Recommendations for Nanomedicine Human Subjects Research Oversight: An Evolutionary Approach for an Emerging Field

Abstract

The nanomedicine field is fast evolving toward complex, “active,” and interactive formulations. Like many emerging technologies, nanomedicine raises questions of how human subjects research (HSR) should be conducted and the adequacy of current oversight, as well as how to integrate concerns over occupational, bystander, and environmental exposures. The history of oversight for HSR investigating emerging technologies is a patchwork quilt without systematic justification of when ordinary oversight for HSR is enough versus when added oversight is warranted. Nanomedicine HSR provides an occasion to think systematically about appropriate oversight, especially early in the evolution of a technology, when hazard and risk information may remain incomplete. This paper presents the consensus recommendations of a multidisciplinary, NIH-funded project group, to ensure a science-based and ethically informed approach to HSR issues in nanomedicine, and integrate HSR analysis with analysis of occupational, bystander, and environmental concerns. We recommend creating two bodies, an interagency Human Subjects Research in Nanomedicine (HSR/N) Working Group and a Secretary’s Advisory Committee on Nanomedicine (SAC/N). HSR/N and SAC/N should perform 3 primary functions: (1) analysis of the attributes and subsets of nanomedicine interventions that raise HSR challenges and current gaps in oversight; (2) providing advice to relevant agencies and institutional bodies on the HSR issues, as well as federal and federal-institutional coordination; and (3) gathering and analyzing information on HSR issues as they emerge in nanomedicine. HSR/N and SAC/N will create a home for HSR analysis and coordination in DHHS (the key agency for relevant HSR oversight), optimize federal and institutional approaches, and allow HSR review to evolve with greater knowledge about nanomedicine interventions and greater clarity about attributes of concern.

Clinical Translation and Regulations of Theranostics

“…Additional oversight measures have been proposed by Susan Wolfe and members of two work groups convened to evalulate potential oversight models for nanostructures and nanosystems [9,16]. The first, in 2009, proposed an oversight structure similar to the one now in place for gene therapy, including oversight by the FDA, Office of Human Research Protection (OHRP), NIH, and local institutional and Institutional Review Board (IRB) review.…”

“…Suggestions for oversight include a suggestion that the private market and manufacturers should be responsible for risk management (although this is complicated due to the current lack of long-term data), an agreement about the acceptable level of risk, and what would trigger additional precautions [15]. The FDA plans to review nanotechnology products according to existing regulations and guidance for drugs and devices, although applications must include specific information about the nanoconstruct, including particle type and size, agglomeration, solubility, and surface properties [9].…”

“…The second proposal is based on the results of a larger working group, which met at the University of Minnesota in 2012 [9]. The consensus again was that additional oversight was needed, but a slightly different solution was proposed and was based on the noted deficiencies in the human subject research oversight system as it currently exists and the difficulty in keeping pace with increasingly complex science.…”

“…The "unknowns" of nanotheranostics may apply to cancer theranostics in general. These include an incomplete understanding of the properties of nanomaterial, the effect on cellular and biological behaviors, duration of effect, biodistribution, ability to cross the blood-brain barrier, questions about clearance, and long-term reproductive, carcinogenic, and immune effects [9].…”

Stakeholder Views on Participant Selection for First-in-Human Trials in Cancer Nanomedicine

“…They provide efficient drug delivery mechanisms and platforms, with better targeting to disease lesions and delivery of higher concentrations of drugs at desired sites, thus improving drug efficiency and reducing side effects 26,27 . Though nanotechnology-based diagnostic and therapeutic interventions are expected to revolutionize the understanding of disease mechanisms and the ability to treat or cure diseases, significant concerns and uncertainties also pertain to the risks and harms caused by nanoparticles to humans and the environment 28 . That tension between immense hope and hype about the potential of nanotechnology in medicine, and the fear and reluctance attributable to its feared toxicity makes nanotechnology an interesting case study, especially to discuss the challenges it poses in translational research.…”