One question that often comes up in empirical work concerns the appropriate way to calculate standard errors, and in particular the correct level of clustering. Here is a specific version of the question that someone posed, slightly paraphrased:
Many important policies are implemented at the national level. Monetary policy, fiscal policy, and many regulations are key examples. Pure time series or before-after analysis of the impacts of changes in these policies on the economy of a country will be contaminated by other changes going on in the economy. Simply trying to difference out global trends will not account for systematic differences in the growth path of the country where the reform took place from the average global growth path. This makes evaluation of the impacts of such policies difficult.