In a “controlled” study, the participants receiving an intervention are compared to a control group of participants who don’t receive the intervention or receive a placebo. Although the intervention and control groups should contain participants as similar as possible, it’s not possible to use clones, so it’s always possible other confounders could affect the results. But in a self-controlled case series study design, the participants comprise both the intervention group and the control group — they are compared against themselves at different periods in time.
Instead of looking at the background rate of an overall population, researchers look at how often a particular event occurs in each individual person over a set amount of time without an intervention. This personal background rate is then compared to what happened during or after the intervention when any possible effects would be expected to occur. This type of design was developed originally to study adverse events from vaccines, but researchers may also sometimes use it to look at effects of other interventions, such as short experimental programs or medications.
Deeper dive
This kind of study cannot be used for just any kind of intervention. For example, if you tried to compare a person taking medication X to themselves before medication X, you still don’t know if whatever is observed happens because of medication X or something else. But if a specific time period exists during which a reaction would be expected, then researchers can compare what happens within that window to what happens outside that window. For example, if an inactivated vaccine is going to cause any kind of reaction in a person, it will happen within the first 48 hours. That’s the only time window when it’s biologically possible for the vaccine to affect a person because that’s the time period during which the immune response occurs.
If researchers are looking to see if a particular vaccine causes a specific reaction, such as a seizure, they can compare what happens in those 48 hours after the vaccine’s administration to several months before and after the vaccine to see if seizures more frequently occur in that 48 hours than other times across the whole group. Similarly, reactions from live vaccines occur approximately one to two weeks after the vaccine is given, so researchers looking for live vaccine reactions would compare what happens in those few weeks to what happens in the months leading up to the vaccine, a few months after the vaccine, and in the period between the vaccine and the window when a reaction is biologically plausible.
A self-controlled case series can also be used for studies involving specific experimental conditions that occur within a clearly defined time period. For example, if a person in a sleep study went through a rigorous experimental schedule for one week to see how their bodies reacted to different sleeping conditions, it would make sense to compare their body’s processes (blood pressure, blood sugar, fatigue, etc.) during the sleep experiment to those same body processes before the experiment and a few week after the experiment, when the body is readjusted to normalcy. If their blood pressure increased only for the period of time during the sleep study, but it’s pretty consistent in the weeks before and several weeks after the experiment, it’s much more likely that the experimental sleep conditions influenced blood pressure, or at least something that occurred during that experiment.
The advantage of self-controlled case series studies, when the conditions are appropriate for them, is that no other cause is likely to lead to the effects being studied in a person except the short time-sensitive intervention; they act as their own controls so that any unidentified, underlying conditions cannot confound the results when compared to other people. More reading is available here and here.