Adequate and well-controlled studies

Category B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well-controlled studies in pregnant women, or animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus. 

B Animal studies have failed to demonstrate risk to fetus no adequate and well-controlled studies in pregnant women. 

Therapeutic confirmatory (Phase III) Demonstrate/confirm efficacy Establish safety profile Provide an adequate basis for assessing the benefit/risk relationship to support licensing Establish dose-response relationship Adequate and well controlled studies to establish efficacy Randomized parallel dose-response studies Clinical safety studies Studies of mortality/morbidity outcomes Large simple trials Comparative studies... 

Therapeutic confirmatory Demonstrate/confirm efficacy Adequate, and well controlled studies to establish efficacy... 

Clarifies the requirements for NDA approval to say that data from one adequate and well-controlled study, together with confirmatory evidence, may, in the discretion of FDA, constitute substantial evidence of effectiveness of a new drug. 

Children Safety and efficacy of montelukast have been established in adequate and well-controlled studies in children with asthma 6 to 14 years of age. Safety and efficacy profiles in this age group are similar to those seen in adults. 

Children There are no adequate and well-controlled studies to document the safety and efficacy of tizanidine in children. 

IV- Use of IV in neonates to 16 years of age (with non-CNS infections) is supported by evidence from adequate and well-controlled studies. IV use is not recommended... 

Controlled clinical trials Adequate and well-controlled studies, combination drug products, including a table of all studies grouped by study type and reports of individual studies in each group. 

Tabulations should be provided for individual patients from initial clinical pharmacology studies, effectiveness data from each adequate and well-controlled study, and safety data from all studies. 

Adequate and well-controlled studies Refusal to approve an abbreviated new drug application Withdrawal of approval of an application or abbreviated application... 

Subpart D FDA Action on Applications and Abbreviated Applications Sec. 314.126 Adequate and Well-Controlled Studies... 

Identification of studies fulfilling the statutory requirements for adequate and well-controlled studies showing that the drug has its intended effect... 

Before a detailed discussion of the information to be included in this section is given, it is useful to review the definition of adequate and well-controlled studies. Approval of a new drug requires substantial evidence of effectiveness. Substantial evidence is defined under the Federal Food, Drug and Cosmetic Act as... 

In this section, an overview of the results should show that the regulatory requirements for approval have been met by adequate and well-controlled studies that support the claimed effect. This is especially important if results are inconsistent or marginal. An examination of study-to-study differences in results, effects in subsets of the treated population, dose-response information, and comparisons with alternative drugs should be addressed. A description of the information to be included in this section is contained in the outline provided earlier in this chapter. 

The first portion of this section is an identification of those studies that fulfill the requirements for adequate and well-controlled studies showing that the drug has its intended effect. This is followed by a discussion of those studies as well as the data from all controlled clinical studies. Any differences in outcome between studies of similar design should be explained where possible. Tables showing major study design features, numbers of patients, numbers of dropouts, and major outcomes are sometimes useful. 

Phase 3 adequate and well-controlled studies used for the determination of product safety and effectiveness... 

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. [Zinacef (ceftiroxime) labeling FDR 2005. p. 1678]... 

Category A Adequate and well-controlled studies indicate no risk to the fetus in the first trimester of pregnancy or later. 

Within Sub-Part E, there is no specific anticipation of a relaxation of the requirement for two adequate and well-controlled studies. These regulations prescribe meetings and schedules, and simply suggest that there ought to be more flexibility in the application of the existing regulations to this type of drug. 

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