Download www.omics-ethics.org Revue de littérature: Mars

Groupe de recherche Omics-Ethics*
www.omics-ethics.org Université de Montréal/Programmes de bioéthique
Mars-Avril 2011 www.omics-ethics.org
Revue de littérature: Mars-Avril 2011 -- Pharmacogénomique
Cette revue de littérature mensuelle a pour but de fournir des références utiles à
une documentation liée à la pharmacogénomique et à ses enjeux éthiques. Les
documents qui n'abordent que les aspects scientifiques de cette science (en
particulier les études fondamentales ou cliniques) ne seront pas intégrés dans
cette section sauf dans les cas où ces documents: (1) abordent ou mentionnent des
enjeux éthiques; (2) proposent une définition ou une description accessible de la
pharmacogénomique et de ses développements potentiels ou futurs; (3) abordent
la portée ou les limites des résultats obtenus dans la recherche en
pharmacogénomique en général; (4) constituent des recommandations ou des
prises de position.
Genetics/genomics advances to influence care for patients with chronic disease Beery TA, Smith CR. Rehabil Nurs. 2011 Mar-­‐Apr; 36(2): 54-­‐9, 88. http://www.rehabnurse.org/apps/ws_resource/public_index.php Authors' abstract: Rapid changes in the field of genetics/genomics are affecting the way we practice nursing. Staying current on this dynamic field is a challenge for all healthcare professionals. This article discusses genetics/genomics issues that are likely to have a strong influence on nurses who care for patients with chronic disease. Complex diseases involving the actions of genes and environment are the most common causes of morbidity and mortality. Pharmacogenetics/pharmacogenomics has the potential to alter the way we choose both medications and appropriate doses. Nutrigenomics promises to help us *Le groupe de recherche Omics-Ethics bénéficie d’une subvention du Fonds de la recherche en santé du
Québec (FRSQ) et des Instituts de recherche en santé du Canada (IRSC).
Groupe de recherche Omics-Ethics
www.omics-ethics.org Mars-Avril 2011
understand how diet affects gene expression and how genetic variants affect the way we use nutrients. Genetic testing can be purchased through the Internet and currently is being marketed directly to consumers. Each of these topics has present and future implications for all healthcare professionals, especially those caring for people with chronic disease. Pharmacogenomics of serious adverse drug reactions in pediatric oncology D Ross CJ, Visscher H, Rassekh SR, Castro-­‐Pastrana LI, Shereck E, Carleton B, Hayden MR. J Popul Ther Clin Pharmacol. 2011; 18(1): e134-­‐51. Epub 2011 Mar 21. http://www.cjcp.ca/pubmed.php?issueId=393 Authors’ abstract: Adverse drug reactions (ADRs) rank as one of the top ten leading causes of death and illness in the developed world. In cancer therapy, more patients are surviving cancer than ever before, but 40% of cancer survivors suffer life-­‐threatening or permanently disabling severe ADRs and are left with long-­‐term sequelae. ADRs are often more frequent and more severe in children, and the consequences for children who experience a severe ADR can be catastrophic. Pharmacogenomics has the potential to improve the safety of these drugs. This review highlights severe ADRs that can occur in cancer therapy that are more frequent and more severe in children, and the pharmacogenomics research that aims to understand, predict, and ultimately prevent these severe reactions. Improving pediatric drug safety: need for more efficient clinical translation of pharmacovigilance knowledge Castro-­‐Pastrana LI, Carleton BC. J Popul Ther Clin Pharmacol. 2011; 18(1): e76-­‐88. Epub 2011 Mar 21. http://www.cjcp.ca/pubmed.php?issueId=393 Authors’ abstract: There is an urgency to improve the evaluation of pediatric drug safety in the pre-­‐market and post-­‐market phases of drug evaluation. The need to improve pharmacovigilance methods concerns not only new drugs but also existing drugs that have been used for many years in an off-­‐label manner in children. Effective methods for early detection of adverse drug reactions (ADRs) and drug safety epidemiologic studies are a pressing need in pediatrics. Moreover, the nature and severity of an ADR as well as the extent to which the suspected drug is being used, will determine how quickly the information about risk needs to be made available to users and what would be the most appropriate method of communication. Based on our experience through the Genotype-­‐
specific Approaches to Therapy in Children study, an active ADR surveillance network of pediatric hospitals across Canada, we present five strategic elements that should be included in pharmacovigilance initiatives in pediatrics: active ADR surveillance; drug or ADR targeted pharmacovigilance; trained surveillance clinicians; case-­‐control methodology and standardized procedures for recognition; reporting and evaluating drug-­‐induced harm. In addition, linking pharmacovigilance with pharmacogenomics to find drug safety solutions is presented as a promising strategy for knowledge generation. Finally, we discuss 2 Groupe de recherche Omics-Ethics
www.omics-ethics.org Mars-Avril 2011
the importance of an efficient translation of the pharmacovigilance knowledge into clinical practice to achieve safer drug therapy in children. The Role and Impact of SNPs in Pharmacogenomics and Personalized Medicine Laing RE, Hess P, Shen Y, Wang J, Hu SX. Curr Drug Metab. 2011 Apr 1. [Epub ahead of print] http://www.benthamscience.com/cdm/index.htm Authors’ abstract: Over 10 million SNPs have been discovered to date as the result of both a private and public effort in the past two decades. Extensive investigations on SNPs have been performed to assess clinical applications for pharmacogenomics and Personalized Medicine. Recently, around the 10(th) anniversary of the first publication by the Human Genome Project, Hamburg and Collins addressed questions regarding the progress of the genomics field and its impact on pharmacogenomics / Personalized Medicine. Similar questions remain around the potential link of SNPs to Personalized Medicine applications, and the extent to which they have impacted "real world" clinical practices. Built upon these previous efforts, and to achieve our objectives of describing and assessing the role of SNPs and their impact on Personalized Medicine, this article analyzes and summarizes the clinical relevance, molecular mechanisms, clinical evidence, and preliminary regulatory and clinical guideline information of relevant SNPs. In addition, it focuses on two applications directly related to Personalized Medicine drug therapeutics: predictive biomarkers for patient stratification and dose selection. In summary, this article attempts to provide a general and comprehensive view of the role of SNPs in pharmacogenomics and Personalized Medicine, as well as a practical view of their impact on clinical practice today. Informed consent in the context of pharmacogenomic research: ethical considerations Howard HC, Joly Y, Avard D, Laplante N, Phillips M, Tardif JC. Pharmacogenomics J. 2011 Mar 29. [Epub ahead of print] http://www.nature.com/tpj/index.html Authors’ abstract: Although the scientific research surrounding pharmacogenomics (PGx) has been relatively plentiful, the ethical research concerning this discipline has developed rather conservatively. Following investigation of the ethical, legal and social issues (ELSI) of PGx research, as well as consulting with key stakeholders, we identified six outstanding ethical issues raised by the informed consent process in PGx research: (1) scope of consent; (2) consent to 'add-­‐on' studies; (3) protection of personal information; (4) commercialization; (5) data sharing; and (6) potential risks stemming from population-­‐
based research. In discussing these six areas as well as offering specific considerations, this article offers a solid base from which future practical guidelines for informed consent in PGx research can be constructed. As such, this effort works toward filling the ELSI gap and provides ethical support to the numerous PGx projects undertaken by researchers every year. 3 Groupe de recherche Omics-Ethics
www.omics-ethics.org Mars-Avril 2011
Pharmacogenetics, Pharmacogenomics, and Individualized Medicine Ma Q, Lu AY. Pharmacol Rev. 2011 Mar 24. [Epub ahead of print] http://pharmrev.aspetjournals.org/content/early/recent Authors’ abstract: Individual variability in drug efficacy and drug safety is a major challenge in current clinical practice, drug development, and drug regulation. For more than 5 decades, studies of pharmacogenetics have provided ample examples of causal relations between genotypes and drug response to account for phenotypic variations of clinical importance in drug therapy. The convergence of pharmacogenetics and human genomics in recent years has dramatically accelerated the discovery of new genetic variations that potentially underlie variability in drug response, giving birth to pharmacogenomics. In addition to the rapid accumulation of knowledge on genome-­‐disease and genome-­‐drug interactions, there arises the hope of individualized medicine. Here we review recent progress in the understanding of genetic contributions to major individual variability in drug therapy with focus on genetic variations of drug target, drug metabolism, drug transport, disease susceptibility, and drug safety. Challenges to future pharmacogenomics and its translation into individualized medicine, drug development, and regulation are discussed. For example, knowledge on genetic determinants of disease pathogenesis and drug action, especially those of complex disease and drug response, is not always available. Relating the many gene variations from genomic sequencing to clinical phenotypes may not be straightforward. It is often very challenging to conduct large scale, prospective studies to establish causal associations between genetic variations and drug response or to evaluate the utility and cost-­‐effectiveness of genomic medicine. Overcoming the obstacles holds promise for achieving the ultimate goal of effective and safe medication to targeted patients with appropriate genotypes. The fallacy of racial pharmacogenomics Pena SD. Braz J Med Biol Res. 2011 Mar 11. pii: S0100-­‐879X2011007500031. [Epub ahead of print] Available on-­‐line: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-­‐
879X2011000400001&lng=en&nrm=iso The communication of pharmacogenetic research results: participants weigh in on their informational needs in a pilot study Madadi P, Joly Y, Avard D, Chitayat DC, Smith MA, D Ross CJ, Carleton BC, Hayden MR, Koren G. J Popul Ther Clin Pharmacol. 2011; 18(1): e152-­‐5. Epub 2011 Mar 21. http://www.cjcp.ca/pubmed.php?issueId=393 Authors’ abstract: In this brief investigation, the informational needs of research participants [n = 62; mothers who had breastfed, taken codeine, and participated in a pharmacogenetic study] were probed during a counselling session in which they received 4 Groupe de recherche Omics-Ethics
www.omics-ethics.org Mars-Avril 2011
their CYP2D6 pharmacogenetic research results and overall study results. In addition to the standard information, developed by a multidisciplinary team and provided to the participants, 38% of individuals had further questions related to potential adverse effects in babies, future codeine or medication use, heredity, and consequences for policies and programmes. The diversity and complexity of the questions raised support the need to communicate the results in the context of personalized genetic counselling information sessions. Guidance for Industry -­‐ Clinical Pharmacogenomics: Premarketing Evaluation in Early Phase Clinical Studies U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Devices and Radiological Health (CDRH) February 2011 Clinical Pharmacology http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
nces/UCM243702.pdf “This guidance is intended to assist the pharmaceutical industry and other investigators engaged in new drug development in evaluating how variations in the human genome could affect the clinical pharmacology and clinical responses of drugs. The guidance provides recommendations on when genomic information should be considered to address questions arising during drug development, and in some cases, during regulatory review. While the application of pharmacogenomic approaches during drug development is an evolutionary process that begins with discovery and continues through confirmation of clinical efficacy and safety outcomes, it is the focus of this guidance to provide advice on general principles of study design, data collection, and data analysis.” 5