Adapting Health Technology Assessment agency standards for surrogate outcomes in early stage cancer trials: what needs to happen?

Introduction: An avalanche of early stage cancer clinical trials is coming. The majority of these solely use surrogate outcomes that have not been validated against a target outcome of interest (e.g.

The Pathway for New Cancer Drug Access in Canada.

Cancer treatment has evolved significantly over the past decade with the emergence of a multitude of new treatments across cancer types. Alongside the pace of drug discovery, the cost of cancer drugs has also increased. In the face of this growth in development and spending, it is crucial to have an understanding of the processes and pressures new drugs navigate to get to the market in Canada.

Efficiently Simulating an Endograft Deployment: A Methodology for Detailed CFD Analyses.

Numerical models of endografts for the simulation of endovascular aneurysm repair are increasingly important in the improvement of device designs and patient outcomes. Nevertheless, current finite element analysis (FEA) models of complete endograft devices come at a high computational cost, requiring days of runtime, therefore restricting their applicability. In the current study, an efficient FEA model of the Anaconda™ endograft (Terumo Aortic, UK) was developed, able to yield results in just over 4 h, an order of magnitude less than similar models found in the literature.

Analysing The Cross-Section of The Abdominal Aortic Aneurysm Neck and Its Effects on Stent Deployment.

Stent graft devices for the treatment of abdominal aortic aneurysms (AAAs) are being increasingly used worldwide. Yet, during modelling and optimization of these devices, as well as in clinical practice, vascular sections are idealized, possibly compromising the effectiveness of the intervention. In this study, we challenge the commonly used approximation of the circular cross-section of the aorta and identify the implications of this approximation to the mechanical assessment of stent grafts.

A Methodology to Quantify the Geometrical Complexity of the Abdominal Aortic Aneurysm.

The abdominal aortic aneurysm (AAA) anatomy influences the technical success of the endovascular aneurysm repair (EVAR), yet very few data regarding the aortic tree angles exist in the literature. This poses great limitations in the numerical analyses of endografts, constraining their design improvement as well as the identification of their operational limitations. In this study, a matrix Φ of 10 angles was constructed for the description of the pathological region and was implemented on a large dataset of anatomies.

Evaluation of a New Approach for Modeling Full Ring Stent Bundles with the Inclusion of Manufacturing Strains.

Ring stent bundles have been used in several biomedical stent-graft devices for decades, yet in the published literature, the numerical models of these structures always present significant simplifications. In this paper, a finite element (FE) ring stent bundle has been developed and evaluated with a combination of beam and surface elements. With this approach, the shape, the global stiffness and the strains of the structure can all be well predicted at a low computational cost while the approach is suitable for application to non-symmetrical, patient-specific implant simulations.

Evolution of drug reimbursement in Canada: the Pan-Canadian Pharmaceutical Alliance for new drugs.

Canada has a unique system of public drug coverage and reimbursement characterized by a centralized review agency that makes funding recommendations along with decentralized authority for delivering health care across 10 provinces and three territories. There has been a significant increase in price negotiation for new pharmaceuticals in the past 10 years, first by individual provinces and now through a collective price negotiation process called the "Pan-Canadian Pharmaceutical Alliance." As of February 2014, the Pan-Canadian Pharmaceutical Alliance has already completed 32 negotiations despite still being in a formative stage; it is anticipated that a formal process will be developed in the coming year.

On the experimental testing of fine Nitinol wires for medical devices.

Nitinol, a nickel titanium alloy, is widely used as a biocompatible metal with applications in high strain medical devices. The alloy exhibits both superelasticity and thermal shape memory behaviour. Basic mechanical properties can be established and are provided by suppliers; however the true stress-strain response under repeated load is not fully understood.

Effects of a spaceflight environment on heritable changes in wheat gene expression.

Once it was established that the spaceflight environment was not a drastic impediment to plant growth, a remaining space biology question was whether long-term spaceflight exposure could cause changes in subsequent generations, even if they were returned to a normal Earth environment. In this study, we used a genomic approach to address this question. We tested whether changes in gene expression patterns occur in wheat plants that are several generations removed from growth in space, compared to wheat plants with no spaceflight exposure in their lineage.

Atmospheric dynamics in the "Laboratory Biosphere" with wheat and sweet potato crops.

Laboratory Biosphere is a 40-m3 closed life system equipped with 12,000 W of high pressure sodium lamps over planting beds with 5.37 m2 of soil. Atmospheric composition changes due to photosynthetic fixation of carbon dioxide and corresponding production of oxygen or the reverse, respiration, are observed in short timeframes, e.

Crop yield and light/energy efficiency in a closed ecological system: Laboratory Biosphere experiments with wheat and sweet potato.

Two crop growth experiments in the soil-based closed ecological facility, Laboratory Biosphere, were conducted from 2003 to 2004 with candidate space life support crops. Apogee wheat (Utah State University variety) was grown, planted at two densities, 400 and 800 seeds m-2. The lighting regime for the wheat crop was 16 h of light-8 h dark at a total light intensity of around 840 micromoles m-2 s-1 and 48.

Technical review of the Laboratory Biosphere closed ecological system facility.

Laboratory Biosphere is a 40 m3 closed life system that commenced operation in May 2002. Light is from 12,000 W of high pressure sodium lamps over planting beds with 5.37 m2 of soil.

Advantages of using subsurface flow constructed wetlands for wastewater treatment in space applications: ground-based Mars Base prototype.

Research and design of subsurface flow wetland wastewater treatment systems for a ground-based experimental prototype Mars Base facility has been carried out, using a subsurface flow approach. These systems have distinct advantages in planetary exploration scenarios: they are odorless, relatively low-labor and low-energy, assist in purification of water and recycling of atmospheric CO2, and will support some food crops. An area of 6-8 m2 may be sufficient for integration of wetland wastewater treatment with a prototype Mars Base supporting 4-5 people.

Initial experimental results from the Laboratory Biosphere closed ecological system facility.

An initial experiment in the Laboratory Biosphere facility, Santa Fe, New Mexico, was conducted May-August 2002 using a soil-based system with light levels (at 12 h per day) of 58-mol m-2 d-1. The crop tested was soybean, cultivar Hoyt, which produced an aboveground biomass of 2510 grams. Dynamics of a number of trace gases showed that methane, nitrous oxide, carbon monoxide, and hydrogen gas had initial increases that were substantially reduced in concentration by the end of the experiment.

Earth applications of closed ecological systems: relevance to the development of sustainability in our global biosphere.

The parallels between the challenges facing bioregenerative life support in artificial closed ecological systems and those in our global biosphere are striking. At the scale of the current global technosphere and expanding human population, it is increasingly obvious that the biosphere can no longer safely buffer and absorb technogenic and anthropogenic pollutants. The loss of biodiversity, reliance on non-renewable natural resources, and conversion of once wild ecosystems for human use with attendant desertification/soil erosion, has led to a shift of consciousness and the widespread call for sustainability of human activities.

Light, plants, and power for life support on Mars.

Regardless of how well other growing conditions are optimized, crop yields will be limited by the available light up to saturation irradiances. Considering the various factors of clouds on Earth, dust storms on Mars, thickness of atmosphere, and relative orbits, there is roughly 2/3 as much light averaged annually on Mars as on Earth. On Mars, however, crops must be grown under controlled conditions (greenhouse or growth rooms).

Airtight sealing a Mars base.

Atmospheric leakage from a Mars base would create a demand for continuous or periodic replenishment, which would in turn require extraction or mining for oxygen and other gases from local resources and attendant equipment and energy requirements for such operations. It therefore becomes a high priority to minimize leakage. This article quantifies leak rates as determined by the size of holes and discusses the implications of pressure for structural configuration.

Potential integration of wetland wastewater treatment with space life support systems.

Subsurface-flow constructed wetlands for wastewater treatment and nutrient recycling have a number of advantages in planetary exploration scenarios: they are odorless, relatively low labor and low energy, assist in purification of water and recycling of atmospheric CO2, and can directly grow some food crops. This article presents calculations for integration of wetland wastewater treatment with a prototype ground-based experimental facility ("Mars on Earth") supporting four people showing that an area of 4-6 m2 may be sufficient to accomplish wastewater treatment and recycling. Discharge water from the wetland system can be used as irrigation water for the agricultural crop area, thus ensuring complete reclamation and utilization of nutrients within the bioregenerative life support system.

Engineering of Biosphere 2: closure and energy.

As an experimental apparatus, Biosphere 2 was predicated on material closure to permit investigation of ecological processes without unknown sources or sinks outside the ecosystems under study. The atmospheric leak rate is demonstrated to be less than 10% per year. The enabling technology to achieve the low leak rate is expansion chambers called "lungs.

Plasma free iron: a possible cause of oedema in kwashiorkor.

Background: Oedema is a sine qua non for the diagnosis of kwashiorkor yet the mechanisms leading to oedema remain ill defined.

Aims: To relate the plasma concentration of radical promoting 'free' iron to the degree of oedema in patients with kwashiorkor.

Setting: University teaching hospital.

Bone marrow and chelatable iron in patients with protein energy malnutrition.

Objectives: To examine the iron status of malnourished children by comparing bone marrow iron deposits in children with protein energy malnutrition with those in well-nourished controls, and measuring chelatable urinary iron excretion in children with kwashiorkor.

Design: Bone marrow iron was assessed histologically in postmortem specimens from children with kwashiorkor or marasmus, and from controls. Twenty-four-hour urinary iron was measured in children with severe kwashiorkor, half of whom received 10 mg/kg of intramuscular desferrioxamine (DFO) on admission.

Living in space: results from Biosphere 2's initial closure, an early testbed for closed ecological systems on Mars.

The following summary of results from the first 2-year closure experiment (September 26, 1991 to September 26, 1993) in Biosphere 2 is excerpted from a chapter written by William Dempster and myself for a book, Strategies for Mars, edited by Carol Stoker and Carter Emmart of NASA Ames Research Center. The book will be published later this year by Krieger Publishers. It brings together a number of the most striking initial results, including food production and nutrition; ecosystem changes; oxygen and carbon dioxide dynamics; and the human role and response to living in a small, recycling life support system.

Misplaced iron in kwashiorkor.

Objectives: To determine the presence of radical promoting iron (non-protein-bound or loosely bound or free iron) in the plasma of children with kwashiorkor.

Design: The bleomycin assay was employed for the quantitation of free or loosely bound iron.

Setting: The Red Cross War Memorial Children's Hospital, Cape Town, Tertiary Care.