Broadening the Definition of Tolerability in Cancer Clinical Trials to Capture the Patient Experience
Click HERE to access the recently published Friends white paper detailing the working group's efforts to develop a working definition of tolerability that better encompasses the patient experience.
The Definition: Tolerability is currently defined as “the degree to which overt adverse effects can be tolerated by the subject” by the International Conference on Harmonization (ICH). A complete understanding of tolerability should include direct measurement from the patient on how they are feeling and functioning while on treatment. The current definition has necessitated the need for a more contemporary definition that better incorporates the patient experience using patient reported outcomes (PRO). Data elements and methodologies that provide a comprehensive characterization of tolerability is currently being explored to better inform patient and clinician treatment decisions.
The Problem: Focused efforts in clinical cancer research have led to treatment options with novel therapeutic modalities for a given cancer target. These drugs are often associated with unique safety profiles and are more frequently administered over prolonged periods of time. Assessment of patient-reported symptomatic adverse events can help better describe the tolerability of a drug and inform patient decision-making. Current assessments of tolerability include clinician reported safety data and other trial data such as dose modifications or discontinuations; however, many symptomatic side effects are unobservable and best known and reported by the patient.
The Solution: Friends of Cancer Research has convened a multi-stakeholder working group to develop a working definition of tolerability that better encompasses patient experience; consider a broader range of data elements and methodologies that more fully characterize tolerability; and generate a trial design framework that includes patient-reported outcome (PRO) endpoints and other clinical outcomes to support patient choice, regulatory and clinician decision-making, and labeling claims. The goal is to facilitate patient-focused drug development, including the development of more patient friendly regimens that may be advanced within currently available trial design frameworks.
Friends of Cancer Research (Friends) has been actively involved in efforts related to patient focused drug development (PFDD).
- Friends hosts a PRO-CTCAE Industry Working Group to identify tactical barriers to implementation and develop solutions for prioritized issues
- Friends actively engages with FDA and other key stakeholders to help inform ongoing guidance development as mandated by 21st century cures
- Friends held a panel discussion in 2015 to optimize the collection and interpretation of PRO data (https://www.focr.org/sites/default/files/FINAL%20PRO-CTCAE%20pre-confer…)