Phase 3 Clinical Trials – Overview
Phase 3 clinical trials are the final phase for experimenting with a new drug to confirm the therapeutic effect observed in phase 2 clinical trials. It ensures that the drug is beneficial, safe and offers treatment for the intended indication.
Billions are spent to progress a drug to phase 3 trials, a vital phase from chemical to drug development. It focuses on efficacy and safety by collecting randomized control data on a larger number of patients in a given disease. This phase involves choosing the experimental scheme, collecting undesirable effects, considering the risk-benefit ratio, and calculating the number of participants necessary to demonstrate certain efficiency in the pathology concerned.
Phase 3 Clinical Trials – Introduction
It is necessary to perform the widest trials as most phase 2 clinical trials ending with a positive result do not succeed in phase 3. It is often due to a lack of therapeutic efficacy or serious adverse effects.
Phase 3 trials are conducted to obtain additional information and verify the new drug’s effectiveness and safety to assess the risk/benefit ratio. This information is used in the drug’s labeling once the FDA approves it. These trials involve large-scale studies and include several hundred to thousand patients.
Phase 3 clinical trials are Randomized Control Trials (RCTs), where the participants receive the experimental drug or placebo randomly. The trials ate double-blinded; neither the investigator nor the participant knows what the latter has received. The average duration of the trial ranges from one to four years.
Before the phase 3 trial, a substance is not considered a drug; however, it becomes a drug after getting positive results in phase 3 trials. It is then approved for registration and accepted by the concerned authorities. Based on valid arguments, it can be subsequently offered to prescribing physicians.
The Center for Drug Evaluation and Research (CDER), a division of the U.S. Food and Drug Administration (FDA), oversees these clinical trials. CDER can bring a clinical on hold if the phase 3 trial design doesn’t meet its objectives or if a study is found unsafe.
- Phase 3 trials are the final three-stage process of clinical drug trials before a new drug or device can be approved for public use.
- These are randomized control trials, double-blinded, and involve large-scale participation, focusing on safety and efficacy.
- Phase 3 trials are expensive and therefore have been blamed for high drug prices.
Phase 3 Clinical Trials – Methodological Bases
Phase 3 clinical trials are generally controlled with blind studies or random assignments between the control and treatment groups. It includes a sufficient number of patients. Though the modalities differ depending on the substance studies, the protocol must satisfy certain general demands.
Choice of scheme
The choice of the experimental scheme depends on factors such as the objectives of the study, stages in the study and the number of participants. The correct evaluation of the effectiveness of the drug requires comparison. The experimental scheme allows this comparison among two or more groups of patients.
The participating patients are divided randomly into two groups who receive the planned treatment throughout the trial period.
Randomization is necessary and is intended to reduce bias in the choice of treatment. In this method, a patient is given treatment by chance.
Randomized clinical trials have contributed immensely to advances in patient care and serve as the standard for research.
Implementing a blind procedure is necessary as the efficacy of treatments can be assessed. It involves two procedures; a Simple blind procedure where the patient is unaware if he/she belongs to the control or treatment group and a double-blind where the patient and the physician both are unaware.
The statistical tests ensure that the differences observed are meaningful. The high comparison levels contribute as the probability of detecting a difference between treatments is maximal.
Phase 3 Clinical Trials – Key Elements
The several key points for phase 3 protocols include:
Want to participate in the trial? Well, the inclusion criteria define the requirements to enter the trial. If the criteria are too vague, the patient may comprise a heterogeneous group, making it difficult to interpret results, thus compromising the objectives of the study. On the other hand, if the inclusion criteria are too restrictive, it becomes impossible to find a sufficient number of patients where the results become difficult to extrapolate.
Several trials are conducted, depending on the substances studied in phase 3. During each trial, a specific population can be studied.
Exclusion or non-inclusion criteria must be indicated to eliminate patients for whom the trial represents an excessive risk. It could also represent those who would make the group too heterogeneous or those whose follow-up is uncertain.
Evaluation or judgment criteria is fundamental to attain the objective of the study and must be chosen in a judicious manner. It includes assessment tools and outcome measurements, evaluating the safety, efficacy, and tolerability of a new treatment.
Adverse or clinical and biological effects should be determined with respect to possible symptoms.
Number of Subjects Required
The number of subjects required for the trial is decided before the trial begins and its length is also determined.
Phase 3 Trial – Associated Costs and Approval Process
Phase 3 trials are extremely expensive, where it has been estimated at around $19 million. However, the costs may vary depending on the drug.
The drug development companies view the steep costs associated with Phase 3 trials as a necessary expense. The drug provides clinical benefits, and the successful completion raises the odds of obtaining marketing approval from the FDA for a new drug.
Drug Approval Process
Despite extensive testing, it can be sometimes difficult to evaluate the effectiveness of the drug. Clinical trials demonstrate if the drug is working or not; however, it does not indicate the reasons. It is also possible that the subjects on which the drug is tested might be healthier than the patients who will be actually using the tested treatment.
After the phase 3 clinical trial, the New Drug Application (NDA) is the formal step and a comprehensive document defining the safety and efficacy of the new drug. It includes data and analyses of the drug on animals and human studies, the drug’s toxicology, pharmacology, dosage, and manufacturing process. NDA has to be submitted to the FDA for approval. Once approved, the new drug is then marketed in the U.S. market.
Phase 3 clinical trials are more intensive extensions of phase 1 and phase 2 clinical trials. These trials determine the ultimate efficacy, safety and dosage of drugs after comparing the results. The dosage levels are modified according to the most beneficial effects while offering the least side effects.