Bernardo Haddock Lobo Goulart, Vice President of Technical, Regulatory Consulting/SME Oncology at Parexel, shared on LinkedIn:
“Should that ‘XX %’ be 20%?
I’ve been hearing from some biotech companies that FDA considers 20% U.S. enrollment as acceptable U.S. representation in oncology Multiregional Clinical Trials (MRCTs). Other companies have asked what proportion of U.S. patients should enroll in an MRCT intended to support FDA approval.
The magic 20% isn’t a fixed expectation of US representation. Nor has the FDA stated publicly the 20% quote, in conferences or in its Guidance.
The Agency will not commit to a threshold of US enrollment as it considers each MRCT individually for its potential to support approvals in the U.S.
Instead, consider the factors below that can influence expectations for U.S. enrollment:
- Cancer epidemiology: MRCTs may enroll higher proportions of non-US patients when the disease of interest is far more prevalent in other countries (e.g., HCC, nasopharyngeal carcinoma).
- Number of countries/regions participating in the trial.
- The sociodemographic characteristics of the non-U.S. population enrolling in the MRCT.
- How closely medical practice in non-U.S. countries reflect U.S. practices.
The extension to which the clinical effects of the investigational drug may differ across the enrolling populations.
The 20% U.S. enrollment could be acceptable in certain circumstances, including when the prevalence of the cancer of interest is similar across countries, the trial is recruiting from 5 or more geographic regions, with the U.S. counting as one of the regions, and when patients from non-US countries mirror the U.S. patient characteristics and medical practice in these countries reflect those of the U.S. In such circumstances, the principle of equal allocation could apply, and 20% U.S. enrollment could characterize U.S. representation.
That doesn’t make 20% a one-size-fits-all metric.
As always, it never hurts asking the FDA if a proposed MRCT will adequately represent the U.S. population.”
