The Value of IAQ: A Review of the Scientific Evidence Supporting the Benefits of Investing in Better Indoor Air Quality

Other studies have examined how ventilation rates, combined with the presence of pollutant sources, can affect productivity. These studies provide evidence that increased ventilation, including increases above common guidance levels such as ASHRAE’s ventilation standards, improve occupant productivity. Increased occupant control over ventilation has also been shown to improve productivity. Higher indoor carbon dioxide (CO2) levels have been directly associated with impaired work performance and increased health symptoms. Historically, it was believed that these associations exist only because higher indoor CO2 concentrations, resulting from lower outdoor air ventilation rates, are also correlated with higher levels of other indoor-generated pollutants that directly cause the adverse effects. More recent studies, however, have found that CO2 itself, even at levels previously considered acceptable, may have adverse effects. Considering the benefits and demonstrated return on investment, building owners and operators should consider proactive methods of improving IAQ. Established strategies and guidelines are readily available to help identify and implement IAQ-related improvements. These include recognizing and addressing potential and real IAQ issues during the design, construction, renovation, and ongoing maintenance of buildings. Research has found that the benefits of IAQ improvement far outweigh the costs, with estimates of 3–6 times returns for increased ventilation, 8 times returns for increased filtration, and up to 60 times returns when all improvements and related benefits are combined. Collectively, the scientific literature demonstrates that improved workplace productivity and reduced absenteeism from improved IAQ have been shown to provide substantial financial benefits, with the benefits often greatly outweighing the associated costs

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

PURPOSEThere is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.METHODSAfter a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved.RESULTSCombinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements.CONCLUSIONAn optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer.</p

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

PURPOSEThere is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders.METHODSAfter a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved.RESULTSCombinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements.CONCLUSIONAn optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer

The Value of IAQ: A Review of the Scientific Evidence Supporting the Benefits of Investing in Better Indoor Air Quality

Other studies have examined how ventilation rates, combined with the presence of pollutant sources, can affect productivity. These studies provide evidence that increased ventilation, including increases above common guidance levels such as ASHRAE’s ventilation standards, improve occupant productivity. Increased occupant control over ventilation has also been shown to improve productivity. Higher indoor carbon dioxide (CO2) levels have been directly associated with impaired work performance and increased health symptoms. Historically, it was believed that these associations exist only because higher indoor CO2 concentrations, resulting from lower outdoor air ventilation rates, are also correlated with higher levels of other indoor-generated pollutants that directly cause the adverse effects. More recent studies, however, have found that CO2 itself, even at levels previously considered acceptable, may have adverse effects. Considering the benefits and demonstrated return on investment, building owners and operators should consider proactive methods of improving IAQ. Established strategies and guidelines are readily available to help identify and implement IAQ-related improvements. These include recognizing and addressing potential and real IAQ issues during the design, construction, renovation, and ongoing maintenance of buildings. Research has found that the benefits of IAQ improvement far outweigh the costs, with estimates of 3–6 times returns for increased ventilation, 8 times returns for increased filtration, and up to 60 times returns when all improvements and related benefits are combined. Collectively, the scientific literature demonstrates that improved workplace productivity and reduced absenteeism from improved IAQ have been shown to provide substantial financial benefits, with the benefits often greatly outweighing the associated costs

Paediatric Strategy Forum for medicinal product development of multi-targeted kinase inhibitors in bone sarcomas ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration

The eighth Paediatric Strategy Forum focused on multi-targeted kinase inhibitors (mTKIs) in osteosarcoma and Ewing sarcoma. The development of curative, innovative products in these tumours is a high priority and addresses unmet needs in children, adolescents and adults. Despite clinical and investigational use of mTKIs, efficacy in patients with bone tumours has not been definitively demonstrated. Randomised studies, currently being planned or in progress, in front-line and relapse settings will inform the further development of this class of product. It is crucial that these are rapidly initiated to generate robust data to support international collaborative efforts. The experience to date has generally indicated that the safety profile of mTKIs as monotherapy, and in combination with chemotherapy or other targeted therapy, is consistent with that of adults and that toxicity is manageable. Increasing understanding of relevant predictive biomarkers and tumour biology is absolutely critical to further develop this class of products. Biospecimen samples for correlative studies and biomarker development should be shared, and a joint academic-industry consortium created. This would result in an integrated collection of serial tumour tissues and a systematic retrospective and prospective analyses of these samples to ensure robust assessment of biologic effect of mTKIs. To support access for children to benefit from these novel therapies, clinical trials should be designed with sufficient scientific rationale to support regulatory and payer requirements. To achieve this, early dialogue between academia, industry, regulators, and patient advocates is essential. Evaluating feasibility of combination strategies and then undertaking a randomised trial in the same protocol accelerates drug development. Where possible, clinical trials and development should include children, adolescents, and adults less than 40 years. To respond to emerging science, in approximately 12 months, a multi-stakeholder group will meet and review available data to determine future directions and priorities