Population genomic structure of a widespread, urban-dwelling mammal: The eastern grey squirrel (Sciurus carolinensis).

Urbanization is a persistent and widespread driver of global environmental change, potentially shaping evolutionary processes due to genetic drift and reduced gene flow in cities induced by habitat fragmentation and small population sizes. We tested this prediction for the eastern grey squirrel (Sciurus carolinensis), a common and conspicuous forest-dwelling rodent, by obtaining 44K SNPs using reduced representation sequencing (ddRAD) for 403 individuals sampled across the species' native range in eastern North America. We observed moderate levels of genetic diversity, low levels of inbreeding, and only a modest signal of isolation-by-distance. Clustering and migration analyses show that estimated levels of migration and genetic connectivity were higher than expected across cities and forested areas, specifically within the eastern portion of the species' range dominated by urbanization, and genetic connectivity was less than expected within the western range where the landscape is fragmented by agriculture. Landscape genetic methods revealed greater gene flow among individual squirrels in forested regions, which likely provide abundant food and shelter for squirrels. Although gene flow appears to be higher in areas with more tree cover, only slight discontinuities in gene flow suggest eastern grey squirrels have maintained connected populations across urban areas in all but the most heavily fragmented agricultural landscapes. Our results suggest urbanization shapes biological evolution in wildlife species depending strongly on the composition and habitability of the landscape matrix surrounding urban areas.

Cost-sharing and adherence, clinical outcomes, health care utilization, and costs: A systematic literature review.

BACKGROUND: US health plans are adopting benefit designs that shift greater financial burden to patients through higher deductibles, additional copay tiers, and coinsurance. Prior systematic reviews found that higher cost was associated with reductions in both appropriate and inappropriate medications. However, these reviews were conducted prior to contemporary benefit design and medication utilization. OBJECTIVE: To assess the relationship and factors associated with cost-sharing and (1) medication adherence, (2) clinical outcomes, (3) health care resource utilization (HRU), and (4) costs. METHODS: A systematic review of literature published between January 2010 and August 2020 was conducted to identify the relationship between cost-sharing and medication adherence, clinical outcomes, HRU, and health care costs. Data were extracted using a standardized template and were synthesized by key questions of interest. RESULTS: From 1,995 records screened, 79 articles were included. Most studies, 71 of 79 (90%), reported the relationship between cost-sharing and treatment adherence, persistence and/or discontinuation; 16 (20%) reported data on cost-sharing and HRU or medication initiation, 11 (14%) on costsharing and health care costs, and 6 (8%) on cost-sharing and clinical outcomes. The majority of publications found that, regardless of disease area, increased cost-sharing was associated with worse adherence, persistence, or discontinuation. The aggregate data suggested the greater the magnitude of cost-sharing, the worse the adherence. Among studies examining clinical outcomes, cost-sharing was associated with worse outcomes in 1 study and the remaining 3 found no significant differences. Regarding HRU, higher-cost-sharing trended toward decreased outpatient and increased inpatient utilization. The available evidence suggested higher cost-sharing has an overall neutral to negative impact on total costs. Studies evaluating elimination of copays found either decreased or no impact in total costs. CONCLUSIONS: The published literature shows consistent impacts of higher cost sharing on initiation and continuation of medications, and the greater the cost-sharing, the worse the medication adherence. The evidence is limited regarding the impact of cost-sharing on clinical outcomes, HRU, and costs. Limited evidence suggests increased cost-sharing is associated with more inpatient care and less outpatient care; however, a neutral to no difference was suggested for other outcomes. Although increased costsharing is intended to decrease total costs, studies evaluating reducing or eliminating cost-sharing found that total costs did not rise. Today's growing cost-containment environment should carefully consider the broader impact cost-sharing has on treatment adherence, clinical outcomes, resource use, and total costs. It may be that cost-sharing is a blunt, rather than precise, tool to curb health care costs, affecting both necessary and unnecessary health care use. DISCLOSURES: This study and the development of this article were funded by the National Pharmaceutical Council. Mr Sils is an employee of the National Pharmaceutical Council. Dr Graff is a former employee of the National Pharmaceutical Council. Drs Fusco and Kistler and Ms Ruiz are employees of Xcenda. Xcenda received funding to conduct the literature review.

Temporal Monitoring of the Floreana Island Galapagos Giant Tortoise Captive Breeding Program.

Captive breeding programs benefit from genetic analyses that identify relatedness between individuals, assign parentage to offspring, and track levels of genetic diversity. Monitoring these parameters across breeding cycles is critical to the success of a captive breeding program as it allows conservation managers to iteratively evaluate and adjust program structure. However, in practice, genetic tracking of breeding outcomes is rarely conducted. Here, we examined the first three offspring cohorts (2017-2020) of the genetically informed captive breeding program for the Floreana Island Galapagos giant tortoise, Chelonoidis niger. This captive breeding program is unique as the Floreana tortoise has been extinct since the 1800s, but its genome persists, in part, in the form of living hybrids with the extant Volcano Wolf tortoise, C. becki. Breeding over the study period took place at the Galapagos National Park Directorate breeding facility in four corrals, each containing three females and two males. Using 17 microsatellite markers, we were able to assign parentage to 94 of the 98 offspring produced over the study period. We observe that despite the addition of more founders since the pilot breeding program, the effective population size remains low, and changes to the arrangements of breeding corrals may be necessary to encourage more equal reproductive output from the males. This study demonstrates the value of hybrids for species restoration and the importance of continually reassessing the outcomes of captive breeding.

The Galapagos giant tortoise Chelonoidis phantasticus is not extinct.

The status of the Fernandina Island Galapagos giant tortoise (Chelonoidis phantasticus) has been a mystery, with the species known from a single specimen collected in 1906. The discovery in 2019 of a female tortoise living on the island provided the opportunity to determine if the species lives on. By sequencing the genomes of both individuals and comparing them to all living species of Galapagos giant tortoises, here we show that the two known Fernandina tortoises are from the same lineage and distinct from all others. The whole genome phylogeny groups the Fernandina individuals within a monophyletic group containing all species with a saddleback carapace morphology and one semi-saddleback species. This grouping of the saddleback species is contrary to mitochondrial DNA phylogenies, which place the saddleback species across several clades. These results imply the continued existence of lineage long considered extinct, with a current known population size of a single individual.

Clinical trial registration was associated with lower risk of bias compared with non-registered trials among trials included in systematic reviews.

OBJECTIVE: To examine the association between clinical trial registration and risk of bias in clinical trials that have been included in systematic reviews. As a secondary objective, we evaluated the risk of bias among trials registered prospectively vs. retrospectively. METHOD: Clinical trials published in 2005 or after included in a sample of 100 Cochrane systematic reviews published from 2014-2019. RESULTS: Of 1,177 clinical trials identified, we verified 368 (31%) had been registered, of which 135 (36.7%) were registered prospectively (i.e., before or up to 1 month after enrollment of the first participant). Across the bias domains (one bias assessment for each domain per trial), the percentage of trials at low risk ranged from 29% to 58%; unclear risk ranged from to 26% to 61% and high risk ranged from 2% to 38%. Trials that had been registered had less high or unclear risk of bias in five domains: random sequence generation (univariate risk ratio [RR] 0.69, 95% confidence interval [95% CI] 0.58-0.81), allocation concealment (RR 0.64, 95% CI 0.57-0.72), performance bias (RR 0.65, 95% CI 0.58-0.72), detection bias (RR 0.70, 95% CI 0.62-0.78), and reporting bias (RR 0.62, 95% CI 0.53-0.73). An association between clinical trial registration and high or unclear risk of attrition bias could not be demonstrated nor refuted (RR 1.02, 95% CI 0.89-1.17). It also was observed in terms of overall risk of bias, that registered trials had less high or unclear overall risk of bias than trials that had not been registered (univariate RR 0.29, 95% CI 0.19-0.46). Prospective clinical trial registration was associated with low risks of selection bias due to inadequate allocation concealment, performance bias, and detection bias compared with retrospective clinical trial registration. CONCLUSION: In a large sample of clinical trials included in recently published systematic reviews of interventions, clinical trial registration was associated with low risk of bias for five of the six domains examined.

Urbanization reduces gene flow but not genetic diversity of stream salamander populations in the New York City metropolitan area.

Natural landscape heterogeneity and barriers resulting from urbanization can reduce genetic connectivity between populations. The evolutionary, demographic, and ecological effects of reduced connectivity may lead to population isolation and ultimately extinction. Alteration to the terrestrial and aquatic environment caused by urban influence can affect gene flow, specifically for stream salamanders who depend on both landscapes for survival and reproduction. To examine how urbanization affects a relatively common stream salamander species, we compared genetic connectivity of Eurycea bislineata (northern two-lined salamander) populations within and between streams in an urban, suburban, and rural habitat around the New York City (NYC) metropolitan area. We report reduced genetic connectivity between streams within the urban landscape found to correspond with potential barriers to gene flow, that is, areas with more dense urbanization (roadways, industrial buildings, and residential housing). The suburban populations also exhibited areas of reduced connectivity correlated with areas of greater human land use and greater connectivity within a preserve protected from development. Connectivity was relatively high among neighboring rural streams, but a major roadway corresponded with genetic breaks even though the habitat contained more connected green space overall. Despite greater human disturbance across the landscape, urban and suburban salamander populations maintained comparable levels of genetic diversity to their rural counterparts. Yet small effective population size in the urban habitats yielded a high probability of loss of heterozygosity due to genetic drift in the future. In conclusion, urbanization impacted connectivity among stream salamander populations where its continual influence may eventually hinder population persistence for this native species in urban habitats.

Leveraging Data and Digital Health Technologies to Assess and Impact Social Determinants of Health (SDoH): a State-of-the-Art Literature Review.

OBJECTIVE: Identify how novel datasets and digital health technology, including both analytics-based and artificial intelligence (AI)-based tools, can be used to assess non-clinical, social determinants of health (SDoH) for population health improvement. METHODS: A state-of-the-art literature review with systematic methods was performed on MEDLINE, Embase, and the Cochrane Library databases and the grey literature to identify recently published articles (2013-2018) for evidence-based qualitative synthesis. Following single review of titles and abstracts, two independent reviewers assessed eligibility of full-texts using predefined criteria and extracted data into predefined templates. RESULTS: The search yielded 2,714 unique database records of which 65 met inclusion criteria. Most studies were conducted retrospectively in a United States community setting. Identity, behavioral, and economic factors were frequently identified social determinants, due to reliance on administrative data. Three main themes were identified: 1) improve access to data and technology with policy - advance the standardization and interoperability of data, and expand consumer access to digital health technologies; 2) leverage data aggregation - enrich SDoH insights using multiple data sources, and use analytics-based and AI-based methods to aggregate data; and 3) use analytics-based and AI-based methods to assess and address SDoH - retrieve SDoH in unstructured and structured data, and provide contextual care management sights and community-level interventions. CONCLUSIONS: If multiple datasets and advanced analytical technologies can be effectively integrated, and consumers have access to and literacy of technology, more SDoH insights can be identified and targeted to improve public health. This study identified examples of AI-based use cases in public health informatics, and this literature is very limited.

Systematic review of context-aware digital behavior change interventions to improve health.

Health risk behaviors are leading contributors to morbidity, premature mortality associated with chronic diseases, and escalating health costs. However, traditional interventions to change health behaviors often have modest effects, and limited applicability and scale. To better support health improvement goals across the care continuum, new approaches incorporating various smart technologies are being utilized to create more individualized digital behavior change interventions (DBCIs). The purpose of this study is to identify context-aware DBCIs that provide individualized interventions to improve health. A systematic review of published literature (2013-2020) was conducted from multiple databases and manual searches. All included DBCIs were context-aware, automated digital health technologies, whereby user input, activity, or location influenced the intervention. Included studies addressed explicit health behaviors and reported data of behavior change outcomes. Data extracted from studies included study design, type of intervention, including its functions and technologies used, behavior change techniques, and target health behavior and outcomes data. Thirty-three articles were included, comprising mobile health (mHealth) applications, Internet of Things wearables/sensors, and internet-based web applications. The most frequently adopted behavior change techniques were in the groupings of feedback and monitoring, shaping knowledge, associations, and goals and planning. Technologies used to apply these in a context-aware, automated fashion included analytic and artificial intelligence (e.g., machine learning and symbolic reasoning) methods requiring various degrees of access to data. Studies demonstrated improvements in physical activity, dietary behaviors, medication adherence, and sun protection practices. Context-aware DBCIs effectively supported behavior change to improve users' health behaviors.

Poor compliance of clinical trial registration among trials included in systematic reviews: a cohort study.

OBJECTIVES: The objective of the study was to examine whether clinical trials that have been included in systematic reviews have been registered in clinical trial registers and, when they have, whether results of the trials were included in the clinical trial register. STUDY DESIGN AND SETTING: This study used a sample of 100 systematic reviews published by the Cochrane Musculoskeletal, Oral, Skin and Sensory Network between 2014 and 2019. RESULTS: We identified 2,000 trials (369,778 participants) from a sample of 100 systematic reviews. The median year of trial publication was 2007. Of 1,177 trials published in 2005 or later, a clinical trial registration record was identified for 368 (31%). Of these registered trials, 135 (37%) were registered prospectively and results were posted for 114 (31%); most registered trials evaluated pharmaceutical interventions (62%). Of trials published in the last 10 years, the proportion of registered trials increased to 38% (261 of 682). CONCLUSION: Although some improvement in clinical trial registration has been observed in recent years, the proportion of registered clinical trials included in recently published systematic reviews remains less than desirable. Prospective clinical trial registration provides an essential role in assessing the risk of bias and judging the quality of evidence in systematic reviews of intervention safety and effectiveness.

A pilot study of animal assisted activity among hospitalized older adults.

Animal Assisted Activity (AAA) is a non-medical intervention that has been shown to reduce anxiety among nursing home patients in various settings. However, AAA has not been tested among acute care hospitalized older adult patients ages 65 and older. This pilot study explored if a visit from a trained dog and its handler would decrease anxiety among hospitalized, older adult patients ages 65 and greater. The participants were recruited from medical surgical/oncology units, and the Speilberger State-Trait Anxiety Inventory (STAI) 6-item short form was used to measure anxiety both pre- and post-interactions with the AAA-team. The data revealed that a one-time, 12-20-min visit, allowing the patients to pet and to interact with the dog, reduced (p = .000) the participants' self-reported anxiety.

Rapid review: Identification of digital health interventions in atherosclerotic-related cardiovascular disease populations to address racial, ethnic, and socioeconomic health disparities.

Disparities in cardiovascular disease (CVD) and associated health and healthcare delivery outcomes have been partially attributed to differential risk factors, and to prevention and treatment inequities within racial and ethnic (including language) minority groups and low socioeconomic status (SES) populations in urban and rural settings. Digital health interventions (DHIs) show promise in promoting equitable access to high-quality care, optimal utilization, and improved outcomes; however, their potential role and impact has not been fully explored. The role of DHIs to mitigate drivers of the health disparities listed above in populations disproportionately affected by atherosclerotic-related CVD was systematically reviewed using published literature (January 2008-July 2020) from multiple databases. Study design, type and description of the technology, health disparities information, type of CVD, outcomes, and notable barriers and innovations associated with the technology utilized were abstracted. Study quality was assessed using the Oxford Levels of Evidence. Included studies described digital health technologies in a disparity population with CVD and reported outcomes. DHIs significantly improved health (eg, clinical, intermediate, and patient-reported) and healthcare delivery (eg, access, quality, and utilization of care) outcomes in populations disproportionately affected by CVD in 24 of 38 included studies identified from 2104 citations. Hypertension control was the most frequently improved clinical outcome. Telemedicine, mobile health, and clinical decision support systems were the most common types of DHIs identified. DHIs improved CVD-related health and healthcare delivery outcomes in racial/ethnic groups and low SES populations in both rural and urban geographies globally.

Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for non-systematic adverse events.

BACKGROUND: Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials or across sources for a single trial may produce inconsistent information about the adverse events associated with interventions. METHODS: We compared the methods authors use to decide which AEs to include in a particular source (i.e., "selection criteria"), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports (CSRs)) of trials for two drug-indications-gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting. RESULTS: We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion "occurring in ≥2% of participants in any treatment group," while only 5/316 (2%) AEs met the criterion "occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group." CONCLUSIONS: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might "cherry-pick" AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.

Harms are assessed inconsistently and reported inadequately part 1: systematic adverse events.

OBJECTIVES: We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials. STUDY DESIGN AND SETTING: We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight. RESULTS: Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information. CONCLUSION: Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.

Harms are assessed inconsistently and reported inadequately Part 2: nonsystematic adverse events.

OBJECTIVE: We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials. STUDY DESIGN AND SETTING: We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as "serious." We recorded whether AEs were grouped by anatomic or physiological system. RESULTS: Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decision-making. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system. CONCLUSION: Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

Caveat emptor: the combined effects of multiplicity and selective reporting.

Clinical trials and systematic reviews of clinical trials inform healthcare decisions. There is growing concern, however, about results from clinical trials that cannot be reproduced. Reasons for nonreproducibility include that outcomes are defined in multiple ways, results can be obtained using multiple methods of analysis, and trial findings are reported in multiple sources ("multiplicity"). Multiplicity combined with selective reporting can influence dissemination of trial findings and decision-making. In particular, users of evidence might be misled by exposure to selected sources and overly optimistic representations of intervention effects. In this commentary, drawing from our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study and evidence from previous research, we offer practical recommendations to enhance the reproducibility of clinical trials and systematic reviews.

Methods to identify and prioritize patient-centered outcomes for use in comparative effectiveness research.

BACKGROUND: We used various methods for identifying and prioritizing patient-centered outcomes (PCOs) for comparative effectiveness research (CER). METHODS: We considered potential PCOs ("benefits" and "harms") related to (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. Part 1 (April 2014 to March 2015): we searched for PCO research and core outcome sets (COSs). We conducted electronic searches of bibliographic databases and key websites and examined FDA prescribing information and reports of clinical trials and systematic reviews. We asked patient and clinician co-investigators to identify PCOs. Part 2 (not part of our original study protocol): in 2015, we surveyed members of The TMJ Association, Ltd., a patient group associated with temporomandibular disorders (4130 invitations sent). Participants prioritized (1) the importance of six potential benefits and (2) 21 potential harms selected by the investigators in part 1, using stated preference methods. We calculated descriptive statistics. RESULTS: In part 1, we identified a COS for pain, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. The COS identified several important benefits, but it lacked specific recommendations about which potential harms to include in CER. We did not identify a COS for bipolar depression. Research reports, prescribing information, and patient co-investigators helped identify but not prioritize outcomes. We abandoned our electronic search for PCO research because we found it would be resource-intensive and yield few relevant reports. In part 2, surveying patients was useful for prioritizing PCOs. Members of The TMJ Association, Ltd., completed the survey (N = 746) and successfully prioritized both benefits and harms. Participants did not identify many benefits other than those we identified in part 1; several participants identified additional harms. CONCLUSIONS: These exploratory results could inform future research about identifying and prioritizing PCOs. We found that stakeholder co-investigators and research reports contributed to identifying PCOs; surveying a patient group contributed to prioritizing PCOs. Prioritizing potential harms was particularly challenging because there are many more potential harms than potential benefits. Methods for identifying and prioritizing potential benefits for CER might not be appropriate for harms. Further research is needed to determine the generalizability of these results.

Correction to: Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol.

The correct title of the article [1] should be "Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol".

Correction to: Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol for a systematic review.

CORRECTION: The correct title of the article [1] should be "Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol". The article is a protocol for a methodological study, not a systematic review.

Practical guidance for using multiple data sources in systematic reviews and meta-analyses (with examples from the MUDS study).

Data for individual trials included in systematic reviews may be available in multiple sources. For example, a single trial might be reported in 2 journal articles and 3 conference abstracts. Because of differences across sources, source selection can influence the results of systematic reviews. We used our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study, and evidence from previous studies, to develop practical guidance for using multiple data sources in systematic reviews. We recommend the following: (1) Specify which sources you will use. Before beginning a systematic review, consider which sources are likely to contain the most useful data. Try to identify all relevant reports and to extract information from the most reliable sources. (2) Link individual trials with multiple sources. Write to authors to determine which sources are likely related to the same trials. Use a modified Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart to document both the selection of trials and the selection of sources. (3) Follow a prespecified protocol for extracting trial characteristics from multiple sources. Identify differences among sources, and contact study authors to resolve differences if possible. (4) Prespecify outcomes and results to examine in the review and meta-analysis. In your protocol, describe how you will handle multiple outcomes within each domain of interest. Look for outcomes using all eligible sources. (5) Identify which data sources were included in the review. Consider whether the results might have been influenced by data sources used. (6) To reduce bias, and to reduce research waste, share the data used in your review.

Cherry-picking by trialists and meta-analysts can drive conclusions about intervention efficacy.

OBJECTIVES: The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). STUDY DESIGN AND SETTING: Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic sources (clinical study reports [CSRs] and individual participant data [IPD]). RESULTS: We found 21 gabapentin RCTs (74 reports, 6 IPD) and 7 quetiapine RCTs (50 reports, 1 IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains "pain intensity" (gabapentin) and "depression" (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD] = -0.45; 95% confidence interval [CI]: -0.63 to -0.27) to ineffective (SMD = -0.06; 95% CI: -0.24 to 0.12). We could change the effect for depression from a medium effect (SMD = -0.55; 95% CI: -0.85 to -0.25) to a small effect (SMD = -0.26; 95% CI: -0.41 to -0.1). CONCLUSIONS: Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.