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Background Threshold regression models are a diverse set of non-regular regression models that all depend on change points or thresholds. They provide a simple but elegant and interpretable way to model certain kinds of nonlinear relationships between the outcome and a predictor. Results The R package chngpt provides both estimation and hypothesis testing functionalities for four common variants of threshold regression models. All allow for adjustment of additional covariates not subjected to thresholding. We demonstrate the consistency of the estimating procedures and the type 1 error rates of the testing procedures by Monte Carlo studies, and illustrate their practical uses using an example from the study of immune response biomarkers in the context of Mother-To-Child-Transmission of HIV-1 viruses. Conclusion chngpt makes several unique contributions to the software for threshold regression models and will make these models more accessible to practitioners interested in modeling threshold effects.

To describe the use and reporting of interrupted time series methods in drug utilization research. We completed a systematic search of MEDLINE, Web of Science, and reference lists to identify English language articles through to December 2013 that used interrupted time series methods in drug utilization research. We tabulated the number of studies by publication year and summarized methodological detail. We identified 220 eligible empirical applications since 1984. Only 17 (8%) were published before 2000, and 90 (41%) were published since 2010. Segmented regression was the most commonly applied interrupted time series method (67%). Most studies assessed drug policy changes (51%, n = 112); 22% (n = 48) examined the impact of new evidence, 18% (n = 39) examined safety advisories, and 16% (n = 35) examined quality improvement interventions. Autocorrelation was considered in 66% of studies, 31% reported adjusting for seasonality, and 15% accounted for nonstationarity. Use of interrupted time series methods in drug utilization research has increased, particularly in recent years. Despite methodological recommendations, there is large variation in reporting of analytic methods. Developing methodological and reporting standards for interrupted time series analysis is important to improve its application in drug utilization research, and we provide recommendations for consideration.

Background The Interrupted Time Series (ITS) is a quasi-experimental design commonly used in public health to evaluate the impact of interventions or exposures. Multiple statistical methods are available to analyse data from ITS studies, but no empirical investigation has examined how the different methods compare when applied to real-world datasets. Methods A random sample of 200 ITS studies identified in a previous methods review were included. Time series data from each of these studies was sought. Each dataset was re-analysed using six statistical methods. Point and confidence interval estimates for level and slope changes, standard errors, p- values and estimates of autocorrelation were compared between methods. Results From the 200 ITS studies, including 230 time series, 190 datasets were obtained. We found that the choice of statistical method can importantly affect the level and slope change point estimates, their standard errors, width of confidence intervals and p- values. Statistical significance (categorised at the 5% level) often differed across the pairwise comparisons of methods, ranging from 4 to 25% disagreement. Estimates of autocorrelation differed depending on the method used and the length of the series. Conclusions The choice of statistical method in ITS studies can lead to substantially different conclusions about the impact of the interruption. Pre-specification of the statistical method is encouraged, and naive conclusions based on statistical significance should be avoided.

Interrupted time series (ITS) is a powerful and increasingly popular design for evaluating public health and health service interventions. The design involves analyzing trends in the outcome of interest and estimating the change in trend following an intervention relative to the counterfactual (the expected ongoing trend if the intervention had not occurred). There are two key components to modeling this effect: first, defining the counterfactual; second, defining the type of effect that the intervention is expected to have on the outcome, known as the impact model. The counterfactual is defined by extrapolating the underlying trends observed before the intervention to the postintervention period. In doing this, authors must consider the preintervention period that will be included, any time-varying confounders, whether trends may vary within different subgroups of the population and whether trends are linear or nonlinear. Defining the impact model involves specifying the parameters that model the intervention, including for instance whether to allow for an abrupt level change or a gradual slope change, whether to allow for a lag before any effect on the outcome, whether to allow a transition period during which the intervention is being implemented, and whether a ceiling or floor effect might be expected. Inappropriate model specification can bias the results of an ITS analysis and using a model that is not closely tailored to the intervention or testing multiple models increases the risk of false positives being detected. It is important that authors use substantive knowledge to customize their ITS model a priori to the intervention and outcome under study. Where there is uncertainty in model specification, authors should consider using separate data sources to define the intervention, running limited sensitivity analyses or undertaking initial exploratory studies.

Interrupted time series are increasingly being used to evaluate the population-wide implementation of public health interventions. However, the resulting estimates of intervention impact can be severely biased if underlying disease trends are not adequately accounted for. Control series offer a potential solution to this problem, but there is little guidance on how to use them to produce trend-adjusted estimates. To address this lack of guidance, we show how interrupted time series can be analysed when the control and intervention series share confounders, i. e. when they share a common trend. We show that the intervention effect can be estimated by subtracting the control series from the intervention series and analysing the difference using linear regression or, if a log-linear model is assumed, by including the control series as an offset in a Poisson regression with robust standard errors. The methods are illustrated with two examples.

Background Interrupted time series (ITS) studies are frequently used to evaluate the effects of population-level interventions or exposures. However, examination of the performance of statistical methods for this design has received relatively little attention. Methods We simulated continuous data to compare the performance of a set of statistical methods under a range of scenarios which included different level and slope changes, varying lengths of series and magnitudes of lag-1 autocorrelation. We also examined the performance of the Durbin-Watson (DW) test for detecting autocorrelation. Results All methods yielded unbiased estimates of the level and slope changes over all scenarios. The magnitude of autocorrelation was underestimated by all methods, however, restricted maximum likelihood (REML) yielded the least biased estimates. Underestimation of autocorrelation led to standard errors that were too small and coverage less than the nominal 95%. All methods performed better with longer time series, except for ordinary least squares (OLS) in the presence of autocorrelation and Newey-West for high values of autocorrelation. The DW test for the presence of autocorrelation performed poorly except for long series and large autocorrelation. Conclusions From the methods evaluated, OLS was the preferred method in series with fewer than 12 points, while in longer series, REML was preferred. The DW test should not be relied upon to detect autocorrelation, except when the series is long. Care is needed when interpreting results from all methods, given confidence intervals will generally be too narrow. Further research is required to develop better performing methods for ITS, especially for short series.

Interrupted time series (ITS) designs are frequently used in public health to examine whether an intervention or exposure has influenced health outcomes. Few reviews have been undertaken to examine the design characteristics, statistical methods, and completeness of reporting of published ITS studies. We used stratified random sampling to identify 200 ITS studies that evaluated public health interventions or exposures from PubMed (2013–2017). Study characteristics, details of statistical models and estimation methods used, effect metrics, and parameter estimates were extracted. From the 200 studies, 230 time series were examined. Common statistical methods used were linear regression (31%, 72/230) and autoregressive integrated moving average (19%, 43/230). In 17% (40/230) of the series, we could not determine the statistical method used. Autocorrelation was acknowledged in 63% (145/230) of the series. An estimate of the autocorrelation coefficient was given for only 1% of the series (3/230). Measures of precision were reported for 63% of effect measures (541/852). Many aspects of the design, methods, analysis, and reporting of ITS studies can be improved, particularly description of the statistical methods and approaches to adjust for and estimate autocorrelation. More guidance on the conduct and reporting of ITS studies is needed to improve this study design.

Interrupted time series is a strong quasi-experimental research design to evaluate the impacts of health policy interventions. Using simulation methods, we estimated the power requirements for interrupted time series studies under various scenarios. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from −0.9 to 0.9 and effect size was 0.5, 1.0, and 2.0, investigating balanced and unbalanced numbers of time periods before and after an intervention. Simple scenarios of autoregressive conditional heteroskedasticity (ARCH) models were also explored. For AR models, power increased when sample size or effect size increased, and tended to decrease when autocorrelation increased. Compared with a balanced number of study periods before and after an intervention, designs with unbalanced numbers of periods had less power, although that was not the case for ARCH models. The power to detect effect size 1.0 appeared to be reasonable for many practical applications with a moderate or large number of time points in the study equally divided around the intervention. Investigators should be cautious when the expected effect size is small or the number of time points is small. We recommend conducting various simulations before investigation.

Interrupted Time Series (ITS) are a type of nonrandomized design commonly used to evaluate public health policy interventions, and the impact of exposures, at the population level. Meta-analysis may be used to combine results from ITS across studies (in the context of systematic reviews) or across sites within the same study. We aimed to examine the statistical approaches, methods, and completeness of reporting in reviews that meta-analyze results from ITS. Eight electronic databases were searched to identify reviews (published 2000–2019) that meta-analyzed at least two ITS. Characteristics of the included reviews, the statistical methods used to analyze the ITS and meta-analyze their results, effect measures, and risk of bias assessment tools were extracted. Of the 4213 identified records, 54 reviews were included. Nearly all reviews (94%) used two-stage meta-analysis, most commonly fitting a random effects model (69%). Among the 41 reviews that re-analyzed the ITS, linear regression (39%) and ARIMA (20%) were most commonly used; 38% adjusted for autocorrelation. The most common effect measure meta-analyzed was an immediate level-change (46/54). Reporting of the statistical methods and ITS characteristics was often incomplete. Improvement is needed in the conduct and reporting of reviews that meta-analyze results from ITS.

A national centralized volume-based procurement policy (NCVBPP) targeting meropenem has been implemented in China since December 2022. Here, the effects of the meropenem NCVBPP upon the prescription of designated antimicrobials for inpatients were explored. The impacts of the meropenem NCVBPP on the consumption of and expenditures for designated antimicrobials prescribed for inpatients were evaluated by means of an interrupted time series analysis (ITSA) using both an autoregressive integrated moving average (ARIMA) model and a segmented regression model. The designated antimicrobials consisted of carbapenem-type antimicrobials and carbapenem-replaced antimicrobials; the latter referred specifically to combinations of penicillins/cephalosporins with beta-lactamase inhibitors and cephamycins. Data on the consumption of and expenditures for designated antimicrobials used in the inpatient sector of our hospital during the period ranging from January 2020 to March 2024 were collected and subjected to an ITSA. The meropenem NCVBPP boosted the consumption of meropenem (generic drug and original counterpart); however, neither the total consumption of carbapenem-type antimicrobials nor that of carbapenem-replaced antimicrobials was affected by the meropenem NCVBPP. On the other hand, the meropenem NCVBPP significantly decreased the expenditures on meropenem. Its impacts on the total expenditures for carbapenem-type antimicrobials were unknown. Although a transient increase in the expenditures for carbapenem-replaced antimicrobials and a reduction in the overall expenditures for carbapenem-type antimicrobials plus carbapenem-replaced antimicrobials were also observed following the meropenem NCVBPP, these results were not necessarily caused by the meropenem NCVBPP. The meropenem NCVBPP triggers increased consumption of but reduced expenditures for meropenem. It has no effects on either the overall consumption of carbapenems or carbapenem-replaced antimicrobials.