Broadening the Definition of Tolerability in Cancer Clinical Trials to Capture the Patient Experience | Friends of Cancer Research

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Broadening the Definition of Tolerability in Cancer Clinical Trials to Capture 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.


The Background:

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 (