Rahbar, Mohammad H.

Background and Objectives: Peroxisome proliferator activated receptor-gamma agonists, such as pioglitazone (PIO) enhanced hematoma resolution and improved functional recovery in our animal model of intracerebral hemorrhage (ICH). We conducted a translational Phase II randomized, controlled clinical trial to determine the maximum tolerated dose (MTD) of PIO in patients with spontaneous ICH and to explore the rate of hematoma resolution and clinical outcome. Methods: Patients with spontaneous ICH within 24 hours of symptom onset were randomly allocated 1:1 to placebo or PIO. Patients received escalating doses of PIO daily for three days, followed by a 30mg maintenance dose for the duration of treatment. Duration of treatment was when 75% of the ICH had resolved as determined by serial MRI or 10 weeks of treatment, whichever occurred first. The primary safety outcome was mortality at Day 14. Secondary measures of safety include any mortality, symptomatic cerebral edema, congestive heart failure, edema, hypoglycemia, anemia, and hepatotoxicity. Secondary measures of efficacy include hematoma resolution and clinical outcome. The MTD was determined using the Continual Reassessment Method. Results: From March 2009 to April 2013, 84 patients (42 PIO, 42 control) were enrolled into 11 dose tiers, with a planned range from 0.1-2.0 mg/kg/d. Table 1 demonstrates preliminary baseline and clinical characteristics of patients by treatment group. Overall, 2/84 patients died within 2 weeks after ICH; however mortality rate never exceeded prespecified criteria. The study will be complete in October 2013 and the treatment team remains blinded to treatment allocation. Secondary outcomes by treatment group and the MTD of PIO will be reported. Conclusions: We have completed the treatment phase of the SHRINC Trial. Long term follow-up is on-going. These results will provide the foundation for an efficacy trial evaluating PIO as a potential treatment for patients with spontaneous ICH.

Purpose To learn the size, composition, and scholarly output of biostatistics, epidemiology, and research design (BERD) units in U.S. academic health centers (AHCs). Method Each year for four years, the authors surveyed all BERD units in U.S. AHCs that were members of the Clinical and Translational Science Award (CTSA) Consortium. In 2010, 46 BERD units were surveyed; in 2011, 55; in 2012, 60; and in 2013, 61. Results Response rates to the 2010, 2011, 2012, and 2013 surveys were 93.5%, 98.2%, 98.3%, and 86.9%, respectively. Overall, the size of BERD units ranged from 3 to 86 individuals. The median FTE in BERD units remained similar and ranged from 3.0 to 3.5 FTEs over the years. BERD units reported more availability of doctoral-level biostatisticians than doctoral-level epidemiologists. In 2011, 2012, and 2013, more than a third of BERD units provided consulting support on 101 to 200 projects. A majority of BERD units reported that between 25% and 75% (in 2011) and 31% to 70% (in 2012) of their consulting was to junior investigators. More than two-thirds of BERD units reported their contributions to the submission of 20 or more non-BERD grant or contract applications annually. Nearly half of BERD units reported 1 to 10 manuscripts submitted annually with a BERD practitioner as the first or corresponding author. Conclusions The findings regarding BERD units provide a benchmark against which to compare BERD resources and may be particularly useful for institutions planning to develop new units to support programs such as the CTSA.