Illegal drug-using subjects pose unique ethical challenges

Even collecting syringes is problematic

IRBs reviewing protocols involving HIV drug-using populations sometimes find that it's impossible to anticipate all of the ethical issues that will arise during the trials.

HIV investigators also might not have imagined certain ethical difficulties, and so additional human subjects protection measures have to be created at the site as the trial is ongoing, an expert says.

"When dealing with a population with a stigmatized behavior there are bound to be ethical issues, especially when this is a population of drug users who are actively using and not in any formal treatment program," says Kaveh Khoshnood, PhD, an assistant professor of epidemiology in the Yale School of Public Health in New Haven, CT.

"I'm not a bioethicist," Khoshnood notes. "I'm an infectious disease epidemiologist, and my research has focused on trying to prevent HIV infection among active drug users."

In the course of interviewing drug-using participants and enrolling them in studies, Khoshnood was bothered by the ethical issues that arose.

"Many of which we had not anticipated, frankly," he says. These ethical issues also weren't on the IRB's protocol as they were brought to light during the field experience.

"I was looking for answers, ways to resolve these ethical issues," Khoshnood says. "I looked in the literature and could not find documents that were helpful and which directly addressed some of the ethical issues that come up in HIV prevention research."

Needle exchange bans

One striking example involved a protocol that called for staff to collect used syringes and test them for HIV and hepatitis infection.

Researchers found that drug users were requesting a replacement syringe. The syringe they gave up was their only one, and they needed a new one or they would be compelled to use a shared syringe. Needle sharing is a major risk factor for HIV and other blood-borne pathogen infections.

So if researchers took subjects' used needles and didn't replace them with clean new ones, they would be indirectly placing these study participants at risk for major illness and/or death.

The ethical answer would be for the trial to include clean syringes to exchange for the used ones, Khoshnood says.

But since the study was funded through a federal grant, and there is a federal ban on needle exchange, investigators were not allowed to use the study's funds for clean needles, he explains.

"The IRB didn't raise that issue," Khoshnood says. "Many IRBs don't have that expertise, and that's not something we thought of putting in the protocol."

So what happened was that investigators, in the interest of protecting their human subjects, paid for clean needles out of their personal finances initially. Eventually, some sites collaborated with existing state or local needle exchange programs, Khoshnood says.

"In one location, needle exchange was not allowed, so investigators decided to use personal funds to make sure the drug users had access to clean syringes," Khoshnood says. "We didn't want to break the law or endanger the life of human subjects."

Confidentiality is another issue that is of particular concern when researchers are dealing with a population that uses illegal drugs, he says.

"Breach of confidentiality is a concern for all human subjects, but for someone who is using drugs the consequences could be far greater if their drug use status becomes known to their family members and community," Khoshnood says.

Since the participants' substance use involves illicit drugs, as opposed to alcohol or nicotine, there are more severe consequences if confidentiality protection is breached, he adds.

For example, if a trial subject is pregnant and actively using drugs, there is a risk that she could be arrested for endangering the fetus, he says.

Obtaining informed consent

IRBs reviewing these protocols might also have to consider the informed consent process differently, Khoshnood suggests.

For years, Khoshnood would provide subjects the informed consent document, read it to them, obtain their signature, and move on, he notes.

"Then I began to ask the question, 'What does it really mean?'" he says. "If someone is dependent on a substance and they approach you when they're craving street medication or are going through withdrawal, is that truly informed consent?"

Khoshnood had to admit that he didn't have a good answer for that question.

"The way we deal with this situation is pragmatic," he says. "If someone is so high they can't think straight, we say, 'Thanks for coming today, but today is not a good day for us to do this. Why don't you come back tomorrow?'"

Enrolling subjects who are obviously high might make a mockery of the informed consent process, Khoshnood says.

"People may get upset when we ask them to come back, but what do you do?" he says. "Do you get their signature knowing their cognitive function is compromised, or do you bring them back at a time when they're more alert?"

This issue isn't unique to people using illegal substances, and a lot of IRBs are raising these issues, Khoshnood says.

"I'm doing a study of IRBs to understand how they handle research protocols that have active drug users," he notes.

"I'm in the beginning phase of the study and have interviewed 15 chairs of IRBs and IRB staff members," Khoshnood says. "And what is beginning to emerge is there is a lot of misinformation about what drug users are and what they look like and how they act and behave and what they are capable of doing."

Drug users cannot be grouped together when it comes to their behaviors.

"If someone is using psychoactive drugs, it is very different than someone using heroin," Khoshnood says. "I find that IRB members, especially those who don't have substance abuse protocols, are not aware of fundamental differences," he adds.

"Many IRB members who are not familiar with the pharmacology of these drugs may put them all into one category, and say that if you as an investigator put them into your study they may not be able to consent." However, the ability to consent varies from drug to drug and person to person, Khoshnood says.

"Many of these people have full-time jobs and families, and clearly are making decisions every day," he adds. "I have found a gap in knowledge of some IRBs about this particular issue."

Compensation concerns

A third issue that often arises involves compensation to subjects.

"Many IRBs have expressed discomfort when the investigator suggests payment of cash to a known drug user in a study," Khoshnood says. "We try to get at what's behind that discomfort."

IRB members will say that they don't want to contribute to the subject's drug use. But is this an ethical or human subjects protection issue?

Is giving a $20 or $50 cash compensation to a heroin user any different than giving the same amount to a college student who will use the money to get drunk on the weekend, he asks?

"It's interesting that IRBs raise this issue exclusively for a drug-using population," Khoshnood says. "They're not concerned about the payment being a risk; they're making a judgment based on their own comfort level and not on any regulation."

Some IRB members might say that cash payment to illegal drug users is coercive and undue inducement, assuming the participant wouldn't enroll in the trial for any other reason, he says.

"If you offer someone hundreds of dollars for an interview then, yes, it could be undue inducement," Khoshnood says.

But if the cash payment is minor and if the study poses no risk other than having subjects answer questions, then there is no increased risk to the subject, he says.