Regulatory approval of new

Unquestionably, many of the new antibiotics isolated in the period 1960-1969 would have constituted significant discoveries in the 1940 s when antibiotics were filling a virtual chemotherapeutic vacuum. Standards for medical and commercial acceptance have risen continuously as have requirements for regulatory approval of new antibiotics. In the past decade these influences properly discouraged the development and commercialization of new antibiotics not possessing significant advantages... 

Snapinn, S., Jiang, Q. Preservation of effect and the regulatory approval of new treatments on the basis of non-inferiority trials. Statistics in Medicine 27 382-391, 2008b. 

Focus of the development process for a new pharmaceutical is an essential aspect of success, but is also difficult to maintain. Clinical research units generally desire to pursue as many or as broad claims as possible for a new agent, and frequently also apply pressure for the development of multiple forms for administration by different routes. These forces must be resisted because they vastly increase the work involved in safety assessment, and they may also produce results (in one route) that cloud evaluation [and impede Institutional Review Board (IRB) and regulatory approval] of the route of main interest. 

The Pharmaceuticals and Cosmetics Division (Koseisho) of the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare (MHW) is the regulatory body in Japan. Also in Japan there have been clear changes in the drug approval system, mainly inspired by ICH. One of the most important recent changes is that, under certain conditions, it is now possible to use also foreign data for the approval of new dmgs in Japan. 

Most regulatory bodies, concerned with the approval of new drugs for clinical use, do not accept the results of uncontrolled studies as stand-alone evidence of efficacy. There are, however, circumstances under which data from uncontrolled studies can provide acceptable evidence of efficacy (a) the treatment results in consistent and clinically significant improvement in a disease with a well-established natural course and remission rate, (b) the treatment consistently results in significant improvement in all or almost all patients. 

FDA approval. Usually evidence of efficacy from two or more adequate and well-controlled clinical trials along with safety information is required for the regulatory approval of a new indication for a drug. The idea is that replication of the results of a single trial is needed to rule out the possibility that a finding of efficacy in a single trial is due to chance. This example describes the application of exposure-response analysis to establish an FDA-approvable claim of drug efficacy based on a dose-reponse relationship that was obtained from two pivotal clinical trials that used different final-treatment doses. 

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