A qualitative assessment of emergency physicians' experiences with robust emergency department buprenorphine bridge programs.

OBJECTIVES: Emergency departments (EDs) are a critical point of entry into treatment for patients struggling with opioid use disorder (OUD). When initiated in the ED, buprenorphine is associated with increased addiction treatment engagement at 30 days when initiated. Despite this association, it has had slow adoption. The barriers to ED buprenorphine utilization are well documented; however, the benefits of prescribing buprenorphine for emergency physicians (EPs) have not been explored. This study utilized semistructured interviews to explore and understand how EPs perceive their experiences working in EDs that have successfully implemented ED bridge programs (EDBPs) for patients with OUD. METHODS: Semistructured interviews were conducted with EPs from four geographically diverse academic hospitals with established EDBPs. Interviews were recorded and transcribed, and emergent themes were identified using codebook thematic analysis. Analysis credibility and transparency were confirmed with peer debriefing. RESULTS: Twenty-two interviews were conducted across the four sites. Three key themes were constructed during the analyses: (1) provided EPs agency; (2) transformed EPs' emotions, attitudes, and behaviors related to treating patients with OUD; and (3) improved EPs' professional quality of life. CONCLUSIONS: Participants in this study reported several common themes related to participation in their hospital's BP. Overall our results suggest that physicians who participate in EDBPs may feel a renewed sense of fulfillment and purpose in their personal and professional lives. These positive changes may lead to increased job satisfaction in hospitals that have successfully launched EDBP.

Immunoinformatic Risk Assessment of Host Cell Proteins During Process Development for Biologic Therapeutics.

The identification and removal of host cell proteins (HCPs) from biologic products is a critical step in drug development. Despite recent improvements to purification processes, biologics such as monoclonal antibodies, enzyme replacement therapies, and vaccines that are manufactured in a range of cell lines and purified using diverse processes may contain HCP impurities, making it necessary for developers to identify and quantify impurities during process development for each drug product. HCPs that contain sequences that are less conserved with human homologs may be more immunogenic than those that are more conserved. We have developed a computational tool, ISPRI-HCP, that estimates the immunogenic potential of HCP sequences by evaluating and quantifying T cell epitope density and relative conservation with similar T cell epitopes in the human proteome. Here we describe several case studies that support the use of this method for classifying candidate HCP impurities according to their immunogenicity risk.

Immunogenicity risk assessment of synthetic peptide drugs and their impurities.

Peptide drugs play an important part in medicine owing to their many therapeutic applications. Of the 80 peptide drugs approved for use in humans, at least five are now off-patent and are consequently being developed as generic alternatives to the originator products. To accelerate access to generic products, the FDA has proposed new regulatory pathways that do not require direct comparisons of generics to originators in clinical trials. The 'Abbreviated New Drug Application' (ANDA) pathway recommends that sponsors provide information on any new impurities in the generic drug, compared with the originator product, because the impurities can have potential to elicit unwanted immune responses owing to the introduction of T-cell epitopes. This review describes how peptide drug impurities can elicit unexpected immunogenicity and describes a framework for performing immunogenicity risk assessment of all types of bioactive peptide products. Although this report primarily focuses on generic peptides and their impurities, the approach might also be of interest for developers of novel peptide drugs who are preparing their products for an initial regulatory review.

Survey Outcome on Immunogenicity Risk Assessment Tools for Biotherapeutics: an Insight into Consensus on Methods, Application, and Utility in Drug Development.

A survey conducted by the Therapeutic Product Immunogenicity (TPI) community within the American Association of Pharmaceutical Scientists (AAPS) posed questions to the participants on their immunogenicity risk assessment strategies prior to clinical development. The survey was conducted in 2 phases spanning 5 years, and queried information about in silico algorithms and in vitro assay formats for immunogenicity risk assessments and how the data were used to inform early developability effort in discovery, chemistry, manufacturing and control (CMC), and non-clinical stages of development. The key findings representing the trends from a majority of the participants included the use of high throughput in silico algorithms, human immune cell-based assays, and proteomics based outputs, as well as specialized assays when therapeutic mechanism of action could impact risk assessment. Additional insights into the CMC-related risks could also be gathered with the same tools to inform future process development and de-risk critical quality attributes with uncertain and unknown risks. The use of the outputs beyond supporting early development activities was also noted with participants utilizing the risk assessments to drive their clinical strategy and streamline bioanalysis.

In silico Immunogenicity Assessment for Sequences Containing Unnatural Amino Acids: A Method Using Existing in silico Algorithm Infrastructure and a Vision for Future Enhancements.

The in silico prediction of T cell epitopes within any peptide or biologic drug candidate serves as an important first step for assessing immunogenicity. T cell epitopes bind human leukocyte antigen (HLA) by a well-characterized interaction of amino acid side chains and pockets in the HLA molecule binding groove. Immunoinformatics tools, such as the EpiMatrix algorithm, have been developed to screen natural amino acid sequences for peptides that will bind HLA. In addition to commonly occurring in synthetic peptide impurities, unnatural amino acids (UAA) are also often incorporated into novel peptide therapeutics to improve properties of the drug product. To date, the HLA binding properties of peptides containing UAA are not accurately estimated by most algorithms. Both scenarios warrant the need for enhanced predictive tools. The authors developed an in silico method for modeling the impact of a given UAA on a peptide's likelihood of binding to HLA and, by extension, its immunogenic potential. In silico assessment of immunogenic potential allows for risk-based selection of best candidate peptides in further confirmatory in vitro, ex vivo and in vivo assays, thereby reducing the overall cost of immunogenicity evaluation. Examples demonstrating in silico immunogenicity prediction for product impurities that are commonly found in formulations of the generic peptides teriparatide and semaglutide are provided. Next, this article discusses how HLA binding studies can be used to estimate the binding potentials of commonly encountered UAA and "correct" in silico estimates of binding based on their naturally occurring counterparts. As demonstrated here, these in vitro binding studies are usually performed with known ligands which have been modified to contain UAA in HLA anchor positions. An example using D-amino acids in relative binding position 1 (P1) of the PADRE peptide is presented. As more HLA binding data become available, new predictive models allowing for the direct estimation of HLA binding for peptides containing UAA can be established.

Validation of a 5-Item Tool to Measure Patient Assessment of Clinician Compassion in Hospitals.

BACKGROUND: We previously validated a 5-item compassion measure to assess patient experience of clinician compassion in the outpatient setting. However, currently, there is no validated and feasible method for health care systems to measure patient experience of clinician compassion in the inpatient setting across multiple hospitals. OBJECTIVE: To test if the 5-item compassion measure can validly and distinctly measure patient assessment of physician and nurse compassion in the inpatient setting. DESIGN: Cross-sectional study between July 1 and July 31, 2020, in a US health care network of 91 community hospitals across 16 states consisting of approximately 15,000 beds. PATIENTS: Adult patients who had an inpatient hospital stay and completed the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. MEASUREMENTS: We adapted the original 5-item compassion measure to be specific for physicians, as well as for nurses. We disseminated both measures with the HCAHPS survey and used confirmatory factor analysis for validity testing. We tested reliability using Cronbach's alpha, as well as convergent validity with patient assessment of physician and nursing communication and overall hospital rating questions from HCAHPS. RESULTS: We analyzed 4756 patient responses. Confirmatory factor analysis found good fit for two distinct constructs (i.e., physician and nurse compassion). Both measures demonstrated good internal consistency (alpha > 0.90) and good convergent validity but reflected a construct (compassionate care) distinct from what is currently captured in HCAHPS. CONCLUSION: We validated two 5-item tools that can distinctly measure patient experience of physician and nurse compassion for use in the inpatient hospital setting in conjunction with HCAHPS.

Socioeconomic, racial and ethnic differences in patient experience of clinician empathy: Results of a systematic review and meta-analysis.

INTRODUCTION: Empathy is essential for high quality health care. Health care disparities may reflect a systemic lack of empathy for disadvantaged people; however, few data exist on disparities in patient experience of empathy during face-to-face health care encounters with individual clinicians. We systematically analyzed the literature to test if socioeconomic status (SES) and race/ethnicity disparities exist in patient-reported experience of clinician empathy. METHODS: Using a published protocol, we searched Ovid MEDLINE, PubMed, CINAHL, EMBASE, CENTRAL and PsychINFO for studies using the Consultation and Relational Empathy (CARE) Measure, which to date is the most commonly used and well-validated methodology for measuring clinician empathy from the patient perspective. We included studies containing CARE Measure data stratified by SES and/or race/ethnicity. We contacted authors to request stratified data, when necessary. We performed quantitative meta-analyses using random effects models to test for empathy differences by SES and race/ethnicity. RESULTS: Eighteen studies (n = 9,708 patients) were included. We found that, compared to patients whose SES was not low, low SES patients experienced lower empathy from clinicians (mean difference = -0.87 [95% confidence interval -1.72 to -0.02]). Compared to white patients, empathy scores were numerically lower for patients of multiple race/ethnicity groups (Black/African American, Asian, Native American, and all non-whites combined) but none of these differences reached statistical significance. CONCLUSION: These data suggest an empathy gap may exist for patients with low SES. More research is needed to further test for SES and race/ethnicity disparities in clinician empathy and help promote health care equity. TRIAL REGISTRATION: Registration (PROSPERO): CRD42019142809.

T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.

Immune responses to protein and peptide drugs can alter or reduce their efficacy and may be associated with adverse effects. While anti-drug antibodies (ADA) are a standard clinical measure of protein therapeutic immunogenicity, T cell epitopes in the primary sequences of these drugs are the key drivers or modulators of ADA response, depending on the type of T cell response that is stimulated (e.g., T helper or Regulatory T cells, respectively). In a previous publication on T cell-dependent immunogenicity of biotherapeutics, we addressed mitigation efforts such as identifying and reducing the presence of T cell epitopes or T cell response to protein therapeutics prior to further development of the protein therapeutic for clinical use. Over the past 5 years, greater insight into the role of regulatory T cell epitopes and the conservation of T cell epitopes with self (beyond germline) has improved the preclinical assessment of immunogenic potential. In addition, impurities contained in therapeutic drug formulations such as host cell proteins have also attracted attention and become the focus of novel risk assessment methods. Target effects have come into focus, given the emergence of protein and peptide drugs that target immune receptors in immuno-oncology applications. Lastly, new modalities are entering the clinic, leading to the need to revise certain aspects of the preclinical immunogenicity assessment pathway. In addition to drugs that have multiple antibody-derived domains or non-antibody scaffolds, therapeutic drugs may now be introduced via viral vectors, cell-based constructs, or nucleic acid based therapeutics that may, in addition to delivering drug, also prime the immune system, driving immune response to the delivery vehicle as well as the encoded therapeutic, adding to the complexity of assessing immunogenicity risk. While it is challenging to keep pace with emerging methods for the preclinical assessment of protein therapeutics and new biologic therapeutic modalities, this collective compendium provides a guide to current best practices and new concepts in the field.

Racial and socioeconomic disparities in patient experience of clinician empathy: a protocol for systematic review and meta-analysis.

INTRODUCTION: Clinician empathy is a vital component of high-quality healthcare. Healthcare disparities may reflect a societal lack of empathy for disadvantaged persons in general, and recent research suggests that socioeconomic disparities exist in patient satisfaction with clinicians. However, it is currently unclear if there are disparities in patient experience of empathy from clinicians. Our objective is to systematically analyse the scientific literature to test the hypothesis that racial and socioeconomic status (SES) disparities exist in patient-reported experience of clinician empathy. METHODS AND ANALYSIS: In accordance with published methodological guidelines for conducting a systematic review, we will analyse studies reporting patient assessment of clinician empathy using the Consultation and Relational Empathy (CARE) measure, which to date is the most commonly used and well-validated methodology in clinical research for measuring clinician empathy from the patient's perspective. We will use a standardised data collection template and assess study quality (risk of bias) using the Newcastle-Ottawa Scale. We will abstract data for the CARE measure stratified by race and SES, and we will contact the corresponding authors to obtain stratified data by race/SES if not reported in the original manuscript. Where appropriate, we will pool the data and perform quantitative meta-analysis to test if non-white (compared to white) patients and low SES (compared to high SES) patients report lower scores for clinician empathy. ETHICS AND DISSEMINATION: No individual patient-level data will be collected and thus the proposed systematic review does not require ethical approval. This systematic review will test if racial and SES differences exist in patient experience of clinician empathy, and will inform future research to help promote healthcare equity. PROSPERO REGISTRATION NUMBER: CRD42019142809.

Validation of a 5-item tool to measure patient assessment of clinician compassion in the emergency department.

BACKGROUND: To test if the 5-item compassion measure (a tool previously validated in the outpatient setting to measure patient assessment of clinician compassion) is a valid and reliable tool to quantify a distinct construct (i.e. clinical compassion) among patients evaluated in the emergency department (ED). METHODS: Cross-sectional study conducted in three academic emergency departments in the U.S. between November 2018 and April 2019. We enrolled adult patients who were evaluated in the EDs of the participating institutions and administered the 5-item compassion measure after completion of care in the ED. Validity testing was performed using confirmatory factor analysis. Cronbach's alpha was used to test reliability. Convergent validity with patient assessment of overall satisfaction questions was tested using Spearman correlation coefficients and we tested if the 5-item compassion measure assessed a construct distinct from overall patient satisfaction using confirmatory factor analysis. RESULTS: We analyzed 866 patient responses. Confirmatory factor analysis found all five items loaded well on a single construct and our model was found to have good fit. Reliability was excellent (Cronbach's alpha = 0.93) among the entire cohort. These results remained consistent on sub-analyses stratified by individual institutions. The 5-item compassion measure had moderate correlation with overall patient satisfaction (r = 0.66) and patient recommendation of the ED to friends and family (r = 0.57), but reflected a patient experience domain (i.e. compassionate care) distinctly different from patient satisfaction. CONCLUSIONS: The 5-item compassion measure is a valid and reliable tool to measure patient assessment of clinical compassion in the ED.

Curricula for empathy and compassion training in medical education: A systematic review.

BACKGROUND: Empathy and compassion are vital components of health care quality; however, physicians frequently miss opportunities for empathy and compassion in patient care. Despite evidence that empathy and compassion training can be effective, the specific behaviors that should be taught remain unclear. We synthesized the biomedical literature on empathy and compassion training in medical education to find the specific curricula components (skills and behaviors) demonstrated to be effective. METHODS: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL using a previously published comprehensive search strategy. We screened reference lists of the articles meeting inclusion criteria to identify additional studies for potential inclusion. Study inclusion criteria were: (1) intervention arm in which subjects underwent an educational curriculum aimed at enhancing empathy and/or compassion; (2) clearly defined control arm in which subjects did not receive the curriculum; (3) curriculum was tested on physicians (or physicians-in-training); and (4) outcome measure assessing the effect of the curriculum on physician empathy and/or compassion. We performed a qualitative analysis to collate and tabulate effects of tested curricula according to recommended methodology from the Cochrane Handbook. We used the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: Fifty-two studies (total n = 5,316) met inclusion criteria. Most (75%) studies found that the tested curricula improved physician empathy and/or compassion on at least one outcome measure. We identified the following key behaviors to be effective: (1) sitting (versus standing) during the interview; (2) detecting patients' non-verbal cues of emotion; (3) recognizing and responding to opportunities for compassion; (4) non-verbal communication of caring (e.g. eye contact); and (5) verbal statements of acknowledgement, validation, and support. These behaviors were found to improve patient perception of physician empathy and/or compassion. CONCLUSION: Evidence suggests that training can enhance physician empathy and compassion. Training curricula should incorporate the specific behaviors identified in this report.

Development and Validation of a Tool to Measure Patient Assessment of Clinical Compassion.

Importance: Clinician compassion is a vital element of health care quality. Currently, there appears to be no validated and feasible method for health care organizations to measure patient assessment of clinician compassion on a large scale. Objective: To develop and validate a tool for measuring patient assessment of clinician compassion that can be used in conjunction with the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) survey. Design, Setting, and Participants: This prospective cohort study took place from June 1 to August 30, 2018, at a US academic health care system among a pilot cohort consisting of 3325 adult patients and a validation cohort consisting of 3483 adult patients, both of whom had an outpatient clinic visit and completed the CG-CAHPS survey. Main Outcomes and Measurements: After a comprehensive literature review, 12 candidate survey items were developed. Face and construct validity were performed. Candidate items were disseminated to patients in conjunction with the CG-CAHPS survey in a series of 2 studies: (1) exploratory factor analysis in one cohort to determine the factor structure and the most parsimonious set of items; and (2) validity testing in a second cohort using confirmatory factor analysis. Reliability was tested using Cronbach α. Convergent validity was tested with patient assessment of clinician communication and overall satisfaction questions from CG-CAHPS survey. Results: Overall, 6493 patient responses were analyzed. The mean (SD) age was 60 (15) years, 4239 patients (65.3%) were women, and 5079 (78.2%) were white. Exploratory factor analyses identified a 5-item compassion measure to be the most parsimonious. Confirmatory factor analyses found good fit. The compassion measure demonstrated good internal consistency (α = 0.94) and convergent validity (clinician communication: ρ = 0.44; overall satisfaction: ρ = 0.52) but reflected a patient experience domain (compassionate care) distinct from what is currently captured in the CG-CAHPS survey. Conclusions and Relevance: A simple 5-item tool to measure patient assessment of clinician compassion was developed and validated for use in conjunction with CG-CAHPS survey.

Lean Six Sigma to Reduce Intensive Care Unit Length of Stay and Costs in Prolonged Mechanical Ventilation.

OBJECTIVE: Patients with prolonged mechanical ventilation (PMV) represent important "outliers" of hospital length of stay (LOS) and costs (∼$26 billion annually in the United States). We tested the hypothesis that a Lean Six Sigma (LSS) approach for process improvement could reduce hospital LOS and the associated costs of care for patients with PMV. DESIGN: Before-and-after cohort study. SETTING: Multidisciplinary intensive care unit (ICU) in an academic medical center. PATIENTS: Adult patients admitted to the ICU and treated with PMV, as defined by diagnosis-related group (DRG). METHODS: We implemented a clinical redesign intervention based on LSS principles. We identified eight distinct processes in preparing patients with PMV for post-acute care. Our clinical redesign included reengineering daily patient care rounds ("Lean ICU rounds") to reduce variation and waste in these processes. We compared hospital LOS and direct cost per case in patients with PMV before (2013) and after (2014) our LSS intervention. RESULTS: Among 259 patients with PMV (131 preintervention; 128 postintervention), median hospital LOS decreased by 24% during the intervention period (29 vs. 22 days, p < .001). Accordingly, median hospital direct cost per case decreased by 27% ($66,335 vs. $48,370, p < .001). CONCLUSION: We found that a LSS-based clinical redesign reduced hospital LOS and the costs of care for patients with PMV.

Cross-sectional assessment of patient attitudes towards participation in clinical trials: does making results publicly available matter?

OBJECTIVES: Previous studies have shown that a majority of patients cite altruistic motives, such as contributing to generalisable medical knowledge, as factors motivating clinical trial participation. We sought to examine the impact of making trial results publicly available on patients' willingness to participate in clinical research. DESIGN: Cross-sectional analysis using a questionnaire developed by a panel with expertise in publication bias, informed consent and survey design. SETTING: A single urban, academic emergency department (ED) in the Northeastern USA. PARTICIPANTS: 799 ED patients. OUTCOME MEASURES: We assessed (1) participants' attitudes towards clinical trial participation, and (2) the impact of whether study results would eventually be made publicly available or not on willingness to participate in a trial. RESULTS: Of 799 patients surveyed, 36% (95% CI 32% to 39%) reported that they would generally like to participate in a trial, and another 50% (95% CI 47% to 54%) reported that they would consider participation depending on study details. For the majority of participants, the publication of trial results was either important (36%; 95% CI 33% to 40%) or very important (48%; 95% CI 44% to 51%). Most (63%; 95% CI 59% to 66%) reported they would be less likely to participate in a trial if investigators had not publicly released results from a prior study. Additionally, 85% (95% CI 82% to 87%) felt that it was important or very important to receive information about the publication track record of sponsors and investigators during the informed consent process. CONCLUSIONS: The majority of patients in this sample would consider participation in a clinical trial. Patients value the public release of trial results, and believe that the informed consent process should address the possibility of non-publication.

Assessment of a point-of-care cardiac troponin I test to differentiate cardiac from noncardiac causes of respiratory distress in dogs.

OBJECTIVES: To (1) determine a reference interval for cardiac troponin I (cTnI) using a point-of-care device in normal dogs and compare the results with those published by the manufacturer and (2) determine if cTnI differs among dogs with cardiogenic and noncardiogenic respiratory distress. DESIGN: Prospective observational study. SETTING: Emergency and referral veterinary hospital. ANIMALS: Twenty-six clinically normal dogs and 67 dogs in respiratory distress. INTERVENTIONS: All dogs underwent whole blood sampling for cTnI concentrations. MEASUREMENTS AND RESULTS: Normal dogs had a median cTnI concentration of 0.03 ng/mL (range 0-0.11 ng/mL). Thirty-six dogs were diagnosed with noncardiogenic respiratory distress with a median cTnI concentration of 0.14 ng/mL (range 0.01-4.31 ng/mL). Thirty-one dogs were diagnosed with cardiogenic respiratory distress with a median cTnI concentration of 1.74 ng/mL (range 0.05-17.1 ng/mL). A significant difference between cTnI concentrations in normal dogs and dogs with noncardiogenic respiratory distress was not detected. Significant differences in cTnI concentrations were found between normals versus cardiogenic and cardiogenic versus noncardiogenic respiratory distress groups. Significant differences in cTnI concentrations were identified in > 10 when compared with the < 5 and the 5-10 years of age groups. Receiver operating curve analysis identified cTnI concentrations > 1.5 ng/mL as the optimal "cut-off point" having a sensitivity of 78% and specificity of 51.5%. The area under the receiver operating curve was 0.72. Overall test accuracy was 65%. CONCLUSIONS: cTnI concentrations were significantly increased in dogs with cardiogenic respiratory distress versus dogs with noncardiogenic respiratory distress and normal dogs. A significant difference between normal dogs and dogs with noncardiogenic causes of respiratory distress was detected. Although highly sensitive when cTnI concentrations exceed 1.5 ng/mL, the test has low specificity. Assessment of cTnI by the methodology used cannot be recommended as the sole diagnostic modality for evaluating the cause of respiratory distress in dogs.

Perspectives on use and protection of genetic information in work settings: results of a preliminary study.

The societal use of genetic information raises ethical concerns, and the views of working persons regarding genetic information have received little attention. We performed an empirical project to characterize perspectives of 63 employees at two sites who expressed strong interest in learning about and protecting their personal genetic information. Genetic data were seen as more sensitive than other health data, and disclosure of genetic susceptibility was perceived as having negative consequences. This study suggests the value of exploring the perspectives of key stakeholders most directly affected by genetic applications across diverse societal settings.

Environmental hazard assessment of Venezuelan equine encephalitis virus vaccine candidate strain V3526.

A hazard assessment of Venezuelan equine encephalitis (VEE) virus sub-types and vaccine candidates was performed according to standard risk assessment procedures. Data from published literature demonstrates a considerable degree of safety of V3526 when compared to TC-83 vaccine, the protective measure that has been used to protect laboratory workers for over four decades. V3526 is a new recombinant vaccine candidate that is a vastly different product with a diminished hazard to public health and the general environment. A weight-of-evidence (WOE)-based scheme was employed to assign weights for relevance, quality, and adequacy of evidence in published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental studies. The results of this assessment indicated that V3526 has a low adverse impact on public health and the general environment. Although there are currently no human infectivity or pathogenicity data for V3526, existing evidence from published experimental animal studies reveals a diminished hazard for environmental transmission and distribution. Recently, the US Centers for Disease Control and Prevention (CDC) excluded V3526 from select agent requirements set forth under the Health and Human Services (HHS) regulations in Title 42 C.F.R. Part 73 and the US Department Agriculture (USDA) regulations set forth in Title 7 C.F.R. Part 331 and Title 9 C.F.R. Part 121. This paper summarizes the background, rationale, and hazard analysis used for assessing the environmental hazard of the VEE vaccine candidate strain V3526.

Patient and psychiatrist ratings of hypothetical schizophrenia research protocols: assessment of harm potential and factors influencing participation decisions.

OBJECTIVE: A central ethical issue in schizophrenia research is whether participants are able to provide informed consent, particularly for protocols entailing medication washouts or placebo treatments. Few data show how patients with schizophrenia and psychiatrists assess such scientific designs regarding potential harm, willingness to participate, and the relative influence of clinicians, family members, and financial incentives upon participation decisions. METHOD: In this preliminary study, structured interviews were conducted with schizophrenia patients (N=59), and parallel surveys were completed by attending and resident psychiatrists (N=70). Four hypothetical research protocols were rated. Patients were asked about their own views; psychiatrists provided both their personal views and predictions of patient views. RESULTS: Patients and psychiatrists both perceived substantially different levels of harm across the four protocols, identifying significantly greater harm for medication washouts or placebo treatments. Participants were less willing to enroll in protocols perceived as more harmful. Schizophrenia patients found enrollment decisions relatively easy. Patients and psychiatrists indicated that doctor recommendations, monetary incentives, and, to a lesser extent, family preferences had a mild influence on participation decisions. CONCLUSIONS: Given hypothetical protocols with variable design elements, schizophrenia patients and psychiatrists made meaningful and discerning harm assessments and participation decisions. These findings suggest that schizophrenia patients may have strengths in the research consent process that may not be fully recognized. The impact of outside influences upon research enrollment decisions remains uncertain. While psychiatrists were often accurate in predicting patient responses, data suggest the importance of clarifying views of individual patients regarding specific protocols.