By Melinda Young, Author

The human research protection community recently learned of a troubling clinical trial that involved private funding, a U.S. medical college researcher who died this summer, and a study held on a Caribbean island.

The troubling part is that the clinical trial was for a live attenuated herpes simplex virus-2 (HSV-2) vaccine injected in human participants, and it was never reviewed by an IRB.

“I have to admit, this is very shocking,” says Brenda Curtis, PhD, MSPH, an IRB member and researcher, as well as an assistant professor in the department of psychiatry at Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

It’s standard practice for university-affiliated researchers to obtain IRB approval — even for research that is privately funded. Researchers can go through their own institution’s IRB review process, or seek an IRB’s approval in the nation where the research is being conducted.

Neither happened in the case of the herpes vaccine trial, which was conducted by Rational Vaccines of Springfield, IL, and William Halford, PhD, a professor at Southern Illinois University (SIU) School of Medicine in Springfield. Halford and Agustin Fernandez III co-founded Rational Vaccines in 2015. Halford conducted the herpes clinical trial in 2016, and died in June 2017 from a rare cancer.

Halford brought study participants to the island of St. Kitts, where they were injected with the investigational vaccine. It’s unclear whether the participants gave informed consent. Rational Vaccines did not respond to repeated requests for an interview, but Fernandez has written about the vaccine trial on his Facebook page, saying that it is about patients being able to take healthcare into their own hands and doctors having more control than lawyers.

In a Foundation for Economic Education article link on Fernandez’s Facebook page, there is a reprinted blog entry by Halford that expressed Halford’s frustration with the FDA and federal research bureaucracy. The blog entry of July 24, 2016, reads, “…The fact that 1 million people worldwide will, this week, contract new HSV-1 or HSV-2 infections has no bearing on their standing within the machine that is the FDA … We can bitch, we can moan, or we can just say, ‘Let’s go to the other 95 percent of the world not under the FDA’s thumb and get a functional HSV vaccine out there and start helping people.’” (The article is available at: http://bit.ly/2xBXgBW.)

The idea that IRBs are major factors in research delay is not accurate, Curtis says.

“I’ve seen very detailed human subjects protocols go through the IRB in a fast-paced time because they were well-written and well-thought-out,” she says.

Protecting human lives is worth waiting an extra month or two, Curtis adds.

One study participant, Rich Mancuso, went public with his experience in the trial, saying he was recruited on Facebook and believed the vaccine stopped his severe outbreaks. On his Facebook page on April 24, 2017, Mancuso called his involvement with Rational Vaccines’ HSV-2 vaccine a “happy ending.”

This herpes vaccine case is part of a recent trend and cultural shift away from the four-decade-long focus on research participant safety, which some people believe has resulted in a loss of lives as individuals wait for new treatments and cures.

“We’re seeing a huge push from the participant rights base, and we’re seeing it through different channels,” says Elizabeth A. Buchanan, PhD, endowed chair in ethics and acting director of the office of research and sponsored programs at the University of Wisconsin-Stout in Menomonie.

Going forward, this cultural shift will involve questions about expertise and who makes decisions and who is in control of research, Buchanan says. “There’s a pushback to the FDA.”

Some people take the stand that they will not work in the system because what they’re doing is for the betterment of society, she says.

“I think it’s risky,” Buchanan says. “There is a reason there are safeguards in place, and IRBs are flexible enough, and the FDA does a very good job of approving experimental treatments.”

The bigger philosophical and ethical issue is that this is part of a shift away from the idea of an expert.

“Zero in on the social media piece,” Buchanan says.

“People recruit on Facebook, which is a very different vibe than traditional recruiting and advertising for a clinical trial,” she explains. “This is making use of all these new outlets, while capitalizing on the idea that we’re in a time of questioning authority and moving away from any acknowledgement of expertise or authority or know-how or experience.”

Some people are pushing back against the things that lead to good science, she adds.

Rational Vaccines’ vaccine trial results have not yet been published in a peer-reviewed journal, and there are some potential consequences of the company circumventing research regulations. For instance, the Ministry of Health in St. Kitts issued a news release, stating the two-island nation had not been approached about the vaccine project. The nation’s chief medical officer also said the nation plans to investigate the clinical trial. (The statement can be found at: http://bit.ly/2xU0DoA.)

When asked if SIU’s IRB, the Springfield Committee for Research Involving Human Subjects, had exempted the study from IRB review, an SIU spokesperson replied that the IRB did not make a decision on exemption because the issue was never brought to the IRB for review.

“To be clear, the IRB and the university are reviewing whether the research and any trial should have been brought to the IRB by the primary investigator, since his research was conducted by a private company, Rational Vaccines — not SIU,” says Karen Carlson, director in the office of public relations SIU School of Medicine. Carlson also says that the university is reviewing its procedures and communication with principal investigators concerning any research they perform independently from their roles as faculty members.

The medical university IRB’s policies state that it is responsible for reviewing proposed research that includes humans as subjects when the study is conducted by a member of the research institution’s faculty, staff, residents, and students.

This is a policy that many academic researchers would understand. “I have always assumed that any research I carry out, once I was a student, employee, or faculty — any research I conduct or participate in — has to be IRB-approved, even if I’m doing contract work,” Curtis says.

“I still went through my IRB, even if it’s for them to tell me I need IRB approval from some other place,” she adds. “I always assumed that’s the way to go.”

Curtis works with corporations in research projects, and they often seek review from external IRBs rather than using the local IRB.

“You send protocols to the IRB, and there’s no reason to not have it done,” she says. “It’s not like you couldn’t have gotten someone to approve your protocol.”

The Theravax HSV-2 vaccine study enrolled 20 American participants, who flew to the Federation of Saint Kitts and Nevis multiple times to receive the vaccine. Halford spent 15 years on herpes immunology research, including studies showing the safety of using a live-attenuated virus vaccine, according to “Game Changer,” an article published by the SIU.

Rational Vaccines reported that the participants were already infected with herpes. They volunteered for the study in hopes it would mitigate outbreaks of the virus and alleviate symptoms. Rational Vaccines also reported that there were no adverse effects during the trial and that the vaccine was a success.

However, there are no regulatory agencies reviewing the study’s outcomes, so it’s difficult to independently verify the company’s claims. The FDA is unlikely to approve the vaccine until it has gone through further rigorous and IRB-approved clinical trials. When asked about whether Halford had provided any information about informed consent, vulnerable populations, and adverse events to the SIU IRB after the clinical trial was completed, SIU’s Carlson answered, “No.”

“Dr. Halford did not bring any information to the IRB because this was not an SIU study,” she says.

SIU SOM issued a statement in late August, acknowledging that Rational Vaccines licensed intellectual property from SIU through SIU’s office of technology transfer. Within that license agreement, both Rational Vaccines and SIU are responsible for upholding all applicable laws and regulations associated with the license.

The statement also says that SIU is not responsible for trials and research conducted by independent companies.

“I haven’t had any communication with [Rational Vaccines],” Carlson says.

REFERENCE

  1. Sandstrom S. Game Changer: Herpes vaccine shows promise. Aspects. 2017:4(1):2-5. Available at: http://bit.ly/2yav8oJ. Accessed Oct. 10, 2017.