Design and statistical analysis reporting among interrupted time series studies in drug utilization research: a cross-sectional survey.

INTRODUCTION: Interrupted time series (ITS) design is a commonly used method for evaluating large-scale interventions in clinical practice or public health. However, improperly using this method can lead to biased results. OBJECTIVE: To investigate design and statistical analysis characteristics of drug utilization studies using ITS design, and give recommendations for improvements. METHODS: A literature search was conducted based on PubMed from January 2021 to December 2021. We included original articles that used ITS design to investigate drug utilization without restriction on study population or outcome types. A structured, pilot-tested questionnaire was developed to extract information regarding study characteristics and details about design and statistical analysis. RESULTS: We included 153 eligible studies. Among those, 28.1% (43/153) clearly explained the rationale for using the ITS design and 13.7% (21/153) clarified the rationale of using the specified ITS model structure. One hundred and forty-nine studies used aggregated data to do ITS analysis, and 20.8% (31/149) clarified the rationale for the number of time points. The consideration of autocorrelation, non-stationary and seasonality was often lacking among those studies, and only 14 studies mentioned all of three methodological issues. Missing data was mentioned in 31 studies. Only 39.22% (60/153) reported the regression models, while 15 studies gave the incorrect interpretation of level change due to time parameterization. Time-varying participant characteristics were considered in 24 studies. In 97 studies containing hierarchical data, 23 studies clarified the heterogeneity among clusters and used statistical methods to address this issue. CONCLUSION: The quality of design and statistical analyses in ITS studies for drug utilization remains unsatisfactory. Three emerging methodological issues warranted particular attention, including incorrect interpretation of level change due to time parameterization, time-varying participant characteristics and hierarchical data analysis. We offered specific recommendations about the design, analysis and reporting of the ITS study.

Simultaneous selection and incorporation of consistent external aggregate information.

Interest has grown in synthesizing participant level data of a study with relevant external aggregate information. Several efficient and flexible procedures have been developed under the assumption that the internal study and the external sources concern the same population. This homogeneity condition, albeit commonly being imposed, is hard to check due to limitedly available external information in aggregate data forms. Bias may be introduced when the assumption is violated. In this article, we propose a penalized likelihood approach that avoids undesirable bias by simultaneously selecting and synthesizing consistent external aggregate information. The proposed approach provides a general framework which incorporate consistent external information from heterogeneous study populations as long as the conditional distribution of the dependent variable under investigation is same and differences in the independent variable distributions are properly accounted for via a semi-parametric density ratio model. The proposed approach also properly accounts for the sampling errors in the external information. A two-step estimator and an optimization algorithm are proposed for computation. We establish the selection and estimation consistency and the asymptotic normality of the two-step estimator. The proposed approach is illustrated with an analysis of gestational weight gain management studies.

The Changes and the Predictors of Suicidal Ideation Among HIV-positive Sexual Minority Men: A Five-year Longitudinal Study from China.

This study aimed to explore whether there were differences in suicidal ideation at different time points among sexual minority men (SMM) within five years of HIV diagnosis, and to investigate the influence of time and psychosocial variables on suicidal ideation. This was a five-year follow-up study focusing on the suicidal ideation among HIV-positive SMM who were recruited when they were newly diagnosed with HIV. Suicidal ideation and psychosocial characteristics including depression, anxiety, HIV-related stress, and social support were assessed within one month, the first year, and the fifth year after HIV diagnosis. A total of 197 SMM newly diagnosed with HIV completed three-time point surveys in this study. The prevalence of suicidal ideation was 27.4%, 15.7%, and 23.9% at one month, the first year, and the fifth year after HIV diagnosis, respectively. The risk of suicidal ideation was lower in the first year than baseline, but there was no significant difference between the fifth year and baseline. Emotional stress and objective support independently predicted suicidal ideation and they had interactions with time. The suicidal ideation of SMM newly diagnosed with HIV decreased in the first year and then increased in the fifth year, not showing a sustained decline trend in a longer trajectory of HIV diagnosis. Stress management, especially long-term stress assessment and management with a focus on emotional stress should be incorporated into HIV health care in an appropriate manner. In addition, social support should also be continuously provided to this vulnerable population.

The relationship between social support and suicidal ideation among newly diagnosed people living with HIV: the mediating role of HIV-related stress.

Evidence have consistently shown social support to be protective against suicidal ideation among people living with HIV (PLWH), but little is known how social support protects PLHW from suicidal ideation. We aimed to explore whether social support could reduce suicidal ideation by reducing HIV-related stress levels or depression among PLWH during the early post-diagnosis phase. A cross-sectional study of 557 newly diagnosed PLWH was conducted. Information on suicidal ideation, social support, HIV-related stress and depression was collected using a self-administered questionnaire. Generalized structural equation modeling (GSEM) analyses were performed to determine the mediating effect of HIV-related stress and depression on the relationship between social support and suicidal ideation. One-fourth of participants reported considering suicide after HIV diagnosis. Higher social support could prevent PLWH from suicidal ideation directly or indirectly via reducing the HIV-related stress levels. The mediating effect of depression, as well as the chain mediating effect of HIV-related stress and depression were not found. Enhancing social support and reducing HIV-related stress are important to prevent suicide among PLWH.

Drinking behavior among government employees in Changsha and its influencing factors. / é•¿æ²™å¸‚å ¬èŒäººå‘˜é¥®é ’è¡Œä¸ºçŽ°çŠ¶åŠå ¶å½±å“å› ç´ .

OBJECTIVES: To analyze the prevalence and influencing factors for drinking behavior and heavy drinking among government employees in Changsha and provide a basis for carrying out interventions for drinking behaviors and formulating public health promotion plans for government employees. METHODS: Government employees were recruited consecutively from the Health Management Center of a general hospital in Changsha between December 2017 and December 2018. Information on sociodemograpic characteristics, drinking behaviors, life events, and psychosocial characteristics was collected using a standard set of questionnaire. Drinking behavior was defined as drinking once or more per week for the past 12 months. The differences in drinking rates and excessive drinking rates among groups with different characteristics were compared. Multivariate analysis was performed to analyze the associated factors of drinking behaviors and heavy drinking for government employees. RESULTS: A total of 6 190 people completed this investigation. The overall drinking rate of government employees in Changsha was 21.9%, and the rate of drinking was higher in males than that in females (44.7% vs 4.0%, P<0.01). Among the participants who drinked, the heavy drinking rates of males and females were 26.4% and 10.1%, respectively, while the harmful drinking rates of males and females were 6.0% and 2.2%, respectively. The results of multivariate logistic regression analysis showed that smoking, below high school education level, frequency of social intercourse ≥ 2 times per week, and having married or the divorced/widowed marital status were associated with alcohol drinking for male governmental employees. While aged 41 to 60 years old, frequency of social intercourse ≥ 2 times per week, life events stimulation ≥8 points were the risk factors for female; male, aged 41 to 60 years old, smoking, frequency of social intercourse≥ 2 times per week, and life events stimulation ≥1 point were the risk factors for heavy drinking. CONCLUSIONS: The drinking and heavy drinking rates of government employees are high in Changsha. Marital status, physical exercise, and frequency of social intercourse are the common influencing factors of male drinking behavior and female drinking behavior. The life events stimulation is the influencing factor of heavy drinking.

Regulation of circadian rhythms by NEAT1 mediated TMAO-induced endothelial proliferation: A protective role of asparagus extract.

Trimethylamine N-oxide (TMAO) promotes atherosclerosis in association with the functions of endothelial cells. Clock and Bmal1, as two main components of molecular circadian clock, play important regulatory roles during progression of atherogenesis. However, whether Clock and Bmal1 are involved in the regulation of endothelial proliferation disturbed by TMAO are unclear. We observed that cell proliferation of human umbilical vein endothelial cells (HUVECs) was inhibited after exposed to TMAO for 24 h. Besides, TMAO caused increased expression of lncRNA-NEAT1, Clock and Bmal1, and inhibited MAPK pathways. While MAPK pathways were blocked, the expression of Clock and Bmal1 was elevated. NEAT1 showed a circadian rhythmic expression in HUVECs, and its overexpression reduced cell proliferation. Knockdown or overexpression of NEAT1 might decrease or increase the expression of Clock and Bmal1 respectively, while raised or suppressed the expression of MAPK pathways correspondingly. Asparagus extract (AE) was found to improve the TMAO-reduced HUVECs proliferation. Moreover, it ameliorated the disorders of NEAT1, Clock, Bmal1, and MAPK signaling pathways induced by TMAO. Therefore, our findings indicated that NEAT1 regulating Clock-Bmal1 via MAPK pathways was involved in TMAO-repressed HUVECs proliferation, and AE improved endothelial proliferation by TMAO, proposing a novel mechanism for cardiovascular disease prevention.

Equity and efficiency of maternal and child health resources allocation in Hunan Province, China.

BACKGROUND: A reasonable allocation of health resources is often characterized by equity and high efficiency. This study aims to evaluate the equity and efficiency of maternal and child health (MCH) resources allocation in Hunan Province, China. METHODS: Data related to MCH resources and services was obtained from the Hunan maternal and child health information reporting and management system. The Gini coefficient and data envelopment analysis (DEA) were employed to evaluate the equity and efficiency of MCH resources allocation, respectively. RESULTS: The MCH resources allocation in terms of demographic dimension were in a preferred equity status with the Gini values all less than 0.3, and the Gini values for each MCH resources' allocation in terms of the geographical dimension ranged from 0.1298 to 0.4256, with the highest values in the number of midwives and medical equipment (≥ CNY 10,000), which exceeds 0.4, indicating an alert of inequity. More than 40% regions in Hunan were found to be relatively inefficient with decreased return to scale in the allocation of MCH resources, indicating those inefficient regions were using more inputs than needed to obtain the current output levels. CONCLUSIONS: The equity of MCH resources by population size is superior by geographic area and the disproportionate distribution of the number of medical equipment (≥ CNY 10,000) and midwives between different regions was the main source of inequity. Policy-makers need to consider the geographical accessibility of health resources among different regions to ensure people in different regions could get access to available health services. More than 40% of regions in Hunan were found to be inefficient, with using more health resources than needed to produce the current amount of health services. Further investigations on factors affecting the efficiency of MCH resources allocation is still needed to guide regional health plans-making and resource allocation.

Changes and determinants of health-related quality of life among people newly diagnosed with HIV in China: a 1-year follow-up study.

PURPOSE: This study aimed to investigate changes in health-related quality of life (HRQoL) among people newly diagnosed with HIV and to identify factors associated with HRQoL. METHODS: Newly diagnosed HIV-positive individuals were consecutively recruited and assessed at baseline and 1-year follow-up after diagnosis. HRQoL was measured through the physical health summary score (PHS) and mental health summary score (MHS) derived from the Medical Outcomes Study HIV Health Survey. Socio-demographic, clinical, and psychological information was also collected at both times. Generalized estimating equations were applied to explore factors associated with HRQoL in 1 year. RESULTS: A total of 410 participants were included. After 1 year, significant increases were observed for both the mean PHS score (53.5-55.0; p = 0.009) and the mean MHS score (44.2-49.0; p < 0.001). Older age (p = 0.024), rural household registration (p = 0.031), HIV-related symptoms (p < 0.001), and depression (p = 0.014) were negatively associated with PHS. Additionally, the negative association between stress and PHS increased over time (ß = - 0.07 for the baseline; ß = - 0.18 for the 12-month follow-up; p < 0.001). HIV-related symptoms, depression, lower social support, and higher levels of stress (all p < 0.001) were negatively associated with MHS. Additionally, the negative relationship between stress and MHS was stronger among participants who were asymptomatic (p = 0.015). CONCLUSION: A relatively lower HRQoL among HIV-infected people shortly after HIV diagnosis and an increase in HRQoL among people 1 year after HIV diagnosis were observed. Additional attention should be paid to individuals of older age, from rural areas, with HIV-related symptoms, with depression, with high levels of stress, and with a lack of social support.

Extraction and analysis of antioxidant compounds from the residues of Asparagus officinalis L.

Asparagus residues were used as materials to obtain antioxidant compounds by solid-liquid extraction in this study. The effects of different extraction parameters including extraction solvents, time, temperature and liquid-solid ratio on the contents of total flavonoids, total phenolics and total antioxidant activity were investigated. Antioxidant activity of the extract from asparagus residues was evaluated by HPLC- ABTS · (+) and the bioactive components were identified by HPLC- MS/MS. The results showed that the extraction yield was significantly influenced (P < 0.05) by solvent composition, extraction time and temperature. The appropriate parameters were preferred as extraction solvent of 50 % ethanol with liquid-solid ratio of 30:1, extraction temperature of 80 °C and time of 2 h. Antioxidant activity evaluation of the extract indicated flavonoids and phenolics were dominant bioactive compounds. Five antioxidant compounds were identified as ferulic acid, kaempferol, quercetin, rutin and isorhamnetin.

Array-wide uniform PEDOT:PSS electroplating from potentiostatic deposition.

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics.

Sample size calculations for randomized controlled trials with repeatedly measured continuous variables as primary outcomes need improvements: a cross-sectional study.

OBJECTIVES: Randomized controlled trials (RCTs) with repeatedly measured continuous variables as primary outcomes are common. Although statistical methodologies for calculating sample sizes in such trials have been extensively investigated, their practical application remains unclear. This study aims to provide an overview of sample size calculation methods for different research questions (e.g., key time point treatment effect, treatment effect change over time) and evaluate the adequacy of current practices in trial design. STUDY DESIGN AND SETTING: We conducted a comprehensive search of PubMed to identify RCTs published in core journals in 2019 that utilized repeatedly measured continuous variables as their primary outcomes. Data were extracted using a predefined questionnaire including general study characteristics, primary outcomes, detailed sample size calculation methods, and methods for analyzing the primary outcome. We re-estimated the sample size for trials that provided all relevant parameters. RESULTS: A total of 168 RCTs were included, with a median of four repeated measurements (interquartile range 3-6) per outcome. In 48 (28.6%) trials, the primary outcome used for sample size calculation differed from the one used in defining the primary outcomes. There were 90 (53.6%) trials exhibited inconsistencies between the hypotheses specified for sample size calculation and those specified for primary analysis. The statistical methods used for sample size calculation in 158 (94.0%) trials did not align with those used for primary analysis. Additionally, only 6 (3.6%) trials accounted for the number of repeated measurements, and 7 (4.2%) trials considered the correlation among these measurements when calculating the sample size. Furthermore, of the 128 (76.2%) trials that considered loss to follow-up, 33 (25.8%) used an incorrect formula (i.e., N∗(1+lose rate) for sample size adjustment. In 53 (49.5%) out of 107 trials, the re-estimated sample size was larger than the reported sample size. CONCLUSION: The practice of sample size calculation for RCTs with repeatedly measured continuous variables as primary outcomes displayed significant deficiencies, with a notable proportion of trials failed to report essential parameters about repeated measurement required for sample size calculation. Our findings highlight the urgent need to use optimal sample size methods that align with the research hypothesis, primary analysis method, and the form of the primary outcome.

A biodegradable and flexible neural interface for transdermal optoelectronic modulation and regeneration of peripheral nerves.

Optoelectronic neural interfaces can leverage the photovoltaic effect to convert light into electrical current, inducing charge redistribution and enabling nerve stimulation. This method offers a non-genetic and remote approach for neuromodulation. Developing biodegradable and efficient optoelectronic neural interfaces is important for achieving transdermal stimulation while minimizing infection risks associated with device retrieval, thereby maximizing therapeutic outcomes. We propose a biodegradable, flexible, and miniaturized silicon-based neural interface capable of transdermal optoelectronic stimulation for neural modulation and nerve regeneration. Enhancing the device interface with thin-film molybdenum significantly improves the efficacy of neural stimulation. Our study demonstrates successful activation of the sciatic nerve in rodents and the facial nerve in rabbits. Moreover, transdermal optoelectronic stimulation accelerates the functional recovery of injured facial nerves.

Does it reasonable to include grid-side energy storage costs in transmission and distribution tariffs? Benefit evaluation based on economic externality.

Grid-side energy storage has become a crucial part of contemporary power systems as a result of the rapid expansion of renewable energy sources and the rising demand for grid stability. This study aims to investigate the rationality of incorporating grid-side energy storage costs into transmission and distribution (T&D) tariffs, evaluating this approach using economic externality theory. We first develop a comprehensive benefit evaluation framework based on economic externality theory considering system stability, renewable energy integration, end-user, and environmental impacts. Then, using the CPLEX solver, an operating model of grid-side energy storage is constructed with the goal of reducing substation load variations. Through a case study, it is found that grid-side energy storage has significant positive externality benefits, validating the rationale for including grid-side energy storage costs in T&D tariffs. Sensitivity analysis suggests that with cost reduction and market development, the proportion of grid-side energy storage included in the T&D tariff should gradually recede. As a result, this study offers important information about whether it is reasonable to include grid-side energy storage costs in T&D tariffs in China.

HIV-related stress predicts depression over five years among people living with HIV.

Introduction: Extant literature has demonstrated significant associations between HIV-related stress, social support, and depression among PLWH. However, little research has been conducted on the changes in such associations over time. Our study aims to explore the longitudinal relationship between HIV-related stress, social support, and depression among PLWH over five years. Methods: 320 PLWH were recruited from Changsha Center for Disease Control and Prevention (CDC), Hunan Province, China. They were assessed for depressive symptoms, HIV-related stress, and social support within 1 month of HIV diagnosis, 1 year after diagnosis, and five years after diagnosis, respectively. Relationships between these variables were examined using a fixed effect model. Result: The prevalence of depressive symptoms within the first month, first year, and fifth years of HIV diagnosis was 35, 12.2, and 14.7%, respectively. Emotional stress (ß: 0.730, 95% CI: 0.648, 0.811), social stress (ß: 0.066, 95% CI: 0.010, 0.123), instrumental stress (ß: 0.133, 95% CI:0.046, 0.221) positively predicted depression, while social support utilization (ß: -0.176, 95% CI: -0.303, -0.049) negatively predicted depression. Conclusion: Our study suggests that HIV-related stress and social support predict depressive symptoms over time among PLWH and that reducing HIV-related stress and improving social support in the early stages of diagnosis is extremely important in preventing depressive symptoms among PLWH.

A 3D biomimetic optoelectronic scaffold repairs cranial defects.

Bone fractures and defects pose serious health-related issues on patients. For clinical therapeutics, synthetic scaffolds have been actively explored to promote critical-sized bone regeneration, and electrical stimulations are recognized as an effective auxiliary to facilitate the process. Here, we develop a three-dimensional (3D) biomimetic scaffold integrated with thin-film silicon (Si)-based microstructures. This Si-based hybrid scaffold not only provides a 3D hierarchical structure for guiding cell growth but also regulates cell behaviors via photo-induced electrical signals. Remotely controlled by infrared illumination, these Si structures electrically modulate membrane potentials and intracellular calcium dynamics of stem cells and potentiate cell proliferation and differentiation. In a rodent model, the Si-integrated scaffold demonstrates improved osteogenesis under optical stimulations. Such a wirelessly powered optoelectronic scaffold eliminates tethered electrical implants and fully degrades in a biological environment. The Si-based 3D scaffold combines topographical and optoelectronic stimuli for effective biological modulations, offering broad potential for biomedicine.

A Bioresorbable and Conductive Scaffold Integrating Silicon Membranes for Peripheral Nerve Regeneration.

Peripheral nerve injury represents one of the most common types of traumatic damage, severely impairing motor and sensory functions, and posttraumatic nerve regeneration remains a major challenge. Electrical cues are critical bioactive factors that promote nerve regrowth, and bioartificial scaffolds incorporating conductive materials to enhance the endogenous electrical field have been demonstrated to be effective. The utilization of fully biodegradable scaffolds can eliminate material residues, and circumvent the need for secondary retrieval procedures. Here, a fully bioresorbable and conductive nerve scaffold integrating N-type silicon (Si) membranes is proposed, which can deliver both structural guidance and electrical cues for the repair of nerve defects. The entire scaffold is fully biodegradable, and the introduction of N-type Si can significantly promote the proliferation and production of neurotrophic factors of Schwann cells and enhance the calcium activity of dorsal root ganglion (DRG) neurons. The conductive scaffolds enable accelerated nerve regeneration and motor functional recovery in rodents with sciatic nerve transection injuries. This work sheds light on the advancement of bioresorbable and electrically active materials to achieve desirable neural interfaces and improved therapeutic outcomes, offering essential strategies for regenerative medicine.

Reporting, handling, and interpretation of time-varying drug treatments in observational studies using routinely collected healthcare data.

BACKGROUND: Time-varying drug treatments are common in studies using routinely collected health data (RCD) for assessing treatment effects. This study aimed to examine how these studies reported, handled, and interpreted time-varying drug treatments. METHODS: A systematic search was conducted on PubMed from 2018 to 2020. Eligible studies were those used RCD to explore drug treatment effects. We summarized the reporting characteristics and methods employed for handling time-varying treatments. Logistic regressions were performed to investigate the association between study characteristics and the reporting of time-varying treatments. RESULTS: Two hundred and fifty-six studies were included, and 225 (87.9%) studies involved time-varying treatments. Of these, 24 (10.7%) reported the proportion of time-varying treatments and 105 (46.7%) reported methods used to handle time-varying treatments. Multivariable logistic regression showed that medical studies, prespecified protocol, and involvement of methodologists were associated with a higher likelihood of reporting the methods applied to handle time-varying treatments. Among the 105 studies that reported methods, as-treated analyses were the most commonly used analysis sets, which were employed in 73.9%, 75.3% and 88.2% of studies that reported approaches for treatment discontinuation, treatment switching and treatment add-on. Among the 225 studies involved time-varying treatments, 27 (12.0%) acknowledged the potential bias introduced by treatment change, of which 14 (51.9%) suggested that potential biases may impact acceptance or rejection of the null hypothesis. CONCLUSIONS: Among observational studies using RCD, the underreporting about the presence and methods for handling time-varying treatments was largely common. The potential biases due to time-varying treatments have frequently been disregarded. Collaborative endeavors are strongly needed to enhance the prevailing practices.

Bioresorbable thin-film silicon diodes for the optoelectronic excitation and inhibition of neural activities.

Neural activities can be modulated by leveraging light-responsive nanomaterials as interfaces for exerting photothermal, photoelectrochemical or photocapacitive effects on neurons or neural tissues. Here we show that bioresorbable thin-film monocrystalline silicon pn diodes can be used to optoelectronically excite or inhibit neural activities by establishing polarity-dependent positive or negative photovoltages at the semiconductor/solution interface. Under laser illumination, the silicon-diode optoelectronic interfaces allowed for the deterministic depolarization or hyperpolarization of cultured neurons as well as the upregulated or downregulated intracellular calcium dynamics. The optoelectronic interfaces can also be mounted on nerve tissue to activate or silence neural activities in peripheral and central nervous tissues, as we show in mice with exposed sciatic nerves and somatosensory cortices. Bioresorbable silicon-based optoelectronic thin films that selectively excite or inhibit neural tissue may find advantageous biomedical applicability.

Missing data were poorly reported and handled in randomized controlled trials with repeatedly measured continuous outcomes: a cross-sectional survey.

BACKGROUND AND OBJECTIVES: Missing data are common in randomized controlled trials (RCTs) involving repeatedly measured continuous outcomes. Evidence on the reporting and handling of such outcome data is lacking, which has prevented further improvement in methods and reporting of RCTs. METHODS: We searched PubMed to identify RCTs published in the Core Clinical Journals in 2019 that reported a continuous primary outcome with repeated measures. A team of investigators conducted a study screening and collected data using pilot-tested, standardized questionnaires from a random sample of eligible RCTs. We thoroughly collected information about the reporting of missing data for the repeatedly measured continuous outcome and the methods used to handle the missing data. RESULTS: We included 200 eligible trials, whose mean number of repeated measures for the continuous primary outcomes was 5.46 (SD = 3.4). Sixty-one (30.5%) trials explicitly reported missing data at both participant and outcome levels, 116 (58.0%) at the participant level only, and 2 (1.0%) at the outcome level only. Sixty (30.0%) trials reported missing data at the participant level by group and by time point, and 53 (26.5%) at the outcome level by group and by time point. Among 179 trials having reported missing data, 162 (90.5%) did not assess the balance of baseline characteristics, 143 (79.9%) did not assume missing mechanism; 65 (36.3%) used suboptimal methods for handling missing data (e.g., complete case analysis); 41 (22.9%) conducted sensitivity analyses, and 5 (11.9%) assumed alternative missing mechanisms for sensitivity analyses. CONCLUSION: The reporting of missing data for repeatedly measured continuous outcomes were inadequate and the use of statistical methods for handling missing data was far from optimal. Substantial efforts are warranted to improve the reporting and statistical handling of these outcome data.

Analyses of repeatedly measured continuous outcomes in randomized controlled trials needed substantial improvements.

OBJECTIVES: Systematic understanding is lacking regarding how current trials handle repeated measure data and the extent to which appropriate statistical methods are used for such data set. This study investigated the current practice of analyzing the repeated measure data among randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: We searched the Core Clinical Journals indexed in PubMed for RCTs published in 2019 and included a continuous primary outcome with repeated measures. We randomly sampled RCTs from the eligible trials. Team of methods trained investigators screened studies for eligibility and collected data using the pilot-tested, standardized questionnaires. We thoroughly documented statistical analyses of the continuous primary outcome with repeated measures and particularly recorded how statistically advanced methods were used to handle these repeated measures. RESULTS: In total, 200 trials were included. Of these trials, the mean number of repeated measures for the continuous primary outcome was 5.46 (SD = 3.4); 58 (29.0%) trials did not specify the time point of primary outcome in the method; 113 (56.5%) trials did not use statistically advanced methods for handling repeated measure data in the primary analyses. Among187 trials included the baseline values, 88 (47.1%) trials did not adjust for outcome value at baseline. Among 87 trials using statistically advanced methods, 49 (56.3%) did not specify correlation structure for model. CONCLUSIONS: The statistical analyses of repeatedly measured continuous outcomes in RCTs need substantial improvements. Careful planning of the primary outcome and the use of statistically advanced methods for analyzing data are warranted.