Review of FDA Amendments Act Section 921 Experience in Posting Data-mining Results from the FAERS Database.

PURPOSE: Title IX, § 921 of the Food and Drug Administration (FDA) Amendments Act of 2007 requires the FDA to mine data on a regular basis, using its adverse events database, the FDA Adverse Event Reporting System, to identify potential signals of serious risks/new safety information. This review of the FDA's quarterly web-posted results is the first to document the contributions of the program to maintaining the continued safe use of approved pharmaceutical drugs/biologics and the lessons that have emerged from this rich experience. METHODS: Details on proprietary prescription drugs/biologics, generic prescription drugs, and over-the-counter drugs were downloaded from the quarterly posts that begin in first quarter of 2008. Key information was tabulated, including proprietary and generic names of products or classes of products, the identified potential signals of serious risks, the labeling-decision category (updated, no action is necessary at this time, or evaluating the need for regulatory action), the labeling section (Warnings and Precautions, Adverse Reactions, Drug Safety Communications, Contraindications, or Boxed Warnings), and estimated times to updated decisions. FINDINGS: Since the beginning of the FDAAA Section 921 posting requirement, the FDA has posted 555 potential signals of serious risk or new safety information. Of these, there have been 262 posts (47%) that resulted in decisions requiring updated product labeling, 75 posts (14%) that resulted in decisions that no action was necessary, and 218 posts (39%) indicating that the FDA was evaluating the need for regulatory action. Of the 262 posts that required updating one or more sections of a product label, there was a preponderance of Warnings and Precautions, with 172 (66%); followed by Adverse Reactions, with 114 (44%); Drug Safety Communications, 44 (18%); Contraindications, 27 (10%); and Boxed Warnings, 19 (7%). The median times to update decisions were 12 months for Warnings & Precautions, Adverse Reactions, and Boxed Warnings, and 11 months for Contraindications. IMPLICATIONS: Important themes from the present analysis include the following: (1) nearly 80% of posts resulted in updated product labeling; (2) 20% of decisions concerned classes of proprietary and generic drug/biologic products; (3) product-use errors, such as name confusion, continue to be important; (4) the safe use of pharmaceuticals in children is gaining attention but still has a long way to go; and (5) drug-drug interactions are of continuing concern. The FDA Amendments Act § 921 program will continue to have an important place in the future of pharmacovigilance practices.

An open-source GIS-enabled lookup service for Nagoya Protocol party information.

The Nagoya Protocol on Access and Benefit Sharing is a transparent legal framework, which governs the access to genetic resources and the fair and equitable sharing of benefits arising from their utilization. Complying with the Nagoya regulations ensures legal use and re-use of data from genetic resources. Providing detailed provenance information and clear re-usage conditions plays a key role in ensuring the re-usability of research data according to the FAIR (findable, accessible, interoperable and re-usable) Guiding Principles for scientific data management and stewardship. Even with the framework provided by the ABS (access and benefit sharing) Clearing House and the support of the National Focal Points, establishing a direct link between the research data from genetic resources and the relevant Nagoya information remains a challenge. This is particularly true for re-using publicly available data. The Nagoya Lookup Service was developed for stakeholders in biological sciences with the aim at facilitating the legal and FAIR data management, specifically for data publication and re-use. The service provides up-to-date information on the Nagoya party status for a geolocation provided by GPS coordinates, directing the user to the relevant local authorities for further information. It integrates open data from the ABS Clearing House, Marine Regions, GeoNames and Wikidata. The service is accessible through a REST API and a user-friendly web form. Stakeholders include data librarians, data brokers, scientists and data archivists who may use this service before, during and after data acquisition or publication to check whether legal documents need to be prepared, considered or verified. The service allows researchers to estimate whether genetic data they plan to produce or re-use might fall under Nagoya regulations or not, within the limits of the technology and without constituting legal advice. It is implemented using portable Docker containers and can easily be deployed locally or on a cloud infrastructure. The source code for building the service is available under an open-source license on GitHub, with a functional image on Docker Hub and can be used by anyone free of charge.

Perspectives of Australian policy-makers on the potential benefits and risks of technologically enhanced communicable disease surveillance - a modified Delphi survey.

BACKGROUND: Event-based social media monitoring and pathogen whole genome sequencing (WGS) will enhance communicable disease surveillance research and systems. If linked electronically and scanned systematically, the information provided by these technologies could be mined to uncover new epidemiological patterns and associations much faster than traditional public health approaches. The benefits of earlier outbreak detection are significant, but implementation could be opposed in the absence of a social licence or if ethical and legal concerns are not addressed. METHODS: A three-phase mixed-method Delphi survey with Australian policy-makers, health practitioners and lawyers (n = 44) was conducted to explore areas of consensus and disagreement over (1) key policy and practical issues raised by the introduction of novel communicable disease surveillance programmes; and (2) the most significant and likely risks from using social media content and WGS technologies in epidemiological research and outbreak investigations. RESULTS: Panellists agreed that the integration of social media monitoring and WGS technologies into communicable disease surveillance systems raised significant issues, including impacts on personal privacy, medicolegal risks and the potential for unintended consequences. Notably, their concerns focused on how these technologies should be used, rather than how the data was collected. Panellists held that social media users should expect their posts to be monitored in the interests of public health, but using those platforms to contact identified individuals was controversial. The conditions of appropriate use of pathogen WGS in epidemiological research and investigations was also contentious. Key differences amongst participants included the necessity for consent before testing and data-linkage, thresholds for action, and the legal and ethical importance of harms to individuals and commercial entities. The erosion of public trust was seen as the most significant risk from the systematic use of these technologies. CONCLUSIONS: Enhancing communicable disease surveillance with social-media monitoring and pathogen WGS may cause controversy. The challenge is to determine and then codify how these technologies should be used such that the balance between individual risk and community benefit is widely accepted. Participants agreed that clear guidelines for appropriate use that address legal and ethical concerns need to be developed in consultation with relevant experts and the broader Australian public.

[Chapter 5. Health and Big Data: the emergence of an infrastructure law in the digital space]. / Chapitre 5. Santé et Big data : l?émergence d?un droit d?infrastructure dans l?espace numérique.

In the field of health, IoT devices, mobile apps, and online communities generate an enormous amount of data. However, health data benefit from a precise legal definition and protection as sensitive data, whereas well-being data have no specific legal regime. Since those data may contribute to identify individuals' health status, there are potential breaches to confidentiality and privacy. Recent European cases (ECHR and ECJ) reaffirms citizens' fundamental rights to privacy and family life, and to an effective remedy. Such decisions contribute to mitigate the misuse of big data broadly speacking, inclunding in the health sector.

Data mining and biological sample exportation from South Africa: A new wave of bioexploitation under the guise of clinical care?

Discovery Health, one of the leading healthcare funders in South Africa (SA), will offer genetic testing to its members for USD250 (approximately ZAR3 400) per test from 2016. On the surface, this appears to be innovative and futuristic. However, a deeper look at this announcement reveals considerable problems in the exportation of biological samples and data out of SA, and brings into sharp focus the lack of protection in place for potential donors. In return for a reduced-cost genetic test, which will nevertheless be billed to a member's savings plan, data from the patient's results, and probably the sample itself, will be sent to the USA for storage, research purposes and possible commercial use, with no further benefit for the patient. This development has demonstrated the need for more stringent protection of the movement of biological samples and data out of SA, particularly with reference to consenting procedures, material transfer agreements, and the export of biological data themselves.

FDA's Activities Supporting Regulatory Application of "Next Gen" Sequencing Technologies.

Applications of next-generation sequencing (NGS) technologies require availability and access to an information technology (IT) infrastructure and bioinformatics tools for large amounts of data storage and analyses. The U.S. Food and Drug Administration (FDA) anticipates that the use of NGS data to support regulatory submissions will continue to increase as the scientific and clinical communities become more familiar with the technologies and identify more ways to apply these advanced methods to support development and evaluation of new biomedical products. FDA laboratories are conducting research on different NGS platforms and developing the IT infrastructure and bioinformatics tools needed to enable regulatory evaluation of the technologies and the data sponsors will submit. A High-performance Integrated Virtual Environment, or HIVE, has been launched, and development and refinement continues as a collaborative effort between the FDA and George Washington University to provide the tools to support these needs. The use of a highly parallelized environment facilitated by use of distributed cloud storage and computation has resulted in a platform that is both rapid and responsive to changing scientific needs. The FDA plans to further develop in-house capacity in this area, while also supporting engagement by the external community, by sponsoring an open, public workshop to discuss NGS technologies and data formats standardization, and to promote the adoption of interoperability protocols in September 2014. LAY ABSTRACT: Next-generation sequencing (NGS) technologies are enabling breakthroughs in how the biomedical community is developing and evaluating medical products. One example is the potential application of this method to the detection and identification of microbial contaminants in biologic products. In order for the U.S. Food and Drug Administration (FDA) to be able to evaluate the utility of this technology, we need to have the information technology infrastructure and bioinformatics tools to be able to store and analyze large amounts of data. To address this need, we have developed the High-performance Integrated Virtual Environment, or HIVE. HIVE uses a combination of distributed cloud storage and distributed cloud computations to provide a platform that is both rapid and responsive to support the growing and increasingly diverse scientific and regulatory needs of FDA scientists in their evaluation of NGS in research and ultimately for evaluation of NGS data in regulatory submissions.

The legal and ethical concerns that arise from using complex predictive analytics in health care.

Predictive analytics, or the use of electronic algorithms to forecast future events in real time, makes it possible to harness the power of big data to improve the health of patients and lower the cost of health care. However, this opportunity raises policy, ethical, and legal challenges. In this article we analyze the major challenges to implementing predictive analytics in health care settings and make broad recommendations for overcoming challenges raised in the four phases of the life cycle of a predictive analytics model: acquiring data to build the model, building and validating it, testing it in real-world settings, and disseminating and using it more broadly. For instance, we recommend that model developers implement governance structures that include patients and other stakeholders starting in the earliest phases of development. In addition, developers should be allowed to use already collected patient data without explicit consent, provided that they comply with federal regulations regarding research on human subjects and the privacy of health information.

[Use of routine data from statutory health insurances for federal health monitoring purposes]. / Nutzungsmöglichkeiten von Routinedaten der Gesetzlichen Krankenversicherung in der Gesundheitsberichterstattung des Bundes.

Federal health monitoring deals with the state of health and the health-related behavior of populations and is used to inform politics. To date, the routine data from statutory health insurances (SHI) have rarely been used for federal health monitoring purposes. SHI routine data enable analyses of disease frequency, risk factors, the course of the disease, the utilization of medical services, and mortality rates. The advantages offered by SHI routine data regarding federal health monitoring are the intersectoral perspective and the nearly complete absence of recall and selection bias in the respective population. Further, the large sample sizes and the continuous collection of the data allow reliable descriptions of the state of health of the insurants, even in cases of multiple stratification. These advantages have to be weighed against disadvantages linked to the claims nature of the data and the high administrative hurdles when requesting the use of SHI routine data. Particularly in view of the improved availability of data from all SHI insurants for research institutions in the context of the "health-care structure law", SHI routine data are an interesting data source for federal health monitoring purposes.

Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

Proposal for a data publication and citation framework when sharing biomedical research resources.

Research data and biospecimen repositories are valuable resources for biomedical investigators. Sharing these resources has great potential benefits including efficient use of resources, avoiding duplicate experiments, gathering adequate sample sizes, and promoting collaboration. However, concerns from data producers about difficulties of getting proper acknowledgement for their data contributions are increasingly becoming obstacles for efficient and large-scale data sharing in reality. In this research project we analyzed the inadequacy of current policy-based solution for promoting data sharing. The recommendations in this paper emphasize data publication and citation. This project aims to promote the acknowledgement of data contributors with realizable informatics tools that augment informal policy-level strategies, and do so in a way that promotes data sharing.

The moral from Sorrell: educate, don't legislate.

This Article argues that in response to the United States Supreme Court's 2011 decision in Sorrell v. IMS Health Inc., state legislators should refrain from enacting prescription confidentiality laws and instead implement policies supporting academic detailing, a form of continuing medical education in which trained health professionals such as physicians, registered nurses, advanced practice nurses, and pharmacists provide evidence-based information about prescription drugs to prescribers. According to Sorrell, pharmaceutical companies may freely use physicians' prescribing data to better promote, or "detail," products to physicians without government interference. While pharmaceutical companies may profit from detailing drugs to physicians, detailing increases health care costs for patients and negatively affects patient health outcomes. These problems motivated Maine, New Hampshire, and Vermont to enact prescription confidentiality laws that banned the use of information about the prescribing habits of physicians to help market drugs to physicians. Recent state attempts to stop drug detailing to physicians have been found to violate the First Amendment. This Article provides a history and background on the pharmaceutical-detailing process and analyzes recent legal decisions relating to prescription confidentiality. It concludes that academic detailing is a viable solution to the negative effects of pharmaceutical detailing and is consistent with the First Amendment.