Background
Although increasing evidence has suggested that an efficacy‐effectiveness gap exists between clinical trial (CT) and real‐world evidence (RWE), to the authors' knowledge, the magnitude of ...this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies.
Methods
Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population‐based databases. The efficacy‐effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1‐year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan‐Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates.
Results
Twenty‐nine indications from 20 systemic therapies were included. Twenty‐eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0‐12.1 months). Lower effectiveness in RWE also was demonstrated through a meta‐analysis of an OS hazard ratio of 1.58 (95% CI, 1.39‐1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%‐22%).
Conclusions
An efficacy‐effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2‐month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real‐world decision making regarding the use of cancer systemic therapies.
Through a review of clinical trial and real‐world evidence for contemporary cancer systemic therapies, an efficacy‐effectiveness gap has been demonstrated. Thus, supportive evidence is provided in the current study for the further investigation of real‐world outcomes of patients to inform real‐world decision making.
Purpose: Perceval sutureless valves have gained popularity. Whether this implant performs superior to the traditional sutured prosthesis remains unclear. This meta- analysis compared the Perceval ...implants versus the sutured conventional valves for aortic valve replacement (AVR).Methods: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The following databases were accessed: PubMed, Google Scholar, Web of Science, Scopus, and EMBASE. All clinical investigations comparing Perceval versus the conventional prostheses for AVR were considered.Results: The Perceval group demonstrated higher rate of pacemaker implantation (P <0.00001). Aortic cross-clamp (ACC) time (P <0.00001) and cardiopulmonary bypass (CPB) time (P <0.00001) were shorter in the Perceval group. Similarity was found in mean and peak pressure gradient (P = 0.8 and P = 0.2, respectively), mean aortic valve area (P = 0.3), length of intensive care unit (P = 0.4) and hospital stay (P = 0.2), rate of revision (P = 0.11), hemorrhages (P = 0.05), paravalvular leak (P = 0.3), cerebrovascular complication (P = 0.7), and early mortality (P = 0.06).Conclusion: Given the shorter ACC time and CPB time, Perceval AVR can be an alternative in high-risk patients. The higher rate of pacemaker implantation following Perceval may limit its routine implantation.
Geographic variation in the vocal behavior of manatees has been reported but is largely unexplored. Vocalizations of wild West Indian manatees (Trichechus manatus) were recorded with hydrophones in ...Florida from Florida manatees (Trichechus manatus latirostris), and in Belize and Panama from Antillean manatees (Trichechus manatus manatus) to determine if calls varied between subspecies and geographic regions. Calls were visually classified into five categories: squeaks, high squeaks, squeals, squeak-squeals, and chirps. From these five categories, only three call types (squeaks, high squeaks and squeals) were observed in all three populations. Six parameters from the temporal and frequency domains were measured from the fundamental frequency of 2878 manatee vocalizations. A repeated measures PERMANOVA found significant differences for squeaks and high squeaks between each geographic location and for squeals between Belize and Florida. Almost all measured frequency and temporal parameters of manatee vocalizations differed between and within subspecies. Variables that may have influenced the variation observed may be related to sex, body size, habitat and/or other factors. Our findings provide critical information of manatee calls for wildlife monitoring and highlight the need for further study of the vocal behavior of manatees throughout their range.
The spectacled bear (Ursidae: Tremarctos ornatus) is an emblematic umbrella species and one of the top carnivores in the Andean mountains. It is also listed as vulnerable by IUCN and as endangered by ...CITES. We analyzed the genetic structure of this species in nine geographical regions representing the three Andean Cordilleras in Colombia. We sequenced six mitochondrial genes in 115 spectacled bears; a subset of these specimens (n = 61) were genotyped at seven nuclear microsatellites. We addressed three objectives: 1) determine the genetic diversity and historical demographic changes of the spectacled bear in Colombia; 2) determine phylogeographic patterns of genetic divergence among spectacled bear populations in Colombia; and 3) estimate the levels of gene flow among different regions of Colombia. Our analyses show evidence of high mitochondrial genetic diversity in spectacled bears, both in Colombia as well as in each of the nine regions, most particularly Norte de Santander, Nariño, and Antioquia-Córdoba. In addition, we detected population expansion in Colombia that occurred around 24,000 years ago, followed by a population decrease during the last 7,000 years, and a sudden expansion in the last 300 years. Phylogenetic analyses showed few well-supported clades, with some haplotypes detected in all the departments and Colombian Andean Cordilleras, and other haplotypes restricted to certain geographical areas (Antioquia, Norte de Santander, Cundinamarca, and Nariño). We detected significant genetic heterogeneity among some departments and among the three Colombian Andean Cordilleras for both mitochondrial and nuclear genes. Nevertheless, the moderate levels of gene flow estimated from FST statistics suggest that geographical barriers have not been definitive obstacles to the dispersion of the spectacled bear throughout Colombia. Despite these gene flow estimates, significant spatial autocorrelation was detected for spectacled bear in Colombia, where two kinds of spatial patterns were discovered: genetic patches of 144 km of diameter, and isolation by distance among bears separated from 578 to 800 km. The two most northern spectacled bear populations of Colombia (Norte de Santander and Antioquia) also were the two most differentiated. Their distinctiveness may qualify them as distinct Management Units (MUs) in the context of conservation policies for the spectacled bear in Colombia.
To quantify the volumetric polymerization shrinkage (VPS) of different conventional and bulk fill resin composites, through micro-computed tomography (μCT), and qualitative comparison of gap ...formation through optical coherence tomography (OCT).
Box-shaped class I cavities were prepared in 30 third-molars and divided into 5 groups (n=6): G1- Filtek Z100 (Z100); G2- Tetric Evoceram Bulk Fill (TEC); G3- Tetric EvoFlow Bulk fill (TEF); G4- Filtek Bulk fill (FBU); and G5- Filtek Bulk fill Flowable (FBF). All groups were treated with Adper Single Bond Plus adhesive and light cured (Bluephase 20i). Each tooth was scanned three times using a μCT apparatus: after cavity preparation (empty scan); after cavity filling (uncured scan) and after light curing of the restorations (cured scan). The μCT images were imported into a three-dimensional rendering software, and volumetric polymerization shrinkage percentage was calculated (%) for each sample. In the same images, interfacial gaps in the pulpal floor were qualitatively evaluated. After μCT evaluation, the pulpal floor from each tooth was polished until a thin tooth structure was obtained and OCT images were obtained by scanning the pulpal portion. Gap formation was observed and qualitatively compared to the μCT images.
VPS means ranged from 2.31 to 3.96% for the studied resin composites. The bulk fill materials, either high viscosity or flowable, were not statistically different from each other (p>0.05). The conventional resin composite Z100 presented statistically higher VPS than both high viscosity bulk fill materials studied (p<0.05), although it was statistically similar to the flowable bulk fill materials studied (p>0.05). Both μCT and OCT methodologies enabled gap formation visualization, and images from both technologies could be associated. Gap formation was mostly observed for G1-Z100, G4-FBU, and G5-FBF. VPS% and pulpal gap formation could not be completely associated with each other for all groups and samples. Voids were observed in most of the resin composite fillings, and most VPS were observed in the occlusal area of the samples.
Volumetric polymerization shrinkage was material-dependent, although bulk fill materials did not differ from each other. Both μCT and OCT enabled interfacial pulpal gap formation visualization. VPS and gap formation cannot be completely associated with one another.
Facet or zygapophysial joint pain is commonly seen in the aging population. Interventional procedures, such as facet joint nerve blocks, facet intraarticular injections, and radiofrequency ...denervation, are used for the diagnosis and treatment of axial spinal chronic neck and low back pain. The focus of this article is to understand how radiofrequency denervation works in the cervical and lumbar spine and to be able to properly select appropriate patients who might benefit from this safe and effective procedure.
Protected areas (PAs) constitute one of the main tools for global landscape conservation. Recently, payments for environmental services (PES) have attracted interest from national and regional ...governments and are becoming one of the leading conservation policy instruments in tropical countries. However, the degree to which areas designated for PES overlap with areas that are critical for maintaining species' landscape connectivity is rarely evaluated. We estimated habitat distributions and connectivity for 16 of the 22 mammalian carnivores occurring in the Caribbean region of Colombia, and identified the overlap between existing PAs and areas identified as being important for connectivity for these species. We also evaluated the potential impact of creation of new PAs versus new PES areas on conserving connectivity for carnivores. Our results show that PAs cover only a minor percentage of the total area that is important for maintaining connectivity (
). On the other hand, PES, if implemented extensively, could contribute substantially to mammalian carnivores' connectivity (
). However, in a more realistic scenario with limited conservation investment in which fewer areas are set aside, a strategy based on implementing new PAs seems superior to PES. We argue that prioritizing designation of new PAs will be the most efficient means through which to maintain connectivity.
Buildings contribute to about 40% of direct and indirect greenhouse gas emissions and more than a third of energy consumption globally. Sustainable building standards and efficiency standards are two ...measures to reduce such emissions and energy consumption in buildings. While better standards improve the sustainability of new buildings, the impact of these actions depends on the ability to improve the existing building stock. Understanding the dynamics of adopting efficiency and sustainable building measures is essential for setting policy targets and mechanisms. This paper proposes a system dynamics model for assessing the energy savings potential from adopting sustainable building and energy efficiency measurements in buildings in systems with incomplete and uncertain information, using prospective scenarios. The model combines a dynamic diffusion model with an aggregate model for the building stock. The model is calibrated for estimating energy savings in the residential and commercial building stock of the four main metropolitan areas of Colombia: Bogotá, Medellín, Cali, and Barranquilla. Simulation results show that the maximum energy savings potential is approximately 12% but could be below 8% if rebound effects are considered. Results show that energy savings are limited if there are no policies for existing old buildings.
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•We developed a system dynamics model for adoption of sustainable buildings standards.•The model estimates the potential energy savings at the city level.•We used the model for testing different scenarios in four Colombian cities.•Current Colombian standards should be extended to consider an old-buildings policy.•Colombian policies require city-specific incentives and planning.
Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of ...biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer.
This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan-Meier methods and Cox proportional hazards regression. Propensity score matching was applied.
From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74-0.98,
-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test
= 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72-2.30,
-value = 0.39) did not significantly differ between treatment groups.
Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments.
Background
In Ontario, FOLFIRINOX (FFX) and gemcitabine + nab‐paclitaxel (GnP) have been publicly funded for first‐line unresectable locally advanced pancreatic cancer (uLAPC) or metastatic ...pancreatic cancer (mPC) since April 2015. We examined the real‐world effectiveness and safety of FFX vs GnP for advanced pancreatic cancer, and in uLAPC and mPC.
Methods
Patients receiving first‐line FFX or GnP from April 2015 to March 2017 were identified in the New Drug Funding Program database. Baseline characteristics and outcomes were obtained through the Ontario Cancer Registry and other population‐based databases. Overall survival (OS) was assessed using Kaplan‐Meier and weighted Cox proportional hazard models, weighted by the inverse propensity score adjusting for baseline characteristics. Weighted odds ratio (OR) for hospitalization and emergency department visits (EDV) were estimated from weighted logistic regression models.
Results
For 1130 patients (632 FFX, 498 GnP), crude median OS was 9.6 and 6.1 months for FFX and GnP, respectively. Weighted OS was improved for FFX vs GnP (HR = 0.77, 0.70‐0.85). Less frequent EDV and hospitalization were observed in FFX (EDV: 67.8%; Hospitalization: 49.2%) than GnP (EDV: 77.7%; Hospitalization: 59.3%). More frequent febrile neutropenia‐related hospitalization was observed in FFX (5.8%) than GnP (3.3%). Risk of EDV and hospitalization were significantly lower for FFX vs GnP (EDV: OR = 0.68, P = .0001; Hospitalization: OR = 0.76, P = .002), whereas the risk of febrile neutropenia‐related hospitalization was significantly higher (OR = 2.12, P = .001). Outcomes for uLAPC and mPC were similar.
Conclusion
In the real world, FFX had longer OS, less frequent all‐cause EDV and all‐cause hospitalization, but more febrile neutropenia‐related hospitalization compared to GnP.
In the real world, implementation of universal public funding of FOLFIRINOX for metastatic pancreatic cancer was associated with improved overall survival, less frequent all‐cause emergency department visits, less frequent all‐cause hospitalization, but increased febrile neutropenia‐related hospitalization compared to patients treated with gemcitabine + nab‐paclitaxel. Expanding funding to include unresectable locally advanced pancreatic cancer was associated with a similar trend in benefits, but with improved absolute survival.
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