The structural test
For any study, state the question it claims to answer, then state the structure that question requires. A therapy question requires a comparison group and forward follow-up. A harm question requires either forward follow-up of exposed and unexposed people or a backward look from outcome to exposure. A diagnosis question requires the test and a reference standard applied to the same patients. If the design cannot produce that structure, the mismatch is fatal and the result cannot answer the question regardless of how well the study was run.
A mismatch in practice
A study reports that among 200 patients who took a supplement, 80 percent reported feeling better after three months, and concludes the supplement is effective. The question implied is a therapy question: does the supplement improve symptoms? The structure required is a comparison between treated and untreated groups followed forward. The design is a case series with no comparator, so the improvement could reflect natural recovery, placebo effect, or regression to the mean. The design cannot answer the question, and this is fatal, not a minor limitation.
Mismatch is not the same as bias
Risk of bias asks whether a design that could answer the question was executed well. Design-question mismatch asks whether the design could answer the question at all. A perfectly conducted case series is still unable to answer a comparative therapy question. Keep these two judgments separate: the first is about execution, the second is about capability.