When information on more than three patients is included, the case series is considered to be a systematic investigation designed to contribute to generalizable knowledge (i.e., research), and therefore submission is required to an institutional review board (IRB).
[4] Case series usually contain demographic information about the patient(s), for example, age, gender, ethnic origin.
Case series are especially vulnerable to selection bias; for example, studies that report on a series of patients with a certain illness and/or a suspected linked exposure draw their patients from a particular population (such as a hospital or clinic) which may not appropriately represent the wider population.
Internal validity of case series studies is usually very low, due to the lack of a comparator group exposed to the same array of intervening variables.
Hence only the presence of a comparator group, which is not a feature of case-series studies, will allow a valid estimate of the true treatment effect.