Don't mention the dots!!RegMe thinks JB needs to understand...

Don't mention the dots!!


Reg

Me thinks JB needs to understand flexibility in an unmet need.
https://www.federalregister.gov/documents/2019/12/20/2019-27524/demonstrating-substantial-evidence-of-effectiveness-for-human-drug-and-biological-products-draft

FDA is announcing the availability of a draft guidance for industry entitled “Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products.” This guidance complements and expands on the 1998 guidance. The 1998 guidance was issued in response to the Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L. 105-115), which stated that the substantial evidence requirement for effectiveness, which had generally been interpreted as calling for two adequate and well-controlled trials, could also be met by a single trial plus confirmatory evidence. The 1998 guidance, therefore, provided many examples of the types of evidence that could be considered confirmatory evidence, with a specific focus on adequate and well-controlled trials of the test agent in related populations or indications, as well as a number of illustrations of a single adequate and well-controlled trial supported by convincing evidence of the drug's mechanism of action in treating a disease or condition.

FDAMA, thus, introduced a specific new area of flexibility in the evidence needed to support effectiveness, but there are many other characteristics of the evidence supporting effectiveness that can vary (notably, trial designs, trial endpoints, statistical methodology), and evidence that varies in such ways potentially can provide substantial evidence of effectiveness but because of these characteristics may provide greater or lesser certainty. These characteristics also deserve consideration and were not discussed in the 1998 guidance. FDA's use of these various designs, endpoints, and analyses which can differ in the strength of evidence they provide, reflects the Agency's longstanding flexibility when considering the types of data and evidence that can meet the substantial evidence requirement.

Although FDA's evidentiary standard for effectiveness has not changed since 1998, the evolution of drug development and science has led to changes in the types of drug development programs submitted to the Agency. Specifically, there are more programs studying serious diseases lacking effective treatment, more programs in rare diseases, and more programs for therapies targeted at disease subsets. There is a need for more Agency guidance on the flexibility in the amount and type of evidence needed to meet the substantial evidence standard in these circumstances. The approaches discussed in this guidance can yield evidence that meets the statutory standard for substantial evidence and reflect the evolving landscape of drug development.

This guidance discusses the quality of evidence to establish effectiveness, including trial designs and trial endpoints. It also discusses the quantity of evidence needed in a given development program, i.e., two adequate and well-controlled trials, one adequate and well-controlled trial plus confirmatory evidence, or reliance on a previous finding of effectiveness of an approved drug when scientifically justified and legally permissible ( i.e., no new effectiveness or pharmacodynamic data would be needed). The guidance also expands upon the discussions included in the 1998 guidance on the types of mechanistic and pharmacologic evidence and non-clinical evidence that can constitute confirmatory evidence.

Although randomized superiority trials with a placebo- or active-control design generally provide the strongest evidence of effectiveness, this guidance discusses the circumstances under which trials not using a placebo control, superiority design, or randomization may be acceptable. In addition, this guidance also discusses situations in which human efficacy trials are not ethical or feasible, and the animal rule may be applied. In all cases, FDA must reach the conclusion that there is substantial evidence of effectiveness to approve a drug; however, the degree of certainty supporting such a conclusion may differ, depending on clinical circumstances ( e.g., severity and rarity of the disease and unmet medical need).

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on “Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.