ABSTRACT
The move toward early detection and treatment of cancer presents challenges for value assessment using traditional endpoints. Current cancer management rarely considers the full economic and societal benefits of therapies. Our study used a modified Delphi process to develop principles for defining and assessing value of cancer therapies that aligns with the current trajectory of oncology research and reflects broader notions of value. 24 experts participated in consensus-building activities across 5 months (16 took part in structured interactions, including a survey, plenary sessions, interviews, and off-line discussions, while 8 participated in interviews). Discussion focused on: 1) which oncology-relevant endpoints should be used for assessing treatments for early-stage cancer and access decisions for early-stage treatments, and 2) the importance of additional value components and how these can be integrated in value assessments. The expert group reached consensus on 4 principles in relation to the first area (consider oncology-relevant endpoints other than overall survival; build evidence for endpoints that provide earlier indication of efficacy; develop evidence for the next generation of predictive measures; use managed entry agreements supported by ongoing evidence collection to address decision-maker evidence needs) and 3 principles in relation to the second (routinely use patient reported outcomes in value assessments; assess broad economic impact of new medicines; consider other value aspects of relevance to patients and society).
ABSTRACT
Recent technical improvements have made it possible to determine trabecular bone structure parameters of the spine using clinical multi-detector computed tomography (MDCT). Therefore, the purpose of this study was to analyze trabecular bone structure parameters obtained from clinical MDCT in relation to high resolution peripheral quantitative computed tomography (HR-pQCT) as a standard of reference and to investigate whether clinical MDCT can predict vertebral bone strength. Fourteen functional spinal segment units between T7 and L3 were harvested from 14 formalin-fixed human cadavers (11 women and 3 men; age 84 ± 10 years). All functional spinal segment units were examined using HR-pQCT (isotropic voxel size of 41 µm(3)) and a clinical whole-body MDCT (interpolated voxel size of 146 × 146 × 300 µm(3)). Trabecular bone structure analyses (histomorphometric and texture measures) were performed in the HR-pQCT as well as MDCT images. Vertebral failure load (FL) of the functional spinal segment units was determined in an uniaxial biomechanical test. The HR-pQCT and MDCT derived trabecular bone structure parameters showed correlations ranging from r = 0.60 to r = 0.90 (p < 0.05). Correlations between trabecular bone structure parameters and FL amounted up to r = 0.86 (p < 0.05) using the HR-pQCT images, and up to r = 0.79 (p < 0.05) using the MDCT images. Correlation coefficients of FL versus trabecular bone structure parameters obtained with HR-pQCT and MDCT were not significantly different (p > 0.05). In this cadaver model, the spatial resolution of clinically available whole-body MDCT scanners was suitable for trabecular bone structure analysis of the spine and to predict vertebral bone strength.
