Restricting selleck chemicals Gemcitabine enrollment to only one study when patients are eligible for more than one is a potentially modifiable barrier to recruitment [1]. Testing two interventions concurrently can be achieved with a factorial design as used successfully by the Acute Respiratory Distress Syndrome Network. In other circumstances, when trials are initiated by different investigators at different times, with different inclusion and exclusion criteria, co-enrollment can facilitate either sequential or simultaneous recruitment (Figure (Figure11).Figure 1Factorial and co-enrollment designs. In this figure, we present a schematic for a factorial design randomized trial, sequential co-enrollment in two randomized trials and simultaneous co-enrollment in two randomized trials.

Co-enrollment in multiple trials, often driven by patient demand, occurs in persons with human immunodeficiency virus (HIV) [2], and was documented among 23% of persons with HIV in six ongoing studies [3]. In this population, co-enrollment is actively encouraged by some research programs [3] but not others [2]. In pre-hospital resuscitation trials, co-enrollment occurs either in series or in parallel [4]. Half of the members of two critical care research consortia reported co-enrollment of a patient in more than one study in the last year [5]. In a parental survey, 74% endorsed enrollment of their premature babies in 2 or more studies, 50% would consent to 3 or more studies, and 10% were willing to join more than 10 studies [6].Some Institutional Review Boards restrict the practice of co-enrollment, while concerned about patient safety, decisional burden or scientific integrity.

Given the dearth of evidence on these issues, trialists have called for consideration of co-enrollment on a case-by-case basis, and reporting on its impact [7]. The primary objective of this study was to document the patterns and predictors of patient co-enrollment in an international heparin thromboprophylaxis trial. The secondary objective was to examine the consequences of co-enrollment on clinical and trial outcomes.Materials and methodsPROTECT (Prophylaxis for ThromboEmbolism in Critical Care Trial) (clinicaltrials.gov NCT00182143) was a randomized, blinded clinical trial comparing unfractionated heparin to dalteparin for thromboprophylaxis [8]. Patients considered eligible were �� 18 years old, weighed > 45 kilograms, and were expected to remain in ICU > 72 hours.

Exclusion criteria were admission diagnosis of trauma, neurosurgery or orthopedic surgery, need for therapeutic anticoagulation, receipt of > 72 hours of heparin, contraindication to heparin, blood or pork products, pregnancy, Drug_discovery life support limitation, and prior enrollment in this or a related trial. The primary outcome was proximal leg deep vein thrombosis (DVT).