Exclusion criteria in randomized clinical trials of subarachnoid hemorrhage

Exclusion criteria are designed to optimize the scientific yield and safety of clinical trials. However, periodic analysis is necessary to understand the impact on trial complexity, enrollment, generalizability, and costs. We analyzed the types of exclusion criteria used among clinical trials performed in subarachnoid hemorrhage (SAH) patients and impact upon exclusion of patients.

We identified trials involving SAH patients that provided a list of exclusion criteria and determined the number and proportion of those trials which used various exclusion criteria, proportion of excluded patients for each of the exclusion criteria and whether Consolidated Standards of Reporting Trials (CONSORT) was used. We also used target trial emulation approach and applied arbitrary trial exclusion criteria to a single center cohort of SAH patients to determine proportions of patients excluded for each of the reasons for exclusion.

A total of 109 trials involving SAH patients were identified, of which 68(62.3%) provided a list of the exclusion criteria. The median number of exclusion criteria was 6 (range 2-9). The most common exclusion criteria were pregnancy (n = 31 trials), SAH due to other causes (trauma, fusiform or mycotic aneurysm, n = 26 trials) and significant liver disease/hepatic insufficiency (n = 19 trials). CONSORT was used in 16(23.5%) trials and 18 (16.5%) trials provided the proportion of patients excluded according to each of the exclusion criteria. In a single center cohort, the highest proportion of patients were excluded because no aneurysm was identified on imaging (23%) followed by withdrawal of care (9.6%) and need for dual anti-platelet treatment (8.6%). The in-hospital mortality was higher in patients who were excluded as compared with those who were included in the hypothetical trial (22 [30.1%] of 73 and 0 [0%] of 31 patients).

Our analysis on exclusion criteria used and proportion of patients excluded in clinical trials involving SAH patients will assist in future trial enrollment, completion, and generalizability. Standardized reporting using CONSORT in clinical trials involving SAH patients is strongly recommended.