Nanomedicine has the potential to transform medical therapy and diagnosis. Its technologies predict improved drug delivery systems with site-specific treatment, precise new surgical techniques that would reduce patient trauma and treatment cause, and even cellular repair that would make age-related conditions such as Alzheimer’s disease a thing of the past. Currently, nanomedicine products are reaching the world market with an annual growth rate of twenty-five percent. However, like any emerging new technology, along with doomsday scenarios of nanoparticles gone amuck, nanomedicine (...) raises serious ethical, moral, and social issues that may potentially limit its technological developments. In this essay, I briefly evaluate some of these issues, and argue that ethical and epistemic issues should be considered prior to research and development. By examining three crucial epistemic challenges in nanomedicine—toxicity, nanodrugs and drug delivery systems, and clinical trials—I argue that by implementing a multi-criterion decision analysis framework as outlined by Linkov, Satterstorm and Corey, these challenges can bridge the knowledge gap between R&D and the introduction of nanomedicine technologies into the market. (shrink)

Although applications are being developed and have reached the market, nanopharmacy to date is generally still conceived as an emerging technology. Its concept is ill-defined. Nanopharmacy can also be construed as a converging technology, which combines features of multiple technologies, ranging from nanotechnology to medicine and ICT. It is still debated whether its features give rise to new ethical issues or that issues associated with nanopharma are merely an extension of existing issues in the underlying fields. We argue here that, (...) regardless of the alleged newness of the ethical issues involved, developments occasioned by technological advances affect the roles played by stakeholders in the field of nanopharmacy to such an extent that this calls for a different approach to responsible innovation in this field. Specific features associated with nanopharmacy itself and features introduced to the associated converging technologies- bring about a shift in the roles of stakeholders that call for a different approach to responsibility. We suggest that Value Sensitive Design is a suitable framework to involve stakeholders in addressing moral issues responsibly at an early stage of development of new nanopharmaceuticals. (shrink)

ABSTRACT Nanotechnologies are an expression of the human ability to control and manipulate matter on a very small scale. Their use will enable an even and constant monitoring of human organisms, in a new and perhaps less invasive way. Debates at all levels – national, European and international – have pointed out the common difficulty of giving a complete, clear definition of nanotechnologies. This is primarily due to the variety of their components, to the fact that there is not just (...) one technology but several. The most significant medical applications of nanotechnologies are in the diagnostic and the therapeutic fields, eg biosensors and molecular imaging, providing diagnosis and drug delivery with no invasive methods involved. Like any other emerging field, such technologies imply new possibilities for improving health but, on the other hand, they are still at an experimental stage and therefore should be implemented under rigorous safety testing before going on general release. For this purpose, the ethical, legal and social implications (ELSI) of nanotechnologies have been elaborated by study groups, in order to develop solutions before the results of the tests are diffused into medical practice. The aim of this paper is to define some of the ethical issues concerning biomedical applications and to evaluate whether there is a need for new or additional guidelines and regulations. (shrink)

Risk–benefit assessment is a routine requirement for research ethics committees that review and oversee biomedical research with human subjects. Nevertheless, it remains unclear how to weigh and balance risks to research participants against the social benefits that flow from generating biomedical knowledge. In this article, we address the question of whether there are any reasonable criteria for defining the limit of permissible risks to individuals who provide informed consent for research participation. We argue against any a priori limit to permissible (...) research risks. However, attention to the uncertainty of potential social benefit that can be derived from any particular study warrants caution in exposing prospective research participants to a substantial likelihood of serious harm. (shrink)

Nanomedicine plays a prominent role among emerging technologies. The spectrum of potential applications is as broad as it is promising. It includes the use of nanoparticles and nanodevices for diagnostics, targeted drug delivery in the human body, the production of new therapeutic materials as well as nanorobots or nanoprotheses. Funding agencies are investing large sums in the development of this area, among them the European Commission, which has launched a large network for life-sciences related nanotechnology. At the same time government (...) agencies as well as the private sector are putting forward reports of working groups that have looked into the promises and risks of these developments. This paper will begin with an introduction to the central ethical themes as identified by selected reports from Europe and beyond. In a next step, it will analyse the most frequently invoked ethical concerns–risk assessment and management, the issues of human identity and enhancement, possible implications for civil liberties (e.g. nanodevices that might be used for covert surveillance), and concerns about equity and fair access. Although it seems that the main ethical issues are not unique to nanotechnologies, the conclusion will argue against shrugging them off as non-specific items that have been considered before in the context of other biomedical technologies, such as gene therapy or xenotransplantation. Rather, the paper will call on ethicists to help foster a rational, fair and participatory discourse on the different potential applications of nanotechnologies in medicine, which can form the basis for informed and responsible societal and political decisions. (shrink)

Clinical gene transfer research has both a unique history and a complex and layered system of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee. This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RAC's oversight is a useful model that should be reproduced for other similar areas of clinical research.Clinical GTR is governed by the same (...) oversight system as most clinical trials, with a significant addition: the RAC. Like other research with human subjects, GTR, if it is affiliated with a federally funded institution, must be approved by an institutional review board whose activities are governed by the common rule, that is, the federal regulations for protection of human subjects in research. Like other research intended to produce a drug, device, or biologic to be marketed in the United States, GTR is also overseen by the Food and Drug Administration. (shrink)

: Despite its mandate on minimizing harms in clinical trials, the Common Rule provides little guidance as to how IRBs should evaluate risk. The Common Rule and derivative commentaries tend to conceptualize risk review as an expert-based endeavor aimed at an objective and universal evaluation of possible harm; they also have tended to locate risk in the research activity itself rather than in the context of the research. These views of risk conflict with scholarship showing that risk evaluations are socially (...) determined even among experts, that the context of harms can influence how persons evaluate risks, and that forums that approach risk assessment as a technical endeavor bracket from discussion the numerous values that ground risk judgments. Possible reforms are proposed for clinical trial risk review that would render it more inclusive of the different types of risks encountered and more attuned to the priorities of trial subjects. (shrink)

The Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products recently issued documents encouraging sponsors to consider microdose testing before launching Phase I trials, and many commentators predict that such methodologies will be applied more routinely in drug development. However, exploratory testing has provoked several ethical criticisms. Skeptics question the value and validity of microdose trials, and whether they present a reasonable balance of risks and benefits for subjects. Another major criticism is that such studies (...) serve mainly commercial ends. The present article explores these and other ethical concerns for studies conducted in the oncology setting. It concludes that microdosing is not inconsistent with prevailing practices in Phase I research, and that in principle, such studies could strengthen the ethical basis for Phase I trials by providing them better evidentiary justification. (shrink)

Many commentators have expressed concern that large investments in biomedical research over the past two decades have not been translated effectively into clinical applications. In its Critical Path Report, the Food and Drug Administration characterized the problem as a “technological disconnect between discovery and the product development process,” and documented that the number of investigational new drugs submitted to the agency had declined “significantly” since 2000. Along a similar vein, another study found that only five of 101 basic science studies (...) showing significant therapeutic promise were successfully translated into clinical applications.This perceived translational lag is stimulating a shift toward human testing of study interventions earlier in the drug development process. One indication of this trend is a recent guidance encouraging sponsors to pursue human “exploratory” studies before embarking on phase I trials. (shrink)

Developments in the last several years have sparked renewed interest in the ethics of research involving humans. Issues relating to the global extent of research and its guiding principles are of particular importance to researchers, health officials, and individual ethics committees who want a deeper and more encompassing inquire regarding the foundation and evolution of human research. This department of CQ launches a long overdue effort to explore these wider issues. Readers are invited to submit papers to Charles MacKay, 5011 (...) Worthington Drive, Bethesda, MD 20816, USA. E-mail: [email protected]. a. (shrink)

First-in-human clinical trials represent a critical juncture in the translation of laboratory discoveries. However, because they involve the greatest degree of uncertainty at any point in the drug development process, their initiation is beset by a series of nettlesome ethical questions [1]: has clinical promise been sufficiently demonstrated in animals? Should trial access be restricted to patients with refractory disease? Should trials be viewed as therapeutic? Have researchers adequately minimized risks? The resolution of such ethical questions inevitably turns on claims (...) about future events like harms, therapeutic response, and clinical translation. Recurrent failures in clinical translation, like Eli Lilly's Alzheimer candidate semagacestat, highlight the severe limitations of current methods of prediction. In this case, patients in the active arm of the placebo-controlled trial had earlier onset of dementia and elevated rates of skin cancer [2]. Various authoritative accounts of human research ethics state that decision-making about risk and benefit should be careful, systematic, and non-arbitrary [3]–[5]. Yet, these sources provide little guidance about what kinds of evidence stakeholders should use to ensure their estimates of such events ground responsible ethical decisions. In this article, we suggest that investigators, oversight bodies, and sponsors often base their predictions on a flawed and inappropriately narrow preclinical evidence base. (shrink)

Nanotechnology, as with many technologies before it, places a strain on existing legislation and poses a challenge to all administrative agencies tasked with regulating technology-based products. It is easy to see how statutory schemes become outdated, as our ability to understand and affect the world progresses. In this article, we address the regulatory problems that nanotechnology posses for the Food and Drug Administration’s (FDA) classification structure for ‘‘drugs’’ and ‘‘devices.’’ The last major modification to these terms was in 1976, with (...) the enactment of the Medical Device Amendments. There are serious practical differences for a classification as a drug or device in terms of time to market and research. Drugs are classified, primarily, as acting by ‘‘chemical action.’’ We lay out some legal, philosophic, and scientific tools that serve to provide a useful, as well as legally and scientifically faithful, distinction between drugs and devices for the purpose of regulatory classification. These issues we raise are worth the consideration of anyone who is interested in the regulation of nano-products or other novel technologies. (shrink)

The risks to groups posed by research involving human beings—including genetics research—should be conceived of as a species of third-party risks. The important task of protecting third parties from the risks posed by the conduct and the findings of research should not be assigned to IRBs because they are not designed or equipped to handle such a broad responsibility. The serious problems raised by third-party risks require an integration of policy-making and regulation that is beyond the scope and competence of (...) IRBs. (shrink)