Clinical Trial

Clinical trials are set of tests in medical research and drug development that generates safety and efficiency data for health intervention in human beings.

Clinical trials are the part of drug development process.

Drug development include the steps like, 

(1) Preclinical test, 

(2) IND (investigation new drug) Application filling, Review and approval, 

(3) Clinical Trials 

(4) NDA (New drug application filling and approval), 

(5) Post marketing.

Applicant before going to clinical trials, one need to complete preclinical on Cell line and Animal, (in vivo/in vitro) test. 

Main evaluation phases in preclinical test are, Pharmacodynamic, Pharmacokinetic, Toxicity profile, Safety and efficiency.

After successful completion of preclinical tests, applicant has to file for IND approval. Once IND approval being done then clinical trial can start.

CLINICAL TRIAL:- 

Clinical trial have five phases from phases 0 to phase IV.

Phase 0:- 

In phase 0 study of drug at micro dosing (1/100 of the dose of test substance) to evaluate pharmacodynamic and Pharmacokinetic properties of drug in human beings. In this study small number of volunteers 10 to 15 are used.

Advantages of phage 0:-

- Less chances of adverse effects,

- Short  duration,

- Less number of volunteers 

- Reduces development time and cost

Limitation of phase 0:-

- Test performed at microdose instead of define dose of drug/chemical,

- Test performed to evaluate pharmacokinetics and pharmacodynamic study not for safety and efficiency.

Phase I:-

Phase I test is design to assess safety, tolerability, pharmacokinetics and pharmacodynamic of drug in human beings. In this test 20 to 25 healthy volunteers are used.

Phase I study includes,

(1) SAD (single ascending dose study)

(2) MAD (Multiple ascending dose study)

By SAD and MAD study MTD (maximum tolerable dose is identified)

Phase I study subject, healthy human volunteers are mostly used, while for cytotoxic therapy and AIDS therapy patients are used.

Advantages:-

- Healthy volunteers are easily available 

- Potential risk are reduced

- More homogeneous groups 

- Greater compliance with protocol

Limitation:-

- Study is limited to homogeneous groups 

- Efficacy study is not covered 

Phase II:-

- Phase II study assess the efficiency and monitor side effects. In this test 20 to 300 subjects (patients) are used.

- The main objective of this phase is to find out Efficacy and secondary to check safety.

- Phase II divided in two parts,

(1) Phase IIA:- Designed to assess dosing requirements, (Therapeutic window, therapeutic dose regimen, dose efficacy relationship, duration of therapy, frequency of administration)

(2) Phase IIB:- Designed to assess efficacy,

Phase III:-

Phase III study assess the overall and raltive therapeutic value of the new drug efficacy, safety and relative properties in large number of population. In this test large population of volunteers 100 to 3000 patients are used. 

The main objective is to establish efficacy of the drug in large number of patients, method of usage, dosage schedule and to collect safety data.

Phase III study divided in two subtype,

(1) Phase IIIA:- To get sufficient and significant data,

(2) Phase IIIB:- allow the patient to continue treatment, Lable expansion ( to check the usage of drugs for other diseases), additional safety data collection,

Phase IV:-

- This study performed post market approval for market surveillance.

- There is no fixed duration and fixed volunteers.

- The main objective is to continue monitor the drug in market, its efficacy, side effects, drug-drug interactions, new usage of drug,

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