Which of the following factors could most affect the internal validity of a cardiovascular clinical trial?

Internal validity refers to how well a study can demonstrate that an intervention caused an effect, without the influence of confounding variables. In the context of a cardiovascular clinical trial, having adequate allocation sequence concealment is crucial for ensuring that the groups being compared are equivalent at baseline, aside from the intervention itself.

When allocation is not concealed properly, there is a risk that participants and researchers may influence which treatment or intervention a participant receives. This could lead to selection bias, where certain characteristics that affect outcomes are overrepresented in one treatment group compared to another, skewing the results of the trial. For example, if a researcher is aware of the allocation and can steer participants based on prior knowledge of their health status, the integrity of the trial is compromised, potentially invalidating the results.

In contrast, while the other factors listed may also impact the generalizability or other aspects of study quality, they do not directly threaten the fundamental ability of the trial to establish cause-and-effect relationships as allocation sequence concealment does. Differences between trial protocol and routine practice may affect external validity or applicability, the impact of the run-in period can influence participant retention and method validity, and underrepresentation of racial minorities can affect generalizability but not necessarily the internal cause-and