How Phase 2 Clinical Trial Works?
Phase 2 clinical trial is built on the results of Phase 1, testing the method on participants to determine the safety and effectiveness of new treatment. Phase 2 trials include the extended duration of the study with an increased number of participants. The information measured is related to how the new medication or method works against the target health condition.
Phase 2 trials involve various activities like collecting blood samples, measuring health levels on a regular basis. These trials keep a log of daily symptoms and activities to learn the effectiveness of the treatment.
Phase 2 Clinical Trial – What It is All About?
Phase 2 clinical trial involves several hundred participants living under the condition that the new medicine is meant to treat. They are given the same dose that was found to be safe in clinical trial 1.
During the phase 2 trial, researchers monitor participants for several months to years to check the effectiveness of the study treatment or medication and gather information regarding side effects it might cause.
While more participants are involved in phase 2, more than earlier phases, still it isn’t enough to demonstrate the drug’s overall safety. However, the data collected in this phase is used by investigators for conducting phase 3.
- A group of 75 to 150 patients with the same type of medical condition get the new treatment in a phase2 clinical trial. Participants are treated with a method or dose found to be the most effective and safest in phase 1 studies.
- Usually, everyone gets the same dose. However, some trials randomly assign participants to different treatment groups where they receive treatment or doses to determine which provides the best balance of response and safety.
- Phase 2 studies are held at the major centers, community hospitals or doctors’ offices.
- Less common side effects may be seen as larger numbers of patients are involved. When enough patients seem to benefit from the treatment with few side effects, phase 3 clinical trials start.
Phase 2 Clinical Trial – Introduction to New Designs
Typically, the conventional Phase 2 clinical trials were single-arm experiments. Their outcome was characterized by one binary response variable. Such methodology poorly served clinical investigators. Single-arm failed to produce a reliable means for selecting therapies that could be investigated in phase 3.
Thus, conventional phase 2 designs were considered inefficient and unreliable. These concern motivated the new paradigm evaluating several therapies based on multiple outcomes. The importance of randomization is stressed in phase 2 clinical trials as these are the basis for selecting agents to be investigated in larger trials.
In randomized trials, researchers determine the best option among several choices. They randomly assign each patient to particular study treatment. In the end, the results are compared between the different study treatments.
In blinded phase 2 clinical trials, participants are unaware of the received study treatment to ensure impartiality and effectiveness. During placebo-controlled trials, participants get sugar-pill or placebo instead of medication or study treatment.
It is common for phase 2 clinical trials to be randomized, blinded, and placebo-controlled. It ensures finding the best study treatment available.
Phase 2 Clinical Trial – Phase 2A and Phase 2B Trials
Phase 2 clinical trials are also known as exploratory therapeutic trials that are conducted in 100-300 patients approximately. It explores the efficacy of the drug and helps to evaluate further safety. With the support of the safety data collected from the phase 1 trials, this phase performs investigatory drug testing on a well designed patient population with the target disease.
Phase 2 clinical trials are sometimes divided into phase 2A and phase 2B trials. Though both phases test the drug’s efficacy and safety, the types of studies are different for each phase.
Phase 2A trials are known as early phase trials, conducted with clinical efficacy and pharmaco-dynamics as the primary endpoint. These are non-pivotal pilot studies that determine the drug mechanism of action and how it affects the body. Phase 2B clinical trials are conducted to test the efficacy of the drug.
Phase 2A Trials
Phase 2A clinical trials are the most important trials in the clinical development of new medicine. At this level, the decisions are taken for proceeding further with drug development. Proof of Concept (POC) studies are performed.
Till this trial, no efficacy data is available in humans. The POC studies are performed with two treatment groups. One group is tested with a test drug and the other with a placebo.
Firstly, the new drug is tested with Maximal Tolerated Dose (MTD) or slightly lower than it. To determine the best possible efficacy, the dose is selected high, closest to MTD. If the drug shows promising efficacy when tested in humans with target condition, further trials ate conducted based on proven concepts.
Phase 2B Trials
On the basis of proven efficacy from Phase 2A trials, phase 2B trials are conducted. It studies dose-ranging by studying dose responses. Now that the efficacy of the new medicine at a high dose has been determined, the potency of the other doses that are lower than the actual effect produced dose is determined at phase 2B trials.
Ascertaining which doses should be selected as test doses other than effect produced dose is difficult to analyze. However, different methods are used, such as log dose spacing, equal dose phasing, etc.
How are Volunteers Added into Groups?
A computer program is used by the Doctors to put volunteers into different group. This is done by the computers at random. Each volunteer, however, has an equal chance of going in any group. This process is called randomization.
This process is known as it keeps the researchers from possibly changing the results of the clinical trials. There might be chances where clinical staff might think a certain participant would benefit from the new treatment. Therefore, they might put that person in the treatment group, which could change the trial results. However, randomization avoids this and is helpful in comparing two treatments.
Phase 2 Clinical Trial – What are Well-Controlled and Adequate Studies?
Phase 2 clinical trials have been designed well enough to distinguish the effect of a drug from other influences, such as spontaneous change. Adequate clinical trials have:
- A clear statement of purpose
- Control for valid comparison
- Appropriate selection of patients
- Appropriate assignment to treatment and control
- Measures to minimize bias
- Reliable and well-defined methods of assessing response
- Planned analyses designed with rigor
Phase 2 Clinical Trial – What to Consider when Defining Benefits in Drug Development?
Phase 2 clinical trial benefit is recognized when there is a favorable effect on the meaningful aspect of how a participant feels, survives or functions as a result of treatment. It may be measured as an improvement or delay in the progression of a medical condition or disease.
- Clarify the goal of drug study while understanding the mechanism of action of the drug.
- Identify the target population. The enrolled participants should provide adequate assurance that they have been documented with the specific medical condition.
- Encourage patient involvement and identify signs/symptoms that would convince the targeted population that they have been benefited from the clinical trial.
- Develop Clinical Outcome Assessment (COA) to measure clinical benefit experienced by the patients. It ensures that the patient with underlying diseases has shown improvements and that the symptoms have not worsened.
- Establish a responder definition using selected COA as to what magnitude of change is considered meaningful and convincing.
- Determine the endpoint or the appropriate timing of efficacy assessment.
Phase 2 Clinical Trial – The Benefits
The potential benefit from participation in clinical trials is highly variable. In early-phase studies, the benefits are lowest for those with a particular disease or disorder. In fact, participants are likely to experience harm than clinically significant benefits.
The goal of phase 2 trials is to determine what benefit the experimental interventions provide for treating the disease. Ideally, if the trial is well implemented and designed, the researchers gain new knowledge that benefits future patients.
Phase 2 Clinical Trial – The Risks
Essentially all clinical studies involve risks of discomfort or harm to the participants. Too often, the risks are minimized by the researchers.
The potential sources of risk from phase 2 clinical trial include adverse effects due to:
- The experimental drug that may cause strokes, liver injury or kidney disease
- Procedures that the subjects undergo such as imaging studies, blood tests or biopsies
- Substandard treatment or no treatment of a potentially serious disease when patients are allocated to the control group and receive a placebo.
Phase 2 Clinical Trial – Where to Find?
Clinical studies are sponsored or funded by academic medical centers, pharmaceutical or voluntary groups, and other organizations.
Additionally, Federal agencies such as the U.S. Department of Defense, the National Institutes of Health, and the U.S. Department of Veterans Affairs, and other health care providers can also sponsor clinical research. For more information, visit https://www.clinicaltrials.gov/ct2/about-studies/learn
Phase 2 clinical trial is a critical part of clinical research. It allows assessing the safety and effectiveness of new drugs or treatments before introducing them to the general public.
Before enrolling in a clinical trial, discuss it in detail with researchers and ask for a consent form for the trial. Consider thoughtfully if the trial is the right choice for your medical condition and learn as much about the proposed research interventions.