PCORnet's Collaborative Research Groups.

The Patient-Centered Outcomes Research Institute (PCORI) launched a multi-institutional "network of networks" in 2013 - Patient-Centered Clinical Research Network (PCORnet) - that is designed to conduct clinical research that is faster, less expensive, and more responsive to the information needs of patients and clinicians. To enhance cross-network and cross-institutional collaboration and catalyze the use of PCORnet, PCORI has supported formation of 11 Collaborative Research Groups focusing on specific disease types (e.g., cardiovascular health and cancer) or particular patient populations (e.g., pediatrics and health disparities). PCORnet's Collaborative Research Groups are establishing research priorities within these focus areas, establishing relationships with potential funders, and supporting development of specific research projects that will use PCORnet resources. PCORnet remains a complex, multilevel, and heterogeneous network that is still maturing and building a diverse portfolio of observational and interventional people-centered research; engaging with PCORnet can be daunting, particularly for outside investigators. We believe the Collaborative Research Groups are stimulating interest and helping investigators navigate the complexity, but only time will tell if these efforts will bear fruit in terms of funded multicenter PCORnet projects

A Hierarchical Multivariate Two-Part Model for Profiling Providers\u27 Effects on Healthcare Charges

Procedures for analyzing and comparing healthcare providers\u27 effects on health services delivery and outcomes have been referred to as provider profiling. In a typical profiling procedure, patient-level responses are measured for clusters of patients treated by providers that in turn, can be regarded as statistically exchangeable. Thus, a hierarchical model naturally represents the structure of the data. When provider effects on multiple responses are profiled, a multivariate model rather than a series of univariate models, can capture associations among responses at both the provider and patient levels. When responses are in the form of charges for healthcare services and sampled patients include non-users of services, charge variables are a mix of zeros and highly-skewed positive values that present a modeling challenge. For analysis of regressor effects on charges for a single service, a frequently used approach is a two-part model (Duan, Manning, Morris, and Newhouse 1983) that combines logistic or probit regression on any use of the service and linear regression on the log of positive charges given use of the service. Here, we extend the two-part model to the case of charges for multiple services, using a log-linear model and a general multivariate log-normal model, and employ the resultant multivariate two-part model as the within-provider component of a hierarchical model. The log-linear likelihood is reparameterized as proposed by Fitzmaurice and Laird (1993), so that regressor effects on any use of each service are marginal with respect to any use of other services. The general multivariate log-normal likelihood is constructed in such a way that variances of log of positive charges for each service are provider-specific but correlations between log of positive charges for different services are uniform across providers. A data augmentation step is included in the Gibbs sampler used to fit the hierarchical model, in order to accommodate the fact that values of log of positive charges are undefined for unused service. We apply this hierarchical, multivariate, two-part model to analyze the effects of primary care physicians on their patients\u27 annual charges for two services, primary care and specialty care. Along the way, we also demonstrate an approach for incorporating prior information about the effects of patient morbidity on response variables, to improve the accuracy of provider profiles that are based on patient samples of limited size

Studying Effects of Primary Care Physicians and Patients on the Trade-Off Between Charges for Primary Care and Specialty Care Using a Hierarchical Multivariate Two-Part Model

Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan. Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads. Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs\u27 effects on patients\u27 annual charges for two types of services, primary care and specialty care, the associations among PCPs\u27 effects, and within-patient associations between charges for the two services. Adjusted Clinical Groups (ACGs) were used to adjust for case-mix. Principal Findings. PCPs with higher case-mix adjusted rates of specialist use were less likely to see their patients at least once during the year (estimated correlation: –.40; 95% CI: –.71, –.008) and provided fewer services to patients that they saw (estimated correlation: –.53; 95% CI: –.77, –.21). Ten of 11 PCPs whose case-mix adjusted effects on primary care charges were significantly less than or greater than zero (p \u3c .05) had estimated, case-mix adjusted effects on specialty care charges that were of opposite sign (but not significantly different than zero). After adjustment for ACG and PCP effects, the within-patient, estimated odds ratio for any use of primary care given any use of specialty care was .57 (95% CI: .45, .73). Conclusions. PCPs and patients contributed independently to a trade-off between utilization of primary care and specialty care. The trade-off appeared to partially offset significant differences in the amount of care provided by PCPs. These findings were possible because we employed a hierarchical multivariate model rather than separate univariate models

PEDSnet: a National Pediatric Learning Health System

A learning health system (LHS) integrates research done in routine care settings, structured data capture during every encounter, and quality improvement processes to rapidly implement advances in new knowledge, all with active and meaningful patient participation. While disease-specific pediatric LHSs have shown tremendous impact on improved clinical outcomes, a national digital architecture to rapidly implement LHSs across multiple pediatric conditions does not exist. PEDSnet is a clinical data research network that provides the infrastructure to support a national pediatric LHS. A consortium consisting of PEDSnet, which includes eight academic medical centers, two existing disease-specific pediatric networks, and two national data partners form the initial partners in the National Pediatric Learning Health System (NPLHS). PEDSnet is implementing a flexible dual data architecture that incorporates two widely used data models and national terminology standards to support multi-institutional data integration, cohort discovery, and advanced analytics that enable rapid learning

Planetary Candidates Observed by Kepler IV: Planet Sample From Q1-Q8 (22 Months)

We provide updates to the Kepler planet candidate sample based upon nearly two years of high-precision photometry (i.e., Q1-Q8). From an initial list of nearly 13,400 Threshold Crossing Events (TCEs), 480 new host stars are identified from their flux time series as consistent with hosting transiting planets. Potential transit signals are subjected to further analysis using the pixel-level data, which allows background eclipsing binaries to be identified through small image position shifts during transit. We also re-evaluate Kepler Objects of Interest (KOI) 1-1609, which were identified early in the mission, using substantially more data to test for background false positives and to find additional multiple systems. Combining the new and previous KOI samples, we provide updated parameters for 2,738 Kepler planet candidates distributed across 2,017 host stars. From the combined Kepler planet candidates, 472 are new from the Q1-Q8 data examined in this study. The new Kepler planet candidates represent ~40% of the sample with Rp~1 Rearth and represent ~40% of the low equilibrium temperature (Teq<300 K) sample. We review the known biases in the current sample of Kepler planet candidates relevant to evaluating planet population statistics with the current Kepler planet candidate sample.Comment: 12 pages, 8 figures, Accepted ApJ Supplemen

Planetary Candidates Observed by Kepler V: Planet Sample from Q1-Q12 (36 Months)

The Kepler mission discovered 2842 exoplanet candidates with 2 years of data. We provide updates to the Kepler planet candidate sample based upon 3 years (Q1-Q12) of data. Through a series of tests to exclude false-positives, primarily caused by eclipsing binary stars and instrumental systematics, 855 additional planetary candidates have been discovered, bringing the total number known to 3697. We provide revised transit parameters and accompanying posterior distributions based on a Markov Chain Monte Carlo algorithm for the cumulative catalogue of Kepler Objects of Interest. There are now 130 candidates in the cumulative catalogue that receive less than twice the flux the Earth receives and more than 1100 have a radius less than 1.5 Rearth. There are now a dozen candidates meeting both criteria, roughly doubling the number of candidate Earth analogs. A majority of planetary candidates have a high probability of being bonafide planets, however, there are populations of likely false-positives. We discuss and suggest additional cuts that can be easily applied to the catalogue to produce a set of planetary candidates with good fidelity. The full catalogue is publicly available at the NASA Exoplanet Archive.Comment: Accepted for publication, ApJ

Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog With Measured Completeness and Reliability Based on Data Release 25

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching four years of Kepler time series photometry (Data Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new and include two in multi-planet systems (KOI-82.06 and KOI-2926.05), and ten high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter which automatically vets the DR25 Threshold Crossing Events (TCEs, Twicken et al. 2016). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discusses the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive.Comment: 61 pages, 23 Figures, 9 Tables, Accepted to The Astrophysical Journal Supplement Serie

Discovery and Rossiter-McLaughlin Effect of Exoplanet Kepler-8b

We report the discovery and the Rossiter-McLaughlin effect of Kepler-8b, a transiting planet identified by the NASA Kepler Mission. Kepler photometry and Keck-HIRES radial velocities yield the radius and mass of the planet around this F8IV subgiant host star. The planet has a radius RP = 1.419 RJ and a mass, MP = 0.60 MJ, yielding a density of 0.26 g cm^-3, among the lowest density planets known. The orbital period is P = 3.523 days and orbital semima jor axis is 0.0483+0.0006/-0.0012 AU. The star has a large rotational v sin i of 10.5 +/- 0.7 km s^-1 and is relatively faint (V = 13.89 mag), both properties deleterious to precise Doppler measurements. The velocities are indeed noisy, with scatter of 30 m s^-1, but exhibit a period and phase consistent with the planet implied by the photometry. We securely detect the Rossiter-McLaughlin effect, confirming the planet's existence and establishing its orbit as prograde. We measure an inclination between the projected planetary orbital axis and the projected stellar rotation axis of lambda = -26.9 +/- 4.6 deg, indicating a moderate inclination of the planetary orbit. Rossiter-McLaughlin measurements of a large sample of transiting planets from Kepler will provide a statistically robust measure of the true distribution of spin-orbit orientations for hot jupiters in general.Comment: 26 pages, 8 figures, 2 tables; In preparation for submission to the Astrophysical Journa

Planetary Candidates Observed by Kepler. VII. The First Fully Uniform Catalog Based on The Entire 48 Month Dataset (Q1-Q17 DR24)

We present the seventh Kepler planet candidate catalog, which is the first to be based on the entire, uniformly processed, 48 month Kepler dataset. This is the first fully automated catalog, employing robotic vetting procedures to uniformly evaluate every periodic signal detected by the Q1-Q17 Data Release 24 (DR24) Kepler pipeline. While we prioritize uniform vetting over the absolute correctness of individual objects, we find that our robotic vetting is overall comparable to, and in most cases is superior to, the human vetting procedures employed by past catalogs. This catalog is the first to utilize artificial transit injection to evaluate the performance of our vetting procedures and quantify potential biases, which are essential for accurate computation of planetary occurrence rates. With respect to the cumulative Kepler Object of Interest (KOI) catalog, we designate 1,478 new KOIs, of which 402 are dispositioned as planet candidates (PCs). Also, 237 KOIs dispositioned as false positives (FPs) in previous Kepler catalogs have their disposition changed to PC and 118 PCs have their disposition changed to FP. This brings the total number of known KOIs to 8,826 and PCs to 4,696. We compare the Q1-Q17 DR24 KOI catalog to previous KOI catalogs, as well as ancillary Kepler catalogs, finding good agreement between them. We highlight new PCs that are both potentially rocky and potentially in the habitable zone of their host stars, many of which orbit solar-type stars. This work represents significant progress in accurately determining the fraction of Earth-size planets in the habitable zone of Sun-like stars. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: Accepted to the Astrophysical Journal Supplement Series. 30 pages, 9 figures, 7 tables. We make the DR24 robovetter decision code publicly available at http://github.com/JeffLCoughlin/robovetter, with input and output examples provided using the same data as contained in the full paper's table

Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations

We present a method to confirm the planetary nature of objects in systems with multiple transiting exoplanet candidates. This method involves a Fourier-Domain analysis of the deviations in the transit times from a constant period that result from dynamical interactions within the system. The combination of observed anti-correlations in the transit times and mass constraints from dynamical stability allow us to claim the discovery of four planetary systems Kepler-25, Kepler-26, Kepler-27, and Kepler-28, containing eight planets and one additional planet candidate.Comment: Accepted to MNRA