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Bio & Life Sciences Healthcare Innovation

Drug Researchers Need to Learn to “Fail Fast”

Author Nader Sanai, MD uses experimental drugs in the course of brain surgery to get early indication about which drugs might prove effective.

“Fail fast” is an adage associated with Silicon Valley–rolling out products and services that can rapidly improve over time. Now that same on-the-fly adjustment is being adapted in healthcare, especially research. For example at the Ivy Brain Tumor Center, which I direct, we are embracing this notion. Those of us conducting clinical research on aggressive conditions know how essential time is to patients who volunteer for our trials. If investigators ‘fail fast’, patients ultimately gain more options to pursue alternative clinical trials or treatments.

In conventional clinical trials, gathering data requires tremendous patience on the part of both researchers and trial participants. That process starts with an educated guess aiming to match a patient to a drug, followed by months of therapy (and, often, side effects), and ends with testing or imaging that provides, at best, an indirect measure of putative drug effect. The entire process can often take years. And despite how painstaking it is, for brain cancer research in particular this type of project design almost always fails to generate meaningful data on a drug’s ability to cross the blood-brain barrier or its direct effects on a brain tumor.

At the Ivy Brain Tumor Center, we fail fast through the adaptation of what are called “Phase 0” clinical trials: patients receive a small dose of an experimental therapeutic drug combination hours before a previously-planned brain tumor operation. Tumor tissue is collected in surgery and then tested to determine if the drug cocktail reached the tumor and impacted its molecular targets. If the answers to both questions are yes, the patient begins post-operative treatment with that drug within days. Alternatively, if the experimental drug does not work, patients avoid enrolling onto a futile therapy and move on to other trials or off-label drug options. 

By designing and executing our Phase 0 clinical trials against a timeline of days, even the failure of a particular drug combination gives the patients more of an extremely limited resource: time. The average patient with glioblastoma, for example, which is the most common primary brain cancer in adults, typically survives fewer than two years post-diagnosis. Patients do not have time to wait months for trial data. If a new drug cocktail does not work for their tumor, they need to know that as soon as possible.

In addition, the entire scientific community needs these data, identifying which new therapies are incapable of reaching the brain and, therefore, should not be pursued further for brain tumor patients. The last FDA-approved drug for brain cancer patients with survival benefit arrived nearly two decades ago. In 2021, brain tumor patients still have very limited treatments options. By rapidly eliminating ineffective therapeutic combinations from the pipeline, investigators can focus their efforts on more promising options.

By extension, the rest of our healthcare system could stand to borrow from this rapid approach to innovation, particularly across the broader field of drug discovery and development. For example, drug brain penetration is essential in the treatment of other neurological disorders such as Alzheimer’s disease or multiple sclerosis. The search for drugs that could work effectively to combat them would very much benefit from more extensive utilization of the Phase 0 approach, to efficiently determine the pharmacokinetic and pharmacodynamic impacts of potential therapies.

The broader philosophy focused on generating and assessing data quickly may be able to broadly streamline the R&D pipeline in drug research. This approach creates a system better aligned with productive drug development that respects patient sacrifice and maximizes the resources invested by the pharmaceutical and biotech industry.

Failure is never the goal in healthcare. However, there is clear evidence that ‘failing fast’ is not at odds with healthcare’s commitment to the patient. On the contrary, it reinforces the critical path of putting the patient first.   

Nader Sanai, MD, FAANS, FACS is the J.N. Harber Professor of Neurological Surgery at Barrow Neurological Institute and the Director of the Ivy Brain Tumor Center.

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