REGULATORY CORNER

The new FDA draft guidance, Key Information and Facilitating Understanding in Informed Consent, (March 2024) provides some food for thought regarding the informed consent process and how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.

I used to think of a Benefit Risk Assessment as part of a marketing application. However, FDA’s recent guidance, Benefit-Risk Assessment for New Drug and Biologic Products, published in October 2023, clearly highlights the role that Benefit-Risk Assessments play throughout the lifecycle of a product, not only at the time of New Drug Application (NDA) or Biologic Licensing Application (BLA) review.

As a full-service CRO who helps many sponsors develop their clinical strategy and the associated study protocols, the release of an International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) protocol template is of great interest to PROMETRIKA. Step 2 of the ICH harmonized guideline on the clinical electronic structured harmonized protocol (CeSHarP) occurred in September 2022. This draft guidance was released for public consultation in December 2022, together with technical specifications and an electronic template. The guidance provides detailed information to be included in each section of a clinical protocol, expanding on the information currently included in the ICH GCP guidance. For those of us working in this regulated industry, it is a welcome addition.

The Cures Act of December 2016 added section 505F to the Federal Food, Drug, and Cosmetic Act (FD&C Act), requiring FDA to create a framework for the use of real-world evidence (RWE) in regulatory decision-making. In response, the draft FDA guideline entitled, “Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products,” issued in August 2023, provides very interesting and useful information for consideration in the planning of a marketing application (NDA/BLA) for a drug or biologic product based on RWE.

The safety of patients receiving drug or biologic products is paramount in both the investigational and post-marketing settings. Preparing routine required safety updates can be an arduous and time-consuming process with different data lock points (DLPs), Reference Safety Information (RSI), and reporting timeframes for clinical studies and post-marketing reports. This month, I thought I would take a step back and talk about periodic safety reporting in both the investigational and post-marketing setting and how one can streamline the process. This blog will focus on routine required reports, not expedited reporting.