Joseph C Del Paggio1, Richard Sullivan2, Deborah Schrag3, Wilma M Hopman4, Biju Azariah5, C S Pramesh6, Ian F Tannock7, Christopher M Booth8. 1. Department of Medicine, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada. 2. Institute of Cancer Policy, King's College London, London, UK; King's Health Partners Comprehensive Cancer Centre, London, UK. 3. Dana Farber Cancer Institute, Boston, MA, USA. 4. Kingston General Hospital Research Institute, Kingston, ON, Canada. 5. Department of Radiation Oncology, Regional Cancer Centre, Trivandrum, India. 6. Department of Surgical Oncology, Tata Memorial Centre, Mumbai, India. 7. Department of Medicine, Division of Medical Oncology, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 8. Departments of Oncology and Public Health Sciences, Queen's University, Kingston, ON, Canada. Electronic address: boothc@kgh.kari.net.
Abstract
BACKGROUND: The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed frameworks that quantify survival gains in light of toxicity and quality of life to assess the benefits of cancer therapies. We applied these frameworks to a cohort of contemporary randomised controlled trials to explore agreement between the two approaches and to assess the relation between treatment benefit and cost. METHODS: We identified all randomised controlled trials of systemic therapies in non-small-cell lung cancer, breast cancer, colorectal cancer, and pancreatic cancer published between Jan 1, 2011, and Dec 31, 2015, and assessed their abstracts and methods. Trials were eligible for inclusion in our cohort if significant differences favouring the experimental group in a prespecified primary or secondary outcome were reported (secondary outcomes were assessed only if primary outcomes were not significant). We assessed trial endpoints with the ASCO and ESMO frameworks at two timepoints 3 months apart to confirm intra-rater reliability. Cohen's κ statistic was calculated to establish agreement between the two frameworks on the basis of the median ASCO score, which was used as an arbitrary threshold of benefit, and the framework-recommended ESMO threshold. Differences in monthly drug cost between the experimental and control groups of each randomised controlled trial (ie, incremental drug cost) were derived from 2016 average wholesale prices. FINDINGS: 109 randomised controlled trials were eligible for inclusion, 42 (39%) in non-small-cell lung cancer, 36 (33%) in breast cancer, 25 (23%) in colorectal cancer, and six (6%) in pancreatic cancer. ASCO scores ranged from 2 to 77; median score was 25 (IQR 16-35). 41 (38%) trials met the benefit thresholds in the ESMO framework. Agreement between the two frameworks was fair (κ=0·326). Among the 100 randomised controlled trials for which drug costing data were available, ASCO benefit score and monthly incremental drug costs were negatively correlated (ρ=-0·207; p=0·039). Treatments that met ESMO benefit thresholds had a lower median incremental drug cost than did those that did not meet benefit thresholds (US$2981 [IQR 320-9059] vs $8621 [1174-13 930]; p=0·018). INTERPRETATION: There is only fair correlation between these two major value care frameworks, and negative correlations between framework outputs and drug costs. Delivery of optimal cancer care in a sustainable health system will necessitate future oncologists, investigators, and policy makers to reconcile the disconnect between drug cost and clinical benefit. FUNDING: None.
BACKGROUND: The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed frameworks that quantify survival gains in light of toxicity and quality of life to assess the benefits of cancer therapies. We applied these frameworks to a cohort of contemporary randomised controlled trials to explore agreement between the two approaches and to assess the relation between treatment benefit and cost. METHODS: We identified all randomised controlled trials of systemic therapies in non-small-cell lung cancer, breast cancer, colorectal cancer, and pancreatic cancer published between Jan 1, 2011, and Dec 31, 2015, and assessed their abstracts and methods. Trials were eligible for inclusion in our cohort if significant differences favouring the experimental group in a prespecified primary or secondary outcome were reported (secondary outcomes were assessed only if primary outcomes were not significant). We assessed trial endpoints with the ASCO and ESMO frameworks at two timepoints 3 months apart to confirm intra-rater reliability. Cohen's κ statistic was calculated to establish agreement between the two frameworks on the basis of the median ASCO score, which was used as an arbitrary threshold of benefit, and the framework-recommended ESMO threshold. Differences in monthly drug cost between the experimental and control groups of each randomised controlled trial (ie, incremental drug cost) were derived from 2016 average wholesale prices. FINDINGS: 109 randomised controlled trials were eligible for inclusion, 42 (39%) in non-small-cell lung cancer, 36 (33%) in breast cancer, 25 (23%) in colorectal cancer, and six (6%) in pancreatic cancer. ASCO scores ranged from 2 to 77; median score was 25 (IQR 16-35). 41 (38%) trials met the benefit thresholds in the ESMO framework. Agreement between the two frameworks was fair (κ=0·326). Among the 100 randomised controlled trials for which drug costing data were available, ASCO benefit score and monthly incremental drug costs were negatively correlated (ρ=-0·207; p=0·039). Treatments that met ESMO benefit thresholds had a lower median incremental drug cost than did those that did not meet benefit thresholds (US$2981 [IQR 320-9059] vs $8621 [1174-13 930]; p=0·018). INTERPRETATION: There is only fair correlation between these two major value care frameworks, and negative correlations between framework outputs and drug costs. Delivery of optimal cancer care in a sustainable health system will necessitate future oncologists, investigators, and policy makers to reconcile the disconnect between drug cost and clinical benefit. FUNDING: None.
Authors: C S Pramesh; Rajendra A Badwe; Nirmala Bhoo-Pathy; Christopher M Booth; Girish Chinnaswamy; Anna J Dare; Victor Piana de Andrade; David J Hunter; Satish Gopal; Mary Gospodarowicz; Sanjeeva Gunasekera; Andre Ilbawi; Sharon Kapambwe; Peter Kingham; Tezer Kutluk; Nirmal Lamichhane; Miriam Mutebi; Jackson Orem; Groesbeck Parham; Priya Ranganathan; Manju Sengar; Richard Sullivan; Soumya Swaminathan; Ian F Tannock; Vivek Tomar; Verna Vanderpuye; Cherian Varghese; Elisabete Weiderpass Journal: Nat Med Date: 2022-04-19 Impact factor: 87.241
Authors: Di Maria Jiang; Kelvin K W Chan; Raymond W Jang; Christopher Booth; Geoffrey Liu; Eitan Amir; Robert Mason; Louis Everest; Elena Elimova Journal: Cancer Med Date: 2019-03-07 Impact factor: 4.452
Authors: Huseyin Naci; Courtney Davis; Jelena Savović; Julian P T Higgins; Jonathan A C Sterne; Bishal Gyawali; Xochitl Romo-Sandoval; Nicola Handley; Christopher M Booth Journal: BMJ Date: 2019-09-18