Key Methodological Factors Research Articles

Lessons learned from a multi-data source research collaboration: The mirabegron post-authorization safety study program.

Many factors contribute to developing and conducting a successful multi-data source, non-interventional, post-authorization safety study (NI-PASS) for submission to multiple health authorities. Such studies are often large undertakings; evaluating and sharing lessons learned can provide useful insights to others considering similar studies. We discuss challenges and key methodological and organizational factors that led to the delivery of a successful post-marketing requirement (PMR)/PASS program investigating the risk of cardiovascular and cancer events among users of mirabegron, an oral medication for the treatment of overactive bladder. We provide context and share learnings, including sections on research program collaboration, scientific transparency, organizational approach, mitigation of uncertainty around potential delays, validity of study outcomes, selection of data sources and optimizing patient numbers, choice of comparator groups and enhancing precision of estimates of associations, potential confounding and generalizability of study findings, and interpretation of results. This large PMR/PASS program was a long-term commitment from all parties and benefited from an effective coordinating center and extensive scientific interactions across research partners, scientific advisory board, study sponsor, and health authorities, and delivered useful learnings related to the design and organization of multi-data source NI-PASS.

The Effect of Methodological Considerations on the Construction of Gene-Based Plant Pan-genomes.

Pan-genomics is an emerging approach for studying the genetic diversity within plant populations. In contrast to common resequencing studies that compare whole genome sequencing data with a single reference genome, the construction of a pan-genome (PG) involves the direct comparison of multiple genomes to one another, thereby enabling the detection of genomic sequences and genes not present in the reference, as well as the analysis of gene content diversity. Although multiple studies describing PGs of various plant species have been published in recent years, a better understanding regarding the effect of the computational procedures used for PG construction could guide researchers in making more informed methodological decisions. Here, we examine the effect of several key methodological factors on the obtained gene pool and on gene presence-absence detections by constructing and comparing multiple PGs of Arabidopsis thaliana and cultivated soybean, as well as conducting a meta-analysis on published PGs. These factors include the construction method, the sequencing depth, and the extent of input data used for gene annotation. We observe substantial differences between PGs constructed using three common procedures (de novo assembly and annotation, map-to-pan, and iterative assembly) and that results are dependent on the extent of the input data. Specifically, we report low agreement between the gene content inferred using different procedures and input data. Our results should increase the awareness of the community to the consequences of methodological decisions made during the process of PG construction and emphasize the need for further investigation of commonly applied methodologies.

Socio-Spatial Experience in Space Syntax Research: A PRISMA-Compliant Review

Characterising and predicting socio-spatial experience has long been a key research question in space syntax research. Due to the lack of synthesised knowledge about it, this review conducts the first systematic scoping review of space syntax research on the relationships between spatial properties and experiential values. Adopting the “Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) framework, this review of space syntax research identifies 38 studies that examine socio-spatial experiences in architectural, medical, and urban spaces. The data arising from this systematic review are used to identify trends in this sub-field of research, including the growth of socio-spatial methods and applications in urban analytics since 2016 and key methodological approaches, characteristics, and factors in space syntax research about socio-spatial experience. The research identified using the systematic framework employs a mixture of descriptive, correlation, and regression methods to examine the dynamic effects of spatial configurations on human experiences. Arising from the results of the review, the article further identifies a collective, predictive model consisting of five syntactic predictors and three categories of experiential values. This article, finally, examines research gaps and limitations in the body of knowledge and suggests future research directions.

Evaluating the effects of analytical decisions in large-scale assessments: analyzing PISA mathematics 2003-2012

Research questionThis paper examines the overarching question of to what extent different analytic choices may influence the inference about country-specific cross-sectional and trend estimates in international large-scale assessments. We take data from the assessment of PISA mathematics proficiency from the four rounds from 2003 to 2012 as a case study.MethodsIn particular, four key methodological factors are considered as analytical choices in the rescaling and analysis of the data: (1) The selection of country sub-samples for item calibration differing at three factor levels. (2) The item sample refering to two sets of mathematics items used within PISA. (3) The estimation method used for item calibration: marginal maximum likelihood estimation method as implemented in R package TAM or an pairwise row averaging approach as implemented in the R package pairwise. (4) The type of linking method: concurrent calibration or separate calibration with successive chain linking.FindingsIt turned out that analytical decisions for scaling did affect the PISA outcomes. The factors of choosing different calibration samples, estimation method and linking method tend to show only small effects on the country-specific cross-sectional and trend estimates. However, the selection of different link items seems to have a decisive influence on country ranking and development trends between and within countries.

Proficiency, language of assessment, and attention to meaning and form during L2 comprehension: Methodological considerations in L2 replication research

AbstractThis study is a replication and extension of Morgan-Short et al.’s (2018) investigation into the role of attention in input processing by L1-Polish learners of L2-Spanish, with proficiency and language of assessment explored as two key methodological factors. Our aims were twofold: to investigate learners’ comprehension in different conditions with their L2 proficiency controlled for, and to examine this process when learners were tested using different languages. Data from three trials (N = 136) were analyzed: Trial-English, Trial-Polish, and Trial-Spanish, where comprehension was tested in English, Polish, or Spanish, respectively. Results showed that both L2 proficiency and language of assessment significantly affected learners’ performance, with their scores being lower in the-nmorpheme condition but only when comprehension was tested in English or Spanish. We discuss these findings both theoretically and methodologically, making recommendations on designing future replication studies and improving the generalizability of L2 findings across multiple research sites.

A systematic review of the psychological impacts of the Canterbury earthquakes on mental health

Objective:This systematic review aims to identify and evaluate all studies that measured psychological distress or mental disorder following the Canterbury earthquakes to establish the psychological consequences of the earthquakes on those exposed. A secondary aim is to outline and emphasise key methodological factors in disaster research. Method:Eligible studies were identified following a comprehensive literature search. A quality assessment was undertaken for all included studies. This was followed by methodological and descriptive review. Results:Thirty‐one papers measuring psychological distress or mental disorder following the Canterbury earthquakes were identified. These papers reported outcomes from 20 separate studies of which seven were rated high‐quality, eight were rated medium and five were rated low‐quality. Key methodological findings and outcomes are discussed for each study. Conclusion:The Canterbury earthquakes were associated with widespread but not universal adverse effects on mental health. Disaster research quality is assisted by representative samples, repeated measures, and the use of appropriate controls to allow accurate assessments of psychological consequences to be made. Implications for public health:The presence of widespread adverse effects as a result of the earthquakes suggests broad‐ranging community initiatives are essential to mitigate the negative consequences of disasters.

Methodological factors affecting quantification of blood pressure variability: a scoping review.

Blood pressure (BP) variability (BPV) may offer independent prognostic information. However, data supporting this notion are inconsistent, and this may be due to the wide variety of methodologies used for measuring BPV. A systematic analysis on the effect of BPV methodologies on BPV itself has never been undertaken and was the aim of this study. We also sought to determine the effect of participant characteristics on BPV. A scoping review process was used to identify the effect of BPV methodologies on BPV magnitude. Key methodological factors assessed were the number of BP readings or visits used to quantify BPV and the duration of BP monitoring. In addition, the relationship between age and mean BP level on BPV was investigated. Analyses were performed across studies that measured BPV over the short-term (using 24-h BP), mid-term (using home BP in the morning, evening or day-to-day) and long-term (using visit-to-visit clinic BP). Data were extracted from 96 studies. The number of BP readings and visits used to quantify BPV were positively associated with mid-term and long-term BPV. Duration was weakly associated with mid-term (morning) BPV. Age was positively associated with long-term and mid-term (day-to-day), but not short-term BPV. Mean BP level was positively associated with BPV, except mid-term BPV (morning and evening). The methodology used to quantify BPV, as well as age and mean BP level, affects the magnitude of BPV itself. This highlights the need to standardize BPV protocols, particularly regarding the number of BP readings and visits.

How strongly related are health status and subjective well-being? Systematic review and meta-analysis.

Health status is widely considered to be closely associated with subjective well-being (SWB), yet this assumption has not been tested rigorously. The aims of this first systematic review and meta-analysis are to examine the association between health status and SWB and to test whether any association is affected by key operational and methodological factors. A systematic search (January 1980-April 2017) using Web of Science, Medline, Embase, PsycInfo and Global health was conducted according to Cochrane and PRISMA guidelines. Meta-analyses using a random-effects model were performed. Twenty nine studies were included and the pooled effect size of the association between health status and SWB was medium, statistically significant and positive (pooled r = 0.347, 95% CI = 0.309-0.385; Q = 691.51, I2 = 94.99%, P < 0.001). However, the association was significantly stronger: (i) when SWB was operationalised as life satisfaction (r = 0.365) as opposed to happiness (r = 0.307); (ii) among studies conducted in developing countries (r = 0.423) than it was in developed countries (r = 0.336) and (iii) when multiple items were used to assess health status and SWB (r = 0.353) as opposed to single items (r = 0.326). Improving people's health status may be one means by which governments can improve the SWB of their citizens. Life satisfaction might be preferred to happiness as a measure of SWB because it better captures the influence of health status.

Contemporaneous International Asthma Guidelines Present Differing Recommendations: An Analysis

Background. Several international groups develop asthma guidelines. Conflicting recommendations across guidelines have been described in several disease areas and may contribute to practice variability. Accordingly, we compared the latest Canadian Thoracic Society (CTS) asthma guideline with contemporaneous international asthma guidelines to evaluate conflicting recommendations and their causes. Methods. We identified the latest CTS asthma guideline update (2012) and the following societies which also updated their guidelines in 2012: the British Thoracic Society and Scottish Intercollegiate Guidelines Network and the Global Initiative for Asthma. We compared these three guidelines on (1) key methodological factors and (2) adult pharmacotherapy recommendations. Results. Methods used and documentation provided for literature search strategy and dates, evidence synthesis, outcomes considered, evidence appraisal, and recommendation formulation varied between guidelines. Criteria used to define suboptimal asthma control varied widely between guidelines. Inhaled corticosteroid dosing recommendations diverged, as did recommendations surrounding use of budesonide/formoterol as a reliever and controller and recommendations in the subsequent step. Conclusions. There are important differences between recommendations provided in contemporaneous asthma guidelines. Causes include differences in methods used for interpreting evidence and formulating recommendations. Adopting a common set of valid and explicit methods across international societies could harmonize recommendations and facilitate guideline implementation.

Impact of the Consolidated Standards of Reporting Trials (CONSORT) checklist on reporting of randomized clinical trials in traditional Chinese medicine.

To examine the reporting characteristics and key methodological factors of randomized controlled trials (RCTs) in the field of traditional Chinese medicine and assess whether use of the Consolidated Standards of Reporting Trials (CONSORT) statement is associated with improvement in the quality of reports of RCTs. RCTs published in two major traditional Chinese medicine journals were retrieved and were systematically reviewed. Of those journals, one adopted the CONSORT statement (Journal of Chinese Integrative Medicine (JCIM)) and one did not (Chinese Journal of Integrative Medicine (CJIM)). Items within the CONSORT 2001 and the CONSORT 2010 statements were taken to develop a 63-item coding manual. The Jadad scale was also used to assess methodological quality of RCTs. Two observers assessed the reporting of reports and extracted data independently. P < 0.05 was considered statistically significant. SPSS was used for all analyses. A total of 76 RCTs were included for the analysis (38 from JCIM and 38 from CJIM). Significant improvements both in the overall quality of reporting (CONSORT score) and reporting of methodological items (Jadad scale) over time were observed in adopter journal (JCIM) (P = 0.001). Overall CONSORT score of studies published during 2010 to 2011 (post-CONSORT) increased 15.30 averagely with 95%CI 8.34 to 22.26 (P = 0.001). Of those, items addressed on reporting of methodological quality were different significantly too. JCIM had more 1.30 items addressed than CJIM in average (95% CI 0.52 to 2.08, P = 0.003). In the multivariate analysis regression, the page length and CONSORT-promoting status have statistically significant associated with the (P = 0.001 and P = 0.040, respectively). Although a large room needs to improve the reporting of randomized clinical trials in traditional Chinese medicine, the impact for improvement of reporting of TCM RCTs has been proven in some extent.

The Lure Technique: Replication and Refinement in a Field Setting

Many techniques designed to gain compliance to a request are presented in the social psychological literature. However, the lure technique has received little attention from scientists. This technique, also called bait-and-switch, is used to influence people's choices and involves three stages: (1) individuals are led to make a rewarding decision to carry out a given behavior; (2) they are informed of the impossibility of carrying out this behavior; (3) a new but less rewarding decision is proposed. Only one formal study has been published on this technique, which failed to control two key methodological factors: the status of the participants and the solicitor, and the delay between the initial decision and the target request. These two factors were controlled in this study. Outside a French campus, 40 female students in the 18-22 age range were solicited by a student to participate in a pleasant experiment for which they would be remunerated. One minute after accepting, they were informed that the number of participants was reached, and they were no longer needed. The solicitor then proposed a different task that was less interesting and not remunerated. Greater compliance with the final request was found in the lure condition (70%) than in the control condition (35%) in which the final request was addressed immediately. The results confirm the effectiveness of the lure technique to increase compliance and show that its effectiveness is not dependent on the solicitor's status.

A retrospective survey of quality of reporting on randomized controlled trials of metformin for polycystic ovary syndrome

BackgroundFrom previous reviews, there still have been controversies over the effect of metformin (MET) on reproductive function in PCOS patients. The reasons for the inconsistent findings especially lie in the transparency and accuracy of randomized controlled trials (RCTs) reports. However, we could find no data about the quality of RCTs reporting in MET for PCOS. Thus, a retrospective survey related to the quality of reporting in MET for PCOS was conducted.MethodsA retrospective survey was conducted by two investigators. Two investigators assessed the quality of overall reporting and key methodological factors reporting using items from the CONSORT 2010 statement.ResultsA total of 39 RCTs were included in full text. The median overall quality score was 9, with a minimum of 2 and a maximum of 13. Good or general reporting existed in 11 items with positive rate of more than or equal to 50%. The median score of key methodological items was 4 with a minimum of 0 and a maximum of 5. Randomization, allocation concealment, blinding, baseline characteristics and intention-to-treat (ITT) analysis were reported in 26 (67%), 19 (49%), 20 (51%), 38 (97%) and 17 (44%) of the 39 RCTs, respectively. After adjustment, the mean overall score increased by about 1.71 for manuscripts with funding source (95% CI, 0.18 to 3.24), while it increased by about 3.51 for manuscripts published in one year increment (95% CI, 1.82 to 5.19). There was a relatively close, significant correlation (r = 0.589, P < 0.001) between the score of overall reporting quality and year of publication.ConclusionAlthough the overall reporting quality of RCTs in MET for PCOS has improved over time, reporting of key methodological items remains poor. Reporting of RCTs on MET for PCOS should keep up with the standards of the CONSORT statement.

Roundtable on the Sociology of Religion: Twenty-Three Theses on the Status of Religion in American Sociology--A Mellon Working-Group Reflection

American sociology has not taken and does not take religion as seriously as it needs to in order to do the best sociology possible. Despite religion being an important and distinctive kind of practice in human social life, both historically and in the world today, American sociologists often neglect religion or treat it reductionistically. We explore several reasons for this negligence, focusing on key historical, conceptual, methodological, and institutional factors. We then turn to offer a number of proposals to help remedy American sociology’s negligence of religion, advance the study of religion in particular, and enhance sociology’s

Comparative Research on Training Simulators in Emergency Medicine

Recent reviews and research agenda in simulation-based training for health care have repeatedly called for more studies comparing the effectiveness of different simulation modalities and approaches. Although a small body of such comparative research does exist, it is apparent that this line of research comes with particular methodological challenges. In this review, 20 studies comparing simulation modalities in emergency medicine were analyzed in terms of key methodological factors. Results of this literature review show that (1) past studies are largely underpowered to detect effects of the magnitude likely to be found, (2) researchers seeking to demonstrate equivalence of training approaches do not use appropriate statistical tests of equivalence, and (3) studies often use performance criterion test beds that may not support valid conclusions about trainees' future performance on the job. We discuss strengths and weaknesses of reviewed studies along these issues and recommend options for improving future comparative research in simulation-based training.

Bedside Estimation of Nonaerated Lung Tissue Using Blood Gas Analysis*

Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. : Prospective observational clinical and laboratory animal investigations. ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of São Paulo, Brazil). PATIENTS, SUBJECTS AND INTERVENTIONS: Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different Fio2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/Fio2 to change this nonlinear relationship into a linear regression problem. We observed strong linear correlations between Riley's approximation of physiological shunt and CT shunt (R = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/Fio2 during pure oxygen ventilation, use of logarithmically transformed PaO2/Fio2 instead of the "raw" PaO2/Fio2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [-200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. During pure oxygen ventilation, logarithmically transformed PaO2/Fio2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [-200 and +100] Hounsfield Units.

Brain Development During the Preschool Years

The preschool years represent a time of expansive mental growth, with the initial expression of many psychological abilities that will continue to be refined into young adulthood. Likewise, brain development during this age is characterized by its "blossoming" nature, showing some of its most dynamic and elaborative anatomical and physiological changes. In this article, we review human brain development during the preschool years, sampling scientific evidence from a variety of sources. First, we cover neurobiological foundations of early postnatal development, explaining some of the primary mechanisms seen at a larger scale within neuroimaging studies. Next, we review evidence from both structural and functional imaging studies, which now accounts for a large portion of our current understanding of typical brain development. Within anatomical imaging, we focus on studies of developing brain morphology and tissue properties, including diffusivity of white matter fiber tracts. We also present new data on changes during the preschool years in cortical area, thickness, and volume. Physiological brain development is then reviewed, touching on influential results from several different functional imaging and recording modalities in the preschool and early school-age years, including positron emission tomography (PET), electroencephalography (EEG) and event-related potentials (ERP), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and near-infrared spectroscopy (NIRS). Here, more space is devoted to explaining some of the key methodological factors that are required for interpretation. We end with a section on multimodal and multidimensional imaging approaches, which we believe will be critical for increasing our understanding of brain development and its relationship to cognitive and behavioral growth in the preschool years and beyond.

Tissue saturation measurement - exciting prospects, but standardisation and reference data still needed

Sepsis and shock result in disturbances in microcirculatory perfusion and tissue oxygen utilisation that may not be reflected in global measures of haemodynamics. Near-infrared spectroscopy enables measurement of tissue oxygen saturation (StO2) and provides information on local microvascular and mitochondrial function. This measure could be incorporated with existing targets of goal-directed therapy to provide an integrated approach to haemodynamic resuscitation of both the macro- and microcirculation in various shock states. However, key methodological factors must be addressed before widespread clinical application.

Driving change in rural workforce planning: the Medical Schools Outcomes Database

The Medical Schools Outcomes Database (MSOD) is an ongoing longitudinal tracking project ofmedical students from all medical schools in Australia and New Zealand. It was established in 2005 to track the career trajectories of medical students and will directly help develop models of workforce flow, particularly with respect to rural and remote shortages. This paper briefly outlines the MSOD project and reports on key methodological factors in tracking medical students. Finally, the potential impact of the MSOD on understanding changes in rural practice intentions is illustrated using data from the 2005 pilot cohort (n = 112). Rural placements were associated with a shift towards rural practice intentions, while those who intended to practice rurally at both the start and end of medical school tended to be older and interested in a generalist career. Continuing work will track these and future students as they progress through the workforce, as well as exploring issues such as the career trajectories of international fee-paying students, workforce succession planning, and the evaluation of medical education initiatives.

The quality of randomized trial reporting in leading medical journals since the revised CONSORT statement

If randomized controlled trials (RCTs) are to fulfill their potential to allow health care providers to make informed inferences about the validity of the trials upon which they base their clinical practice, then the reporting of key methodological factors must improve. The revised Consolidated Standards for Reporting Trials (CONSORT) were developed to improve the suboptimal reporting of RCTs. We aimed to determine the extent to which RCTs report key methodological factors included in the revised CONSORT recommendations following publication of these recommendations. We conducted an observational study of RCTs published between July 2002 and June 2003 in 5 leading general medicine journals. We determined the proportion and 95% confidence intervals of RCTs that reported sequence generation, allocation concealment, randomization implementation, blinding status of participants, health care providers, outcome assessors, and data analysts, sample size justification, method of analysis (e.g. intention-to-treat), and a participant flow diagram. We included a total of 253 RCTs. RCTs reported: sequence generation 80% (95% CI 75–80%), allocation concealment 48% (95% CI 42–54%), randomization implementation 55% (95% CI 49–61%), blinding status of participants 40% (34–46%), health care providers 17% (95% CI 13–22%), outcome assessors 47% (95% CI 41–53%), data analysts 15% (10–19%), sample size justification 83% (95% CI 78–87%), method of analysis 87% (95% CI 83–91%)), and participant flow diagrams 86% (95% CI 82–90%). Although reporting of some CONSORT recommendations is high, reporting of several essential recommendations remains suboptimal. Authors need to comply with and journals need to enforce reporting of the revised CONSORT recommendations.

The reporting of methodological factors in randomized controlled trials and the association with a journal policy to promote adherence to the Consolidated Standards of Reporting Trials (CONSORT) checklist

The “Consolidated Standards of Reporting Trials” (CONSORT) was developed to improve the suboptimal reporting of randomized controlled trials (RCTs). However, little is known about the quality of reporting since this publication. We undertook an observational study to determine the quality of reporting key methodological factors in RCTs since the publication of the CONSORT statement and if a journal policy to promote adherence to the CONSORT checklist was associated with superior reporting. We recorded the reporting of 11 key methodological factors in 105 RCTs from 29 medical journals published subsequent to the CONSORT statement. We examined the quality of reporting in relation to whether a journal was a “CONSORT promoter” as defined by inclusion of the CONSORT checklist in a journal's “information to authors” section or a requirement that authors, manuscript reviewers, or copy editors complete the CONSORT checklist. Multivariate analysis controlled for journal impact factor, study outcome, and time of publication. Six of the 11 methodological factors were reported <50% of the time. The number of methodological factors reported was greater in CONSORT promoters than in journals not promoting CONSORT in both unadjusted (6.0 and 5.1, respectively, p-value = 0.03) and adjusted (6.4 and 4.8 of the 11 methodological factors, respectively, p-value = 0.0001) analyses. While journals that promote CONSORT demonstrate superior reporting of RCTs, persistent inadequacies in reporting remain. Until these inadequacies are resolved health-care providers will remain limited in their ability to make informed inferences about the validity of the studies upon which they base their clinical practice.