Skip to main content
SpringerLink
Log in

Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies

  • Special focus: Governance of Nanobiotechnology
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health & Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bainbridge WS (2002) Public attitudes toward nanotechnology. J Nanopart Res 4:561–570

    Article  Google Scholar 

  • Bawa R (2010) Regulating nanomedicine—Can the FDA handle it? Raj Bawa Biotechnology Consulting LLC. www.medical.wesrch.com/User_images/Pdf/XXF_1278627200.pdf. Accessed 2 Oct 2010

  • Bawa R, Johnson S (2008) Emerging issues in nanomedicine and ethics. In: Allhoff F, Lin P (eds) Nanotechnology & society: current and emerging ethical issues. Springer, Dordrecht, pp 207–223

    Google Scholar 

  • Beach JE (1999) Restructuring of the RAC. Food Drug Law J 54:49–53

    CAS  Google Scholar 

  • Bereano PL (1984) Institutional biosafety committees and the inadequacies of risk regulation. Sci Tech Hum Values 9:16–34

    Google Scholar 

  • Chan VS (2006) Nanomedicine: an unresolved regulatory issue. Regul Toxicol Pharm 46:218–224

    Article  CAS  Google Scholar 

  • Charrow R (2007) Symposium: censorship and institutional review board: protection of human subjects: is expansive regulation counter-productive? Northwest Univ Law Rev 101:707–721

    Google Scholar 

  • Christian MC, Goldberg J, Killen J, Abrams J, McCabe M, Mauer J, Wittes R (2002) A central institutional review board for multi-institutional trials. N Engl J Med 346:1405–1408

    Article  Google Scholar 

  • Code of Federal Regulations (1974) 29 C.F.R. part 1910

  • Code of Federal Regulations (1981) 21 C.F.R. parts 50, 56

  • Code of Federal Regulations (1991) 45 C.F.R. part 46

  • Cohen J (2006) Checking the box. HRPP Blog. hrpp.blogspot.com/2006/02/checking-box.html. Accessed 27 Dec 2010

  • Davies JC (2009) Oversight of next generation nanotechnology. www.nanotechproject.org/process/assets/files/7316/pen-18.pdf. Accessed 9 Dec 2010

  • Department of Health and Human Services (DHHS) (2009) Approaches to safe nanotechnology: managing the health and safety concerns associated with engineered nanomaterials. DHHS (NIOSH) Pub. No. 2009-125. www.cdc.gov/niosh/docs/2009-125/pdfs/2009-125.pdf. Accessed 3 Apr 2010

  • Department of Health and Human Services (DHHS), National Institutes of Health (NIH), Office of Biotechnology Activities (OBA) (2010) Recombinant DNA research: proposed actions under the NIH guidelines for research involving recombinant DNA molecules (NIH Guidelines). Federal Register 75:21,008-21,010

  • Department of Health and Human Services (DHHS), National Science Advisory Board for Biosecurity (NSABB) (2010) Addressing biosecurity concerns related to synthetic biology, draft report. oba.od.nih.gov/biosecurity/pdf/NSABB%20SynBio%20DRAFT%20Report-FINAL%20(2)_5-21-10.pdf. Accessed 30 Aug 2010

  • Department of Health and Human Services (DHHS), Office for Human Research Protections (OHRP) (2010) What research does the Federalwide Assurance (FWA) cover? www.answers.hhs.gov/ohrp/questions/7143. Accessed 4 Jan 2011

  • DeVille KA (2008) Regulation and medical use of nanotechnology. In: Jotterand F (ed) Emerging conceptual ethical and policy issues in bionanotechnology. Springer, Dordrecht, pp 181–200

    Chapter  Google Scholar 

  • Drazen JM, Wood AJ (2010) Don’t mess with the DSMB. N Engl J Med 363:477–478

    Article  CAS  Google Scholar 

  • Edgar H, Rothman DJ (1995) The Institutional Review Board and beyond: future challenges to the ethics of human experimentation. Milbank Q 73:489–506

    Article  CAS  Google Scholar 

  • Environmental Protection Agency (EPA) (2009) Nanomaterial research strategy. Office of Research and Development. www.epa.gov/nanoscience/files/nanotechresearch_strategy_final.pdf. Accessed 20 Jan 2010

  • Environmental Protection Agency (EPA) (2010) Expanded protections for subjects in human studies research. www.epa.gov/oppfead1/guidance/human-test.htm. Accessed 28 Aug 2010

  • Fadeel B, Garcia-Bennett AE (2009) Better safe than sorry: understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical application. Adv Drug Deliv Rev 62:362–374

    Article  Google Scholar 

  • Faunce T, Shats K (2007) Researching safety and cost-effectiveness in the life cycle of nanomedicine. J Law Med 15:128–135

    Google Scholar 

  • Food and Drug Administration (FDA) (2001) PHS guideline on infectious disease issues in xenotranplantation. OMB Control No. 0910-0456. www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Xenotransplantation/UCM092858.pdf. Accessed 8 Sep 2010

  • Food and Drug Administration (FDA) (2006) Using a centralized IRB review process in multicenter clinical trials. www.fda.gov/RegulatoryInformation/Guidances/ucm127004.htm. Accessed 1 Dec 2010

  • Food and Drug Administration (FDA) (2010) Reporting format for nanotechnology-related information in CMC review. Center for Drug Evaluation and Research: Mapp 5015.9. www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/UCM214304.pdf. Accessed 29 Aug 2010

  • Gile TJ (2010) Complete guide to laboratory safety, 3rd edn. HCPro, Marblehead

    Google Scholar 

  • Glasser SP, Williams OD (2008) Data Safety and Monitoring Boards (DSMBs). In: Glasser SP (ed) Essentials of clinical research. Springer, Berlin, pp 151–158

    Chapter  Google Scholar 

  • Goodman SN (2007) Stopping at nothing? Some dilemmas of data monitoring in clinical trials. Ann Intern Med 146(12):882–887

    Google Scholar 

  • Gordon VM, Sugarman J, Kass N (1998) Toward a more comprehensive approach to protecting human subjects: the interface of Data Safety Monitoring Boards and Institutional Review Boards in randomized clinical trials. IRB 20(1):1–5

    Article  Google Scholar 

  • Grizzle WE, Bell WC, Fredenburgh J (2010) General considerations concerning safety in biomedical research laboratories. In: Patrinos G, Ansorge W (eds) Molecular diagnostics, 2nd edn. Elsevier, London, pp 563–572

    Chapter  Google Scholar 

  • Hansen SF (2010) Multicriteria mapping of stakeholder preference in regulating nanotechnology. J Nanopart Res 12:1959–1970

    Article  Google Scholar 

  • Harris S (2009) The regulation of nanomedicine: will the existing regulatory scheme of the FDA suffice? Richmond J Law Technol 17(2):1–25

    Google Scholar 

  • Hoeltge GA (2001) Laboratory safety. In: McClatchey KD (ed) Clinical laboratory medicine, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 78–96

    Google Scholar 

  • Hoet P, Legiest B, Geys J, Nemery B (2009) Do nanomedicines require novel safety assessments to ensure their safety for long-term human use? Drug Saf 32(8):625–636

    Article  CAS  Google Scholar 

  • Hoffman S (2001) Continued concern: human subject protection, the Institutional Review Board, and continuing review. Tenn Law Rev 68:725–770

    CAS  Google Scholar 

  • Hook CC, DiMagno EP, Tefferi A (2004) Primer on medical genomics Part XIII: ethical and regulatory issues. Mayo Clin Proc 79:645–650

    Article  Google Scholar 

  • Institute of Medicine (IOM) (2001) Preserving public trust: accreditation and human research participant protection programs. www.nap.edu/catalog.php?record_id=10085. Accessed 7 Dec 2010

  • Institute of Medicine (IOM) (2002) Responsible research: a systems approach to protecting research participants. www.nap.edu/catalog.php?record_id=10508. Accessed 7 Dec 2010

  • Jastone LO (2006) Federal protection for human subjects research. Novinka, New York

    Google Scholar 

  • Kessler D, Siegel J, Noguchi P, Zoon K, Feiden K, Woodcock J (1993) Regulation of somatic-cell therapy and gene therapy by the Food and Drug Administration. New Eng J Med 329:1169–1173

    Article  CAS  Google Scholar 

  • Kimmelman J (2005) Medical research, risk, and bystanders. IRB 27(4):1–6

    Article  Google Scholar 

  • King NMP (2002) RAC oversight of gene transfer research: a model worth extending? J Law Med Ethics 30:381–389

    Article  Google Scholar 

  • Klein LW, Miller DL, Balter S, Laskey W, Haines D, Norbash A, Mauro MA, Goldstein J (2009) Occupational health hazards in intervention laboratory: time for a safer environment. J Vasc Interv Radiol 20(7S):S278–S283

    Google Scholar 

  • Krimsky S, Ozonoff D (1979) Recombinant DNA research: the scope and limits of regulation. Am J Pub Health 69(12):1252–1259

    Article  CAS  Google Scholar 

  • Lawrenz F, Sobotka S (2008) Empirical analysis of current approaches to incidental findings. J Law Med Ethics 36(2):249–255

    Article  Google Scholar 

  • Lenk C, Biller-Andorno N (2007) Nanomedicine: emerging or re-emerging ethical issues? A discussion of four ethical themes. Med Health Care Philos 10:173–184

    Article  Google Scholar 

  • Levine C, Caplan AL (1986) Beyond localism: a proposal for a national research review board. IRB 8(2):7–9

    Article  Google Scholar 

  • Levine C, Faden R, Grady C, Hammerschmidt D, Eckenwiler L, Sugarman J (2004) “Special scrutiny”: a targeted form of research protocol review. Ann Int Med 140:220–223

    Google Scholar 

  • Lo B, Grady D (2009) Strengthening Institutional Review Board review of highly innovative interventions in clinical trials. JAMA 302(24):2697–2698

    Article  CAS  Google Scholar 

  • McLemore MR (2006) The role of the data safety monitoring board: why was the Avastin Phase III clinical trial stopped? Clin J Oncol Nurs 10(2):153–154

    Article  Google Scholar 

  • McWilliams R, Hoover-Fong J, Hamosh A, Beck S, Beaty T, Cutting G (2003) Problematic variation in local institutional review of multicenter genetic epidemiology study. JAMA 290(3):360–366

    Article  Google Scholar 

  • Morse MA, Califf RM, Sugarman J (2001) Monitoring and ensuring safety during clinical research. JAMA 285(9):1201–1205

    Article  CAS  Google Scholar 

  • National conference on alternative IRB models: optimizing human subject protection (2006). www.aamc.org/download/75240/data/irbconf06rpt.pdf. Accessed 4 Jan 2011

  • National Institutes of Health (NIH) (2009) NIH guidelines for research involving recombinant DNA molecules (NIH Guidelines). oba.od.nih.gov/oba/rac/guidelines_02/NIH_Gdlnes_lnk_2002z.pdf. Accessed 29 Aug 2010

  • National Nanotechnology Initiative (NNI) (2010) FAQs: nanotechnology. www.nano.gov/html/facts/faqs.html. Accessed 28 Aug 2010

  • Occupational Safety & Health Administration (OSHA) (2010) Laboratories. www.osha.gov/SLTC/laboratories/index.html. Accessed 4 Jan 2011

  • Office for Human Research Protections (OHRP) (2005) Special protections for children as research subjects. www.hhs.gov/ohrp/children/guidance_407process.html. Accessed 7 Sep 2010

  • Office for Human Research Protections (OHRP) (2009) Assurances. www.hhs.gov/ohrp/assurances/assurances_index.html. Accessed 10 Oct 2010

  • Office for Human Research Protections (OHRP) (2010) Use of a centralized Institutional Review Board (IRB) (2010). www.hhs.gov/ohrp/policy/correspond/CIRB20100430.html. Accessed 1 Dec 2010

  • Office of Biotechnology Activities (OBA) (2010) Institutional Biosafety Committees. www.oba.od.nih.gov/rdna_ibc/ibc.html. Accessed 8 Dec 2010

  • Office of Protection from Research Risks (OPRR) (1996) OPRR reports. www.hhs.gov/ohrp/humansubjects/guidance/hsdc97-01.htm. Accessed 30 Nov 2010

  • Ogren MP (2003) An accident waiting to happen? Scientist 17(2):30

    Google Scholar 

  • Paradise J, Wolf SM, Kuzma J, Ramachandran G, Kokkoli E (2009) Symposium introduction: the challenge of developing oversight approaches to nanobiotechnology. J Law Med Ethics 37(4):543–545

    Article  Google Scholar 

  • Race MS, Hammond E (2008) An evaluation of the role and effectiveness of Institutional Biosafety Committees in providing oversight and security at biocontainment laboratories. Biosec Bioterror Biodef Strat Pract Sci 6(1):19–35

    Article  Google Scholar 

  • Ramachandran G et al (2010) Recommendations for oversight of nanobiotechnology: dynamic oversight for complex and convergent technology. J Nanopart Res. doi:10.1007/s11051-011-0233-2

  • Resnik DB, Tinkle SS (2007) Ethics in nanomedicine. Nanomedicine 2(3):345–350

    Article  Google Scholar 

  • Shweder RA (2006) Protecting human subjects and preserving academic freedom: prospects at the University of Chicago. Am Ethnol 33(4):507–518

    Article  Google Scholar 

  • Staggers N, McCasky T, Brazelton N, Kennedy R (2008) Nanotechnology: the coming revolution and its implication for consumers, clinicians, and informants. Nurs Outlook 56(5):268–274

    Article  Google Scholar 

  • Sydes MR, Spiegelhalter D, Altman D, Babiker A, Parmar M (2004) Systematic qualitative review of the literature on data monitoring committees for randomized controlled trials. Clin Trials 1:60–79

    Article  Google Scholar 

  • The Sunshine Project (2004) Mandate for failure: the state of Institutional Biosafety Committees in an age of biological weapons research. www.sunshine-project.org/biodefense/tspibc.pdf. Accessed 8 Dec 2010

  • U.S. Code Service (1993) 42 U.S.C.S. §289g-1

  • Virdi J (2008) Bridging the knowledge gap: examining potential limits in nanomedicine. Spontaneous Gener 2(1):25–44

    Google Scholar 

  • Wagner V, Dullaart A, Boek AK, Zweck A (2006) The emerging nanomedicine landscape. Nat Biotechnol 24:1211–1217

    Article  CAS  Google Scholar 

  • Woodward B (1999) Challenges to human subjects protections in US medical research. JAMA 282:1947–1952

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Preparation of this article was supported in part by National Science Foundation (NSF) grant #SES-0608791 on “NIRT: Evaluating Oversight Models for Active Nanostructures and Nanosystems: Learning from Past Technologies in a Societal Context” (Susan M. Wolf, PI; Efrosini Kokkoli, Jennifer Kuzma, Jordan Paradise, Gurumurthy Ramachandran, Co-PIs) and by National Institutes of Health (NIH), National Human Genome Research Institute (NHGRI) grant #1RC-1HG005338-01 on “Nanodiagnostics and Nanotherapeutics: Building Research Ethics and Oversight” (Susan M. Wolf, PI; Ralph Hall, Jeffrey Kahn, Jeffrey McCullough, Co-Is). All views expressed in this article are those of the authors and not necessarily the views of NSF, NIH, or NHGRI. Thanks for helpful discussion to members of the NIH-funded project who participated in discussion of exceptional oversight, including Linda Hogle, Jeff Kahn, George Khushf, Nancy King, Gary Marchant, and Andrea Mosher. Thanks also to Moira Keane for helpful comments.

Author information

Authors and Affiliations

  1. Consortium on Law and Values in Health, Environment & the Life Sciences, Law School, Medical School, Center for Bioethics, University of Minnesota, Minneapolis, MN, 55455, USA

    Susan M. Wolf

  2. University of Minnesota Law School, Minneapolis, MN, 55455, USA

    Cortney M. Jones

Authors
  1. Susan M. Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cortney M. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susan M. Wolf.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wolf, S.M., Jones, C.M. Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies. J Nanopart Res 13, 1449–1465 (2011). https://doi.org/10.1007/s11051-011-0237-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11051-011-0237-y

Keywords

Search

Navigation