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Has the FDA Stopped Accepting Multinational Clinical Trials for Oncology Drugs?
(Thursday, September 19, 2024) Clinical trials have become increasingly globalized over the last three decades with sponsors routinely conducting multinational clinical trials to evaluate new drugs. A new guidance document from the FDA seems to indicate that the FDA would like to buck that trend. The guidance document lists several previous requirements with a new tone that seems to be intended to discourage sponsors from using non-US clinical sites for oncology studies. Clinical trials are hard to run mostly due to the lack of patients and physicians willing to participate in them. In the US, more than 95% of the patients and 97% of the physicians do not participate in clinical trials making it hard to recruit sufficient patients in clinical trials, in general. In oncology clinical trials, the numbers are slightly better with 13% of the physicians and 7-22% of the patients participating in clinical research depending on the design of a given clinical trial. So, sponsors go to other countries to make up for the shortage of patients and physicians in the US. Non-US sites also help address the issue of lack of diversity in US patients in clinical trials. And it has worked well for the last two decades with more than 3 out of 4 Phase 3 studies and about half of all clinical trials conducted internationally. There is no question that multinational clinical trials have contributed significantly to the approval of almost all products approved by the FDA in the last 20 years, including almost every drug for cancer. However, it seems that the FDA is concerned that non-US sites are putting US clinical trials at a competitive disadvantage and wants to stop it. There is no better way to say it. The FDA’s new guidance document for its expectations from multiregional clinical trials for oncology lists many concerns about the acceptability of data from non-US clinical sites. Some of the issues listed in the new guidance are an expanded clarification of the ICH E5 guidance from two decades ago regarding the acceptance of clinical data from one region in another region that has formed the basis of global clinical trials, while others are an expansion of the FDA’s guidance from 2012 regarding quality expectations from non-US clinical trial data. The FDA primarily prefers that most clinical trials be conducted at clinical sites in the US citing various issues that differentiate US clinics from non-US sites. Although the guidance is specifically for oncology trials, like most other FDA guidance documents, one should expect other FDA divisions to have similar expectations. The new guidance aims to formalize the FDA’s concerns about Chinese companies trying to use China-only data for FDA approval of oncology drugs which led to the FDA rejecting several such applications about two years ago. “China-only” was in the FDA’s mind for this guidance as hinted by a sentence in the guidance “FDA recommends that such a trial be conducted across major geographical regions (e.g., across several continents) rather than predominantly in a single country or in a single geographical region (e.g., Asia)”. Sponsors must consider including at least 50% or a majority of the patients in the US (“equal allocation” and “proportional allocation” considerations) for pivotal studies and a significant number of the patients for non-pivotal studies as well per this guidance. This statement seems literally directed at sponsors using the China-dominant clinical development plans. These requirements were already described in ICH E5 and ICH E17 guidance documents. All the issues that the FDA raises in the guidance are scientifically valid and have been described in previous guidance documents. However, it is the tone of the guidance that would discourage the sponsors from using non-US sites. This FDA preference for US-located sites is not just for pivotal studies but also for earlier phases of development starting from proof-of-concept studies. Sponsors are strongly recommended to discuss any non-US study plans with the FDA prior to implementation. The silver lining is that this guidance gives a detailed review of the issues sponsors need to address allowing better planning. Country-specific data requirements are not uncommon. Many countries require clinical data generated from within the country for market approval. The US is one of the most open countries with regard to using foreign clinical data for market approval. It seems that the sponsors have pushed the envelope too far triggering this push-back from the FDA. 
AUTHOR
Dr. Mukesh Kumar Founder & CEO, FDAMap Email: [email protected] Linkedin: Mukesh Kumar, PhD, RAC Instagram: mukeshkumarrac Twitter: @FDA_MAP Youtube: MukeshKumarFDAMap |
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