esearch ethics committees in Switzerland and Canada \[[@pone.0165605.ref001]\].

Estimated proportion of discontinued studies applying different assumptions for missing data with or without excluding studies that were stopped for intervention-related reasons such as harm, benefit, and futility (see text for a rationale).

Abbreviations: NPSs, non-randomised prospective studies; RCTs, randomised controlled trials.

Discussion {#sec012}
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We compared the risk of discontinuation between NPSs and RCTs in a sample of clinical studies approved by a German REC.

Overall, NPSs were at lower risk of discontinuation than RCTs (14% versus 27%, p\<0.001). The difference was robust to sensitivity analyses using different assumptions for missing data, however, when we excluded studies stopped for harm, benefit, or futility, the difference in the proportion of discontinued studies diminished and was no longer significant. This is obviously due to the fact that cohort studies are not being stopped for harm, benefit, or futility.

A strength of our study is that we had access to the full REC correspondence from a period of three years. Consequently, we could take into account relevant information from the application form, the study protocol with its amendments, patient information sheets and additional correspondence. In addition, we achieved a high response rate in our survey. The included RCTs were remarkably similar to RCTs that were approved at the same time by five RECs in Switzerland and Canada. This increases our confidence that the findings will be generalizable to clinical research settings in other high-income countries.

A main limitation of our study was that for some studies only little information was available, e.g. due to missing or poor reporting in study documents. When a study protocol was missing, we extracted relevant information from application forms and patient information sheets. While all RCTs conducted in the jurisdiction of the REC needed to obtain ethical approval, the regulations were less