Digital pills for the remote monitoring of medication intake: a stakeholder analysis and assessment of marketing approval and patent granting policies.

This article explores whether 'digital pills' that track medication intake should be used to enhance adherence. We concentrate on psychiatric conditions since these pose unique challenges. We analyze two public policies that potentially encourage the development of systems for remote monitoring of intake, namely the granting of patents and marketing authorization, and identify key stakeholders and their main interests so as to discuss whether these policies provide disproportionate benefits to some. The stakeholders identified are patients, system providers, drug manufacturers, insurers or healthcare systems, physicians, data users, and society at large. We discuss relevant industry reports, regulatory data, patent documents, and academic literature, and argue that there is concern that the drivers for these tracking systems are revenue and the monitoring of 'compliance' rather than 'adherence'. While accepting that the use of these systems can be justified in some circumstances, in our view these systems pose risks to patient autonomy, Shared Decision-Making, and privacy. We also find that policies on granting patents and marketing authorization overly favor the commercial actors and put patients' interests at risk. Accordingly, we propose that additional safeguards are required.

Remote digital monitoring of medication intake: methodological, medical, ethical and legal reflections.

In 2017, regulatory approval was given in the US for a 'digital pill', a pill for which actual ingestion could be remotely monitored. The pill, Abilify Mycite is marketed by Otsuka but the monitoring system derives from Proteus Digital Health. In this paper, we focus on this digital pill and another equivalent system from AiCure which relies on facial recognition. Both systems not only remind the patient to take a pill but also verify the actual intake. In this process, patient-related data beyond the fact that the pill has been taken are also collected and sent to a remote computer system of the system-providing company and possibly to third parties.Although marketed as 'innovative', the introduction of such systems raises questions as to the limitation of patient autonomy, secondary uses of patient data, impact on the physician's liability, and artificial inflation of drug prices. Whereas incorrect medication taking can be problematic, it can be questioned whether remote intake-monitoring systems are, from an ethical, legal and social perspective, the ideal way to address this. In this paper, we will reflect on this question from the position of the different potential stakeholders involved.

Similar or the Same? Why Biosimilars are not the Solution.

Advancements in the field of biotechnology have accelerated the development of drugs that are manufactured from cultures of living cells, commonly referred to as "biologics." Due to the complexity of the production process, generic biologics are unlikely to be chemically identical to the reference product, and accordingly are referred to as "biosimilars." Encouraging the development of biosimilars has been presented as the key solution to decrease prices and increase access to biologics, but the development and use of biosimilars continues to raise problems, none of which can easily be addressed. Developing a biosimilar requires considerable time and financial resources, and legitimate safety concerns necessitate elaborate clinical testing of biosimilars. As a consequence, the introduction of biosimilars onto the market has not resulted in significant price reductions, and concerns regarding the substitution and interchangeability of original biologics with biosimilars persist. This article will explain how the biologics production process distorts the trade-offs that traditionally guided both patent protection and regulatory exclusivities: disclosure as a key condition for benefiting from the corresponding monopoly position. Hence, we propose establishing a mechanism of mandatory deposit of the original biologic's cell line at the stage of the regulatory approval as the most effective remedy.

Patenting Foundational Technologies: Lessons From CRISPR and Other Core Biotechnologies.

In 2012, a new and promising gene manipulation technique, CRISPR-Cas9, was announced that seems likely to be a foundational technique in health care and agriculture. However, patents have been granted. As with other technological developments, there are concerns of social justice regarding inequalities in access. Given the technologies' "foundational" nature and societal impact, it is vital for such concerns to be translated into workable recommendations for policymakers and legislators. Colin Farrelly has proposed a moral justification for the use of patents to speed up the arrival of technology by encouraging innovation and investment. While sympathetic to his argument, this article highlights a number of problems. By examining the role of patents in CRISPR and in two previous foundational technologies, we make some recommendations for realistic and workable guidelines for patenting and licensing.

Ethical sharing of health data in online platforms - which values should be considered?

Intensified and extensive data production and data storage are characteristics of contemporary western societies. Health data sharing is increasing with the growth of Information and Communication Technology (ICT) platforms devoted to the collection of personal health and genomic data. However, the sensitive and personal nature of health data poses ethical challenges when data is disclosed and shared even if for scientific research purposes.With this in mind, the Science and Values Working Group of the COST Action CHIP ME 'Citizen's Health through public-private Initiatives: Public health, Market and Ethical perspectives' (IS 1303) identified six core values they considered to be essential for the ethical sharing of health data using ICT platforms. We believe that using this ethical framework will promote respectful scientific practices in order to maintain individuals' trust in research.We use these values to analyse five ICT platforms and explore how emerging data sharing platforms are reconfiguring the data sharing experience from a range of perspectives. We discuss which types of values, rights and responsibilities they entail and enshrine within their philosophy or outlook on what it means to share personal health information. Through this discussion we address issues of the design and the development process of personal health data and patient-oriented infrastructures, as well as new forms of technologically-mediated empowerment.

Raising the Barriers to Access to Medicines in the Developing World - The Relentless Push for Data Exclusivity.

Since the adoption of the WTO-TRIPS Agreement in 1994, there has been significant controversy over the impact of pharmaceutical patent protection on the access to medicines in the developing world. In addition to the market exclusivity provided by patents, the pharmaceutical industry has also sought to further extend their monopolies by advocating the need for additional 'regulatory' protection for new medicines, known as data exclusivity. Data exclusivity limits the use of clinical trial data that need to be submitted to the regulatory authorities before a new drug can enter the market. For a specified period, generic competitors cannot apply for regulatory approval for equivalent drugs relying on the originator's data. As a consequence, data exclusivity lengthens the monopoly for the original drug, impairing the availability of generic drugs. This article illustrates how the pharmaceutical industry has convinced the US and the EU to impose data exclusivity on their trade partners, many of them developing countries. The key arguments formulated by the pharmaceutical industry in favor of adopting data exclusivity and their underlying ethical assumptions are described in this article, analyzed, and found to be unconvincing. Contrary to industry's arguments, it is unlikely that data exclusivity will promote innovation, especially in developing countries. Moreover, the industry's appeal to a property rights claim over clinical test data and the idea that data exclusivity can prevent the generic competitors from 'free-riding' encounters some important problems: Neither legitimize excluding all others.

Time-lapse microscopy patent upheld in Europe: response to Pearce.

In this piece, we comment on the article by Pearce earlier in this journal. As Pearce correctly points out, what is fundamentally at issue in ESHRE et al's opposition to Stanford University's European patent on time-lapse microscopy is whether an exclusion from patentability, here of methods of medical diagnosis, should be interpreted narrowly or not. In the present case, the dominant piece of case law from the European Patent Office (EPO) gives a narrow interpretation of what a method of diagnosis must be in order not to be patentable. In their submissions to the EPO, ESHRE et al. have argued that this narrow interpretation is unfounded and incorrect.

Patenting medical diagnosis methods in Europe: Stanford University and time-lapse microscopy.

In 2013, a European Patent for the technique of time-lapse microscopy was granted by the European Patent Office (EPO) to Stanford University and was subsequently opposed by Unisense FertiliTech A/S and by the European Society for Human Reproduction and Embryology (ESHRE), Sigrid Sterckx, Julian Cockbain and Guido Pennings. ESHRE et al.'s opposition was based on the argument that Stanford's patent was directed to a method of medical diagnosis, methods that are excluded from patentability by Article 53(c) of the European Patent Convention. The Opposition Division of the EPO rejected the oppositions in November 2015, and both opponents have now filed their appeals. In this paper, we comment on the Opposition Division decision and the grounds of appeal put forward by ESHRE et al.

"You hoped we would sleep walk into accepting the collection of our data": controversies surrounding the UK care.data scheme and their wider relevance for biomedical research.

An 'Information Centre' has recently been established by law which has the power to collect, collate and provide access to the medical information for all patients treated by the National Health Service in England, whether in hospitals or by General Practitioners. This so-called 'care.data' scheme has given rise to major and ongoing controversies. We will sketch the background of the scheme and look at the responses it has elicited from citizens and medical professionals. In Autumn 2013, NHS England set up a care.data website where citizens could record their concerns regarding the collection of health-related data by the Information Centre. We have reviewed all the comments on this website up until June 2015. We have also analysed the readers' comments on the coverage of the care.data scheme in one of the main national UK newspapers. When discussing the responses of citizens, we will make a distinction between the problems that citizens detect and the solutions they propose. The solutions that are being perceived as the most relevant ones can be summarized as follows: citizens wish to further the common good without being manipulated into doing it, while at the same time being safeguarded against various abuses. The issue of trust turns out to figure prominently. Our analysis of reactions to the scheme in no way pretends to be exhaustive, yet it provides various relevant insights into the concerns identified by citizens as well as medical professionals. These concerns, moreover, have a more general relevance in relation to other contexts of medical data-mining as well as biobank research. Our analysis also offers important pointers as to how those concerns might be addressed.

The UK National Health Service's 'innovation agenda': lessons on commercialisation and trust.

The UK National Health Service (the 'NHS'), encouraged by the 2011 report Innovation Health and Wealth, Accelerating Adoption and Diffusion in the NHS, and empowered by the Health and Social Care Act 2012, is in the process of adopting a new agenda for stimulating innovation in healthcare. For this, the bodies, body materials, and confidential health information of NHS patients may be co-opted. We explain why this brings the NHS into a moral conflict with its basic goal of providing a universal healthcare service. Putting NHS databases at the disposal of industry, without addressing ethical concerns regarding the privacy, autonomy, and moral integrity of patients and without requiring a 'kick-back' to enhance the service that the NHS provides, is inappropriate. As this article shows, with reference to the commercial arena of direct-to-consumer genetic testing, it is crucial that patient and public trust in the NHS is not eroded.

Patenting time-lapse microscopy: the European story.

European Patent No. 2430454 of Stanford University is open to opposition before the European Patent Office if such opposition is filed by 23 October 2013. This is the European equivalent of the US Patent that raised such controversy in this journal in August 2013 as being a patent on time. The European Patent, which is directed to a method of selecting embryos for implantation using the results of time-lapse microscopy, should, in the present authors' opinion, be revoked as being directed to a method of medical diagnosis, which is unpatentable under European patent law. The only party currently opposing Stanford's patent is a competitor, Unisense FertiliTech A/S which is itself seeking to patent similar methods in Europe; the objection that Stanford has patented a method of diagnosis has not been raised by Unisense FertiliTech. We submit that Stanford's patent should be opposed to safeguard competition and to protect the freedom to operate of clinicians. In this paper we explain how Stanford's patent should fail under European law.

"Trust is not something you can reclaim easily": patenting in the field of direct-to-consumer genetic testing.

PURPOSE: Recently, 23andMe announced that it had obtained its first patent, related to "polymorphisms associated with Parkinson's disease" (US-B-8187811). This announcement immediately sparked controversy in the community of 23andMe users and research participants, especially with regard to issues of transparency and trust. The purpose of this article was to analyze the patent portfolio of this prominent direct-to-consumer genetic testing company and discuss the potential ethical implications of patenting in this field for public participation in Web-based genetic research. METHODS: We searched the publicly accessible patent database Espacenet as well as the commercially available database Micropatent for published patents and patent applications of 23andMe. RESULTS: Six patent families were identified for 23andMe. These included patent applications related to: genetic comparisons between grandparents and grandchildren, family inheritance, genome sharing, processing data from genotyping chips, gamete donor selection based on genetic calculations, finding relatives in a database, and polymorphisms associated with Parkinson disease. CONCLUSION: An important lesson to be drawn from this ongoing controversy seems to be that any (private or public) organization involved in research that relies on human participation, whether by providing information, body material, or both, needs to be transparent, not only about its research goals but also about its strategies and policies regarding commercialization.

Are natural products and medical diagnostic tests still eligible for patents in the USA?

In 2010, the biotechnology and molecular diagnostics industries were shocked by the decision from a US District Court to the effect that isolated endogenous DNA and diagnostic tests based on newly discovered DNA sequences were not eligible for US patents. The case related to the BRCA1/2 genes for breast and ovarian cancer. On appeal, the decision was almost entirely overturned. However, in March 2012, the US Supreme Court vacated the appeal court decision and instructed the appeals court to rehear the case in the light of its very recent decision, which suggested that products of nature and their obvious uses should not be patentable. This commentary explores the points at issue.

Something more is necessary: are genes and genetic diagnostic tests statutory subject matter for US patents?

In a recent decision (AMP v. USPTO) from the US District Court, patent claims directed at DNA sequences corresponding to human genes and to diagnostic tests based on such genes have been found to be invalid, primarily on the basis that the DNA molecules claimed, which included cDNA, primers and probes, are 'products of nature' and are thus unpatentable. If upheld, this decision will have considerable impact on the ability of biotechnical companies and universities to patent the results of their research. In this article, we will explain the basis for this decision and discuss the appropriateness of patenting discoveries and their (obvious) uses in the light of this fascinating case. While our focus will primarily be on the product claims, diagnostic method claims were also revoked in AMP v. USPTO on the basis that they were for mental acts or did not involve any 'transformation of matter'. This will be discussed in the light of the recent US Supreme Court decision in Bilski v. Kappos, which focused on the patent-eligibility of process claims.