REGULATORY CORNER

In August 2025, FDA issued the draft guidance, Approaches to Assessment of Overall Survival in Oncology Clinical Trials. This guidance is based in part on discussions held at a joint FDA, American Association for Cancer Research (AACR), and American Statistical Association (ASA) public workshop held in July 2023. It also puts into writing feedback that I have received from the Agency on oncology clinical trials and guidance that I have related to our oncology clients.

Continuation of marketing approval of a product differs between the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Marketing applications approved by the EMA are valid for 5 years and must be renewed to continue marketing of the product. If conditional approval was granted by EMA, a yearly reassessment is required. In the US, the situation is quite different. Once an application is approved by FDA, this approval continues unless the company requests that FDA withdraw the application or the FDA initiates a withdrawal process.

When FDA published the guidance, Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases in August 2024, I read it with great interest. At first, I thought that it was a draft guideline, as this was the first time I had seen a guideline addressing dose selection in the oncology setting. But I quickly realized that this final guidance implements the information gathered in the FDA’s Project Optimus.

When I first read the guideline, Considerations for the Conduct of Clinical Trials of Medical Products During Major Disruptions Due to Disasters and Public Health Emergencies, which FDA issued in September 2023, my initial reaction was, ‘do we really need such a guideline?’ We have just gotten over the impact of the COVID pandemic on clinical trials, and business is getting back to usual or normal or whatever we want to call our new normal. That said, I found some interesting and very useful information in this guidance. Having lived through one pandemic, one thing I have learned is that we need to be prepared for the unexpected. While I hope that I will not experience another pandemic, other natural disasters and disruptions in clinical trial are increasingly more likely, especially in our current environment of global clinical studies.

The new FDA draft guidance, Key Information and Facilitating Understanding in Informed Consent, (March 2024) provides some food for thought regarding the informed consent process and how we should organize our informed consents to best inform potential study participants about the studies we are conducting. I’ve recently read Patient H.M. (Luke Dittrich, 2016), about a patient with severe epilepsy who was treated with a lobotomy in an effort to reduce the seizures. While seizures remained severe, the procedure resulted in eliminating the patient’s ability to establish short-term memory and erased or jumbled most of the patient’s long-term memory. While it was noted that this particular patient did consent to the procedure, the book also chronicles stories of asylum patients with mental disorders who were given lobotomies without their or their legal representative’s prior consent. I am always both amazed and horrified when reminded that these types of research methods occurred in my lifetime. The processes we currently follow in generating informed consent forms (ICFs) for use in today’s clinical studies were not always standard procedure. Remembering this and understanding the importance of having each trial subject freely give consent, after being fully informed of the trial’s objectives, risks and benefits, is an interesting, important and relevant topic for consideration as we design and execute clinical studies.