HOW CAN ADVERSE EVENTS INFORMATION BE USED TO MORE EFFECTIVELY INFORM CANCER PATIENT CARE?

Due to advances in screening and therapy design, cancer patients are living longer while on or following therapy. Therapy-related adverse events (AEs) are an unintended, but not infrequent, outcome of these treatments. AEs can impact quality of life, adherence to therapy, economic status, and treatment decision-making. This novel qualitative study is the first to undertake a multi-stakeholder evaluation of the impact of AE information on informing cancer patient care in the context of extended survival. The evaluation focuses on a growing subset of cancer patients – those receiving adjuvant therapy. Adjuvant therapies, used to manage many common cancers, lower the risk that the cancer will return. In this setting, mediating the impact of potential acute or delayed adjuvant treatment-related AEs relative to an uncertain potential for tumor recurrence presents important challenges in balancing risks versus benefits. Stakeholder perspectives on generating, disseminating, and/or adjuvant treatment-related AE information were elicited via key informant interviews with patient advocacy, clinical care, regulatory, drug development, and healthcare payer representatives. The stakeholders identified future needs in four key areas: 1) information resources, 2) information integration and implementation, 3) value systems and culture, and 4) alignment and ownership of collective efforts to improve the use of AE information in the adjuvant setting. This study revealed the following novel insights: 1) there is cross-stakeholder agreement that change is needed to improve the use of AE information in the adjuvant setting to improve patient outcome, 2) the directionality of needed changes are similar across stakeholders, although specific priorities varied, and 3) the potential to realize broad systemic progress in the use of adjuvant-related AE information is a challenge that lacks clear ownership. This lack of ownership has adversely impacted resourcing, efficiency, and collective progress and is likely to be a progress-limiting factor in realizing transformational change. To address the system-limiting challenges identified in this research, a proposed approach to incentivize and support stakeholders in forward action is offered. The proposal offers an infrastructure to promote collaborative and independent efforts in fulfillment of the many scientific, economic, communication, social, and implementation challenges identified in this research study.Doctor of Public Healt

Ascension

Ope

Challenging the status quo: a framework for mechanistic and human-relevant cardiovascular safety screening

Traditional approaches to preclinical drug safety assessment have generally protected human patients from unintended adverse effects. However, these assessments typically occur too late to make changes in the formulation or in phase 1 and beyond, are highly dependent on animal studies and have the potential to lead to the termination of useful drugs due to liabilities in animals that are not applicable in patients. Collectively, these elements come at great detriment to both patients and the drug development sector. This phenomenon is particularly problematic in the area of cardiovascular safety assessment where preclinical attrition is high. We believe that a more efficient and translational approach can be defined. A multi-tiered assessment that leverages our understanding of human cardiovascular biology, applies human cell-based in vitro characterizations of cardiovascular responses to insult, and incorporates computational models of pharmacokinetic relationships would enable earlier and more translational identification of human-relevant liabilities. While this will take time to develop, the ultimate goal would be to implement such assays both in the lead selection phase as well as through regulatory phases

Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories

<p>Abstract</p> <p>Background</p> <p>The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies could yield useful information on baseline fluctuations in gene expression, although control animal data has not been available on a scale and in a form best served for data-mining.</p> <p>Results</p> <p>A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques.</p> <p>Conclusion</p> <p>The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomics studies and in the interpretation of their results.</p

Guest Editorial: Toxicogenomics in Risk Assessment: Communicating the Challenges-0

<p><b>Copyright information:</b></p><p>Taken from "Guest Editorial: Toxicogenomics in Risk Assessment: Communicating the Challenges"</p><p>Environmental Health Perspectives 2004;112(12):A662-A662.</p><p>Published online Jan 2004</p><p>PMCID:PMC1277120.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose.</p