Target trial emulation: teaching epidemiology and beyond

Observational epidemiology is continually held to thestandard of randomized trials. A typical epidemiology article references previous trials in the introduction (or reasons why trials are not feasible) and, when possible, compares the results to previous trials in the discussion. When the results from an observational study and trial disagree, we nearly always begin by questioning the former. Curiously, the methods section of an observational study — an undeniably crucial part of an article — rarely references trial methods or designs. Explicit target trial emulation aims to remedy this

Enterovirus hypothesis for motor neurone disease

Letter to the Edito

Firearm access and adolescent suicide risk: Toward a clearer understanding of effect size

Background: Strong and consistent associations between access to firearms and suicide have been found in ecologic and individual-level observational studies. For adolescents, a seminal case-control study estimated that living in a home with (vs without) a firearm was associated with a fourfold increase in the risk of death by suicide. Methods: We use data from a nationally representative study of 10 123 US adolescents aged 13-18 years to (1) measure how much adolescents who live in a home with a firearm differ from those who do not in ways related to their risk of suicide, and (2) incorporate these differences into an updated effect estimate of the risk of adolescent suicide attributable to living in a home with firearms. Results: Almost one-third (30.7%) of adolescents reported living in a home with firearms. Relative to those who did not, adolescents reporting living in a home with a firearm were slightly more likely to be male, older and reside in the South and rural areas, but few differences were identified for mental health characteristics. The effect size found by Brent and colleagues appeared robust to sources of possible residual confounding: updated relative risks remained above 4.0 across most sensitivity analyses and at least 3.1 in even the most conservative estimates. Conclusions: Although unmeasured confounding and other biases may nonetheless remain, our updated estimates reinforce the suggestion that adolescents' risk of suicide was increased threefold to fourfold if they had lived in homes with a firearm compared with if they had not

Application of the Instrumental Inequalities to a Mendelian Randomization Study With Multiple Proposed Instruments

BACKGROUND: Investigators often support the validity of Mendelian randomization (MR) studies, an instrumental variable approach proposing genetic variants as instruments, via. subject matter knowledge. However, the instrumental variable model implies certain inequalities, offering an empirical method of falsifying (but not verifying) the underlying assumptions. Although these inequalities are said to detect only extreme assumptio

Partial Identification of the Average Treatment Effect Using Instrumental Variables: Review of Methods for Binary Instruments, Treatments, and Outcomes

Several methods have been proposed for partially or point identifying the average treatment effect (ATE) using instrumental variable (IV) type assumptions. The descriptions of these methods are widespread across the statistical, economic, epidemiologic, and computer science literature, and the connections between the methods have not been readily apparent. In the setting of a binary instrument, treatment, and outcome, we review proposed methods for partial and point identification of the ATE under IV assumptions, express the identification results in a common notation and terminology, and propose a taxonomy that is based on sets of identifying assumptions. We further demonstrate and provide software for the application of these methods to estimate bounds. Supplementary materials for this article are available online

Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?

Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different ver

Hawking Spectrum and High Frequency Dispersion

We study the spectrum of created particles in two-dimensional black hole geometries for a linear, hermitian scalar field satisfying a Lorentz non-invariant field equation with higher spatial derivative terms that are suppressed by powers of a fundamental momentum scale $k_0$. The preferred frame is the ``free-fall frame" of the black hole. This model is a variation of Unruh's sonic black hole analogy. We find that there are two qualitatively different types of particle production in this model: a thermal Hawking flux generated by ``mode conversion" at the black hole horizon, and a non-thermal spectrum generated via scattering off the background into negative free-fall frequency modes. This second process has nothing to do with black holes and does not occur for the ordinary wave equation because such modes do not propagate outside the horizon with positive Killing frequency. The horizon component of the radiation is astonishingly close to a perfect thermal spectrum: for the smoothest metric studied, with Hawking temperature $T_H\simeq0.0008k_0$, agreement is of order $(T_H/k_0)^3$ at frequency $\omega=T_H$, and agreement to order $T_H/k_0$ persists out to $\omega/T_H\simeq 45$ where the thermal number flux is $O(10^{-20}$). The flux from scattering dominates at large $\omega$ and becomes many orders of magnitude larger than the horizon component for metrics with a ``kink", i.e. a region of high curvature localized on a static worldline outside the horizon. This non-thermal flux amounts to roughly 10\% of the total luminosity for the kinkier metrics considered. The flux exhibits oscillations as a function of frequency which can be explained by interference between the various contributions to the flux.Comment: 32 pages, plain latex, 16 figures included using psfi