CROs must design their abuse liability studies to cope with volunteers who arrive under the influence or give misleading patient histories, says a specialist consultancy.
Recruiting patients for any trial is tough. Analysis in 2010 showed that 80% of studies fail to meet enrolment deadlines, causing delays that increase costs and time to market. Finding people to assess abuse potential – an increasingly common regulatory requirement – is even harder, according to Altreos Research Partners.
Director Naama Levy-Cooperman told Outsourcing-Pharma.com volunteers skilled at judging a pill’s potential for abuse are not always reliable study participants and around 30 to 60% are eventually dropped, making over-enrolment and qualification tests vital.
Abuse liability studies have different restrictions and challenges to standard Phase I clinical studies, Levy-Cooperman told us.
“CROs struggle with recruitment challenges when they’re identifying appropriate populations of subjects among recreational drug users, and how to handle these subjects in-house,” she said. Contract researchers have to deal with positive urine drug screens, and adapt their protocol designs so they’re not losing too many subjects.”
Altreos recommends that positive drug tests be tolerated at the initial screening phase. “That being said, after they’ve signed the consent form and they’re moving forward in the study, we require that they don’t have a positive urine drug screen for their treatment.”
CROs could also consider accepting participants who test positive for THC (tetrahydrocannabinol, the main psychoactive component of cannabis) or benzodiazepines, as residual levels can show in screenings long after their effects have worn off.
As long as results show the participants have stable or decreasing amounts of these substances, they should remain in the study to prevent unnecessary loss, said Levy-Cooperman. “You can also build in to the protocols allowing them to come back at another time.”
Needle experience: required
As well as finding an adequate source of recreational drug users, clinical trial leaders need to find subjects with the right sort of illicit drug experience, said Altreos’s director. Participants may need a specific background beyond opioid use, such as intranasal or intravenous abuse. “Subjects may claim they have experience but when it comes to time for them to chew or snort a drug, rather than take it orally [it becomes clear they do not],” she said.
CROs doing these studies develop databases of drug-taking volunteers – “unfortunately, or fortunately, there is usually a pool” which can help with necessary levels of over-enrolment, especially for less-abused drugs such as sedatives.
Levy-Cooperman said the company strongly urges CROs performing abuse liability studies to have a standardised protocol for training subjects before the trial. “They will be under the influence of a narcotic for part of the time so they may not be able to attend as well to the task.”
Abuse liability studies should include a qualification phase, she said. “It’s a pre-study, usually a double-blind two-way crossover. They receive the opioid and a placebo and they have to show they can distinguish between them – that’s how we know they’re appropriate.”
Altreos has advised Cambridge Cognition since February on developing its iPad tool for testing cognitive responses during abuse liability and abuse-deterrent studies.