FDA Finalizes Guidance on Integrated Summary of Effectiveness

On August 28, 2008, FDA announced a draft guidance entitled “Integrated Summary of Effectiveness.” On Wednesday of this week, more than seven years later, the Agency released the final version of the guidance.

The long awaited final version describes how an integrated summary of effectiveness (ISE) should be prepared by sponsors looking to submit an NDA or BLA. It was published to improve the quality of applications by providing more detail regarding what efficacy information FDA needs to make a regulatory decision.

An ISE is defined by FDA as “comprehensive integrated analysis of the effectiveness of a study drug,” and its purpose is to provide a description of the effectiveness information, delineate strengths and weaknesses, and highlight any important information that is missing.

According to 21 CFR 314.50(d)(5)(v), an ISE must be part of an NDA submission, “but the regulation does not describe the specific components of the ISE in detail except for the components listed below:

• An integrated summary of the data demonstrating substantial evidence of effectiveness for each claimed indication.
• Evidence that supports the dosage and administration section of the labeling, including support for the recommended dosage and dose interval.
• Effectiveness data analyzed by sex, age, and racial subgroups, identifying any modifications of dosing for specific subgroups.
• Effectiveness data from other subgroups of the population of patients treated, when appropriate, such as patients with renal failure or patients with different levels of severity of the disease.”

The guidance includes recommendations for sponsors developing an ISE regarding the format and content, including:

• “Listing and brief results of individual studies”
• “Analysis of study designs”
• “Overall Analysis of effectiveness results”
• “Comparison of results in subpopulations”
• “Analysis of clinical information relevant to dosing recommendations”
• “Time Course of Effect, Persistence of Effect and/or Tolerance, Distribution of Responses”
• “Exploratory Issues”

For more details, view the full guidance here.

Are you trying to compiling an ISE for your NDA? We can help. We have written hundreds of ISE’s as part of the submission work we undertake. Using our proprietary approach, we have a track record of helping our clients achieve successful interactions with FDA. We can help develop your ISE, the entire NDA, or any other FDA submission. To learn more about how we can help you, please contact us.