Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development

The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Here, 46 leading experts from all stakeholders - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - worldwide have analyzed existing challenges and hurdles along the MPS-based assay life cycle in a second workshop of this kind in June 2019. They identified that the level of qualification of MPS-based assays for a given context of use and a communication gap between stakeholders are the major challenges for industrial adoption by end-users. Finally, a regulatory acceptance dilemma exists against that background. This t4 report elaborates on these findings in detail and summarizes solutions how to overcome the roadblocks. It provides recommendations and a roadmap towards regulatory accepted MPS-based models and assays for patients' benefit and further laboratory animal reduction in drug development. Finally, experts highlighted the potential of MPS-based human disease models to feedback into laboratory animal replacement in basic life science research.

Substance Use Stigma and Antiretroviral Therapy Adherence Among a Drug-Using Population Living with HIV.

Among people living with HIV (PLWH), HIV-related stigma predicts nonadherence to antiretroviral therapy (ART); however, the role of stigma associated with drug use is largely unknown. We examined the association between substance use (SU) stigma and optimal ART adherence in a sample of 172 self-reported HIV-infected drug users. Participants completed surveys on SU, stigma, and ART adherence. The three substance classes with the greatest number of participants exhibiting moderate/high-risk scores were for cocaine/crack cocaine (66.28%), cannabis (64.53%), and hazardous alcohol consumption (65.70%). Multivariable logistic regression was conducted to investigate associations between levels of SU stigma and optimal ART adherence, adjusting for sociodemographic characteristics, severity of illicit drug use (alcohol, smoking and substance involvement screening test) and alcohol use severity (Alcohol Use Disorders Identification Test-C), HIV-related stigma, and social support. The odds of optimal adherence among participants experiencing moderate [Adjusted Odds Ratio (AOR) = 0.36, p = 0.039] and very high (AOR = 0.25, p = 0.010) levels of anticipated SU stigma were significantly lower than participants experiencing low levels of anticipated SU stigma. No other stigma subscales were significant predictors of ART adherence. Interventions aiming to improve ART adherence among drug-using PLWH need to address anticipated SU stigma.

Advancing nonclinical innovation and safety in pharmaceutical testing.

Nonclinical tests are considered crucial for understanding the safety of investigational medicines. However, the effective translation from nonclinical to human application is limited and must be improved. Drug development stakeholders are working to advance human-based in vitro and in silico methods that may be more predictive of human efficacy and safety in vivo because they enable scientists to model the direct interaction of drugs with human cells, tissues, and biological processes. Here, we recommend test-neutral regulations; increased funding for development and integration of human-based approaches; support for existing initiatives that advance human-based approaches; evaluation of new approaches using human data; establishment of guidelines for procuring human cells and tissues for research; and additional training and educational opportunities in human-based approaches.

Virtual reality assessment of medication compliance in patients with schizophrenia.

Medication compliance is essential to treating the symptoms of schizophrenia effectively. This study utilized a virtual reality (VR) apartment paradigm to assess medication compliance behaviors in 25 patients with schizophrenia and in 16 healthy control subjects. Participants were assigned a prescription consisting of three medications and were asked to self-administer this regimen in 15 min. Results demonstrate that patients had considerably more difficulty in complying with the medication regimen than did controls. They manifested significantly more quantitative errors, and were much less accurate in consuming the medications at the assigned time. Significant differences in performance between these groups were also evidenced by a variety of validated neuropsychological measures. Correlations between the data may suggest a convergent validity for this new VR task. Future research will investigate the validity of this task in predicting additional measures of psychosocial functioning.