Regulatory Science

The FDA draft oncology guidance “Core Patient-Reported Outcomes in Cancer Clinical Trials” proposes that trial sponsors capture information on both treatment-related symptoms and overall bother associated with treatment. However, tolerability – the degree to which overt adverse effects can be tolerated by a patient (as defined by ICH) - may be a more multidimensional concept than the incidence, severity, or bother of symptoms/side effects. For example, it may include perceived advantages vs disadvantages, convenience, constraints with treatment, beliefs about this treatment, etc. A Friends of Cancer research white paper recently proposed an alternative definition - the degree to which symptomatic and non-symptomatic adverse events associated with the product’s administration affect the ability or desire of the patient to adhere to the dose or intensity of therapy – which better encompasses the patient experience receiving a given treatment. However, the Friends of Cancer working group was small, it focused only on conceptual data elements most proximal to the effects of the therapy in the clinical trial setting, did not discuss patient-level trade-off decisions (benefits, harms) or individual definitions of tolerable medication, and did not propose a single measurement of tolerability using a Patient Reported Outcome (PRO) instrument. Some PRO instruments have been developed to understand individual benefit-risk appraisal (e.g. PQAT, PGI-BR, WIWI, and PRO-CTCAE) but these have not been examined within the context of assessing tolerability, per se.

DIA is convening a working group to collaborate on Research that aims to understand and measure treatment tolerability of immune-oncology (IO) treatment in selected cancers, with the ultimate goal to identify, discuss and/or develop tolerability PRO instrument(s). The working group should also develop guidance on:

Phase 1. Currently Launching! Landscape Research

Develop a comprehensive compilation of information on tolerability key concepts based on a literature review and interviews/focus groups’ inputs. For more information on the purpose of this effort, click here.

Phase 2. Develop or adapt a PRO instrument

Create an instrument for the measurement of treatment tolerability in a selected line of treatment in cancer.

To learn more about DIA’s Research projects, contact Science@DIAglobal.org

Regulatory System Innovation through Collaboration and Reliance

Reliance is considered the hallmark of a modern, efficient regulatory framework and a 21st-century regulatory tool, as it can effectively be used to focus resources and speed up approval timelines while strengthening regulatory systems.

At the margins of DIA Europe 2023, regulators from different regions and industry experts came together for a Workshop to discuss the practical aspects of collaboration and reliance. This workshop highlighted practical experiences by regulators from around the world and industry, leveraging case studies showing different collaborative and reliance pathways and discussing critical factors to identify effective reliance models that enable efficient use of resources and faster access to medicines. The breakout groups discussed: What are the gaps in information sharing to enable risk-based abridged reviews? Risk-Based Review - What is product sameness for you and what do you need it to be? How can we minimize country regulatory requirements that are not necessarily justified from the point of view of modern international regulatory science?

Key issues that had been identified as important enablers for regulatory reliance are:

• Global dossier submission vs complying with country-specific requirements
• Use of assessment reports containing confidential information
• Ensuring sameness of the product assessed in the reference country
• Efficient management of post-approval changes

For workshop highlights and the next steps, please refer to DIA Global Forum.

To access the final Outcomes report, click here.

To watch more content on this subject, check the recording of the DIA Europe 2023 “International Collaboration: Reliance in Action” DIAmond Session, here.