Navigating the Intersection between Genomic Research and Clinical Practice.

The Risk Assessment Program (RAP) at Fox Chase Cancer Center (Philadelphia, PA) is a multi-generational prospective cohort, enhanced for personal and family history of cancer, consisting of over 10,000 individuals for whom data on personal and family history of cancer, risk factors, genetic and genomic data, health behaviors, and biospecimens are available. The RAP has a broad research agenda including the characterization of genes with known or potential relevance to cancer, gene-gene and gene-environment interactions, and their contribution to clinically useful risk assessment and risk reduction strategies. Increasingly, this body of research is identifying genetic changes which may have clinical significance for RAP research participants, leading us to confront the issue of whether to return genetic results emerging from research laboratories. This review will describe some of the important fundamental points that must be debated as we develop a paradigm for return of research results. The key issues to address as the scientific community moves toward adopting a policy of return of research results include the best criteria for determining which results to offer, the consent document components necessary to ensure that the participant makes a truly informed decision about receiving their results, and associated logistical and cost challenges.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.

International Divergence in Gene Patenting.

This review explores the recent divergence in international patent law relating to genes and associated subject matter. This divergence stems primarily from decisions of the highest courts in the United States and Australia on the eligibility of patent claims relating to the BRCA gene sequences. Patent offices, courts, and policy makers have struggled for many years to clearly articulate the bounds of patent claims on isolated and synthetic DNA and related products and processes, including methods for their use in genetic diagnostics. This review provides context to the current divergence by mapping key events in the gene patent journey from the early 1980s onward in five key jurisdictions: the United States, the member states of the European Patent Convention, Australia, Canada, and China. Early approaches to gene patenting had some commonalities across jurisdictions, which makes exploration of the recent divergence all the more interesting.There is insufficient empirical evidence to date to confidently predict the consequences of this recent divergence. However, it could potentially have a significant effect on local industry and on consumer access.

Clasificación del sujeto de derecho frente al avance de la genómica y la procreática / Subjects of rights classification facing genomic and proteomic development / Classificação do sujeito de direito contra o avanço da genômica e da procriativa

Resumen: El Derecho cataloga la vida humana de acuerdo al estado con el cual se presenta en sociedad con la finalidad de darle una adecuada seguridad. La teoría del sujeto de derecho se sustenta en la conceptualización jurídica de la vida humana. Como teoría, fue creada para reconocer una real y efectiva regulación jurídica a las relaciones que lleve a cabo el hombre en la sociedad, tomando en cuenta que la vida humana tiene numerosas formas de presentarse en sociedad. La vida es una, pero -sea biológica o social- adopta diversos estadios que merecen una regulación acorde con su estatus. Es esta esencia y forma como la vida se presenta en sociedad lo que permite categorizarla jurídicamente y de esto se encarga la teoría del sujeto de derecho. De esta forma se regula la vida humana en su verdadera esencia y dimensión; sin embargo, la biotecnología procreática y genómica vienen alterando su clásica taxonomía, variándolo, al presentar nuevos actores en un mundo de relación.

Abstract: Law categorizes human life according to its situation in society with the goal to provide adequate safety. The theory of the subject of rights is based on the juridical conceptualization of human life. As theory, it was created to recognize a real and effective legal regulation to human relations in society, taking into account that human life has many ways to appear in society. Life is one, but -be biological or social- it adopts diverse stages which deserves regulation according to their status. This essence and way in which life is presented allows its juridical categorization by the subject of rights theory. In this way, human life is regulated in its true essence and dimension; nevertheless, genomic and proteomic biotechnology have being altering their classic taxonomy, changing it when presenting new actors in a world of relations.

Resumo: O Direto cataloga a vida humana de acordo com o estado com a qual se apresenta na sociedade com a finalidade de dá-la um nível adequado de segurança. A teoria do sujeito de direito é baseada no conceito jurídico de vida humana. Como teoria, foi criada para reconhecer uma real e efetiva regulação jurídica das relações realizadas pelo homem na sociedade, tendo em conta que a vida humana tem inúmeras maneiras de se apresentar na sociedade. A vida é uma, embora -seja biológica ou social- adota diferentes fases que merecem uma regulação em conformidade com o seu estatuto. É essa essência e forma como a vida surge na sociedade é o que permite categorizá-la juridicamente e disso se encarga a teoria do sujeito do direito. Assim, regula a vida humana na sua verdadeira essência e dimensão; no entanto, a biotecnología procriativa e genômica vem alterando sua taxonomia clássica, variando-a, introduzindo novos atores em um mundo de relações.

Considerations of developing an NGS assay for clinical applications in precision oncology: The NCI-MATCH NGS assay experience.

Next generation sequencing (NGS) technologies have been widely adapted in clinical oncology by utilizing the profiled genetic mutation information to select patients and to guide the choice of target therapy. To fulfill the regulatory compliance, development of an NGS assay that will be used in clinical trials requires an analytical validation to meet its intend clinical use. NCI-MATCH trial is the largest precision oncology basket trial which uses a single NGS assay (NCI-MATHC NGS assay) to screen the actionable mutations in 6000 patients, who have relapsed/refractory solid tumors and lymphomas after standard systemic treatment, and assigns matched treatment. This article reviews on the critical considerations during development and validation of NGS assays as an investigational device for genomic based clinical trials and provides the experiences from the development of NCI-MATCH NGS assay.

Some Legal Issues Regarding the Patenting of Human Genetic Materials.

This article examines issues of ethics, science and law in the context of a recent High Court decision involving an application by Yvonne D'Arcy to revoke patents granted to Myriad Genetics Inc for various genetic sequences found in the BRCA1 gene once isolated (which, when certain mutations were present, had been found to be linked to the occurrence of breast and ovarian cancer). This article provides a brief discussion on the history of patent law and an extensive discussion of the requirements under s 18(1) of the Patents Act 1990 (Cth) for the granting of a patent involving the use of human genetic material.

Preferences Regarding Return of Genomic Results to Relatives of Research Participants, Including after Participant Death: Empirical Results from a Cancer Biobank.

Data are lacking with regard to participants' perspectives on return of genetic research results to relatives, including after the participant's death. This paper reports descriptive results from 3,630 survey respondents: 464 participants in a pancreatic cancer biobank, 1,439 family registry participants, and 1,727 healthy individuals. Our findings indicate that most participants would feel obligated to share their results with blood relatives while alive and would want results to be shared with relatives after their death.

MYRIAD VOICES AGAINST GENE PATENTS IN THE HIGH COURT.

The Australian High Court's recent landmark decision in D'Arcy v Myriad Genetics Inc overturned the decision by the Federal Court in Cancer Voices Australia v Myriad Genetics Inc regarding patenting of genetic material. The Federal Court had found that isolated DNA and RNA can constitute a patentable invention under s 18(1)(a) of the Patents Act 1990 (Cth). The decision by the High Court unanimously reversed this and declared it was appropriate to look to the policy implications at the heart of the legal question: are genes a category of things that can be patented? This column critically examines the implications of the High Court decision for both research and public health in Australia.

NIH broadens genomic data-sharing policy.

The NIH's new Genomic Data-Sharing policy, which goes into effect on January 25, 2015, outlines data sharing and informed consent expectations for researchers who generate large amounts of genomic data during NIH-funded studies.

Genomics education for the public: perspectives of genomic researchers and ELSI advisors.

AIMS: For more than two decades genomic education of the public has been a significant challenge. As genomic information becomes integrated into daily life and routine clinical care, the need for public education is even more critical. We conducted a pilot study to learn how genomic researchers and ethical, legal, and social implications advisors who were affiliated with large-scale genomic variation studies have approached the issue of educating the public about genomics. METHODS/RESULTS: Semi-structured telephone interviews were conducted with researchers and advisors associated with the SNP/HAPMAP studies and the Cancer Genome Atlas Study. Respondents described approach(es) associated with educating the public about their study. Interviews were audio-recorded, transcribed, coded, and analyzed by team review. Although few respondents described formal educational efforts, most provided recommendations for what should/could be done, emphasizing the need for an overarching entity(s) to take responsibility to lead the effort to educate the public. Opposing views were described related to: who this should be; the overall goal of the educational effort; and the educational approach. Four thematic areas emerged: What is the rationale for educating the public about genomics?; Who is the audience?; Who should be responsible for this effort?; and What should the content be? Policy issues associated with these themes included the need to agree on philosophical framework(s) to guide the rationale, content, and target audiences for education programs; coordinate previous/ongoing educational efforts; and develop a centralized knowledge base. Suggestions for next steps are presented. CONCLUSION: A complex interplay of philosophical, professional, and cultural issues can create impediments to genomic education of the public. Many challenges, however, can be addressed by agreement on a guiding philosophical framework(s) and identification of a responsible entity(s) to provide leadership for developing/overseeing an appropriate infrastructure to support the coordination/integration/sharing and evaluation of educational efforts, benefiting consumers and professionals.

Gene patents and personalized cancer care: impact of the Myriad case on clinical oncology.

Genomic discoveries have transformed the practice of oncology and cancer prevention. Diagnostic and therapeutic advances based on cancer genomics developed during a time when it was possible to patent genes. A case before the Supreme Court, Association for Molecular Pathology v Myriad Genetics, Inc seeks to overturn patents on isolated genes. Although the outcomes are uncertain, it is suggested here that the Supreme Court decision will have few immediate effects on oncology practice or research but may have more significant long-term impact. The Federal Circuit court has already rejected Myriad's broad diagnostic methods claims, and this is not affected by the Supreme Court decision. Isolated DNA patents were already becoming obsolete on scientific grounds, in an era when human DNA sequence is public knowledge and because modern methods of next-generation sequencing need not involve isolated DNA. The Association for Molecular Pathology v Myriad Supreme Court decision will have limited impact on new drug development, as new drug patents usually involve cellular methods. A nuanced Supreme Court decision acknowledging the scientific distinction between synthetic cDNA and genomic DNA will further mitigate any adverse impact. A Supreme Court decision to include or exclude all types of DNA from patent eligibility could impact future incentives for genomic discovery as well as the future delivery of medical care. Whatever the outcome of this important case, it is important that judicial and legislative actions in this area maximize genomic discovery while also ensuring patients' access to personalized cancer care.

Incorporating genomics into breast and prostate cancer screening: assessing the implications.

Individual risk prediction and stratification based on polygenic profiling may be useful in disease prevention. Risk-stratified population screening based on multiple factors including a polygenic risk profile has the potential to be more efficient than age-stratified screening. In this article, we summarize the implications of personalized screening for breast and prostate cancers. We report the opinions of multidisciplinary international experts who have explored the scientific, ethical, and logistical aspects of stratified screening. We have identified (i) the need to recognize the benefits and harms of personalized screening as compared with existing screening methods, (ii) that the use of genetic data highlights complex ethical issues including discrimination against high-risk individuals by insurers and employers and patient autonomy in relation to genetic testing of minors, (iii) the need for transparency and clear communication about risk scores, about harms and benefits, and about reasons for inclusion and exclusion from the risk-based screening process, and (iv) the need to develop new professional competences and to assess cost-effectiveness and acceptability of stratified screening programs before implementation. We conclude that health professionals and stakeholders need to consider the implications of incorporating genetic information in intervention strategies for health-care planning in the future.

The triad of success in personalised medicine: pharmacogenomics, biotechnology and regulatory issues from a Central European perspective.

The population of the world has recently passed the 7 billion milestone and as the cost of human genome sequencing is rapidly declining, sequence data of billions of people should be accessible much sooner than anyone would have predicted 10 years ago. This will form the basis of personalised medicine. However it is still not clear, even in principle, whether these data, combined with data of the expression of one's genome in various cells and tissues relevant to different diseases, could be used effectively in clinical medicine and healthcare, or in predicting responses to different therapies. Therefore this is an important issue which needs to be addressed before more resources are wasted on less than informative studies and surveys simply because technologies exist. As a typical example, we have selected and summarise here key studies from the biomedical literature that focus on gene expression profiling of the response to biologic therapies in peripheral blood and biopsy samples in autoimmune diseases such as rheumatoid arthritis, spondylarthropathy, inflammatory bowel diseases and psoriasis. We also present the state of the biotechnology market from a European perspective, discuss how spin-offs leverage the power of genomic technologies and describe how they might contribute to personalised medicine. As ethical, legal and social issues are essential in the area of genomics, we analysed these aspects and present here the European situation with a special focus on Hungary. We propose that the synergy of these three issues: pharmacogenomics, biotechnology and regulatory issues should be considered a triad necessary to succeed in personalised medicine.

Overview of personalized medicine in the disease genomic era.

Sir William Osler (1849-1919) recognized that "variability is the law of life, and as no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions we know as disease". Accordingly, the traditional methods of medicine are not always best for all patients. Over the last decade, the study of genomes and their derivatives (RNA, protein and metabolite) has rapidly advanced to the point that genomic research now serves as the basis for many medical decisions and public health initiatives. Genomic tools such as sequence variation, transcription and, more recently, personal genome sequencing enable the precise prediction and treatment of disease. At present, DNA-based risk assessment for common complex diseases, application of molecular signatures for cancer diagnosis and prognosis, genome-guided therapy, and dose selection of therapeutic drugs are the important issues in personalized medicine. In order to make personalized medicine effective, these genomic techniques must be standardized and integrated into health systems and clinical workflow. In addition, full application of personalized or genomic medicine requires dramatic changes in regulatory and reimbursement policies as well as legislative protection related to privacy. This review aims to provide a general overview of these topics in the field of personalized medicine.