Clinical Assistant Professor, Psychiatry and Behavioral Sciences
Honors & Awards
Learning Health Innovation Pilot Grant, Stanford Center for Clinical and Translational Education and Research (2017)
Small Grant Award, Department of Psychiatry and Behavioral Sciences (2016)
B.A., Columbia University (2004)
A.M., Harvard University, Statistics (2005)
Ph.D., Columbia University, Statistics (2009)
Current Research and Scholarly Interests
I am interested in the application of statistical methods to improve public mental health. My areas of expertise are the robustness of regression-based inference in randomized or non-randomized studies, methods for analyzing survival data subject to non-standard sampling schemes, and spatial statistics.
Demonstrating Patterns in the Views Of Stakeholders Regarding Ethically-Salient Issues in Clinical Research: A Novel Use of Graphical Models in Empirical Ethics Inquiry.
AJOB empirical bioethics
; 6 (2): 33–42
Empirical ethics inquiry works from the notion that stakeholder perspectives are necessary for gauging the ethical acceptability of human studies and assuring that research aligns with societal expectations. Although common, studies involving different populations often entail comparisons of trends that problematize the interpretation of results. Using graphical model selection - a technique aimed at transcending limitations of conventional methods - this report presents data on the ethics of clinical research with two objectives: (1) to display the patterns of views held by ill and healthy individuals in clinical research as a test of the study's original hypothesis and (2) to introduce graphical model selection as a key analytic tool for ethics research.In this IRB-approved, NIH-funded project, data were collected from 60 mentally ill and 43 physically ill clinical research protocol volunteers, 47 healthy protocol-consented participants, and 29 healthy individuals without research protocol experience. Respondents were queried on the ethical acceptability of research involving people with mental and physical illness (i.e., cancer, HIV, depression, schizophrenia, and post-traumatic stress disorder) and non-illness related sources of vulnerability (e.g., age, class, gender, ethnicity). Using a statistical algorithm, we selected graphical models to display interrelationships among responses to questions.Both mentally and physically ill protocol volunteers revealed a high degree of connectivity among ethically-salient perspectives. Healthy participants, irrespective of research protocol experience, revealed patterns of views that were not highly connected.Between ill and healthy protocol participants, the pattern of views is vastly different. Experience with illness was tied to dense connectivity, whereas healthy individuals expressed views with sparse connections. In offering a nuanced perspective on the interrelation of ethically relevant responses, graphical model selection has the potential to bring new insights to the field of ethics.
View details for PubMedID 25961066
View details for PubMedCentralID PMC4423405
The Utility and Acceptability of a Self-Help Smartphone Application for Eating Disorder Behaviors.
Journal of technology in behavioral science
2018; 3 (3): 161–64
Objective: Smartphone applications (apps) for eating disorders are a promising approach to assist individuals who do not receive traditional treatment. This study examines usage characteristics, perceptions regarding the acceptability of a new self-help intervention developed for users with eating disorders, and associations between attitudes and use patterns.Methods: 189 individuals pilot-tested a personalized app-based program, and 133 completed the required components of the pilot-test over an 8-day period. Of these, 64 individuals (49%) completed an exit survey pertaining to acceptability.Results: Seventy percent of those who pilot-tested the app-based program completed the required components, i.e. a baseline review and then a 1-week assessment. Body mass index was associated with the total number of recorded meal logs. Study participants rated the app as highly suitable and acceptable, providing evidence of the feasibility and appropriateness of the program.Conclusion: The app-based program demonstrated feasibility of deploying the app across user groups and high acceptability.
View details for PubMedID 30374444
Accelerated failure time model under general biased sampling scheme
2016; 17 (3): 576-588
Right-censored time-to-event data are sometimes observed from a (sub)cohort of patients whose survival times can be subject to outcome-dependent sampling schemes. In this paper, we propose a unified estimation method for semiparametric accelerated failure time models under general biased estimating schemes. The proposed estimator of the regression covariates is developed upon a bias-offsetting weighting scheme and is proved to be consistent and asymptotically normally distributed. Large sample properties for the estimator are also derived. Using rank-based monotone estimating functions for the regression parameters, we find that the estimating equations can be easily solved via convex optimization. The methods are confirmed through simulations and illustrated by application to real datasets on various sampling schemes including length-bias sampling, the case-cohort design and its variants.
View details for DOI 10.1093/biostatistics/kxw008
View details for Web of Science ID 000379762000012
View details for PubMedID 26941240
View details for PubMedCentralID PMC5006413
A Unified Approach to Semiparametric Transformation Models Under General Biased Sampling Schemes
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
2013; 108 (501): 217-227
We propose a unified estimation method for semiparametric linear transformation models under general biased sampling schemes. The new estimator is obtained from a set of counting process-based unbiased estimating equations, developed through introducing a general weighting scheme that offsets the sampling bias. The usual asymptotic properties, including consistency and asymptotic normality, are established under suitable regularity conditions. A closed-form formula is derived for the limiting variance and the plug-in estimator is shown to be consistent. We demonstrate the unified approach through the special cases of left truncation, length-bias, the case-cohort design and variants thereof. Simulation studies and applications to real data sets are presented.
View details for DOI 10.1080/01621459.2012.746073
View details for Web of Science ID 000316648200017
View details for PubMedCentralID PMC3649773
- Rejoinder to "A Note on Using Regression Models to Analyze Randomized Trials: Asymptotically Valid Hypothesis Tests Despite Incorrectly Specified Models" BIOMETRICS 2013; 69 (1)
Validation of Reported Predialysis Nephrology Care of Older Patients Initiating Dialysis
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2012; 23 (6): 1078-1085
The Centers for Medicare and Medicaid Services (CMS) Medical Evidence Report (form CMS-2728) queries providers about the timing of the patient's first nephrologist consultation before initiation of dialysis. The monitoring of disease-specific goals in the Healthy People 2020 initiative will use information from this question, but the accuracy of the reported information is unknown. We defined a cohort of 80,509 patients aged ≥67 years who initiated dialysis between July 2005 and December 2008 with ≥2 years of uninterrupted Medicare coverage as their primary payer. The primary referent, determined from claims data, was the first observed outpatient nephrologist consultation; secondary analyses used the earliest nephrology consultation, whether inpatient or outpatient. We used linear regression models to assess the associations among the magnitude of discrepant reporting and patient characteristics and we tested for any temporal trends. When using the earliest recorded outpatient nephrology encounter, agreement between the two sources of ascertainment was 48.2%, and the κ statistic was 0.29 when we categorized the timing of the visit into four periods (never, <6, 6-12, and >12 months). When we dichotomized the timing of first predialysis nephrology care at >12 or ≤12 months, accuracy was 70% (κ=0.36), but it differed by patient characteristics and declined over time. In conclusion, we found substantial disagreement between information from the CMS Medical Evidence Report and Medicare physician claims on the timing of first predialysis nephrologist care. More-specific instructions may improve reporting and increase the utility of form CMS-2728 for research and public health surveillance.
View details for DOI 10.1681/ASN.2011080871
View details for PubMedID 22518002
- A composite likelihood approach for spatially correlated survival data Computational Statistics and Data Analysis 2012; 56 (1): 209-216
Attitudes Regarding Enrollment in a Genetic Research Project: An Informed Consent Simulation Study Comparing Views of People With Depression, Diabetes, and Neither Condition.
Journal of empirical research on human research ethics : JERHRE
In this study, participants with a self-reported history of depression, diabetes, or no illness underwent a simulated informed consent process for a hypothetical genetic study related to depression or diabetes. Participants completed a survey assessing their perceived understanding of the research process, perceptions of its risks and benefits, their satisfaction with the informed consent process, and their readiness to make a hypothetical enrollment decision. All participants indicated strong readiness to make an enrollment decision regarding the research characterized in the simulation. Participants reported understanding the consent process relatively well and being generally satisfied with it. Greater concerns were expressed regarding psychosocial risks than biological risks for genetic studies on mental disorders. Our study documented positive attitudes toward volunteering for research that involved the collection of genetic data.
View details for DOI 10.1177/1556264619862467
View details for PubMedID 31328612
Do human subject safeguards matter to potential participants in psychiatric genetic research?
Journal of psychiatric research
2019; 116: 95–103
Despite longstanding concerns about the adequacy of human research protections in mental illness investigations, minimal work has focused on the perspectives of key stakeholders regarding these safeguards. This investigation examined the perspectives of potential research participants regarding safeguards for psychiatric genetic research. Individuals with mental illness (n = 71), first-degree family members of individuals with mental illness (n = 54), and individuals with no personal or close family history of mental illness (n = 57) provided responses to items regarding perceptions of: 1) protectiveness of a range of research safeguards in genetic research on mental illness; 2) influence of these safeguards on research participation decision-making; and 3) importance of these safeguards depending on the nature of the research (i.e., genetic vs. non-genetic mental illness research; and genetic research on mental illness vs. physical illness). Potential research participants perceived existing safeguard procedures as generally protective. The three groups did not differ in their ratings of protectiveness, with the exception of the safeguard domain of "Informed Consent or Alternative Decision-Making Procedures," which was viewed as more protective by family members of people with mental illness than by individuals with mental illness or comparison participants. Safeguard procedures were perceived as strongly influential with respect to willingness to enroll in psychiatric genetic research. These findings suggest that the presence of safeguards positively influences enrollment decision-making by research volunteers and indicate that potential psychiatric genetic research participants find safeguards to be protective, underscoring the responsibility to implement safeguard practices conscientiously.
View details for DOI 10.1016/j.jpsychires.2019.06.004
View details for PubMedID 31226581
Views of the importance of psychiatric genetic research by potential volunteers from stakeholder groups.
Journal of psychiatric research
2018; 106: 69–73
Few studies have explored potential volunteers' attitudes toward genetic research. To address this gap in the literature, we developed an empirical project to document views held by individuals who may wish to enroll in genetic studies involving mental disorders. People living with mental illness, family members of people with mental illness, and community comparison volunteers were queried regarding their views on the importance of genetic research generally, in comparison with medical research, and in relation to 12 health conditions categorized in four types. T-tests and univariate and multivariate analysis of variance were used as appropriate. Participants expressed support for the importance of genetic research (mean = 9.43, scale = 1-10) and endorsed genetic research more highly compared with non-genetic medical research (mean = 9.43 vs. 8.69, P value = <0.001). The most highly endorsed genetic research was for cognitive disorders, followed by mental illness disorders, physical illness disorders, and addiction disorders (means = 8.88, 8.26, 8.16 and 7.55, respectively, P value = <0.001). Overall, this study provides evidence of strong endorsement of genetic research over non-genetic research by potential volunteers.
View details for PubMedID 30292779
Perspectives of psychiatric investigators and IRB chairs regarding benefits of psychiatric genetics research.
Journal of psychiatric research
2018; 106: 54–60
There is hope that psychiatric genetics inquiry will provide important insights into the origins and treatment of mental illness given the burden of these conditions. We sought to examine perspectives of psychiatric genetic investigators regarding the potential benefits of genetic research in general and the potential benefits of genetic research for the diagnosis and treatment of mental illnesses specifically. We compared investigator attitudes with those of chairs of Institutional Review Boards (IRBs) entrusted with evaluating the benefits and risks of human research studies. Two groups directly engaged with the conduct and oversight of psychiatric genetic research were examined (psychiatric investigators, n = 203; IRB Chairs, n = 183). Participants rated 15 survey items regarding current and future benefits of general genetic research, possible benefits of psychiatric genetic research, and the importance to society of genetic vs. non-genetic research examining causes and treatments of illnesses. Investigators and IRB Chairs strongly endorsed the future benefits of general genetic research for society and for the health of individuals; compared to IRB Chairs, investigators were more positive about these benefits. Even after adjusting for demographic variables, psychiatric genetic investigators were significantly more optimistic about genetic research compared with IRB Chairs. Both groups were moderately optimistic about the possible benefits of genetic research related to mental illness. Greater optimism was seen regarding new or personalized medications for mental illnesses, as well as genetic predictive testing of mental illnesses. Greater precision and circumspection about the potential benefits of psychiatric genetic research are needed.
View details for PubMedID 30273801
Does informed consent given by healthy individuals when enrolling in clinical research feel less voluntary than for ill individuals?
Journal of psychiatric research
2018; 103: 33–37
Clinical research is predicated ethically on the authentic voluntarism of individuals who choose to enroll in human studies. Existing literature has focused on aspects of informed consent for clinical research other than voluntarism. The objective of this study was to compare the perspectives of clinical research participants who are in good health and who are ill regarding voluntarism-related aspects of informed consent and to assess situational influences that enable voluntarism in the process of obtaining clinical research consent. A 23-item written survey, the Informed Consent Questionnaire (ICQ), was administered in a "piggyback" semi-structured interview study of ill and healthy volunteers enrolled in IRB-approved clinical research studies. A total of 150 (60 mentally ill, 43 physically ill, and 47 healthy) clinical research participants participated. Respondents expressed positive views of their experiences with the informed consent processes for their respective clinical research protocols and respondents strongly endorsed items related to voluntarism irrespective of their illness type (range of means = [3.9, 4.8]). Ill participants more highly endorsed items relating to informed consent conditions (mentally ill vs healthy: 0.54 on a 5-point scale, P value = 0.01) (physically ill vs. healthy: 0.47 on a 5-point scale, P value = 0.01). The favorable views of clinical research participants regarding their experience of giving informed consent to enroll in a study were not surprising. Contrary to our a priori hypothesis, healthy individuals did not feel as positively as their ill counterparts.
View details for PubMedID 29772484
Subgrouping the users of a specialized app for eating disorders.
Although mobile technologies for eating disorders (EDs) are burgeoning, there is limited data about the clinical characteristics of individuals using specialized smartphone applications (apps) without accompanying traditional forms of treatment. This study evaluated whether the users of an ED app cluster in clinically meaningful groups. Participants were 1,280 app users (91.3% female; mean age 27) who reported not being in a weekly treatment for their ED. A hierarchical cluster analysis distinguished five groups of participants, all approximating DSM-5 ED categories. One cluster comprised of non-female, ethnically diverse users with Bulimia Nervosa features. Findings suggest that app users resemble known patient classifications.
View details for PubMedID 29452025
The Transition to Precision Psychiatry and Pragmatic Inquiry Methods in Academic Psychiatry: The Example of Point-of-Care Clinical Trials.
Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry
View details for PubMedID 29134550
Receptiveness to participation in genetic research: A pilot study comparing views of people with depression, diabetes, or no illness
JOURNAL OF PSYCHIATRIC RESEARCH
2017; 94: 156–62
Genetic research in human health relies on the participation of individuals with or at-risk for different types of diseases, including health conditions that may be stigmatized, such as mental illnesses. This preliminary study examines the differences in attitudes toward participation in genetic research among individuals with a psychiatric disorder, individuals with a physical disorder, and individuals with no known illness.Seventy-nine individuals with a history of diabetes or depression, or no known illness, underwent a simulated consent process for a hypothetical genetic research study. They were then surveyed about their willingness to participate in the hypothetical study and their attitudes about future and family participation in genetic research.Participants with and without a history of depression ranked participating in genetic and medical research as very important and indicated that they were likely to participate in the hypothetical genetics study. Expressed willingness to participate was generally stable and consistent with future willingness. Individuals less strongly endorsed willingness to ask family members to participate in genetic research.Individuals with and without a history of mental illness viewed genetic and medical research favorably and expressed willingness to participate in real-time and in the future. Informed consent processes ideally include an exploration of influences upon volunteers' enrollment decisions. Additional empirical study of influences upon genetic research participation is important to ensure that volunteers' rights are respected and that conditions that greatly affect the health of the public are not neglected scientifically.
View details for PubMedID 28719815
View details for PubMedCentralID PMC5621512
Lifetime anxiety disorder and current anxiety symptoms associated with hastened depressive recurrence in bipolar disorder.
Journal of affective disorders
2017; 219: 165-171
To assess differential relationships between lifetime anxiety disorder/current anxiety symptoms and longitudinal depressive severity in bipolar disorder (BD).Stanford BD Clinic outpatients enrolled during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form while receiving naturalistic treatment for up to two years. Baseline unfavorable illness characteristics/current mood symptoms and times to depressive recurrence/recovery were compared in patients with versus without lifetime anxiety disorder/current anxiety symptoms.Among 105 currently recovered patients, lifetime anxiety disorder was significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics, hastened depressive recurrence (driven by earlier onset age), and a significantly (> two-fold) higher Kaplan-Meier estimated depressive recurrence rate, whereas current anxiety symptoms were significantly associated with 10/27 (37.0%) demographic/other unfavorable illness characteristics/current mood symptoms/current psychotropics and hastened depressive recurrence (driven by lifetime anxiety disorder), but only a numerically higher Kaplan-Meier estimated depressive recurrence rate. In contrast, among 153 currently depressed patients, lifetime anxiety disorder/current anxiety symptoms were not significantly associated with time to depressive recovery or depressive recovery rate.American tertiary BD clinic referral sample, open naturalistic treatment.Research is needed regarding differential relationships between lifetime anxiety disorder and current anxiety symptoms and hastened/delayed depressive recurrence/recovery - specifically whether lifetime anxiety disorder versus current anxiety symptoms has marginally more robust association with hastened depressive recurrence, and whether both have marginally more robust associations with hastened depressive recurrence versus delayed depressive recovery, and related clinical implications.
View details for DOI 10.1016/j.jad.2017.05.007
View details for PubMedID 28558363
Healthy individuals' perspectives on clinical research protocols and influences on enrollment decisions
AJOB Empirical Bioethics
2017; 8 (2): 89-98
View details for DOI 10.1080/23294515.2016.1271062
Perceptions of the Professional Development Value of Honorary Fellowship Award Experiences.
2016; 40 (5): 761-767
Professional societies engage in activities with the aim of nurturing highly talented early career members of their field. Little is known about the value of honorary fellowship awards given annually by professional societies. Following up on the only known prior study of this topic, authors queried fellowship awardees in one psychiatric society to better understand the perceived value of honorary fellowships and other outcomes, such as subsequent involvement in professional societies.The authors queried former participants in the Laughlin and Psychiatry Resident-In-Training Examination® (PRITE®) Programs regarding their fellowship experiences and their subsequent involvement in The American College of Psychiatrists and other psychiatry membership organizations. The authors obtained frequency data and analyzed responses using t-tests and chi-squared tests. Associations between the outcomes and demographic characteristics such as age, gender, and fellowship type was tested.Responses were gathered from 143 individuals who had participated in the Laughlin Fellowship and 22 in the PRITE Fellowship. Respondents felt that that the fellowship experience had been helpful professionally. Laughlin fellows were older and more likely to have assumed a leadership role in professional organizations (60 % vs 36 %, p = 0.04). Laughlin fellows also more strongly endorsed professional recognition as a benefit at the time of receiving their award. Survey respondents reported increased participation in professional organizations and assumed leadership roles in The College and other professional organizations subsequent to the fellowship experience.On the whole, fellows were generally positive about their experiences. Many respondents became involved with The College subsequent to their fellowship, but a larger proportion became involved with other organizations, including in leadership roles. Professional societies with early career programs such as the Laughlin Fellowship and the PRITE Fellowship appear to identify and support future leaders as intended, but these leaders may engage more with other professional societies.
View details for DOI 10.1007/s40596-015-0482-y
View details for PubMedID 26911491
Are individuals living with mental illness and their preferred alternative decision-makers attuned and aligned in-their attitudes regarding treatment decisions?
JOURNAL OF PSYCHIATRIC RESEARCH
2016; 78: 42-47
Mental disorders account for considerable suffering and societal burden. Prospective alternative decision-makers may be engaged in helping make treatment decisions for those who live with serious mental disorders. Little is known about the ways in which alternative decision makers arrive at treatment recommendations and whether the perspectives of alternative decision makers and ill individuals are aligned.The authors queried community-dwelling individuals diagnosed with schizophrenia, anxiety, or mood disorders and their preferred alternative decision-makers on issues regarding treatment decisions and underlying ethically-salient perspectives using a written survey instrument. Complete data were obtained on 26 pairs (n = 52, total). Outcomes included perspectives on clinical decision-making and underlying values that may shape their life choices. Two-sided paired t-tests and graphical representations were used.We found that preferred alternative decision-makers overall accurately predicted the views of ill individuals with respect to the role of the individual and of family in treatment decision making. Preferred alternative decision-makers slightly overestimated autonomy-related perspectives. The personal views of ill individuals and preferred alternative decision-makers were aligned with respect to different physical and mental disorders, except in relation to alcohol and substance use where alternative decision-makers placed greater emphasis on autonomy. Alignment was also discovered on underlying life values, except the role of spirituality which was greater among alternative decision-makers.Preferred alternative decision-makers are an ethical safeguard to ensure the wellbeing and rights of seriously ill individuals. In this pilot study, preferred alternative decision makers were aligned with their ill family members concerning treatment-related decisions and underlying life values. Future research should continue to explore and clarify the views of ill individuals and alternative decision makers to determine the quality of this safeguard used in clinical settings.
View details for DOI 10.1016/j.jpsychires.2016.03.004
View details for PubMedID 27058644
Attunement and alignment of people with schizophrenia and their preferred alternative decision-makers: An exploratory pilot study comparing treatment and research decisions
JOURNAL OF PSYCHIATRIC RESEARCH
2015; 71: 70-77
Schizophrenia is a serious mental disorder that may affect the decisional capacity, and as a consequence, preferred alternative decision-makers may be engaged to help with clinical care and research-related choices. Ideally, alternative decision-makers will seek to make decisions that fit with the views and preferences of the ill individual. Few data exist, however, comparing the views of alternative decision-makers to those of individuals with schizophrenia.We conducted a written survey with individuals with schizophrenia living in a community setting, and a parallel survey with the person whom the ill individual identified as being a preferred alternative decision-maker. Complete data were obtained on 20 pairs (n = 40, total). Domains queried included (a) burden, happiness, and safety of the ill individual and of his or her family in treatment and research decisions and (b) importance of ethical principles in every day life. Two-sided paired t-tests and graphical summaries were used to compare responses.Individuals with schizophrenia and their linked preferred alternative decision-makers were attuned on four of six aspects of treatment decision-making and on all six aspects of research decision-making that we queried.The preferred alternative decision-makers overall demonstrated attunement to the views of the ill individuals in this small study. Ill individuals and their preferred alternative decision-makers were aligned in their views of ethically-salient aspects of every day life. These novel findings suggest that alternative decision-makers identified by ill individuals may be able to guide choices based on an accurate understanding of the ill individuals' views and values.
View details for DOI 10.1016/j.jpsychires.2015.09.014
View details for Web of Science ID 000365053900009
View details for PubMedID 26453915
Informal Health Care Practices of Residents: "Curbside" Consultation and Self-Diagnosis and Treatment
2015; 39 (1): 22-30
The authors explore the experiences of residents with respect to informal care related to personal health, including "curbside consultation," self-diagnosis, and self-prescription-self-care practices that run counter to ethical guidelines in medicine.Residents at one medical school completed a written survey regarding their personal health care practices, including their experiences in seeking or providing informal consultation, self-diagnosis, and self-prescribing. The authors obtained frequency data and analyzed responses via cross-tabulation. They used logistic regression models to assess the association of reported informal care practices and potential confounders, such as age, gender, and training program.One hundred and fifty-five residents volunteered (71 % response rate). Most respondents had sought health care formally (70 %), and more had sought informal care in the previous 12 months (80 %). Of those who had pursued informal care, 90 % endorsed having requested a physical exam, a laboratory test, or a medication prescription from an attending, resident, or medical student. Respondents (28 %) commonly endorsed prescribing medication for themselves. Most respondents (90 %) reported being approached for informal care at least once in the previous year, including 84 % who were approached for prescriptions and 22 % who were approached by attending physicians. Main reasons endorsed for informal care seeking related to busy schedules and to cost and confidentiality advantages. Psychiatry residents reported using both formal and informal channels for personal health care, and 31 % acknowledged prescribing medications for themselves.Informal care was a common practice among the residents in this study. Residents reported time constraints as the greatest influence on informal care seeking, rather than reasons found in previous studies related to cost and quality of care, protection of confidentiality, or prevention of embarrassment. The effects of informal care practices involving resident physicians warrant additional study.
View details for DOI 10.1007/s40596-014-0170-3
View details for Web of Science ID 000349304800005
View details for PubMedID 24923781
- Caring for patients takes time: dr. Peabody says so! Academic psychiatry 2015; 39 (1): 1-5
Giving voice to study volunteers: Comparing views of mentally ill, physically ill, and healthy protocol participants on ethical aspects of clinical research
JOURNAL OF PSYCHIATRIC RESEARCH
2014; 56: 90-97
Ethical controversy surrounds clinical research involving seriously ill participants. While many stakeholders have opinions, the extent to which protocol volunteers themselves see human research as ethically acceptable has not been documented. To address this gap of knowledge, authors sought to assess views of healthy and ill clinical research volunteers regarding the ethical acceptability of human studies involving individuals who are ill or are potentially vulnerable.Surveys and semi-structured interviews were used to query clinical research protocol participants and a comparison group of healthy individuals. A total of 179 respondents participated in this study: 150 in protocols (60 mentally ill, 43 physically ill, and 47 healthy clinical research protocol participants) and 29 healthy individuals not enrolled in protocols. Main outcome measures included responses regarding ethical acceptability of clinical research when it presents significant burdens and risks, involves people with serious mental and physical illness, or enrolls people with other potential vulnerabilities in the research situation.Respondents expressed decreasing levels of acceptance of participation in research that posed burdens of increasing severity. Participation in protocols with possibly life-threatening consequences was perceived as least acceptable (mean = 1.82, sd = 1.29). Research on serious illnesses, including HIV, cancer, schizophrenia, depression, and post-traumatic stress disorder, was seen as ethically acceptable across respondent groups (range of means = [4.0, 4.7]). Mentally ill volunteers expressed levels of ethical acceptability for physical illness research and mental illness research as acceptable and similar, while physically ill volunteers expressed greater ethical acceptability for physical illness research than for mental illness research. Mentally ill, physically ill, and healthy participants expressed neutral to favorable perspectives regarding the ethical acceptability of clinical research participation by potentially vulnerable subpopulations (difference in acceptability perceived by mentally ill - healthy = -0.04, CI [-0.46, 0.39]; physically ill - healthy = -0.13, CI [-0.62, -.36]).Clinical research volunteers and healthy clinical research-"naïve" individuals view studies involving ill people as ethically acceptable, and their responses reflect concern regarding research that poses considerable burdens and risks and research involving vulnerable subpopulations. Physically ill research volunteers may be more willing to see burdensome and risky research as acceptable. Mentally ill research volunteers and healthy individuals expressed similar perspectives in this study, helping to dispel a misconception that those with mental illness should be presumed to hold disparate views.
View details for DOI 10.1016/j.jpsychires.2014.05.007
View details for Web of Science ID 000340318600012
View details for PubMedID 24931849
View details for PubMedCentralID PMC4109648
Do investigators understand ethically-important perspectives of clinical research participants?: A 'piggy-back' study of attunement and alignment in serious illness research.
Journal of psychiatric research
2014; 52: 36-43
The authors sought to compare investigators' predictions of clinical research participants' attitudes regarding ethically-important considerations in serious illness research with attitudes expressed by participants ("attunement"), to compare the personal attitudes of investigators and clinical research participants ("alignment"), and to explore the association between views expressed and covariates.The authors queried clinical research participants with either physical or mental illness (n=100) and faculty investigators conducting the clinical research protocols in which these participants were enrolled (n=77). Outcomes included attitudes regarding importance of medical research, attributes of seriously ill people in the research situation, and influences on enrollment decisions by seriously ill people. Generalized estimating equations and linear regression models were used.Investigators underestimated the importance of research about physical illness, mental illness, and healthy people to participants (βPI=0.59, 95% CI [0.36, 0.83]; βMI=0.60, 95% CI [0.27, 0.92]; βH=0.93, 95% CI [0.57, 1.29]). Investigators incorrectly predicted that participants would assess seriously ill people as more vulnerable in the research situation than participants did (β=-0.68, 95% CI [-1.11, -0.25]). Investigators and participants were aligned on the importance of illness research. Participants expressed greater agreement than investigators regarding the influences of ill individuals indicative of will and cognition in their enrollment decisions (β=0.69, 95% CI [0.25, 1.13]).Investigators are attuned to and aligned with research participants in many, but not all, respects. Investigators may bring a protective bias in their predictions of the vulnerabilities of ill volunteers.
View details for DOI 10.1016/j.jpsychires.2014.01.012
View details for PubMedID 24507883
Moving Beyond Community Mental Health: Public Mental Health as an Emerging Focus for Psychiatry Residency Training.
Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry
View details for PubMedID 25339288
Randomized Clinical Trial to Evaluate the Efficacy and Safety of Valganciclovir in a Subset of Patients With Chronic Fatigue Syndrome
JOURNAL OF MEDICAL VIROLOGY
2013; 85 (12): 2101-2109
There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted.
View details for DOI 10.1002/jmv.23713
View details for PubMedID 23959519
Real-Time Optical Biopsy of Colon Polyps With Narrow Band Imaging in Community Practice Does Not Yet Meet Key Thresholds for Clinical Decisions
2013; 144 (1): 81-91
Accurate optical analysis of colorectal polyps (optical biopsy) could prevent unnecessary polypectomies or allow a "resect and discard" strategy with surveillance intervals determined based on the results of the optical biopsy; this could be less expensive than histopathologic analysis of polyps. We prospectively evaluated real-time optical biopsy analysis of polyps with narrow band imaging (NBI) by community-based gastroenterologists.We first analyzed a computerized module to train gastroenterologists (N = 13) in optical biopsy skills using photographs of polyps. Then we evaluated a practice-based learning program for these gastroenterologists (n = 12) that included real-time optical analysis of polyps in vivo, comparison of optical biopsy predictions to histopathologic analysis, and ongoing feedback on performance.Twelve of 13 subjects identified adenomas with >90% accuracy at the end of the computer study, and 3 of 12 subjects did so with accuracy ≥90% in the in vivo study. Learning curves showed considerable variation among batches of polyps. For diminutive rectosigmoid polyps assessed with high confidence at the end of the study, adenomas were identified with mean (95% confidence interval [CI]) accuracy, sensitivity, specificity, and negative predictive values of 81% (73%-89%), 85% (74%-96%), 78% (66%-92%), and 91% (86%-97%), respectively. The adjusted odds ratio for high confidence as a predictor of accuracy was 1.8 (95% CI, 1.3-2.5). The agreement between surveillance recommendations informed by high-confidence NBI analysis of diminutive polyps and results from histopathologic analysis of all polyps was 80% (95% CI, 77%-82%).In an evaluation of real-time optical biopsy analysis of polyps with NBI, only 25% of gastroenterologists assessed polyps with ≥90% accuracy. The negative predictive value for identification of adenomas, but not the surveillance interval agreement, met the American Society for Gastrointestinal Endoscopy-recommended thresholds for optical biopsy. Better results in community practice must be achieved before NBI-based optical biopsy methods can be used routinely to evaluate polyps; ClinicalTrials.gov number, NCT01638091.
View details for DOI 10.1053/j.gastro.2012.09.054
View details for Web of Science ID 000312965100029
View details for PubMedID 23041328
Donor Recipient Sex Mismatch in Kidney Transplantation
2012; 9 (5): 335-347
The lack of reliable human proxies for minor (ie, non-HLA) histocompatibility loci hampers the ability to leverage these factors toward improving transplant outcomes. Despite conflicting reports of the effect of donor-recipient sex mismatch on renal allografts, the association between acute rejection of renal allografts and the development of human alloantibodies to the male H-Y antigen suggested to us that donor-recipient sex mismatch deserved re-evaluation.To evaluate whether the relationships between donor sex and allograft failure differed by recipient sex.We studied recipients of deceased-donor (n = 125,369) and living-donor (n = 63,139) transplants in the United States Renal Data System. Using Cox proportional hazards models stratified by donor type, we estimated the association between donor-recipient sex mismatch and death-censored allograft failure with adjustment for known risk factors, with and without the use of multiple imputation methods to account for potential bias and/or loss of efficiency due to missing data.The advantage afforded by male donor kidneys was more pronounced among male than among female recipients (8% vs 2% relative risk reduction; interaction P < 0.01). This difference is of the order of magnitude of several other risk factors affecting donor selection decisions.Donor-recipient sex mismatch affects renal allograft survival in a direction consistent with immune responses to sexually determined minor histocompatibility antigens. Our study provides a paradigm for clinical detection of markers for minor histocompatibility loci.
View details for DOI 10.1016/j.genm.2012.07.004
View details for PubMedID 22906727
The diagnostic yield of CT-guided percutaneous lung biopsy in solid organ transplant recipients
2012; 26 (4): 615-621
Despite the widespread use of computed tomography(CT)-guided percutaneous lung biopsy (PLB) in immunocompetent patients, the diagnostic yield and safety in solid organ transplant (SOT)recipients is unknown. The purpose of this investigation was to determine the test performance of CT-PLB in SOT recipients.We performed a 10-yr single-center, retrospective analysis among heart, lung, kidney, and liver transplant recipients. We included all adult patients who underwent a PLB of a parenchymal lung nodule following their transplantation.Within the study period, 1754 SOTs were performed, of which 45 biopsies met study criteria. Overall, the incidence of PLB in SOT was 3%.PLB established a diagnosis in 24 of 45 cases. The yield of PLB was better for combined biopsy technique (fine-needle aspiration biopsy [FNAB]) and core biopsy than for FNAB alone (odds ratio [OR]: 4.2, 95% confidence interval [CI]: 1.2, 15.6), and for lesions that were malignant (OR: 10.0, 95%CI: 1.8, 75.4) or caused by an invasive fungal infection (OR: 5.0, 95% CI:1.1, 27.9). Complications occurred in 13% (6/45) of patients.CT-guided PLB is a safe modality that provides a moderate yield for diagnosing pulmonary nodules of malignant or fungal etiology in SOT recipients.
View details for DOI 10.1111/j.1399-0012.2011.01582.x
View details for Web of Science ID 000307344400032
View details for PubMedID 23050274
View details for PubMedCentralID PMC3473075
Trends in Acute Nonvariceal Upper Gastrointestinal Bleeding in Dialysis Patients
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2012; 23 (3): 495-506
Impaired kidney function is a risk factor for upper gastrointestinal (GI) bleeding, an event associated with poor outcomes. The burden of upper GI bleeding and its effect on patients with ESRD are not well described. Using data from the US Renal Data System, we quantified the rates of occurrence of and associated 30-day mortality from acute, nonvariceal upper GI bleeding in patients undergoing dialysis; we used medical claims and previously validated algorithms where available. Overall, 948,345 patients contributed 2,296,323 patient-years for study. The occurrence rates for upper GI bleeding were 57 and 328 episodes per 1000 person-years according to stringent and lenient definitions of acute, nonvariceal upper GI bleeding, respectively. Unadjusted occurrence rates remained flat (stringent) or increased (lenient) from 1997 to 2008; after adjustment for sociodemographic characteristics and comorbid conditions, however, we found a significant decline for both definitions (linear approximation, 2.7% and 1.5% per year, respectively; P<0.001). In more recent years, patients had higher hematocrit levels before upper GI bleeding episodes and were more likely to receive blood transfusions during an episode. Overall 30-day mortality was 11.8%, which declined significantly over time (relative declines of 2.3% or 2.8% per year for the stringent and lenient definitions, respectively). In summary, despite declining trends worldwide, crude rates of acute, nonvariceal upper GI bleeding among patients undergoing dialysis have not decreased in the past 10 years. Although 30-day mortality related to upper GI bleeding declined, perhaps reflecting improvements in medical care, the burden on the ESRD population remains substantial.
View details for DOI 10.1681/ASN.2011070658
View details for PubMedID 22266666
Validity of Surrogate Measures for Functional Nephron Mass
2011; 92 (12): 1335-1341
Transplanted nephron mass is an important determinant of long-term allograft survival, but accurate assessment before organ retrieval is challenging. Newer radiologic imaging techniques allow for better determination of total kidney and cortical volumes.Using volume measurements reconstructed from magnetic resonance or computed tomography imaging from living donor candidates, we characterized total kidney (n=312) and cortical volumes (n=236) according to sex, age, weight, height, body mass index (BMI), and body surface area (BSA).The mean cortical volume was 204 mL (range 105-355 mL) with no significant differences between left and right cortical volumes. The degree to which existing anthropomorphic surrogates predict nephron mass was quantified, and a diligent attempt was made to derive a better surrogate model for nephron mass. Cortical volumes were strongly associated with sex and BSA, but not with weight, height, or BMI. Four prediction models for cortical volume constructed using combinations of age, sex, race, weight, and height were compared with models including either BSA or BMI.Among existing surrogate measures, BSA was superior to BMI in predicting renal cortical volume. We were able to construct a statistically superior proxy for cortical volume, but whether relevant improvements in predictive accuracy could be gained needs further evaluation in a larger population.
View details for DOI 10.1097/TP.0b013e31823705ef
View details for PubMedID 22011765
Intradialytic Hypotension and Vascular Access Thrombosis
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2011; 22 (8): 1526-1533
Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.
View details for DOI 10.1681/ASN.2010101119
View details for PubMedID 21803971
Epidemiologic trends in penile anomalies and hypospadias in the state of California, 1985-2006
JOURNAL OF PEDIATRIC UROLOGY
2011; 7 (3): 294-298
Using statewide data, we evaluated whether the changing incidence of penile anomalies and hypospadias is reflected in the diverse California population of newborn males over the past 20 years.Discharge data from all California hospitals, prepared by the OSHPD (Sacramento, CA) was reviewed for the years 1985-2006 for male infant births with an ICD-9 code (752.6) for hypospadias, epispadias or other penile anomalies. Trends were examined by Generalized Estimation Equations for Poisson regression.From 1985 to 2006, the birth incidence of newborn penile anomalies increased in California from 47 to 57 cases per 10,000 newborn discharges, yet the trend for hypospadias alone appears stable from 1997. The rates for penile anomalies in newborns increased 1.4% annually (p < 0.001). All racial/ethnic groups analyzed showed this increase (p < 0.001 for each). During the study period there was a 2% increase per year in plural births (p < 0.001). Interestingly, the rate of change in penile anomaly incidence was greater in males of plural births compared to their singleton cohorts (2% vs 1% annually) (p < 0.001). The birth incidence of cleft palate, another congenital anomaly known to be stable over time, remained unchanged over this period.From 1985 to 2006 in California the incidence of penile anomalies increased in a statistically significant manner, but the incidence of hypospadias appears stable for the last decade. Our data support the notion that different racial/ethnic groups have distinct incidences of penile anomaly formation and that an association with plural births appears to be present.
View details for DOI 10.1016/j.jpurol.2011.03.006
View details for PubMedID 21527236
Updated comorbidity assessments and outcomes in prevalent hemodialysis patients
2010; 14 (4): 478-485
When evaluating clinical characteristics and outcomes in patients on hemodialysis, the prevalence and severity of comorbidity may change over time. Knowing whether updated assessments of comorbidity enhance predictive power will assist the design of future studies. We conducted a secondary data analysis of 1846 prevalent hemodialysis patients from 15 US clinical centers enrolled in the HEMO study. Our primary explanatory variable was the Index of Coexistent Diseases score, which aggregates comorbidities, as a time-constant and time-varying covariate. Our outcomes of interest were all-cause mortality, time to first hospitalization, and total hospitalizations. We used Cox proportional hazards regression. Accounting for an updated comorbidity assessment over time yielded a more robust association with mortality than accounting for baseline comorbidity alone. The variation explained by time-varying comorbidity assessments on time to death was greater than age, baseline serum albumin, diabetes, or any other covariates. There was a less pronounced advantage of updated comorbidity assessments on determining time to hospitalization. Updated assessments of comorbidity significantly strengthen the ability to predict death in patients on hemodialysis. Future studies in dialysis should invest the necessary resources to include repeated assessments of comorbidity.
View details for DOI 10.1111/j.1542-4758.2010.00468.x
View details for PubMedID 20955281