Smoller Lab at PNGU


Accuracy Requirements for Cost-effective Suicide Risk Prediction Among Primary Care Patients in the US

Ross EL, Zuromski KL, Reis BY, Nock MK, Kessler RC, Smoller JW - JAMA Psychiatry doi: 10.1001/jamapsychiatry.2021.0089.
Importance: Several statistical models for predicting suicide risk have been developed, but how accurate such models must be to warrant implementation in clinical practice is not known.
Objective: To identify threshold values of sensitivity, specificity, and positive predictive value that a suicide risk prediction method must attain to cost-effectively target a suicide risk reduction intervention to high-risk individuals.
Design, setting, and participants: This economic evaluation incorporated published data on suicide epidemiology, the health care and societal costs of suicide, and the costs and efficacy of suicide risk reduction interventions into a novel decision analytic model. The model projected suicide-related health economic outcomes over a lifetime horizon among a population of US adults with a primary care physician. Data analysis was performed from September 19, 2019, to July 5, 2020.
Interventions: Two possible interventions were delivered to individuals at high predicted risk: active contact and follow-up (ACF; relative risk of suicide attempt, 0.83; annual health care cost, $96) and cognitive behavioral therapy (CBT; relative risk of suicide attempt, 0.47; annual health care cost, $1088).
Main outcomes and measures: Fatal and nonfatal suicide attempts, quality-adjusted life-years (QALYs), health care sector costs and societal costs (in 2016 US dollars), and incremental cost-effectiveness ratios (ICERs) (with ICERs ≤$150 000 per QALY designated cost-effective).
Results: With a specificity of 95% and a sensitivity of 25%, primary care-based suicide risk prediction could reduce suicide death rates by 0.5 per 100 000 person-years (if used to target ACF) or 1.6 per 100 000 person-years (if used to target CBT) from a baseline of 15.3 per 100 000 person-years. To be cost-effective from a health care sector perspective at a specificity of 95%, a risk prediction method would need to have a sensitivity of 17.0% or greater (95% CI, 7.4%-37.3%) if used to target ACF and 35.7% or greater (95% CI, 23.1%-60.3%) if used to target CBT. To achieve cost-effectiveness, ACF required positive predictive values of 0.8% for predicting suicide attempt and 0.07% for predicting suicide death; CBT required values of 1.7% for suicide attempt and 0.2% for suicide death.
Conclusions and relevance: These findings suggest that with sufficient accuracy, statistical suicide risk prediction models can provide good health economic value in the US. Several existing suicide risk prediction models exceed the accuracy thresholds identified in this analysis and thus may warrant pilot implementation in US health care systems.

Pleiotropy and Cross-Disorder Genetics Among Psychiatric Disorders

Lee PH, Feng YA, Smoller JW - Biological Psychiatry doi: 10.1016/j.biopsych.2020.09.026.

Genome-wide analyses of common and rare genetic variations have documented the heritability of major psychiatric disorders, established their highly polygenic genetic architecture, and identified hundreds of contributing variants. In recent years, these studies have illuminated another key feature of the genetic basis of psychiatric disorders: the important role and pervasive nature of pleiotropy. It is now clear that a substantial fraction of genetic influences on psychopathology transcend clinical diagnostic boundaries. In this review, we summarize evidence in psychiatry for pleiotropy at multiple levels of analysis: from overall genome-wide correlation to biological pathways and down to the level of individual loci. We examine underlying mechanisms of observed pleiotropy, including genetic effects on neurodevelopment, diverse actions of regulatory elements, mediated effects, and spurious associations of genomic variation with multiple phenotypes. We conclude with an exploration of the implications of pleiotropy for understanding the genetic basis of psychiatric disorders, informing nosology, and advancing the aims of precision psychiatry and genomic medicine.

Keywords: Cross-disorder; GWAS; Genetic correlation; Nosology; Pleiotropy; Precision psychiatry; Psychiatric genetics.


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