New Drug Clinical Trial Design Path: Phase II Clinical Trials.

This article follows: New Drug Clinical Trial Design Path: Phase I Clinical Trials 1 Preamble In Phase I Clinical Trials, the drug's human tolerance, safety, pharmacokinetic characteristics, and the recommended PR2D (Recommended Phase Dose II) can begin, i.e. can start Phase II clinical trials.
Phase II clinical trial, also known as exploratory clinical trial, is the first clinical trial of a new drug in a patient with the aim of exploring efficacy.
because of the high cost and long cycle of clinical research on new drugs, it is important to be the design of Phase II clinical trials under the promise of the onset.
bidders hope that future drug discoveries will be detected as soon as Phase II clinical trials do not terminate the study too soon, and that further trials of ineffective new drugs will be terminated as soon as possible. the Panorama Phase I trial of the
Phase II Clinical Trials focused on new drug safety and pharmacokinetics, while the focus of Phase II trials shifted to pharmacodynamics. The main objective of the phase II clinical trial of
is to examine the ability of new drugs to establish relatively consistent pharmacodynamics and acceptable toxicity levels among the target patients.
2.1 What (Who) Phase II clinical trials are primarily used to evaluate the initial efficacy and safety of new drugs in target patients.
2.2 Why (Why) Phase II clinical trials are related to the effectiveness of the study drug, and the questions sought to answer include: (1) how effective the drug is effective for a particular indication within the safe dose of Phase I clinical confirmation? 2What are the adverse reactions and risks of short-term new drugs in patients? 2.3 What to do (What) Phase II clinical trials include: (1) determining the maximum and minimum effective dose range of new drugs acting on target patients, providing reference for the dose of Phase III clinical trials, and (2) the relationship between the blood concentration of the efficacy of the new drug and the pharmacodynamic parameters, i.e. pharmacodynamics and pharmacodynamics.
clinically divided into Phase II and IIb, depending on the purpose.
2.4 How (How) Test Order: Generally implemented in the iIa, IIb period; Design principle: Phase II as an exploratory test, can use a variety of design methods, such as contemporaneous control, self-control, open test, three-arm test (positive drug, placebo, test drug), dose-effect relationship, etc. research;
3 New Cancer Drug Phase II Clinical Trial Design Method is divided into single-arm trials and randomized controlled trials based on whether there is a control group set.
, in addition, also includes random withdrawal test design.
3.1 Single Arm Clinical Trial Design Single Arm Study: single-group clinical trials, as the name suggests, are only one group of studies, without a corresponding control group designed for the trial group;
new cancer drug Phase II clinical trials, often to explore multiple tumor species, multiple doses or usage, the purpose is to eliminate invalid doses, screening sensitive tumor species, for further in-depth study.
single-arm test is divided into single-arm single-stage and single-arm multi-stage, the simplest test design is a single-arm single-stage test, in which the planned sample number of patients are treated, according to the treatment effect of the final conclusion of the test.
the flaw in the design of the one-arm single-stage trial is that if the treatment is found to be ineffective and cannot be terminated before the final sample size is reached, it cannot be terminated, resulting in waste of resources and ethical dilemmas.
single-arm multi-stage trial design can avoid the defects of single-stage trial design, it can be in a test group when the efficacy is not achieved, the study of the experimental group to avoid more subjects to receive ineffective treatment.
the above-mentioned one-arm multi-stage experiment to calculate the specific sample size, it is divided into optimal design (optimal design) and very small design (min-max design).
single-arm multi-stage design is generally used for exploratory research, the advantage is that multi-phase design has clear guidelines for early termination of research, when the effectiveness of the experimental drug is low, can be terminated at an early stage, to avoid more subjects to receive ineffective treatment;
3.2 Randomized Controlled Clinical Design Because Phase II Clinical Trials are exploratory human trials with small sample sizes, most Phase II clinical trials are designed to be single-arm, non-randomized, and do not have a control group, but use historical data control, which increases the uncertainty of the new drug effectiveness judgment. in order to reduce the risk of failure of Phase III clinical trials, the
, as a forward-looking outpost, the Phase II clinical encouragement of randomized controlled design, and to ensure that the sample size has a statistical basis for estimation.
Although Phase II randomized controlled clinical design does not have sufficient statistical certainty to evaluate the decision between new drugs and standard treatments, this design can provide a quantitative basis for the priority entry of promising new drugs into Phase III trials.
Phase II randomized controlled clinical trial design can be used for evaluation: multi-dose, multi-dose protocol, experimental treatment and standard treatment comparison of the study, for The Third Phase III clinical trial design to provide more useful data. The general process for the design of phase II randomized controlled clinical trials
is shown in the figure below. The main purpose of phase II randomized controlled clinical trials
is to select the most efficient dose, dosing option or candidate drug for Phase III clinical trial by evaluating the efficiency of the drug under test.
the sample size required for Phase II randomized clinical trials is not sufficient to infer the efficacy, non-poor efficacy, or equivalence of the experimental drug.
3.3 Random withdrawal design Random withdrawal study refers to the fact that the active drug is consistently assigned to continue to be treated with the subject drug or treated with a placebo (i.e., deactivation of active drugs) after the patient who received a certain period of time in the drug treatment, and any difference between the continued treatment group and the placebo group can demonstrate the efficacy of the active drug. the advantage sized
randomized withdrawal design: patients were less likely to have a placebo use phase and a significantly lower ethical risk.
randomized withdrawal method sedituated for recurrent disease attacks (e.g. antidepressants), clinical lying trials of drugs that inhibit symptoms or signs (chronic pain, high blood pressure, angina), etc.
4 Thinking Phase II clinical trialist is generally the first time a new drug has been applied to a target patient to observe the initial efficacy and safety data of the new drug.
Because Phase III clinical trials are generally large-scale confirmed trials, they are often multi-center, large-sample, long-cycle clinical trials, is the FDA evaluation, approval of new drugs the most critical evidence, and as a pioneer force of Phase II clinical trials for Phase III is of great significance.
reasonable scientific Phase II clinical trial design, not only can identify the value of further development of new drugs in the early stage, but also can recommend reasonable clinical positioning for Phase III clinical trials, intended for the treatment of indications, suitable selection of people with disease, the main efficacy indicators, safety indicators, dose, administration methods, courses, etc., can be said to be a great responsibility.
late toxicity is one of the problems in Phase II clinical trials, and it is recommended that Phase II clinical trials pay attention to simultaneous detection of reaction and toxic variables. in addition,
, orphan drugs or new drugs with significant breakthrough therapies after the completion of Phase II clinical trials, the applicant can apply to the FDA for listing, fda after assessing the patient interest/risk ratio, the FDA can "conditionally approve" the new drug based on clinical Phase II data for early marketing;
is the so-called "scale although small pressure jack", Phase II clinical trials in the entire new drug clinical trials play a role in the start-up.
References: 1. Clinical Trial Design and Analysis 2. Drug Clinical Trial Methodology 3. Multi-phase Design of Phase II Clinical Trials of New Oncology Drugs 4. General Principles of Clinical Research on New Chinese Medicines 6. Phase II Clinical Trials of Anti-Tumor Drugs - Introduction of Conventional Design and New Strategies for the Age of Targeting Therapy.