190 Chapter 6 We would like to congratulate David Card, Joshua Angrist and Guido Imbens for winning the Nobel Memorial Prize in Economic Sciences 2021 for their pioneering work on natural experiments [1]. The committee acknowledged their work for “…shifting the focus in empirical research using observational data towards relying on quasi-experimental variation to establish causal effects.”. On the occasion of their Nobel Prize, we would like to share a thought on learnings gained during our PhD trajectories in public health focused on natural experiments. In public health, the opportunity of natural experiments to address global health challenges have been discussed for some years [2-5]. Natural experiments allow the retrospective and prospective evaluation of policies, interventions or programs in real-world settings [2]. Importantly, they present a valuable alternative to evaluate changes to a system for which it would be unethical, unfeasible or simply impossible to conduct randomised controlled trials (RCTs). Although there is not a widely accepted definition, the key element of natural experiments is that the change in exposure is caused by external shocks or factors outside researchers’ control, and that manipulation of exposure by researchers is not possible [2]. This allows the identification of intervention and control groups. While under ideal circumstances there is an “as-if” random allocation to the intervention, it is not uncommon that potential confounding remains in the effect of exposures on outcomes of interest. In combining good knowledge of the allocation process, careful choice of methods, and transparent reporting and assumption testing, studies based on natural experiments can approximate causal evidence [2]. It is likely that with this Nobel prize, opportunities for evaluations by means of natural experiments will be further explored. On a global scale, numerous of opportunities will arise from the sudden and disruptive changes linked to COVID-19 resulting from the global variation in national responses [6]. Therefore, it is important to understand the barriers to evaluate them. In this essay we build on learnings gained during our PhD trajectories focused on natural experiments. We discuss three key aspects hindering the potential of this type of research. We argue that, paradoxically, some level of control is needed to shape conditions in which evaluations of natural experiments is possible. THE CONVENIENCE OF UNPREDICTABILITY There is considerable unpredictability in researching natural experiments, which may pose serious challenges for its evaluation. Unpredictability can be related to the implementation of the intervention (e.g. timing, intensity and reach), but also to aspects related to the study conduction (e.g. suitability of datasets and power). Studies using natural experiments in prospective evaluations may face difficulties aligning implementation, evaluation and funding timelines. For example, infrastructural interventions can be substantially delayed, while legislation is sometimes sooner implemented than anticipated; both impact
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