Clinical Trial Endpoints



With nearly 700,000 Americans living with a brain tumor, and only four (4) U.S. Food & Drug Administration (FDA)-approved therapies in the last 30 years, and no cure – the needs of the brain tumor community are clear. Brain tumor patients need new therapies that will either eradicate their brain tumor or better manage the tumor and its manifestations; as many brain tumor patients also experience adverse changes in their physical, cognitive, and psycho-social well being which significantly impacts their ability to maintain ‘normal’ lives while receiving treatment.

A number of key issues in brain tumor drug development are related to measuring whether a new treatment is effective in delivering benefit to patients. The goals or benefits of a drug are called “endpoints.” The endpoint primarily used in brain tumor drug evaluation is the extension of overall survival (OS). Other endpoints may relate to reducing the symptoms of brain tumors including the retention of neuro-cognitive function, reduction of the need for steroids, reduction in fatigue, improving in other functional areas.

While the FDA has authority to approve therapies based on clinical trials endpoints other than OS, it remains the one that is used the most and is often the sole endpoint for a trial. A recent analysis of current brain tumor drugs within the clinical trial pipeline illustrates the lack of phase II or III trials with primary endpoints other than overall survival. However, demonstrating OS in brain tumor clinical trials is complex, lengthy, expensive, and has proven the hardest measure to meet.

This suggests a number of challenges including: lack of guidance from regulatory bodies about alternative endpoints for brain tumor drugs, ad a lack of standards for metrics and data collection procedures which industry can use to demonstrate efficacy based on alternative endpoints

The promise of new therapies that could address overall survival rates and improve net symptoms would be ideal for the brain tumor community, however, drugs which possess either overall survival or another improvement to quality of life are still of great value.

With a more clear-cut pathway through the regulatory process, further biotech and pharmaceutical investment into brain tumor drug development may be incentivized and early stage treatments showing promise will stand a greater chance of gaining accelerated approval, hopefully encouraging a new pipeline for treatments that can help patients.


National Brain Tumor Society’s Clinical Trial Endpoints Initiative will strive to create change and illustrate the value of pursuing the use of alternative endpoints in the therapy evaluation and approval process.

To determine, more specifically, the impediments to more widespread use of acceptable alternative endpoints in brain tumor clinical trials, the National Brain Tumor Society formed an expert Endpoints Steering Committee. Led by Patrick Wen, M.D. and Terri Armstrong, Ph.D., this Committee serves as an advisory board for current and future issues related to brain tumor clinical trial endpoints. Working together with the Endpoints Steering Committee, the National Brain Tumor Society requested a meeting with the U.S. Food and Drug Administration (FDA) to discuss how various stakeholders in brain tumor drug development could work together to increase the volume and speed of approvals for new treatments. The FDA graciously agreed, and the subsequent meeting made clear the need to convene an even larger cross-section of the brain tumor drug development field to advance the conversation.

National Brain Tumor Society suggested holding a series of workshops to present the state of the field in brain tumor endpoint measurement and contribute to the development of criteria required for designing valid clinical trials using alternative endpoints. It is our hope these changes will create more incentives for future research and investment in brain tumor treatments and deliver a pipeline of new drugs to the community. The FDA again offered their support to participate in the workshops if the brain tumor community came together.

From there, the Jumpstarting Brain Tumor Drug Development Coalition was created to convene all the necessary stakeholders (patients advocacy and philanthropic organizations; medical imaging companies; biotech and pharmaceutical companies; neuro-radiologists; neuro-oncologists; contract research organizations; the National Cancer Institute; and the FDA) in two separate workshops to advance alternative endpoints for brain tumor clinical trials.

Learn more about the Brain Tumor Clinical Trial Endpoints Workshops here.