How Endpoints are Used for Drug Approval

Quick Overview

Endpoints are crucial in the drug approval process as they are targeted outcomes that show the effectiveness and safety of a drug. These outcomes are measured using tools called outcome measures, which should capture what matters most to patients and caregivers. The FDA requires that these measures be appropriate and clearly captured in the drug’s labeling. Biomarkers, on the other hand, are objective characteristics that can help understand the effects of a drug in a more objective way. They can also be used as surrogate endpoints when clinical measures take a long time to read out. However, using biomarkers as surrogate endpoints requires a deep understanding of their relationship to the disease and clinical outcomes. Regulatory flexibility may be exercised in cases where a drug shows promise based on biomarker data, even if it fails to meet its primary endpoint. Natural history studies play a crucial role in helping researchers understand outcome measures and biomarkers in order to develop effective clinical trials.


In this talk, we will explore the use of endpoints in the approval of drugs. Endpoints are targeted outcomes that are analyzed to demonstrate the effectiveness or safety of a drug. It is important for families to understand this process as their input and participation play a critical role. By understanding how endpoints are utilized and interpreted, families can better engage in the drug approval process.

Background on Endpoints

Endpoints are specific outcomes that are measured to determine the effectiveness or safety of a drug. In the context of Angelman syndrome, relevant endpoints may include communication, sleep, cognition, and seizures. Outcome measures are tools used to assess these endpoints and should capture what matters most to caregivers and patients. It is crucial to ensure that the measures used are appropriate and able to accurately capture the desired changes. The results of these measures are then included in the drug’s labeling, which provides information on the drug’s safety, effects, and usage instructions.

Incorporating Caregiver Input

To determine the most important outcomes for individuals with Angelman syndrome, efforts are made to gather input from caregivers and patients. This can be done through surveys or qualitative research efforts such as disease concept models. The top symptoms identified by caregivers include communication, motor function, seizures, and other related factors. These insights are incorporated into the design of clinical trials to ensure that the studies focus on outcomes that matter most to the affected individuals and their caregivers.

The Role of the ABOM Consortium

The ABOM consortium, which includes organizations such as ASF and FAST, works together to identify and develop appropriate tools for measuring outcomes in clinical trials. The goal is to have a range of tools ready to be used in these trials. Significant progress has been made in identifying and measuring the important symptoms of Angelman syndrome, and ongoing efforts continue to expand the toolkit of available options.

Using Endpoints in Drug Approval

To illustrate how endpoints are used in the approval of a drug, let’s consider a trial in Rett syndrome. In this trial, the primary outcome of interest was behavior, as identified by caregivers in a report. The Rett syndrome behavioral questionnaire was used as the outcome measure to assess behavior, and the endpoint was the change in behavior on this scale after 12 weeks of treatment. The results showed that the treated group had a larger reduction in behavioral score compared to the placebo group, meeting the study’s co-primary endpoints. Based on these results, the drug was approved, and the labeling clearly described the outcomes measured and the drug’s effects.

The Role of Biomarkers

Biomarkers are objective characteristics, such as blood tests or imaging scans, that can provide insights into the effects of a drug. While they do not measure how a person feels or functions, they can help understand the impact of a drug in a more objective way. Biomarkers can also serve as surrogate endpoints, predicting clinical benefit based on changes in lab values. However, using biomarkers as surrogate endpoints requires a thorough understanding of their relationship to the disease and their ability to predict clinical outcomes. The ABOM consortium focuses on identifying biomarkers that can be used as endpoints in clinical trials, potentially revolutionizing the drug development process.

Regulatory Flexibility and Surrogate Endpoints

Regulatory flexibility can be exercised when using surrogate endpoints based on biomarkers. This flexibility allows for the approval of drugs even if they do not meet their primary endpoints, as long as there is evidence that the biomarker predicts clinical benefit. This approach has been seen in the approval of drugs for rare diseases, where the unmet medical need is significant. However, it is important to confirm clinical benefit through further studies.


Understanding how endpoints are used in the approval of drugs is crucial for families affected by Angelman syndrome. By participating in natural history studies and providing input on outcome measures and biomarkers, families play a vital role in shaping the drug development process. The ongoing efforts of organizations like the ABOM consortium aim to improve the understanding and measurement of important symptoms, ultimately leading to more effective treatments for Angelman syndrome.

Talk details

  • Title: How Endpoints are Used for Drug Approval
  • Author(s): Jennifer Panagoulias
  • Author(s)’ affiliation: FAST
  • Publication date: 2023-11-12
  • Collection: 2023 FAST Science Summit