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Abstract Background There has been little research on design of studies based on routinely collected data when the clinical endpoint of interest is not recorded, but can be inferred from a prescription. This often happens when exploring the effect of a drug on chronic diseases. Using the LifeLink claims database in studying the possible anti-inflammatory effects of statins in rheumatoid arthritis (RA), oral steroids (OS) were treated as surrogate of inflammatory flare-ups. We compared two cohort study designs, the first using time to event outcomes and the second using quantitative amount of the surrogate. Methods RA patients were extracted from the LifeLink database. In the first study, patients were split into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first record of RA). Using Cox models we evaluated the association between time-varying exposure to statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date. In the second study, we matched new statin users to non users on age and sex. Zero inflated negative binomial models were used to contrast the number of days' prescriptions of OS in the year following date of statin initiation for the two exposure groups. Results In the unmatched study, the statin exposure hazard ratio (HR) of initiating OS in the 31451 non-users of OS at RA index date was 0.96(95% CI 0.9,1.1) and the statin exposure HR of cessation of OS therapy in the 6026 users of OS therapy at RA index date was 0.95 (0.87,1.05). In the matched cohort of 6288 RA patients the statin exposure rate ratio for duration on OS therapy was 0.88(0.76,1.02). There was digit preference for outcomes in multiples of 7 and 30 days. Conclusions The 'time to event' study design was preferable because it better exploits information on all available patients and provides a degree of robustness toward confounding. We found no convincing evidence that statins reduce inflammation in RA patients.

Structural quantitative work in international economics typically models trade costs as a log‐linear function of exogenous trade‐policy variables. We propose a structural approach that allows for a nonparametric relationship and for treating tariff and nontariff trade‐policy variables as potentially endogenous. The data reject the assumption of log‐linearity of trade costs in both tariff‐ and nontariff‐policy variables. We assess the effects of a unilateral increase of US tariffs on Chinese imports by 10 percentage points and document that the estimated effects on real bilateral trade‐flow changes would be substantially underestimated by standard approaches. [ABSTRACT FROM AUTHOR]

Earlier work found evidence for geographic linkages of aggregate foreign direct investment across countries and country-pairs. From a theoretical point of view, such linkages at the macroeconomic level may root in between-firm as well as within-firm linkages and originate from information spillovers across or within firms in exploring unknown markets, and vertical linkages between production plants across different locations within the firm. We use data on the universe of German multinational enterprises (MNEs) to empirically explore how marginal investments at one foreign affiliate depend on investments at other affiliates within the same MNE. The empirical approach employs two channels or modes of cross-affiliate interdependence: mere geography (capturing horizontal linkages through correlated learning and horizontal competition within the firm) and input-output relationships within or across industries (which capture vertical linkages). Adding to earlier findings at the aggregate level, we find evidence of a significant interdependence of investments within the firm. In the firm-level data at hand, vertical linkages appear to be more important than horizontal ones. Investments at one location tend to stimulate investments at other locations of the same MNE, particularly if input linkages are strong. The opposite seems to be true for output linkages. Beyond vertical linkages, mere geographic proximity matters only to a minor extent. This suggests that evidence of linkages through geographic closeness at aggregate data levels accrue mainly to reasons of vertical linkages within networks of affiliates. (JEL C31, D22, F21, F23, F68, G31, H32), I. INTRODUCTION In general equilibrium and under resource constraints at the level of countries, aggregate bilateral foreign investments and foreign affiliate sales are known to be interdependent across host countries [...]

Preferential trade agreements (PTAs) have proliferated over the past 60 years. While a small number of recent studies have examined empirically the economic determinants of the likelihood of a pair of countries having a PTA, this study explains empirically the timing of all PTA formations and enlargements from 1950 through 2006 using duration analysis. Our main and novel goal is to predict (in- and out-of-sample) a substantive share of these 1,560 PTA events using a parsimonious model with mainly economic variables, taking selection dynamics into account. Our analysis reveals that we can predict correctly in-sample the actual year of entry into force for 26% of the 1,560 bilateral PTA formations/enlargements in the period 1950-2006 among 10,518 pairings of 146 countries using only a few economic and political variables. Moreover, we can predict correctly in-sample 57% of these PTA events within a 10-year window leading up to the event using this model. The model also performs well out-of-sample for the near term (82%), but not if the out-of-sample period is very long. We conclude with an evaluation of the model's ability to predict the timing of the North American Free Trade Agreement, the European Union's formation and enlargements, and the model's ten most likely post-2006 PTA events. (JEL F14, F15), I. INTRODUCTION One of the most notable economic events since World War II is the proliferation of preferential trade agreements (PTAs), including free trade agreements (FTAs) and customs unions (CUs). [...]