Once the stuff of sci-fi novels and movies, nanotechnology (NT) — the manipulation of matter on the tiny nanoscale — now has practical applications in everyday areas such as engineering and healthcare. NT is currently being used in clinical trials to develop diagnostic tests and targeted drug delivery devices, especially for cancer treatment, experts say.

“One of the biggest uses where nanotechnology has been introduced is in medicine,” says Gregory Nichols, MPH, CPH, program manager of Nanotechnology Studies at ORAU in Oak Ridge, TN. “There are a ton of new inventions that can really benefit society.”

Current clinical trials are looking at ways in which NT can be used to deliver chemotherapy treatments in ways that can reduce side effects or improve efficacy, says Piotr Grodzinski, PhD, director of the National Cancer Institute (NCI) Office of Cancer Nanotechnology Research in Bethesda, MD. “There are a few that are [FDA] approved,” he says. “We are also seeing more nanoparticle delivery vehicles using active targeting allowing for increased accumulation of particles and drug at the tumor site.”

While using NT in medicine to create “superhumans” is still firmly rooted in fiction, IRBs could have legitimate concerns about using nanomedicine in human subjects, Nichols says.

“One of the main problems is that not everyone in the general public knows what nanotechnology is,” he says. “It’s a pretty complicated topic: Try telling someone, ‘We’re going to take atoms and manipulate them one at a time to make a drug or a device’ — what does that mean? How do you make human subjects aware of what it really means? How will it be used, and what risk management tools will be developed to handle those issues? As nanotechnology research comes more into human subjects research, it will raise some of these questions.”

Evaluating risks

“Taking it beyond IRB, there has been discussion about whether nanotechnology needs particular attention or should be scrutinized in different ways than traditional protocols,” Grodzinski says. About eight years ago, he says, the FDA pondered whether to have a separate drug approval path for nanotechnology and nanomedicine. After public discussion, the agency determined that IND (Investigational New Drug) or IDE (Investigational Device Exemption) approvals would be the same as with any other drug or device. “The only difference is that in some cases the nanotechnology constructs are multifunctional and it’s not always clear what the final mode of action will be, and whether the product will be considered a drug or device,” he says.

While nanotechnology clinical trials don’t raise any truly unique ethical issues, there are other bioethical issues for IRBs to consider, says David Resnik, JD, MD, bioethicist and IRB chair at the National Institute for Environmental Health Sciences in Research Triangle Park, NC.

“The main IRB issue is going to be trying to get a handle on the risks of exposure to the nanotechnology drugs,” Resnik says. For instance, there are more and more applications of NT in creams and other transdermal delivery systems that would be applied topically. “Some may penetrate different areas that they were not planned to go to and could cause problems,” he says. Other NT particles could aggregate and accumulate in different areas in the body and have effects that can change their properties in unpredictable and possibly hazardous ways, he says.

Many of the issues IRBs may consider with NT protocols are ones that IRBs already face, Resnik says. “One of the things that the IRB is supposed to do is make sure the risks are minimized and reasonable in relation to the potential benefits to the subjects and the knowledge expected to be gained — the main two things you keep in mind when evaluating the risk of a study,” he says. “Another consideration is that if you think that a product is fairly high risk, there should be significant benefit to justify that risk.”

Evaluating the risks depends on the nature of the protocol and what the researcher is trying to do, he says. “If they are testing for something in the blood, there may be almost no risk at all if it’s just a blood donation,” Resnik says. “More risky is applying nanotechnology products on the skin, and most risky would be requiring that products be ingested, taken intravenously, or possibly inhaled.”

IRBs should consider not only the risks to the research subjects, but also to third parties such as family members who may come into contact with a subject, Resnik says.

“For example, suppose that a research protocol requires participants to dermally administer a nanomedicine product at home. Children in the home could come into contact with this product if it sheds, which could pose a risk to their health. Participants also might not dispose of the product properly, which could pose a risk to people in the home or contaminate the environment. Exposure could also occur when nanomedicine products are excreted (e.g., urine, breast milk),” Resnik wrote in a Journal of Law, Medicine & Ethics article on the topic. “The IRB could ensure that the protocol includes procedures for instructing participants on how to minimize identifiable third party exposures and for disposal of products containing nanomaterials.”1

A lot of clinical trials are currently being conducted and several have passed Phase I and reached Phase II or even Phase III in a few cases, Grodzinski says. “The general consensus is that these techniques can be made safe,” he says.

Informed consent issues

Informing subjects on the risks and benefits of nanomedicine clinical trials may be complicated by different biases, Resnik says. “Subjects may feel that this is something new and really great and may get more benefits than they are likely to get,” he says. “This is especially true in Phase I and Phase II studies where the study is not designed to provide benefits and is more of a risk assessment-type of testing.” The benefits of nanotechnology may be overstated or exaggerated by researchers or in the media, leading subjects to believe they will receive more benefits than anticipated in the protocol, he says.

The opposite is also possible: “Research subjects might be biased against the study from what they hear in the media and TV and movies and might think it’s more risky than it really is,” Resnik says.

NCI’s Office of Cancer Nanotechnology Research, as well as many other government agencies, provides information on the risks and benefits of nanomedicine through its Alliance for Nanotechnology in Cancer website, nano.cancer.gov, and through discussions at scientific and patient advocate meetings. “The website is designed to provide information in lay-oriented language,” Grodzinski says. “I think the topic is talked about quite a bit such that the general public is at least exposed to it.”

As far as safety concerns of future nanotechnology uses, “that discussion has its own facets well beyond the IRB,” Grodzinski says. “I think the overall conclusion is that if characterization protocols for nanomaterials are carefully implemented and evaluation of interventions for use in humans is conducted rigorously with standards similar to implementation of any other new technology, there aren’t any major concerns.”

 

Reference

  1. Resnik DB. Responsible Conduct in Nanomedicine Research: Environmental Concerns Beyond the Common Rule. J Law Med Ethics 2012;40(4):848-855. doi:10.1111/j.1748-720X.2012.00713.x.