Using human beings as “guinea pigs” for unethical experiments becomes so much easier when the subjects belong to marginalized and stigmatized groups. The Food and Drug Administration (FDA) was recently informed about the testing of a naltrexone implant without clinical protections in a Louisiana Department of Public Safety and Corrections program. People of color who are addicted to drugs and incarcerated were treated much like those unfortunate laboratory animals without whom most human medications would never be developed.
The prison system was working directly with the drug developer, BioCorRx, to test the surgically implantable version of naltrexone. Neither the drug nor the trial were approved by the FDA, and Public Citizen wrote a letter of complaint to the FDA.
The FDA has approved an oral and an injectable form (Vivitrol, which is still under patent) of naltrexone to treat opioid use disorder and alcohol use disorder. Not the surgical implant.
Institutional Review Boards are an essential requirement, per the FDA, for medical testing on human subjects. In this case, there was no IRB.
The layers of stigma that made this experiment possible are instructive. It is difficult to imagine, for example, cancer patients being treated in this way, even if they were incarcerated people of color.
But the shady and exploitative procedure is far from unique.
While news outlets only picked up the story in the fall, BioCorRx itself initially announced the program in a May 2 press release. The way the press release makes it clear that the “pilot program” is meant to “demonstrate the effectiveness” of the drug showed that it was a test. Somehow, this passed through the news cycle without any notice—perhaps because reporters share similar biases to those who conducted the trial.
Filter reached out to the FDA about the case. BioCorRx is compounding the naltrexone (mixing it with other ingredients) “into a new implantable substance,” an FDA spokesperson said, noting that “compounded drugs are not FDA-approved,” which means that “they have not undergone FDA review of safety, effectiveness or manufacturing quality before they are marketed.”
The spokesperson added that compounded drugs can pose health risks. “Therefore, when an FDA-approved drug is commercially available, the FDA recommends that practitioners prescribe the FDA-approved drug rather than a compounded drug unless the prescribing practitioner has determined that a compounded product is necessary for the particular patient and would provide a significant difference for the patient as compared to the FDA-approved commercially available drug product.”
None of this constituted a specific criticism of what’s going on in Louisiana, but the FDA never communicates about particular cases except with the parties involved. The FDA has made no public response to the Public Citizen letter.
But the shady and exploitative procedure is far from unique. In fact, it is arguably reminiscent of how Vivitrol itself originally got approved for the treatment of opioid use disorder.
That happened via testing in Russia, where it could not be compared with methadone or buprenorphine, because those medications were not allowed there. This led to a furor after a letter accusing the researchers of duplicity was published in the Lancet in 2011.
A randomized controlled trial—the gold standard for medical testing—could not be conducted in the Russia study. But the researchers behind it, including the highly respected George Woody, MD, of the University of Pennsylvania, called the Lancet letter “absolutely terrible and potentially harmful.” Neither did the people who received the medication and found it helpful like being called “guinea pigs.”
To find out more about the ethical boundaries that should apply to testing addiction drugs on incarcerated people, Filter spoke with to a researcher who has conducted studies of prisoners and a law professor who specializes in human rights and harm reduction.
“The description as guinea pigs is apt,” said Leo Beletsky, professor of Law and Health Sciences at Northeastern University. “People in the criminal legal system have been used as guinea pigs for various medical experiments.”
“Given that people of color are overrepresented in that system,” he added, “it also intersects with the very sordid history of [treatment of] those communities.”
Obvious examples include the notorious Tuskegee Experiment, in which black men did not give informed consent for a study in which syphilis was not treated over a 40-year period, ending in 1972. Then there was Henrietta Lacks, a black woman with cancer whose cells were taken without her consent in 1951.
“Would it even make sense to conduct it in a criminal justice setting, where there are all kinds of questions about whether people have the opportunity to consent?”
Beletsky also referred to the broader story of naltrexone being marketed in inappropriate ways as an illustration that people with addiction are viewed as lesser.
“There’s literal incarceration and there’s metaphorical incarceration,” he said of “treatment” in Russia. “People in Russia are incarcerated by the toxic reality,” he said. “Makers of Vivitrol were incredibly shrewd in choosing the location for the trial,” he said, noting that a trial must compare the new drug to “usual care”—which anyplace else in the world would have been methadone or buprenorphine.”
Beletsky noted that there’s an increasing tendency for pharmaceutical companies to conduct clinical trials abroad, including in India, China and Eastern Europe. “It does raise questions about how generalizable those findings are to US settings,” he said.
“You want to protect vulnerable people,” he summarized. “If this were a clinical trial, would it even make sense to conduct it within a criminal justice setting, where there are all kinds of questions about whether people have the opportunity to consent?”
That’s why the IRB system exists even in correctional settings—in fact, in correctional settings the IRB should be even stronger, said Beletsky. “Prisoners are, like kids, a vulnerable population, so it automatically raises red flags as possibly abusive and coercive.”
“A lot of the marketing of naltrexone, either overtly or implied, tries to put down buprenorphine and methadone.”
What are the sanctions for an unapproved clinical trial? “There could be professional censure, there could be criminal liability,” said Beletsky. But he noted that the power imbalance is so egregious that it’s rare for unscrupulous researchers to be penalized appropriately.
In addition, the promotion of naltrexone occurs in the context of most prisoners not wanting it—they largely want methadone or buprenorphine, as a 2018 Rhode Island study showed.
Pharmaceutical companies marketing naltrexone have armed themselves with lobbyists and former corrections officials, noted Beletsky. “A lot of the marketing, either overtly or implied, tries to put down buprenorphine and methadone specifically. This very aggressive set of tactics is being deployed to try to increase market share for this medication when in fact we should be redoubling our efforts to get agonists to patients.”
“There is certainly a lot of BS therapy in the addiction space over the years that lacks efficacy or effectiveness data but is marketed as effective,” said Joshua D. Lee, MD, an associate professor in the department of Population Health at NYU School of Medicine, who has conducted and is conducting research with on OUD treatment medications with prisoners.
This happens even without the involvement of criminal justice agencies and racial bias, he said, citing equine therapy, exorbitant rehabs and Prometa—an “instant cure” for methamphetamine addiction which was proven no more effective than placebo, but not until after corrections and criminal justice officials had bought into it.
Lee noted that people with addiction are one of several populations that are vulnerable to targeted marketing from a health perspective. “Is this different from pain management, weight loss, diet cures, supplements, vitamins, etc?,” he asked.
Lee urged, however, that “snake oil” marketing should not be confused with practical harm reduction interventions that aren’t necessarily proven by randomized controlled trials, but which reduce overdose or HIV and hepatitis C transmission among people who use drugs. There is a “strong evidence base” for such interventions, he said, “but mostly from ecological studies, as you can’t practically randomize persons to a needle exchange versus using dirty needles.”
Amid the opioid-involved overdose crisis, we continually see the development of non-standard treatments, such as the “Bridge,” a device designed to reduce opioid withdrawal symptoms, or lofexidine, a non-opioid withdrawal medication.
“I’m not sure that is a bad thing,” Lee said, adding that “the FDA has clearly been encouraging exploration of opioid solutions of any type.”
Drug trials still use placebo-controlled designs, said Lee, but studies of devices or therapy inventions (like apps) are more difficult to set up in this way.
“We ask prisoners if they would like to participate, make clear it is voluntary and data collection confidential, and we usually firewall health care from judicial status.”
Lee is an expert on prisoner research ethics, and cited standards established by the US Office for Human Research Protections. “OHRP/DHHS lay out fairly rigorous standards for adjudicating correctional health research,” he said. “IRBs, NIDA/NIH, and [principal investigators] generally follow these principles. On the one hand, we want to protect against coercion and lack of informed consent; on the other hand we do not want to deny prisoners beneficial therapies or interventions which may improve prevalent and important conditions, like HIV and opioid use disorders.”
“Clearly many of us in the field of CJS [criminal justice system] health service research think properly designed trials are an important service to these vulnerable and neglected populations,” he continued. And he noted that taking away the chance to participate in potentially life-changing studies from incarcerated populations might also not be fair.
“This got a fresh look during the HIV epidemic when CJS populations were essentially shut out from experimental drug trials and advancements in HAART,” he said. However, “the longer legacy of exploitative research in prisoners is quite horrible (Nazis, for example) so there must be constant safeguards against that, as with all vulnerable populations.”
So how does Lee himself work with incarcerated populations? “Generally we ask prisoners if they would like to participate in a clinical trial and make clear participation is voluntary, data collection confidential, and we usually firewall health care from judicial status,” he said, meaning that the study does not report to the parole board or judges, for example. ”This is similar to most community-based trials.”
He added that “All research volunteers must benefit above and beyond usual care, and placebo-controlled trials are discouraged for this reason.”
But even so, Lee admitted, “I agree you can then debate how truly voluntary prisoner participation can ever be. There is no right answer to that question.”
Pharma-criminal justice collaborations have high potential—to say the least—to exploit vulnerable patients.
As for the BioCoreRx implant pilot, Lee told Filter that it did seem to be use of a non-approved medical therapy, which would be prohibited by OHRP guidelines.
“However, there is no OHRP oversight of non-federal research; the guidelines technically do not apply,” he noted. “But it is a high bar to bring unproven and unapproved medical therapies into a prison, and it may well have been exploitative or coercive.”
The bad press about the Louisiana program seems to have put a halt to it—for now. But Pharma-criminal justice collaborations have high potential—to say the least—to exploit vulnerable patients. If they exist, they must always be subject to the strongest regulatory and public scrutiny.