T98. CHALLENGES AND ETHICAL CONSIDERATIONS IN RECRUITING PATIENTS WITH ``EXTREME'' TREATMENT-RESISTANT SCHIZOPHRENIA FOR GENOMIC INVESTIGATIONS: THE PASH STUDY

Many patients (∼30%) with schizophrenia experience little or no benefit from antipsychotic medications (“treatment-resistant schizophrenia” - TRS). Extreme cases with severe symptoms and minimal self-care often require long-term care in state psychiatric hospitals (“extreme”-TRS). Unfortunately, these individuals are usually excluded from research activity, even though studies of severe phenotypes have identified high-impact rare genetic variants in several complex disorders. The Pennsylvania state hospitals (PASHs) allowed our team to conduct a genomic study of ``extreme''-TRS. PASHs are controlled, funded, and operated by the PA Department of Human Services (DHS) of the Commonwealth of Pennsylvania. They are singularly devoted to providing long-term clinical services for individuals with severe mental illnesses. Research is not part of their mission, nor is any funding provided. Here we present challenges encountered and ethical considerations when conducting a genomic study in five PASHs. Overall authority to approve research rests with the DHS Secretary (who represents the Governor), in consultation with other DHS officials. These individuals hold political appointments and have varying levels of interest and/or expertise in psychiatric research. Thus, extensive communication is essential, framed within the bioethical principles of beneficence, non-maleficence, autonomy, and justice. With DHS approval, each PASH made an independent decision regarding participation. Those that opted to participate assembled an ad hoc research committee (including a patient advocate with lived experience) to review the project. If approved, hospital wide informational meetings were convened (including PI). Our activity then moved to inpatient units where core issues were discussed with the clinical team: (1) purpose of study; (2) primacy of clinical activity over research activity; (3) recruitment; (4) input from the clinical team regarding each potential subject; (5) space allocation; (6) access to patient charts; and (7) commitment to discuss study missteps. The patient advocate or clinical staff member attended each recruitment session and signed the informed consent form (ICF) attesting that consent was voluntary. A unique subject number was assigned to de-identify each subject and link future study data. Copies of the ICF were placed on the hospital chart and in medical records. With the ICF completed, hospital records were reviewed for enrollment criteria. Those enrolled provided a blood sample and proceeded with testing and clinical ratings. Study procedures spanned several days to avoid interference with clinical activity. De-identified data were entered into REDCAP onsite. 509 extreme-TRS cases enrolled. Individuals with “extreme”-TRS can be included in research studies. Relationships must be established with patients, state officials, and hospital staff in order to conduct this study within the complex network that provides care for a highly vulnerable population. Ethically-informed recruitment is essential as it: (1) begins a critical relationship between subject and investigators; (2) enables judgement of patient comprehension and capacity; (3) allows hospital staff to form realistic opinions regarding the ethical standard of the research activity; and, perhaps most importantly, (4) it creates a relational atmosphere that will be discussed (whispered) among patients and staff, and is a primary factor leading to success or failure.