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Clinical trial data are the gold standard for evaluating pharmaceutical safety and efficacy. There is an ethical and scientific imperative for transparency and data sharing to confirm published results and generate new knowledge. The Open Translational Science in Schizophrenia (OPTICS) Project was an open-science initiative aggregating Janssen clinical trial and NIH/NIMH data from real-world studies and trials in schizophrenia. The project aims were to show the value of using shared data to examine: therapeutic safety and efficacy; disease etiologies and course; and methods development. The success of project investigators was due to collaboration from project applications through analyses, with support from the Harvard Catalyst. Project work was independent of Janssen; all intellectual property was dedicated to the public. Efforts such as this are necessary to gain deeper insights into the biology of disease, foster collaboration, and to achieve the goal of developing better treatments, reducing the overall public health burden of devastating brain diseases.

The Positive and Negative Syndrome Scale (PANSS) is frequently described with five latent factors, yet published factor models consistently fail to replicate across samples and related disorders. We hypothesize that (1) a subset of the PANSS, instead of the entire PANSS scale, would produce the most replicable five-factor models across samples, and that (2) the PANSS factor structure may be different depending on the treatment phase, influenced by the responsiveness of the positive symptoms to treatment. Using exploratory factor analysis, confirmatory factor analysis and cross validation on baseline and post-treatment observations from 3647 schizophrenia patients, we show that five-factor models fit best across samples when substantial subsets of the PANSS items are removed. The optimal model at baseline (five factors) omits 12 items: Motor Retardation, Grandiosity, Somatic Concern, Lack of Judgment and Insight, Difficulty in Abstract Thinking, Mannerisms and Posturing, Disturbance of Volition, Preoccupation, Disorientation, Excitement, Guilt Feelings and Depression. The PANSS factor models fit differently before and after patients have been treated. Patients with larger treatment response in positive symptoms have larger variations in factor structure across treatment stage than the less responsive patients. Negative symptom scores better predict the positive symptoms scores after treatment than before treatment. We conclude that sparse factor models replicate better on new samples, and the underlying disease structure of Schizophrenia changes upon treatment.

BackgroundCollecting longitudinal data during and shortly after pregnancy is difficult, as pregnant women often avoid studies with repeated surveys. In contrast, pregnant women interact with certain websites at multiple stages throughout pregnancy and the postpartum period. This digital connection presents the opportunity to use a website as a way to recruit and enroll pregnant women into a panel study and collect valuable longitudinal data for research. These data can then be used to learn new scientific insights and improve health care. ObjectiveThe objective of this paper is to describe the approaches applied and lessons learned from designing and conducting an online panel for health care research, specifically perinatal mood disorders. Our panel design and approach aimed to recruit a large sample (N=1200) of pregnant women representative of the US population and to minimize attrition over time. MethodsWe designed an online panel to enroll participants from the pregnancy and parenting website BabyCenter. We enrolled women into the panel from weeks 4 to 10 of pregnancy (Panel 1) or from weeks 28 to 33 of pregnancy (Panel 2) and administered repeated psychometric assessments from enrollment through 3 months postpartum. We employed a combination of adaptive digital strategies to recruit, communicate with, and build trust with participants to minimize attrition over time. We were transparent at baseline about expectations, used monetary and information-based incentives, and sent personalized reminders to reduce attrition. The approach was participant-centric and leveraged many aspects of flexibility that digital methods afford. ResultsWe recruited 1179 pregnant women—our target was 1200—during a 26-day period between August 25 and September 19, 2016. Our strategy to recruit participants using adaptive sampling tactics resulted in a large panel that was similar to the US population of pregnant women. Attrition was on par with existing longitudinal observational studies in pregnant populations, and 79.2% (934/1179) of our panel completed another survey after enrollment. There were 736 out of 1179 (62.4%) women who completed at least one assessment in both the prenatal and postnatal periods, and 709 out of 1179 (60.1%) women who completed the final assessment. To validate the data, we compared participation rates and factors of perinatal mood disorders ascertained from this study with prior research, suggesting reliability of our approach. ConclusionsA suitably designed online panel created in partnership with a digital media source that reaches the target audience is a means to leverage a conveniently sized and viable sample for scientific research. Our key lessons learned are as follows: sampling tactics may need to be adjusted to enroll a representative sample, attrition can be reduced by adapting to participants’ needs, and study engagement can be boosted by personalizing interactions with the flexibility afforded by digital technologies.

A genome wide linkage scan for opioid dependence (OD) and related traits is presented. An attempt is made to identify the chromosomal location of genes that increase risk of OD and related traits identified using data reduction and cluster analytic approaches.

The purpose of this case study is to assess a Medicaid health maintenance organization quality initiative designed to screen new members for behavioral health treatment needs on enrollment. New members [...]

Background. Previously, the authors have shown that an important component of the ability to survive to exceptionally old age is family health history. This study assessed the age at onset of age-related diseases in centenarian offspring. Methods. The health histories of 177 offspring of centenarians enrolled in the nationwide New England Centenarian Study, and 166 controls were assessed from 1997 to 2000. Controls were the offspring of parents born in the same years as the centenarians but at least one of whom died at average life expectancy. Ages at onset of heart disease, hypertension, diabetes, cancer, osteoporosis, cataracts, glaucoma, macular degeneration, depression, thyroid disease, and stroke were compared in the two groups. Results. The median ages of onset for coronary heart disease (p < .001), hypertension (p < .001), diabetes (p = .002), and stroke (p = .017) were significantly delayed in the centenarian offspring by 5.0, 2.0, 8.5, and 8.5 years, respectively, compared with the age-matched controls. Adjusted hazard ratios were 0.388 (p = .0004), 0.39 (p < .0001), 0.302 (p = .008), and 0.328 (p = .06). No differences were found in the ages of onset for the other diseases investigated. Conclusions. The offspring of centenarians show a marked delay in the age of onset for cardiovascular disease, diabetes, hypertension, and stroke but not for other age-related diseases such as cancer, osteoporosis, and thyroid disease. These results suggest that the children of centenarians may be following in their parents' footsteps, markedly delaying the onset of lethal diseases that commonly affect older persons.

Background. A significant component of the ability to survive to exceptional old age may be familial. This study assessed the prevalence of age-related diseases in the offspring of centenarians. Methods. The health histories of centenarian offspring (n = 177) and controls (n = 166) were assessed from 1997-2000 using a cross-sectional study design. The offspring of 192 centenarian subjects enrolled in the nationwide New England Centenarian Study were recruited and enrolled. Controls consisted of offspring whose parents were born in the same years as the centenarians but at least 1 of whom died at an average life expectancy. Prevalence of age-related diseases including heart disease, hypertension, diabetes, cancer, osteoporosis, stroke, dementia, cataracts, glaucoma, macular degeneration, depression, Parkinson's disease, thyroid disease, and chronic obstructive pulmonary disease were compared between the two groups. Results. Centenarian offspring had a 56% reduced relative prevalence of heart disease (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.24, 0.80), a 66% reduced relative prevalence of hypertension (OR 0.34, 95% CI 0.21, 0.55), and 59% reduced relative prevalence of diabetes (OR 0.41, 95% CI 0.15, 1.12) after multivariate adjusted analyses. Conclusions. The offspring of centenarians demonstrate a markedly reduced prevalence of diseases associated with aging, in particular for cardiovascular disease and cardiovascular risk factors. Along with their parents, the centenarian offspring, who are in their 70s and 80s, may prove to be a valuable cohort to study genetic and environmental factors conducive to the ability to live to very old age in good health.

Introduction: Janssen received reports of needle detachments for Risperdal® CONSTA® and, in response, redesigned the kit. Objective: The study objective was to estimate the rate of Risperdal® CONSTA® needle detachments prior to and after the introduction of a redesigned kit. Methods: This retrospective study used record abstraction in the US Department of Veterans Affairs (VA). The 3 phases included: (1) a pilot study for methods evaluation in a sample of 6 hospitals with previously reported detachments; (2) a baseline study to ascertain the baseline detachment rate; and (3) a follow-up study to ascertain the rate for the redesigned kit. Administrative codes and natural language processing with clinical review were used to identify detachments. Results: Pilot: we identified a subset of spontaneously reported detachments and several previously unreported events. In the baseline study (original device), from January through December 2013, 22 needle detachments were identified among 47,934 administrations of the drug in a census of administrations in the VA; an incidence of 0.0459%. In the follow-up study (redesigned device), from December 2015 through December 2016, there were 14 reported detachments in 41,819 injections, 0.0335%. This represents a reduction of 27% from the baseline. Conclusion: This approach enabled us to identify needle detachments we would not have otherwise found ("solicited"). However, it likely resulted in incomplete outcome ascertainment. While this may have resulted in lower overall rates, it did not bias the comparison of the baseline and follow-up studies. The results showed that the redesigned Risperdal® CONSTA® kit reduced the incidence of needle detachment events in the VA. Funding: Janssen Pharmaceuticals, Inc. [ABSTRACT FROM AUTHOR]