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To evaluate the effects of state opioid prescribing cap laws on opioid prescribing after surgery.OptumLabs Data Warehouse administrative claims data covering all 50 states from July 2012 through June 2019.We included individuals from 20 states that had implemented prescribing cap laws without exemptions for postsurgical pain by June 2019 and individuals from 16 control states plus the District of Columbia. We used a difference-in-differences approach accounting for differential timing in law implementation across states to estimate the effects of state prescribing cap laws on postsurgical prescribing of opioids. Outcome measures included filling an opioid prescription within 30 days after surgery; filling opioid prescriptions of specific doses or durations; and the number, days' supply, daily dose, and pill quantity of opioid prescriptions. To assess the validity of the parallel counterfactual trends assumption, we examined differences in outcome trends between law-implementing and control states in the years preceding law implementation using an equivalence testing framework.We included the first surgery in the study period for opioid-naïve individuals undergoing one of eight common surgical procedures.State prescribing cap laws were associated with 0.109 lower days' supply of postsurgical opioids on the log scale (95% Confidence Interval [CI]: -0.139, -0.080) but were not associated with the number (Average treatment effect on the treated [ATT]: -0.011; 95% CI: -0.043, 0.021) or daily dose of postsurgical opioid prescriptions (ATT: -0.013; 95% CI: -0.030, 0.005). The negative association observed between prescribing cap laws and the probability of filling a postsurgical opioid prescription (ATT: -0.041; 95% CI: -0.054, -0.028) was likely spurious, given differences between law-implementing and control states in the pre-law period.Prescribing cap laws appear to have minimal effects on postsurgical opioid prescribing.

The objective of this study is to determine county-level factors associated with anxiety, depression, and isolation during the coronavirus disease 2019 (COVID-19) pandemic. This study used daily data from 23,592,355 respondents of a nationwide Facebook-based survey from April 2020 to July 2021, aggregated to the week-county level to yield 212,581 observations. Mental distress prevalences were modeled using weighted linear mixed-effects models with a county random effect. These models revealed that weekly percentages of mental distress were higher in counties with higher unemployment rates, populations, and education levels; higher percentages of females, young adults, individuals with a medical condition, and individuals very worried about their finances and COVID-19; and lower percentages of individuals who were working outside the home, living with children, without health insurance, and Black. Anxiety peaked in April 2020, depression in October 2020, and isolation in December 2020. Therefore, United States counties experienced the mental health effects of the pandemic differently dependent upon their characteristics, and mental distress prevalence varied across time.

Background Avoiding “causal” language with observational study designs is common publication practice, often justified as being a more cautious approach to interpretation. Objectives We aimed to i) estimate the degree to which causality was implied by both the language linking exposures to outcomes and by action recommendations in the high-profile health literature, ii) examine disconnects between language and recommendations, iii) identify which linking phrases were most common, and iv) generate estimates by which these phrases imply causality. Methods We identified 18 of the most prominent general medical/public health/epidemiology journals, and searched and screened for articles published from 2010 to 2019 that investigated exposure/outcome pairs until we reached 65 non-RCT articles per journal (n=1,170). Two independent reviewers and an arbitrating reviewer rated the degree to which they believed causality had been implied by the language in abstracts based on written guidance. Reviewers then rated causal implications of linking words in isolation. For comparison, additional review was performed for full texts and for a secondary sample of RCTs. Results Reviewers rated the causal implication of the sentence and phrase linking the exposure and outcome as None (i.e., makes no causal implication) in 13.8%, Weak in 34.2%, Moderate in 33.2%, and Strong in 18.7% of abstracts. Reviewers identified an action recommendation in 34.2% of abstracts. Of these action recommendations, reviewers rated the causal implications as None in 5.3%, Weak in 19.0%, Moderate in 42.8% and Strong in 33.0% of cases. The implied causality of action recommendations was often higher than the implied causality of linking sentences (44.5%) or commensurate (40.3%), with 15.3% being weaker. The most common linking word root identified in abstracts was “associate” (n=535/1,170; 45.7%) (e.g. “association,” “associated,” etc). There were only 16 (1.4%) abstracts using “cause” in the linking or modifying phrases. Reviewer ratings for causal implications of word roots were highly heterogeneous, including those commonly considered non-causal. Discussion We found substantial disconnects between causal implications used to link an exposure to an outcome and the action implications made. This undercuts common assumptions about what words are often considered non-causal and that policing them eliminates causal implications. We recommend that instead of policing words, editors, researchers, and communicators should increase efforts at making research questions, as well as the potential of studies to answer them, more transparent. Summary box

Generalizability methods are increasingly used to make inferences about the effect of interventions in target populations using a study sample. Most existing methods to generalize effects from sample to population rely on the assumption that subgroup-specific effects generalize directly. However, researchers may be concerned that in fact subgroup-specific effects differ between sample and population. In this brief report, we explore the generalizability of subgroup effects. First, we derive the bias in the sample average treatment effect estimator as an estimate of the population average treatment effect when subgroup effects in the sample do not directly generalize. Next, we present a Monte Carlo simulation to explore bias due to unmeasured heterogeneity of subgroup effects across sample and population. Finally, we examine the potential for bias in an illustrative data example. Understanding the generalizability of subgroup effects may lead to increased use of these methods for making externally valid inferences of treatment effects using a study sample.

High-dose and long-duration opioid prescriptions remain relatively common among children and adolescents, but there is insufficient research on the association of state laws limiting the dose and/or duration of opioid prescriptions (referred to as opioid prescribing cap laws) with opioid prescribing for this group.To examine the association between state opioid prescribing cap laws and the receipt of opioid prescriptions among children and adolescents.This repeated cross-sectional study used a difference-in-differences approach accounting for staggered policy adoption to assess the association of state opioid prescribing cap laws in the US from January 1, 2013, to December 31, 2019, with receipt of opioid prescriptions among children and adolescents. Analyses were conducted between March 22 and December 15, 2021. Data were obtained from the OptumLabs Data Warehouse, a national commercial insurance claims database. The analysis included 482 118 commercially insured children and adolescents aged 0 to 17 years with full calendar-year continuous insurance enrollment between 2013 and 2019. Individuals were included for every year in which they were continuously enrolled; they did not need to be enrolled for the entire 7-year study period. Those with any cancer diagnosis were excluded from analysis.Implementation of a state opioid prescribing cap law between January 1, 2017, and July 1, 2019. This date range allowed analysis of the same number years for both pre-cap and post-cap data.Outcomes of interest included receipt of any opioid prescription and, among those with at least 1 opioid prescription, the mean number of opioid prescriptions, mean morphine milligram equivalents (MMEs) per day, and mean days' supply.Among 482 118 children and adolescents (754 368 person-years of data aggregated to the state-year level), 245 178 (50.9%) were male, with a mean (SD) age of 9.8 (4.8) years at the first year included in the sample (data on race and ethnicity were not collected as part of this data set, which was obtained from insurance billing claims). Overall, 10 659 children and adolescents (2.2%) received at least 1 opioid prescription during the study period. Among those with at least 1 prescription, the mean (SD) number of filled opioid prescriptions was 1.2 (0.8) per person per year. No statistically significant association was found between state opioid prescribing cap laws and any outcome. After opioid prescribing cap laws were implemented, a -0.001 (95% CI, -0.005 to 0.002) percentage point decrease in the proportion of youths receiving any opioid prescription was observed. In addition, percentage point decreases of -0.01 (95% CI, -0.10 to 0.09) in high-dose opioid prescriptions (50 MMEs per day) and -0.02 (95% CI, -0.12 to 0.08) in long-duration opioid prescriptions (7 days' supply) were found after cap laws were implemented.In this cross-sectional study, no association was observed between state opioid prescribing cap laws and the receipt of opioid prescriptions among children and adolescents. Alternative strategies, such as opioid prescribing guidelines tailored to youths, are needed.

IntroductionAssessing the impact of COVID-19 policy is critical for informing future policies. However, there are concerns about the overall strength of COVID-19 impact evaluation studies given the circumstances for evaluation and concerns about the publication environment. This study systematically reviewed the strength of evidence in the published COVID-19 policy impact evaluation literature.MethodsWe included studies that were primarily designed to estimate the quantitative impact of one or more implemented COVID-19 policies on direct SARS-CoV-2 and COVID-19 outcomes. After searching PubMed for peer-reviewed articles published on November 26, 2020 or earlier and screening, all studies were reviewed by three reviewers first independently and then to consensus. The review tool was based on previously developed and released review guidance for COVID-19 policy impact evaluation, assessing what impact evaluation method was used, graphical display of outcomes data, functional form for the outcomes, timing between policy and impact, concurrent changes to the outcomes, and an overall rating.ResultsAfter 102 articles were identified as potentially meeting inclusion criteria, we identified 36 published articles that evaluated the quantitative impact of COVID-19 policies on direct COVID-19 outcomes. The majority (n=23/36) of studies in our sample examined the impact of stay-at-home requirements. Nine studies were set aside because the study design was considered inappropriate for COVID-19 policy impact evaluation (n=8 pre/post; n=1 cross-section), and 27 articles were given a full consensus assessment. 20/27 met criteria for graphical display of data, 5/27 for functional form, 19/27 for timing between policy implementation and impact, and only 3/27 for concurrent changes to the outcomes. Only 1/27 studies passed all of the above checks, and 4/27 were rated as overall appropriate. Including the 9 studies set aside, reviewers found that only four of the 36 identified published and peer-reviewed health policy impact evaluation studies passed a set of key design checks for identifying the causal impact of policies on COVID-19 outcomes.DiscussionThe reviewed literature directly evaluating the impact of COVID-19 policies largely failed to meet key design criteria for inference of sufficient rigor to be actionable by policy-makers. This was largely driven by the circumstances under which policies were passed making it difficult to attribute changes in COVID-19 outcomes to particular policies. More reliable evidence review is needed to both identify and produce policy-actionable evidence, alongside the recognition that actionable evidence is often unlikely to be feasible.

Background: The COVID-19 pandemic has had an impact on mental health and alcohol use in the US, however there is little research on its impacts on cannabis use. Considering the role of cannabis as a coping strategy or self-medicating behavior, there is a need to understand how individuals who use cannabis have adapted their use amid the pandemic. Therefore, this study examined changes in self-reported cannabis use among US adults in the context of COVID-19 pandemic by (1) describing trends of use during the first 8 months of the pandemic among adults who used cannabis in this period; and (2) characterizing trajectories of use within sociodemographic subgroups and by state cannabis policy status. Methods and Findings: The sample consisted of 1,761 US adults who used cannabis at least once during the 8 month study period from the nationally representative Understanding America Study. Linear mixed-effect models were used to model changes in the number of days of past-week cannabis use across 16 waves from March 10, 2020, to November 11, 2020. Compared to early March, the number of days cannabis was used per week was significantly higher at the start of April (β=0.11, 95% CI=0.03, 0.18) and May (β=0.21,95% CI=0.05, 0.36). In subsequent months (June - November), the number of days of cannabis use returned to levels comparable to early March. Trajectories of cannabis use across the study period generally did not differ across sociodemographic groups. Conclusions: In the US, adults who used cannabis reported statistically significant increases in cannabis use days at the start of the pandemic (April - May 2020), compared to March 2020, in the overall sample and among several sociodemographic groups. In Summer and Fall 2020, cannabis use days attenuated to levels comparable to March. Though increases in use were marginal among many groups, the evolving pandemic and the growing concern for the mental health of segments of the U.S. population warrant close monitoring of coping behaviors, including substance use.

In response to the role of opioid prescribing in the U.S. opioid crisis, states have enacted laws intended to curb high risk opioid prescribing practices. This study assessed the effects of state prescribing cap laws that limit the dose and/or duration of dispensed opioid prescriptions on opioid prescribing patterns and opioid overdose.We identified 1,414,908 adults from a large U.S. administrative insurance claims database. Treatment states included 32 states that implemented a prescribing cap law between 2017 and 2019. Comparison states included 16 states and DC without a prescribing cap law by 2019. A difference-in-differences approach with staggered policy adoption was used to assess effects of these laws on opioid analgesic prescribing and opioid overdose.State opioid prescribing cap laws were not associated with changes in the proportion of people receiving opioid analgesic prescriptions, the dose or duration of opioid prescriptions, or opioid overdose. States with laws that imposed days' supply limits only versus days' supply and dosage limits, as well as with specific law provisions also showed no association with opioid prescribing or opioid overdose outcomes.State opioid prescribing cap laws did not appear to impact outcomes related to opioid analgesic prescribing or opioid overdose. These findings are potentially due to the limited scope of these laws, which often apply only to a subset of opioid prescriptions and include professional judgment exemptions.

Evidence‐based policy at the local level requires predicting the impact of an intervention to inform whether it should be adopted. Increasingly, local policymakers have access to published research evaluating the effectiveness of policy interventions from national research clearinghouses that review and disseminate evidence from program evaluations. Through these evaluations, local policymakers have a wealth of evidence describing what works, but not necessarily where. Multisite evaluations may produce unbiased estimates of the average impact of an intervention in the study sample and still produce inaccurate predictions of the impact for localities outside the sample for two reasons: (1) the impact of the intervention may vary across localities, and (2) the evaluation estimate is subject to sampling error. Unfortunately, there is relatively little evidence on how much the impacts of policy interventions vary from one locality to another and almost no evidence on the implications of this variation for the accuracy with which the local impact of adopting an intervention can be predicted using findings from an evaluation in other localities. In this paper, we present a set of methods for quantifying the accuracy of the local predictions that can be obtained using the results of multisite randomized trials and for assessing the likelihood that prediction errors will lead to errors in local policy decisions. We demonstrate these methods using three evaluations of educational interventions, providing the first empirical evidence of the ability to use multisite evaluations to predict impacts in individual localities—i.e., the ability of “evidence‐based policy” to improve local policy.

Mediation analysis aims to investigate the "mechanisms of action" behind the effects of interventions or treatments. Originally developed in psychology, a robust set of mediation methods are now used across a range of fields. Given the history and common use of mediation in mental health research, this review aimed to understand how mediation analysis is implemented in psychology and psychiatry and whether analyses adhere to, address, or justify the key underlying assumptions of their approaches. All articles (N=206) came from top academic psychiatry or psychology journals in the PsycInfo database, published in the English language from 2013-2018. Information extracted from each article related to: study design, covariates adjusted for in the analysis, temporal ordering of variables, and the specific method used to perform the mediation analysis. Most papers did not adhere to their underlying assumptions. Only approximately 20% of papers had full temporal ordering of exposure, mediator, and outcome. Fewer than half of the papers controlled for confounding of the exposure-mediator and/or mediator-outcome relationships. Almost none discussed the underlying assumptions of their approaches or used causal mediation methods. These results provide insights for how methodologists should aim to communicate methods, and motivation for more outreach to the research community on best practices for mediation analysis. Mediation analysis is an appealing method in many areas within epidemiology. However, mediation analysis is complex, and it is unclear how well the underlying assumptions and alternative analytic approaches have been disseminated and understood.

Causal mediation analysis is complicated with multiple effect definitions that require different sets of assumptions for identification. This article provides a systematic explanation of such assumptions. We define five potential outcome types whose means are involved in various effect definitions. We tackle their mean/distribution’s identification, starting with the one that requires the weakest assumptions and gradually building up to the one that requires the strongest assumptions. This presentation shows clearly why an assumption is required for one estimand and not another, and provides a succinct table from which an applied researcher could pick out the assumptions required for identifying the causal effects they target. Using a running example, the article illustrates the assembling and consideration of identifying assumptions for a range of causal contrasts. For several that are commonly encountered in the literature, this exercise clarifies that identification requires weaker assumptions than those often stated in the literature. This attention to the details also draws attention to the differences in the positivity assumption for different estimands, with practical implications. Clarity on the identifying assumptions of these various estimands will help researchers conduct appropriate mediation analyses and interpret the results with appropriate caution given the plausibility of the assumptions.

The incorporation of causal inference in mediation analysis has led to theoretical and methodological advancements-effect definitions with causal interpretation, clarification of assumptions required for effect identification, and an expanding array of options for effect estimation. However, the literature on these results is fast-growing and complex, which may be confusing to researchers unfamiliar with causal inference or unfamiliar with mediation. The goal of this article is to help ease the understanding and adoption of causal mediation analysis. It starts by highlighting a key difference between the causal inference and traditional approaches to mediation analysis and making a case for the need for explicit causal thinking and the causal inference approach in mediation analysis. It then explains in as-plain-as-possible language existing effect types, paying special attention to motivating these effects with different types of research questions, and using concrete examples for illustration. This presentation differentiates 2 perspectives (or purposes of analysis): the explanatory perspective (aiming to explain the total effect) and the interventional perspective (asking questions about hypothetical interventions on the exposure and mediator, or hypothetically modified exposures). For the latter perspective, the article proposes tapping into a general class of interventional effects that contains as special cases most of the usual effect types-interventional direct and indirect effects, controlled direct effects and also a generalized interventional direct effect type, as well as the total effect and overall effect. This general class allows flexible effect definitions which better match many research questions than the standard interventional direct and indirect effects. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background The COVID-19 pandemic has had an impact on mental health and alcohol use in the US, however there is little research on its impacts on cannabis use. Considering the role of cannabis as a coping strategy or self-medicating behavior, there is a need to understand how individuals who use cannabis have adapted their use amid the pandemic. Therefore, this study examined changes in self-reported cannabis use among US adults in the context of COVID-19 pandemic by (1) describing trends of use during the first 8 months of the pandemic among adults who used cannabis in this period; and (2) characterizing trends of use within sociodemographic subgroups and by state cannabis policy status. Methods The sample consisted of 1,761 US adults who used cannabis at least once during the 8-month study period from the nationally representative Understanding America Study. Linear mixed-effect models were used to model changes in the number of days of past-week cannabis use across 16 waves from March 10, 2020, to November 11, 2020. Results Compared to early March, the number of days cannabis was used per week was significantly higher at the start of April (β=0.11, 95% CI=0.03, 0.18) and May (β=0.21,95% CI=0.05, 0.36). In subsequent months (June - November), the number of days of cannabis use attenuated to levels comparable to March. Trends of cannabis use across the study period generally did not differ across sociodemographic characteristics and state cannabis policy status. Conclusion Though increases in use were marginal among many groups, the evolving pandemic and the growing concern for the mental health of segments of the U.S. population warrant close monitoring of coping behaviors, including substance use.

Propensity score methods have become commonplace in pharmacoepidemiology over the past decade. Their adoption has confronted formidable obstacles that arise from pharmacoepidemiology’s reliance on large healthcare databases of considerable heterogeneity and complexity. These include identifying clinically meaningful samples, defining treatment comparisons, and measuring covariates in ways that respect sound epidemiologic study design. Additional complexities involve correctly modeling treatment decisions in the face of variation in healthcare practice and dealing with missing information and unmeasured confounding. In this review, we examine the application of propensity score methods in pharmacoepidemiology with particular attention to these and other issues, with an eye towards standards of practice, recent methodological advances, and opportunities for future progress. Propensity score methods have matured in ways that can advance comparative effectiveness and safety research in pharmacoepidemiology. These include natural extensions for categorical treatments, matching algorithms that can optimize sample size given design constraints, weighting estimators that asymptotically target matched and overlap samples, and the incorporation of machine learning to aid in covariate selection and model building. These recent and encouraging advances should be further evaluated through simulation and empirical studies, but nonetheless represent a bright path ahead for the observational study of treatment benefits and harms.

Randomized trials are considered the gold standard for assessing the causal effects of a drug or intervention in a study population, and their results are often utilized in the formulation of health policy. However, there is growing concern that results from trials do not necessarily generalize well to their respective target populations, in which policies are enacted, due to substantial demographic differences between study and target populations. In trials related to substance use disorders (SUDs), especially, strict exclusion criteria make it challenging to obtain study samples that are fully "representative" of the populations that policymakers may wish to generalize their results to. In this paper, we provide an overview of post-trial statistical methods for assessing and improving upon the generalizability of a randomized trial to a well-defined target population. We then illustrate the different methods using a randomized trial related to methamphetamine dependence and a target population of substance abuse treatment seekers, and provide software to implement the methods in R using the "generalize" package. We discuss several practical considerations for researchers who wish to utilize these tools, such as the importance of acquiring population-level data to represent the target population of interest, and the challenges of data harmonization.