Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine applications that includes drugs, biological products, and implantable medical devices incorporating nanoscale materials. These nanomedicine products can enable new or improved treatments and diagnostics for many diseases and disorders. Human subjects research (HSR) on nanomedicine interventions is already under way, with a number of products approved for use. Such research is subject to existing federal and institutional oversight rules and regulations, including Food and Drug Administration (FDA) rules on HSR for all FDA-regulated products and the Department of Health and Human Services (DHHS) Common Rule for HSR funded or conducted by NIH or any of the other signatory agencies. Both of these regimes require HSR protocols to obtain approval from an Institutional Review Board (IRB), based on assessment of the ethical appropriateness of research on human participants. However, some nanomedicine HSR may raise safety and ethics concerns that pose challenges to the existing system of oversight and that may merit consideration of additional oversight. The concerns that may warrant additional oversight include marked uncertainty about hazard and risk to human subjects and about occupational exposures of researchers and lab workers, exposures of bystanders such as family members, and environmental effects.
Concerns posed by some nanomedicine HSR reflect the emergence of increasingly complex, active, and interactive products. These concerns also reflect the limits of an HSR oversight system developed over 30 years ago, with widely recognized problems and limitations. We are not arguing that the ethical issues raised by nanomedicine HSR are unique to that field and arise in no other domain of HSR for emerging science and technology. To the contrary, our recommendations regarding nanomedicine HSR offer an opportunity to examine the larger issue of the adequacy of the current HSR oversight system in the face of increasingly sophisticated science and technologies.
This article presents the first published recommendations on how to comprehensively approach the challenges raised by nanomedicine research in human beings. While some nanomedicine HSR requires no extra oversight, we suggest an oversight approach that can identify research that may need extra oversight, that can structure that extra oversight in a targeted way, and that can evolve with greater knowledge about nanomedicine materials and interventions. We recommend the formation of two complementary bodies: (1) an interagency group comprised of governmental officials, and (2) a federal advisory committee comprised of outside experts and stakeholders who can offer advice in a public forum. Creation of both bodies ensures the administrative power to coordinate among agencies while also having a forum for all stakeholders.
An interagency Humans Subjects Research in Nanomedicine (HSR/N) Working Group should be established to coordinate among federal agencies and offices addressing nanomedicine HSR oversight. We suggest that this HSR/N Working Group be housed within DHHS with member representatives from federal agencies and offices that are key to nanomedicine HSR.
A Secretary's Advisory Committee on Nanomedicine (SAC/N) should additionally be established under the Federal Advisory Committee Act (FACA) to provide recommendations on sound approaches to nanomedicine human subjects research and a forum for public discussion. SAC/N may be created as a subcommittee of the Secretary's Advisory Committee on Human Research Protections (SACHRP) or as a separate body.
HSR/N and SAC/N should initially serve (1) analytical, (2) advisory, and (3) information review functions. A fourth potential function, new federal protocol-by-protocol review (as was conducted in the past, for example, in the Recombinant DNA Advisory Committee's (RAC's) review of human gene transfer protocols), does not appear to be warranted at this time.
For the purposes of nanomedicine HSR oversight and data collection, HSR/N and SAC/N in coordination with other nano-focused offices (including the Nanoscale Science, Engineering, and Technology Subcommittee (NSET) and National Nanotechnology Initiative (NNI)) should consider how best to establish an interim definition of nanomedicine, which may ultimately lead to a different approach, based on identifying key attributes of concern. Federal definitions of “nanotechnology” in general have varied, though NNI's definition focusing on functionalities engineered to emerge at dimensions of up to 100 nm has been most prominent. However, identifying “nanomedicine” products specifically for the purposes of HSR oversight raises somewhat different issues, calling for a more inclusive set of criteria in order to err on the side of capturing HSR concerns. It may be that any such definition should ultimately yield to a roster of relevant attributes of concern.1 Yet the creation of a roster of attributes of concern is difficult at present, given the state of scientific and toxicological knowledge. HSR/N and SAC/N may thus need to start with a size-based definition, in keeping with the traditional commitment of HSR review to anticipating and preventing harm to human subjects.
Upon considering the recommendations of SAC/N, HSR/N should facilitate cross-agency coordination on a Points-to-Consider document to help guide institutions and researchers crafting and overseeing protocols for nanomedicine HSR. This Points-to-Consider document should articulate what information is needed to facilitate sound, science-based analysis of ethical and safety questions. It should also provide guidance for information-gathering by institutional review bodies such as IRBs, Data and Safety Monitoring Boards (DSMBs), and committees responsible for occupational and environmental review of research protocols.
Our recommendations avoid the creation of additional regulation for nanomedicine HSR as a class. Instead we recommend establishing a means to convene and coordinate federal oversight authorities for the purposes of setting priorities, collecting information, and building infrastructure for effective oversight of nanomedicine HSR, relying on inputs from top experts in the field and key stakeholders as nanomedicine progresses to more complex, active, and interactive interventions. HSR/N and SAC/N will provide governmental and public forums to address nanomedicine HSR issues as the science and HSR challenges evolve. This flexible approach will reduce the burden on individual agencies and oversight bodies to independently develop their own analyses and data sets, by instead facilitating a coordinated process among relevant agencies, institutions, and centers. This will reduce duplication of effort, help avoid gaps in analysis and oversight, and will ensure a more science-based approach to HSR oversight, thus avoiding unnecessary impediments to innovation. This flexible and evolutionary approach to HSR oversight, including consideration of occupational, bystander, and environmental analysis, may provide a model for HSR oversight in other areas of emerging science and technology.
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