Summary and Recent Trends of Clinical Trials Processes in New Drug Development, and Changes of Relating Regulations

Lim, Young Chai

Abstract

The establishment of safty and efficacy in developing new drugs is accomplished only by the clinical trials which are done in human beings. Through after the drug accidents of "sulfanilamide elixir tragedy" in 1938 and "phochomelia" by thalidomide in the 1960s, the process of clinical trials have taken the shape of scientific and ethical ones. Current GCP (Good Clinical Practices) was finally carried out in USA since 1981. KGCP (Korean Good Clinical Practices) was not implemented until October 1, 1995. The first step in new drug development is the discovery or development of candidate effective new substances. Preclinical safety and efficacy testing using animal experiments follows. After obtaining investigational new drug (IND) from Korean Food and Drug Administration (KFDA), the execution of clinical trials is possible. In phase 1 trials in which new drug was first exposed to human beings, the safety, tolerability and pharmacokinetics of the candidate drugs are evaluated in a small number of healthy volunteers by the specially trained clinical pharmacologists. In phase 2, the drug is first studied in patients with the target disease to determine efficacy and safety for the relatively short period. In phase 3, by the multicenter study the drug is assessed in much larger number of patients to futher obtain the final and definite evidences of safety and efficacy. If phase 3 results meet expectations, new drug application (NDA) is submitted to KFDA. Once approval to a market has been obtained, phase 4, in which adverse reactions of the new drug are monitored under actual conditions of use in large numbers of patients, begins. Institutional review board (IRB), which plays the key role in clinical trials, tests the ethical and scientific adequacy of protocol, and monitors the trial processes performed in the same institution. The informed consent from the subject is based upon the "Declaration of Helsinki" in 1964 and is the necessity for safeguarding the right of subjects. If the new drugs will be used in the elderly or children, the clinical trials in corresponding groups of subjects are required in recent. For the life-thretening or seriously-debilitating illness, the FDA may permit extensive but controlled marketing of a new drug even in phase 2 or phase 3 stages (treatment IND), unless there are ever the effective drugs or treatmet modalities for the disease. Under the influence of ICH (international conferences on harmonization)-GCP, the domestic regulations related with clinical trials is to be changed soon. According to ICH E5 code, bridging studies is going to be rather increased for ethnic differences. Finally, the solution to activation of domestic clinical trials has been sought briefly.