Rationale and Design of the Statins Use in Intracerebral Hemorrhage Patients (SATURN) Trial.

INTRODUCTION: The benefits and risks of HMG-CoA reductase inhibitor (statin) drugs in survivors of intracerebral hemorrhage (ICH) are unclear. Observational studies suggest an association between statin use and increased risk of lobar ICH, particularly in patients with apolipoprotein-E (APOE) ε2 and ε4 genotypes. There are no randomized controlled trials (RCTs) addressing the effects of statins after ICH leading to uncertainty as to whether statins should be used in patients with lobar ICH who are at high risk for ICH recurrence. The SATURN trial aims to evaluate the effects of continuation versus discontinuation of statin on the risk of ICH recurrence and ischemic major adverse cerebro-cardio-vascular events (MACCE) in patients with lobar ICH. Secondary aims include the assessment of whether the APOE genotype modifies the effects of statins on ICH recurrence, functional and cognitive outcomes and quality of life. METHODS: The SATURN trial is a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment. A planned total of 1456 patients with lobar ICH will be recruited from 140 sites in the United States, Canada and Spain. Patients presenting within seven days of a spontaneous lobar ICH that occurred while taking a statin, will be randomized (1:1) to continuation (control) vs. discontinuation (intervention) of the same statin drug and dose that they were using at ICH onset. The primary outcome is the time to recurrent symptomatic ICH within a two-year follow-up period. The primary safety outcome is the occurrence of ischemic MACCE. CONCLUSION: The results will help to determine the best strategy for statin use in survivors of lobar ICH and may help to identify if there is a subset of patients who would benefit from statins.

Screen failure data in clinical trials: Are screening logs worth it?

BACKGROUND: Clinical trials frequently spend considerable effort to collect data on patients who were assessed for eligibility but not enrolled. The Consolidated Standards of Reporting Trials (CONSORT) guidelines' recommended flow diagram for randomized clinical trials reinforces the belief that the collection of screening data is a necessary and worthwhile endeavor. The rationale for collecting screening data includes scientific, trial management, and ethno-socio-cultural reasons. PURPOSE: We posit that the cost of collecting screening data is not justified, in part due to inability to centrally monitor and verify the screening data in the same manner as other clinical trial data. METHODS: To illustrate the effort and site-to-site variability, we analyzed the screening data from a multicenter, randomized clinical trial of patients with transient ischemic attack or minor ischemic stroke (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke (POINT)). RESULTS: Data were collected on over 27,000 patients screened across 172 enrolling sites, 95% of whom were not enrolled. Although the rate of return of screen failure logs was high overall (95%), there were a considerable number of logs that were returned with 'no data to report' (23%), often due to administrative reasons rather than no patients screened. CONCLUSION: In spite of attempts to standardize the collection of screening data, due to differences in site processes, multicenter clinical trials face challenges in collecting those data completely and uniformly. The efforts required to centrally collect high-quality data on an extensive number of screened patients may outweigh the scientific value of the data. Moreover, the lack of a standardized definition of 'screened' and the challenges of collecting meaningful characteristics for patients who have not signed consent limits the ability to compare across studies and to assess generalizability and selection bias as intended.

Honest signalling with costly gambles.

Costly signalling theory is commonly invoked as an explanation for how honest communication can be stable when interests conflict. However, the signal costs predicted by costly signalling models often turn out to be unrealistically high. These models generally assume that signal cost is determinate. Here, we consider the case where signal cost is instead stochastic. We examine both discrete and continuous signalling games and show that, under reasonable assumptions, stochasticity in signal costs can decrease the average cost at equilibrium for all individuals. This effect of stochasticity for decreasing signal costs is a fundamental mechanism that probably acts in a wide variety of circumstances.