Ongoing Academic Research and Pre-Competitive Collaborations
Comparative tolerability
Alicyn began publicly advocating for comparative tolerability claims in 2014
In diseases like lung cancer, “we know that treatment effectiveness is associated with alleviation of symptoms such as cough, shortness of breath and difficulty breathing,” Genentech Inc. Global Head of Patient-Centered Outcomes Research for Oncology Alicyn Campbell says. “Patient-reported changes in lung cancer symptoms are an important component for assessing the impact of new medicines.”
“This can be particularly helpful in the absence of overall survival, which becomes increasingly difficult to achieve as patients receive numerous lines of therapy,” Campbell says. Comparative tolerability – how treatments impact patients in their daily life – is also important to document, and is useful in diseases like renal cell carcinoma or breast cancer, “where patients don’t experience tumor-related symptoms that can be readily measured.”
Comparative tolerability working group: friends of cancer research
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.
Patient-Reported Outcomes in Clinical Oncology: The Jakafi and Zytiga Exceptions
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.
Organized by Mark Stewart, VP of Science Policy at Friends of Cancer Research, a multi-stakeholder team of experts spent 2018 discussing how we define comparative tolerability and what potential endpoints for a comparative tolerability trial design might like like.
Working Group Members:
Ethan Basch, University of North Carolina at Chapel Hill
Alicyn Campbell
Stacie Hudgens, Clinical Outcomes Solutions
Lee Jones, Research and Patient Advocate
Bellinda King-Kallimanis, U.S. Food and Drug Administration
Paul Kluetz, U.S. Food and Drug Administration
Daniel O'Connor, The Medicines and Healthcare Products Regulatory Agency (MHRA)
Oliver Rosen, Deciphera Pharmaceuticals
(source: https://www.focr.org/tolerability)
Alicyn presented an update on the WG and moderated a panel discussion on the topic with Paul Kluetz Associate Director of Patient Outcomes (Acting), Oncology Center of Excellence, FDA, Lee Jones, Patient Advocate and 15 year CRC survivor, and Mark Stewart, VP of Science and Policy at Friends of Cancer Research, at the 2018 Critical Path Consortium Meeting. Slides are available here. Audio recording of the panel is available here.
setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints consortium (SISAQOL)
Organized by the EORTC through annual research grants, The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints (SISAQOL) consortium comprises multi-disciplinary experts, including HRQoL researchers, statisticians, advisory and regulatory bodies (EMA, FDA and HealthCanada), academic societies, payers (NICE, IQWIG), pharmaceutical industry, cancer institutes and patient advocacy organizations. The goal is to set and communicate consensus guidelines on endpoint development and statistical analyses for the assessment of health-related quality of life in oncology clinical trials. Their latest paper has been submitted to Lancet Oncology. Sample papers are listed below.
https://www.ejcancer.com/article/S0959-8049(17)30529-4/fulltext
https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(18)30418-2.pdf
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30510-1/fulltext
Founder and Co-chair Industry PRO-CTCAE working group
This working group came out of the 2015 Friends of Cancer Research / Brookings Institute Annual Clinical Cancer Meeting where Alicyn was the lead industry presenter. There was reservation amongst the sponsor community regarding the implementation challenges of PRO-CTCAE in multinational global trials. To meet address this unmet need, Alicyn invited interested sponsors and academic researchers to join the PRO-CTCAE Industry Working Group. This group tackles short and long term obstacles to including and analyzing the tool in a pre-competitive collaboration form, Individual sponsor members work as a team to own specific topics and engage in quarterly meetings with FDA and Instrument Developer, NCI to discuss key technical and scientific questions such as translation generation and methodology (completed), Item selection (completed manuscript published), statistical analysis plan core principles (on-going) and evidence generation for global health authority and HTA acceptance (ongoing).
Friends of cancer research & brookings INSTITUTE clinical cancer meeting (2015)
Alicyn was the lead sponsor member and presenter at this meeting, on the panel “Capturing Symptomatic Adverse Events From the Patients’ Perspective: The Potential Role of the National Cancer Institute’s PRO-CTCAE Measurement System.” and included the following speakers.
Patty Spears, Cancer Information and Support Network
Sandra Mitchell, National Cancer Institute
Ethan Basch, University of North Carolina at Chapel Hill
Alicyn Campbell, Genentech
Paul Kluetz, US Food and Drug Administration
Source: FOCR Link
Use of Patient-Reported Outcomes to Enhance Patient Access for cell and gene therapies
Alicyn lends her subject matter expertise to multi-stakeholder efforts engaged in working to influence how patient-reported outcomes (PROs) are used by payors to make coverage decisions. This work is taking on increasing importance as transformative cell therapies and therapies with ultra-rare indications advance to market. PROs provide vitally important empirical evidence that can support more informed use and a more comprehensive assessment of the value these therapies provide.
Chimeric Antigen Receptor (CAR) T-cell Therapies
Alicyn recently served as a subject matter expert for a Friends of Cancer Research working group that provided comments on the Centers for Medicare & Medicaid Services (CMS) National Coverage Determination for CAR-T therapies.
The multi-stakeholder group supported the inclusion of PROs as a factor in coverage decisions for CAR-T therapies, particularly where they pertain to breakthrough designated therapies and where investigational CAR-Ts have the potential to significantly improve health-related quality of life. Because autologous cell therapies (including CAR-Ts and also emerging technologies such as TCR-based therapies) are individualized per patient, robust clinical trial data are difficult to obtain. These challenges are amplified among Medicare patients, who by simple life expectancy may not experience the same duration of survival as younger patients. While collection of PROs and other patient experience endpoints does not resolve the difficulty of conducting trials in these populations, doing so contributes empirical evidence that informs both product development and patient access.
Incorporating PROs into Value Assessments
Alicyn is working to influence CMS’ understanding of how PRO assessments can support health outcomes research and consequently, coverage determinations. Before PROs can be optimally integrated into coverage decisions, it will be necessary to identify key PRO measures for value assessments. Alicyn collaborated on the development of a table included in the multi-stakeholder Friends of Cancer Research comments highlighting key data elements for PRO assessment (Link to Table 1).
Among Alicyn’s key contributions to the Friends of Cancer Research multi-stakeholder comments was a comprehensive table (Table 2) mapping concepts relevant to CAR-Ts to their representation among the PRO tools endorsed by CMS for evidence generation for CAR-Ts (PROMIS, PRO-CTCAE, EORTC, and MDASI). The table will be made available via publication and is intended to help companies and other stakeholders, including CMS, understand how to incorporate PRO assessments into clinical studies of CAR-T therapies. This is of special interest to CMS, which held a 2018 meeting of the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) that explored specific PRO assessment tools, their important characteristics, and their applicability to CAR-T therapies. If you are developing a new treatment for CAR-T and require endpoint suggestions, PRE looks forward to hearing from you. info@patientrelevantevidence.com