Site Variability in Regulatory Oversight for an International Study of Pediatric Sepsis

Objectives: Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. Design: Survey. Setting: Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. Subjects: Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. Interventions: None. Measurements and Main Results: Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). Conclusions: Variability in regulatory oversight was evident for this minimal-risk observational research study, most notably in the category of type of review conducted. Duplicative review prolonged time to protocol approval at some sites. Use of a single institutional review board for U.S. sites was rare and did not improve efficiency of protocol approval. Suggestions for minimizing these challenges are provided

Fluid balance in critically ill children with acute lung injury

OBJECTIVES: In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms. DESIGN: Multicentered retrospective cohort study. SETTING: Five pediatric intensive care units. PATIENTS: Mechanically ventilated children (age\u3e/=1 month toyrs) with acute lung injury admitted in 2007-2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluid intake, output, and net fluid balance were collected on days 1-7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p=.02). Adjusted for weight, daily fluid balance on days 1-3 and cumulative fluid balance on days 1-7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p\u3c.001, each day) and was similar to adults in the liberal arm. CONCLUSIONS: Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial

Growth and Changing Characteristics of Pediatric Intensive Care 2001-2016

OBJECTIVES: We assessed the growth, distribution, and characteristics of pediatric intensive care in 2016. DESIGN: Hospitals with PICUs were identified from prior surveys, databases, online searching, and clinician networking. A structured web-based survey was distributed in 2016 and compared with responses in a 2001 survey. SETTING: PICUs were defined as a separate unit, specifically for the treatment of children with life-threatening conditions. PICU hospitals contained greater than or equal to 1 PICU. SUBJECTS: Physician medical directors and nurse managers. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: PICU beds per pediatric population (\u3c 18 yr), PICU bed distribution by state and region, and PICU characteristics and their relationship with PICU beds were measured. Between 2001 and 2016, the U.S. pediatric population grew 1.9% to greater than 73.6 million children, and PICU hospitals decreased 0.9% from 347 to 344 (58 closed, 55 opened). In contrast, PICU bed numbers increased 43% (4,135 to 5,908 beds); the median PICU beds per PICU hospital rose from 9 to 12 (interquartile range 8, 20 beds). PICU hospitals with greater than or equal to 15 beds in 2001 had significant bed growth by 2016, whereas PICU hospitals with less than 15 beds experienced little average growth. In 2016, there were eight PICU beds per 100,000 U.S. children (5.7 in 2001), with U.S. census region differences in bed availability (6.8 to 8.8 beds/100,000 children). Sixty-three PICU hospitals (18%) accounted for 47% of PICU beds. Specialized PICUs were available in 59 hospitals (17.2%), 48 were cardiac (129% growth). Academic affiliation, extracorporeal membrane oxygenation availability, and 24-hour in-hospital intensivist staffing increased with PICU beds per hospital. CONCLUSIONS: U.S. PICU bed growth exceeded pediatric population growth over 15 years with a relatively small percentage of PICU hospitals containing almost half of all PICU beds. PICU bed availability is variable across U.S. states and regions, potentially influencing access to care and emergency preparedness

Growth and Changing Characteristics of Pediatric Intensive Care 2001-2016

OBJECTIVES: We assessed the growth, distribution, and characteristics of pediatric intensive care in 2016. DESIGN: Hospitals with PICUs were identified from prior surveys, databases, online searching, and clinician networking. A structured web-based survey was distributed in 2016 and compared with responses in a 2001 survey. SETTING: PICUs were defined as a separate unit, specifically for the treatment of children with life-threatening conditions. PICU hospitals contained greater than or equal to 1 PICU. SUBJECTS: Physician medical directors and nurse managers. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS:: PICU beds per pediatric population (\u3c 18 yr), PICU bed distribution by state and region, and PICU characteristics and their relationship with PICU beds were measured. Between 2001 and 2016, the U.S. pediatric population grew 1.9% to greater than 73.6 million children, and PICU hospitals decreased 0.9% from 347 to 344 (58 closed, 55 opened). In contrast, PICU bed numbers increased 43% (4,135 to 5,908 beds); the median PICU beds per PICU hospital rose from 9 to 12 (interquartile range 8, 20 beds). PICU hospitals with greater than or equal to 15 beds in 2001 had significant bed growth by 2016, whereas PICU hospitals with less than 15 beds experienced little average growth. In 2016, there were eight PICU beds per 100,000 U.S. children (5.7 in 2001), with U.S. census region differences in bed availability (6.8 to 8.8 beds/100,000 children). Sixty-three PICU hospitals (18%) accounted for 47% of PICU beds. Specialized PICUs were available in 59 hospitals (17.2%), 48 were cardiac (129% growth). Academic affiliation, extracorporeal membrane oxygenation availability, and 24-hour in-hospital intensivist staffing increased with PICU beds per hospital. CONCLUSIONS: U.S. PICU bed growth exceeded pediatric population growth over 15 years with a relatively small percentage of PICU hospitals containing almost half of all PICU beds. PICU bed availability is variable across U.S. states and regions, potentially influencing access to care and emergency preparedness

Site Variability in Regulatory Oversight for an International Study of Pediatric Sepsis.

OBJECTIVES: Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. DESIGN: Survey. SETTING: Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. SUBJECTS: Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). CONCLUSIONS: Variability in regulatory oversight was evident for this minimal-risk observational research study, most notably in the category of type of review conducted. Duplicative review prolonged time to protocol approval at some sites. Use of a single institutional review board for U.S. sites was rare and did not improve efficiency of protocol approval. Suggestions for minimizing these challenges are provided