected.
At various time points, samples are collected and analyzed to determine how the body processes the drug. The dose is subsequently escalated for further participants to determine the safety level for repeat dose administration.
- Food Effect
Food effect is a short trial designed to assess differences in absorption of the compound when administered after a specifically designed meal.
Such studies are conducted following a crossover design with volunteers given drugs on different occasions while fasting and after being fed. These studies contribute to the prescription as to when drugs should be administered.
Phase 1 Clinical Trial – Is the Treatment Safe?
In the United States, the development of drugs and their approval is a complex process. The treatment goes through scientific oversight that makes the treatment safe to a certain extent.
Institutional Review Board (IRB)
An IRB is an independent committee of members, including doctors, statisticians, and community members who sponsor a clinical trial. The purpose is to ensure that the rights of the participants are protected and that the proper protocols and ethics are being followed.
It is required by all U.S. clinical trials to have an IRB. An IRB approves research that deals with significant medical questions responsibly and scientifically. It also keeps a check on the ongoing results of the trial.
Office for Human Research Protections
The Office for Human Research Protection (OHRP) under the U.S. Department of Health and Human Services (HHS) oversees the research done or supported by HHS. The OHRP protects the rights and well-being of research participants. It develops educational programs and offers advice on research-related issues.
Food and Drug Administration
In the United States, The Center for Drug Evaluation and Research (CDER), a division of the U.S. Food and Drug Administration (FDA), manages clinical trials. The FDA reviews applications for new drugs or medical devices before testing them directly on humans and ensures that the proposed studies have informed consent and protection for human subjects.
Patient Rights: Informed Consent
The FDA protects participants in clinical trials and ensures that people have reliable information. Researchers must give participants complete and accurate information about the trial.
Prospective participants are required to sign an “informed consent” document indicating the known risks of the research, and they can leave the trial at any time.
Informed consent is the process of giving all the details and facts to the trial participants. It includes information on the tests, treatments, benefits, and risks involved in the trial. It happens before the trial begins and during the trial.
Phase 1 Clinical Trial – Patients’ Benefits of Participating
A well-designed and executed clinical trial provides participants an opportunity to play an active role in improving their health care. Here are some of the other additional benefits.
- Phase trial 1 helps in reducing or controlling the disease. When other treatments have failed, a patient can benefit from participating.
- A patient can obtain expert medical care at leading healthcare facilities where they feel overall satisfied with their experiences.
- As a part of the phase 1 trial, a patient undergoes routine physical examination that helps them receive more information about their disease and alleviates some fear about the severity of their disease.
- The nature of toxicity reported in the phase 1 clinical trial positively impacts the patient as their every symptom is scrutinized. The participants feel empowered as they attempt to control the disease and contribute to the health of future patients.
Phase 1 Clinical Trial – Patient Risks of Participating
Some researchers view early access to a helpful drug as a benefit; however, this early access may also be risky. Here are some of the risks involved in participation in phase 1 clinical trials.
- The primary risk is death. The investigatory agent or malignancy progression or complications can cause it.
- Additionally, patients may also experience the risk of acute or delayed toxicities, which might not be detected until the phase 1 clinical trial is complete.
- Patients usually do not feel better or satisfied until their trial participation is complete.
- Several early-phase trials require fresh biopsies. These are subject to risks without any direct benefit to the patient.
Phase 1 clinical trial is the first step towards medical studies where a new or improved drug is tested on humans. It involves risks as well as benefits associated with it.
The primary purpose is to determine if a drug is safe and know the best suitable dose. Yet, the benefits may outweigh the risks of phase 1 clinical trials. It brings hope by improving survival.
Participating in these clinical trials is a personal decision where a patient can leave the problem any time. Talk with your doctor about all the available treatment options; you can make a better choice together!