New oncology drugs undergo detailed review prior to public funding in a single-payer healthcare system. The aim of this study was to assess how cancer drug review times impact funding recommendations. Drugs reviewed by the pan-Canadian Oncology Drug Review (pCODR) between the years 2012 and 2020 were included. Data were collected including Health Canada approval dates, initial and final funding recommendations, treatment intent, drug class, clinical indications, and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Of the 164 applications submitted, 130 received a positive final recommendation. Median time from Health Canada (HC) approval to final recommendation was longer for drugs indicated for the treatment of gastrointestinal (GI) and lung cancer compared to breast, genitourinary (GU), and other tumours (205 vs. 198 vs. 111 vs. 129 vs. 181 days, respectively; Kruskal–Wallis p = 0.0312). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for tumour type, drug class, and intent of therapy (157 vs. 298 days; Wilcoxon p = 0.0003, OR 1.002 95% CI [1.000–1.004].). There was no association between funding recommendation and tumour type or class of drug. The exploration of factors associated with variance in review times will be important in ensuring timely patient access to cancer drugs.

In the era of rapid development of new, expensive cancer therapies, value frameworks have been developed to quantify clinical benefit (CB). We assessed the evolution of CB since the 2015 introduction of The American Society of Clinical Oncology and The European Society of Medical Oncology value frameworks. Randomized clinical trials (RCTs) assessing systemic therapies for solid malignancies from 2010 to 2020 were evaluated and CB (Δ) in 2010–2014 (pre-value frameworks (PRE)) were compared to 2015–2020 (POST) for overall survival (OS), progression-free survival (PFS), response rate (RR), and quality of life (QoL). In the 485 studies analyzed (12% PRE and 88% POST), the most common primary endpoint was PFS (49%), followed by OS (20%), RR (12%), and QoL (6%), with a significant increase in OS and decrease in RR as primary endpoints in the POST era (p = 0.011). Multivariable analyses revealed significant improvement in ΔOS POST (OR 2.86, 95% CI 0.46 to 5.26, p = 0.02) while controlling for other variables. After the development of value frameworks, median ΔOS improved minimally. The impact of value frameworks has yet to be fully realized in RCTs. Efforts to include endpoints shown to impact value, such as QoL, into clinical trials are warranted.

Figure skaters typically have higher bone mineral density (BMD) than the general population. However, the current literature is limited to cross-sectional studies. The objective of this study was to determine two-year changes in volumetric BMD, bone microarchitecture, and estimated bone strength in elite national and development level Canadian figure skaters. Eleven female figure skaters aged 14+ years were recruited for this longitudinal study. Measurements occurred annually. High-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia underwent three-dimensional image registration. Total (Tt), cortical (Ct) and trabecular (Tb) volumetric BMD (mg HA/cm3), trabecular thickness (TbTh, mm) and cortical thickness (CtTh, mm) were determined. Finite element analysis estimated bone strength. Linear mixed effects models with subject random intercept and time×level interaction evaluated the influence of TtBMD over two-years. Eleven figure skaters completed baseline and one-year data collection, and nine completed the two-year study. All skaters were included in our models and were either national (n=5, 18.6-28.1 years) or development (n=6; 14.4-17.7 years) athletes. Significant time-by-level status (development or national) interactions indicated increases over time in development level athletes only for TtBMD, CtBMD, CtTh and bone strength at the radius and TtBMD, TbBMD, TbTh and bone strength at the tibia (p<0.01 for all). Bone outcomes did not change significantly over the two years in national level figure skaters. Changes in bone density, microarchitecture and strength were only observed in the younger, development level athletes. Given the differences in age between development and national level figure skaters, these results are understandable.

Sleep and circadian disruption adversely impacts mental health and physiology. Such disruption varies in degree and emerges from numerous causes, ranging from severe disruption arising from rotating shift work or frequent jetlag to more mild circadian stress experienced by people with circadian rhythm sleep disorders (CRSD). While the effects of extreme circadian disruption such as jetlag are established through animal studies, less is understood about more subtle mismatches between external zeitgeber cycles and internal circadian periods as is observed with CRSDs. The present study employed a slightly mismatched ~1-h disruption paradigm, whereby Black and Tan BRachyury (BTBR) and C57BL/6 mice were housed from conception onwards in a conventional 24-h light/dark (LD) cycle or a 22.75-h LD cycle closer to the endogenous period of BTBR mice. Starting on postnatal day 90-110, mice underwent a battery of anxiety screens (open field, LD box, elevated plus maze) or a spatial navigation task (Morris water maze) to assess how mild circadian disruption impacts learning and anxiety-like behavior in these strains. Mice raised in a LD cycle that was mismatched from their endogenous rhythm (LD22.75 for C57BL/6 and LD24 for BTBR) displayed more anxiety-like behavior during the open field test and the LD box test and more impulsive behavior during the elevated plus maze. While both disrupted mice and controls showed evidence of learning during the Morris water maze during training, disrupted female mice did not show significant improvements between day 1 and 5 of training, and disrupted mice spent less time in the target quadrant on the probe day. This shows that even a mild form of circadian disruption throughout the lifespan is sufficient to elicit deficits in learning and memory and increased anxiety-like behavior in mice. While circadian disruption in humans may be confounded with other factors, such as diet and socioeconomic status, this study demonstrates that mild circadian disruption alone can alter cognitive and psychological functioning in mice.