Comparative Analysis of Instrumental Variables on the Assignment of Buprenorphine/Naloxone or Methadone for the Treatment of Opioid Use Disorder.

BACKGROUND: Instrumental variable (IV) analysis provides an alternative set of identification assumptions in the presence of uncontrolled confounding when attempting to estimate causal effects. Our objective was to evaluate the suitability of measures of prescriber preference and calendar time as potential IVs to evaluate the comparative effectiveness of buprenorphine/naloxone versus methadone for treatment of opioid use disorder (OUD). METHODS: Using linked population-level health administrative data, we constructed five IVs: prescribing preference at the individual, facility, and region levels (continuous and categorical variables), calendar time, and a binary prescriber's preference IV in analyzing the treatment assignment-treatment discontinuation association using both incident-user and prevalent-new-user designs. Using published guidelines, we assessed and compared each IV according to the four assumptions for IVs, employing both empirical assessment and content expertise. We evaluated the robustness of results using sensitivity analyses. RESULTS: The study sample included 35,904 incident users (43.3% on buprenorphine/naloxone) initiated on opioid agonist treatment by 1585 prescribers during the study period. While all candidate IVs were strong (A1) according to conventional criteria, by expert opinion, we found no evidence against assumptions of exclusion (A2), independence (A3), monotonicity (A4a), and homogeneity (A4b) for prescribing preference-based IV. Some criteria were violated for the calendar time-based IV. We determined that preference in provider-level prescribing, measured on a continuous scale, was the most suitable IV for comparative effectiveness of buprenorphine/naloxone and methadone for the treatment of OUD. CONCLUSIONS: Our results suggest that prescriber's preference measures are suitable IVs in comparative effectiveness studies of treatment for OUD.

A generalized Hosmer-Lemeshow goodness-of-fit test for a family of generalized linear models.

Generalized linear models (GLMs) are very widely used, but formal goodness-of-fit (GOF) tests for the overall fit of the model seem to be in wide use only for certain classes of GLMs. We develop and apply a new goodness-of-fit test, similar to the well-known and commonly used Hosmer-Lemeshow (HL) test, that can be used with a wide variety of GLMs. The test statistic is a variant of the HL statistic, but we rigorously derive an asymptotically correct sampling distribution using methods of Stute and Zhu (Scand J Stat 29(3):535-545, 2002) and demonstrate its consistency. We compare the performance of our new test with other GOF tests for GLMs, including a naive direct application of the HL test to the Poisson problem. Our test provides competitive or comparable power in various simulation settings and we identify a situation where a naive version of the test fails to hold its size. Our generalized HL test is straightforward to implement and interpret and an R package is publicly available. Supplementary Information: The online version contains supplementary material available at 10.1007/s11749-023-00912-8.

Improving the Hosmer-Lemeshow goodness-of-fit test in large models with replicated Bernoulli trials.

The Hosmer-Lemeshow (HL) test is a commonly used global goodness-of-fit (GOF) test that assesses the quality of the overall fit of a logistic regression model. In this paper, we give results from simulations showing that the type I error rate (and hence power) of the HL test decreases as model complexity grows, provided that the sample size remains fixed and binary replicates (multiple Bernoulli trials) are present in the data. We demonstrate that a generalized version of the HL test (GHL) presented in previous work can offer some protection against this power loss. These results are also supported by application of both the HL and GHL test to a real-life data set. We conclude with a brief discussion explaining the behavior of the HL test, along with some guidance on how to choose between the two tests. In particular, we suggest the GHL test to be used when there are binary replicates or clusters in the covariate space, provided that the sample size is sufficiently large.

Random forests for survival data: which methods work best and under what conditions?

Few systematic comparisons of methods for constructing survival trees and forests exist in the literature. Importantly, when the goal is to predict a survival time or estimate a survival function, the optimal choice of method is unclear. We use an extensive simulation study to systematically investigate various factors that influence survival forest performance - forest construction method, censoring, sample size, distribution of the response, structure of the linear predictor, and presence of correlated or noisy covariates. In particular, we study 11 methods that have recently been proposed in the literature and identify 6 top performers. We find that all the factors that we investigate have significant impact on the methods' relative accuracy of point predictions of survival times and survival function estimates. We use our results to make recommendations for which methods to use in a given context and offer explanations for the observed differences in relative performance.