Sander Greenland

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

This report proposes a stepwise process covering the range of considerations to systematically consider key choices for study design and data analysis for non-interventional studies with the central objective of fostering generation of reliable and reproducible evidence. These steps include (1) formulating a well defined causal question via specification of the target trial protocol; (2) describing the emulation of each component of the target trial protocol and identifying fit-for-purpose data; (3) assessing expected precision and conducting diagnostic evaluations; (4) developing a plan for robustness assessments including deterministic sensitivity analyses, quantitative bias analyses, and net bias evaluation; and (5) inferential analyses.

Methods Are Just Means to Test Hypotheses So We Shoud Know What the Applicants are Trying to Test

The current controversy surrounding research replication in biomedical and psychosocial sciences often overlooks the uncertainties surrounding both the original and replication studies. Overemphasizing single attempts as definitive replication successes or failures, as exemplified by media coverage of the landmark Reproducibility Project: Psychology, fosters misleading dichotomies and erodes public trust. To avoid such unintended consequences, science communicators should more clearly articulate statistical variation and other uncertainty sources in replication, while emphasizing the cumulative nature of science in general and replication in particular.

IntroductionOpioid agonist treatment (OAT) tapering involves a gradual reduction in daily medication dose to ultimately reach a state of opioid abstinence. Due to the high risk of relapse and overdose after tapering, this practice is not recommended by clinical guidelines, however, clients may still request to taper off medication. The ideal time to initiate an OAT taper is not known. However, ethically, taper plans should acknowledge clients’ preferences and autonomy but apply principles of shared informed decision-making regarding safety and efficacy. Linked population-level data capturing real-world tapering practices provide a valuable opportunity to improve existing evidence on when to contemplate starting an OAT taper. Our objective is to determine the comparative effectiveness of alternative times from OAT initiation at which a taper can be initiated, with a primary outcome of taper completion, as observed in …

There are two distinct definitions of “P‐value” for evaluating a proposed hypothesis or model for the process generating an observed dataset. The original definition starts with a measure of the divergence of the dataset from what was expected under the model, such as a sum of squares or a deviance statistic. A P‐value is then the ordinal location of the measure in a reference distribution computed from the model and the data, and is treated as a unit‐scaled index of compatibility between the data and the model. In the other definition, a P‐value is a random variable on the unit interval whose realizations can be compared to a cutoff α to generate a decision rule with known error rates under the model and specific alternatives. It is commonly assumed that realizations of such decision P‐values always correspond to divergence P‐values. But this need not be so: Decision P‐values can violate intuitive single‐sample …

BackgroundWe noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies.MethodsWe recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied.ResultsWe stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR)(ie, the instantaneous rate ratio) over …

BackgroundWe have examined the primary efficacy results of 23,551 randomized clinical trials from the Cochrane Database of Systematic Reviews.MethodsWe estimate that the great majority of trials have much lower statistical power for actual effects than the 80 or 90% for the stated effect sizes. Consequently, “statistically significant” estimates tend to seriously overestimate actual treatment effects, “nonsignificant” results often correspond to important effects, and efforts to replicate often fail to achieve “significance” and may even appear to contradict initial results. To address these issues, we reinterpret the P value in terms of a reference population of studies that are, or could have been, in the Cochrane Database.ResultsThis leads to an empirical guide for the interpretation of an observed P value from a “typical” clinical trial in terms of the degree of overestimation of the reported effect, the probability of the effect’s …