Generating synthetic data from administrative health records for drug safety and effectiveness studies

Introduction Administrative health records (AHRs) are used to conduct population-based post-market drug safety and comparative effectiveness studies to inform healthcare decision making. However, the cost of data extraction, and the challenges associated with privacy and securing approvals can make it challenging for researchers to conduct methodological research in a timely manner using real data. Generating synthetic AHRs that reasonably represent the real-world data are beneficial for developing analytic methods and training analysts to rapidly implement study protocols. We generated synthetic AHRs using two methods and compared these synthetic AHRs to real-world AHRs. We described the challenges associated with using synthetic AHRs for real-world study. Methods The real-world AHRs comprised prescription drug records for individuals with healthcare insurance coverage in the Population Research Data Repository (PRDR) from Manitoba, Canada for the 10-year period from 2008 to 2017. Synthetic data were generated using the Observational Medical Dataset Simulator II (OSIM2) and a modification (ModOSIM). Synthetic and real-world data were described using frequencies and percentages. Agreement of prescription drug use measures in PRDR, OSIM2 and ModOSIM was estimated with the concordance coefficient. Results The PRDR cohort included 169,586,633 drug records and 1,395 drug types for 1,604,734 individuals. Synthetic data for 1,000,000 individuals were generated using OSIM2 and ModOSIM. Sex and age group distributions were similar in the real-world and synthetic AHRs. However, there were significant differences in the number of drug records and number of unique drugs per person for OSIM2 and ModOSIM when compared with PRDR. For the average number of days of drug use, concordance with the PRDR was 16% (95% confidence interval [CI]: 12%-19%) for OSIM2 and 88% (95% CI: 87%-90%) for ModOSIM. Conclusions ModOSIM data were more similar to PRDR than OSIM2 data on many measures. Synthetic AHRs consistent with those found in real-world settings can be generated using ModOSIM. Synthetic data will benefit rapid implementation of methodological studies and data analyst training

IGEMS : The Consortium on Interplay of Genes and Environment Across Multiple Studies - An Update

The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene-environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14-103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.Peer reviewe

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

Genome-wide association for milk production and lactation curve parameters in Holstein dairy cows

The aim of this study was to identify genomic regions associated with 305-day milk yield and lactation curve parameters on primiparous (n = 9,910) and multiparous (n = 11,158) Holstein cows. The SNP solutions were estimated using a weighted single-step genomic BLUP approach and imputed high-density panel (777k) genotypes. The proportion of genetic variance explained by windows of 50 consecutive SNP (with an average of 165 Kb) was calculated, and regions that accounted for more than 0.50% of the variance were used to search for candidate genes. Estimated heritabilities were 0.37, 0.34, 0.17, 0.12, 0.30 and 0.19, respectively, for 305-day milk yield, peak yield, peak time, ramp, scale and decay for primiparous cows. Genetic correlations of 305-day milk yield with peak yield, peak time, ramp, scale and decay in primiparous cows were 0.99, 0.63, 0.20, 0.97 and -0.52, respectively. The results identified three windows on BTA14 associated with 305-day milk yield and the parameters of lactation curve in primi- and multiparous cows. Previously proposed candidate genes for milk yield supported by this work include GRINA, CYHR1, FOXH1, TONSL, PPP1R16A, ARHGAP39, MAF1, OPLAH and MROH1, whereas newly identified candidate genes are MIR2308, ZNF7, ZNF34, SLURP1, MAFA and KIFC2 (BTA14). The protein lipidation biological process term, which plays a key role in controlling protein localization and function, was identified as the most important term enriched by the identified genes

IGEMS: The Consortium on Interplay of Genes and Environment Across Multiple Studies

The Interplay of Genes and Environment across Multiple Studies (IGEMS) group is a consortium of eight longitudinal twin studies established to explore the nature of social context effects and gene-environment interplay in late-life functioning. The resulting analysis of the combined data from over 17,500 participants aged 25–102 at baseline (including nearly 2,600 monogygotic and 4,300 dizygotic twin pairs and over 1,700 family members) aims to understand why early life adversity, and social factors such as isolation and loneliness, are associated with diverse outcomes including mortality, physical functioning (health, functional ability), and psychological functioning (well-being, cognition), particularly in later life

Expert-based development of a generic HACCP-based risk management system to prevent critical negative energy balance in dairy herds

The objective of this study was to develop a generic risk management system based on the Hazard Analysis and Critical Control Point (HACCP) principles for the prevention of critical negative energy balance (NEB) in dairy herds using an expert panel approach. In addition, we discuss the advantages and limitations of the system in terms of implementation in the individual dairy herd. For the expert panel, we invited 30 researchers and advisors with expertise in the field of dairy cow feeding and/or health management from eight European regions. They were invited to a Delphi-based set-up that included three inter-correlated questionnaires in which they were asked to suggest risk factors for critical NEB and to score these based on 'effect' and 'probability'. Finally, the experts were asked to suggest critical control points (CCPs) specified by alarm values, monitoring frequency and corrective actions related to the most relevant risk factors in an operational farm setting. A total of 12 experts (40 %) completed all three questionnaires. Of these 12 experts, seven were researchers and five were advisors and in total they represented seven out of the eight European regions addressed in the questionnaire study. When asking for suggestions on risk factors and CCPs, these were formulated as 'open questions', and the experts' suggestions were numerous and overlapping. The suggestions were merged via a process of linguistic editing in order to eliminate doublets. The editing process revealed that the experts provided a total of 34 CCPs for the 11 risk factors they scored as most important. The consensus among experts was relatively high when scoring the most important risk factors, while there were more diverse suggestions of CCPs with specification of alarm values and corrective actions. We therefore concluded that the expert panel approach only partly succeeded in developing a generic HACCP for critical NEB in dairy cows. We recommend that the output of this paper is used to inform key areas for implementation on the individual dairy farm by local farm teams including farmers and their advisors, who together can conduct herd-specific risk factor profiling, organise the ongoing monitoring of herd-specific CCPs, as well as implement corrective actions when CCP alarm values are exceeded

Educational attainment of same-sex and opposite-sex dizygotic twins : An individual-level pooled study of 19 twin cohorts

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.Peer reviewe

Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a(2)=0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c(2)=0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a(2)=0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a(2)=0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c(2)=0.31; 0.29-0.33 and c(2)=0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.Peer reviewe