1. VPS and Research Overview Barry P. Markovitz MD MPH

2. Why Research? Epidemiology – What disease is out there? Etiology – What causes disease Diagnosis – How do we diagnose disease Therapy – How do we treat this disease If you can’t measure it, you can’t understand it – If you can’t understand it, you can’t make it better 2

3. Types of Research Randomized controlled clinical trial – “Gold standard” for therapeutic interventions Expensive, time-consuming, generalizability issues Prospective cohort – Can be high quality Expensive, slow, care variation issues Retrospective cohort – Dependent on data source and level of detail – Improving with EHR’s, computational power, statistical methods – Increasing recognition by funding agencies – Increasing interest by hospitals: benchmarking, quality improvement 3

4. Begin with the end in mind: VPS Premiere international clinical multi-center database in pediatric critical care Validated data entry and quality control Site profiles: beds, care models, etc. Patient level data: diagnosis, risk adjustment, interventions, outcomes VPS was built and continually updated as a data source for research 4

5. 5 http://www.myvps.org/research.html > 73 publications to date

6. Examples (more to follow as individual presentations) 6 (Crit Care Med 2003; 31:2657–2664)

7. Kurachek et al. 2,794 patients in 16 PICU’s 6.2% failure rate Predisposing conditions: age, genetic syndrome, duration of intubation… 7

8. 8 Pediatr Crit Care Med 2009; 10:562–570

9. Typpo et al. 44,693 patients from 28 hospitals Patients with Day 1 MODS mortality: 10.0% vs. those without MODS on Day 1: 1.2% Longer length of stay and worse functional outcomes as well 9

10. 10 Pediatr Crit Care Med 2011; 12:184 –189

11. Czaja et al. 9,208 patients with cardiac surgery PIM 2 with fair discrimination and poor calibration Overpredicted mortality for perioperative patients and underpredicted for preoperative patients 11

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13. Sala et al. 3,318 children with status asthmaticus admitted to 48 PICU’s in 2007-2008. 6.1% with respiratory failure (invasive ventilation) African-American children more likely to be intubated (OR 1.4, 95% CI 1.0-1.9) 13

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16. 16 Crit Care Med. 2012 Jul;40(7):2196-203.

17. Edwards et al. 52,791 admissions to 54 PICUs 53% had a complex chronic condition (CCC) 74% of deaths had a CCC Increased risk of death with most CCC’s: aOR 1.7 (95% CI 1.43 – 2) Interestingly, adding CCC’s to a model did not change the SMR by PICU 17

18. 18 J Pediatr 2013;163:835-40

19. Ghuman et al. 74 PICU’s from 2006-2008 Postpubertal females had lower mortality from sepsis than postpubertal males Postpubertal female gender was independently associated with lower risk of mortality. 19

20. 20 JAMA Pediatr. 2014 Mar;168(3):243-9.

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22. 22 Clin Cardiol. 2015 Feb 23. doi: 10.1002/clc.22374. [Epub ahead of print]

23. VPS Research Policy/Procedures Policy and study list at myvps.org Research staff and committee review – Avoid duplicate studies – Gauge feasibility – Accountability: timeliness, VPS updates, etc. – Appropriate representation of VPS – Protection of subjects and institutions – Advice but no editorial restriction 23

24. 24 Feedback welcome!!

25. VPS Research Policy highlights Distinction between internal benchmarking and research Must be a VPS site or collaborate with one Data use agreement Brief study proposal, data request form – Aims, hypotheses – Design – ? Funding – Timetable Local IRB approval or waiver first VPS acknowledgement 25 VPS data was provided by the VPS, LLC. No endorsement of editorial restriction of the interpretation of these data or opinions of the authors has been implied or stated.

26. VPS Research policy highlights (2) New – One year limitation on a study question (extensions possible) – Quarterly updates – Data destruction upon completion – Requesting additional VPS resources? (Appropriate costs charged) Data analysis Statistical support Project coordination Quality control – Research committee to review all abstracts, manuscripts, presentations in advance “to ensure proper representation of the use of VPS data and to offer comments regarding other aspects of the publication/presentation.” – Must submit all final publications to VPS 26

27. VPS Research Policy highlights (3) Research committee review: – Turn around time: 4 weeks – Outcomes (2 reviewers): Consensus agreement to proceed Full committee quorum review needed Clarification requested from PIs Rejection – PIs may then request full committee review 27

28. VPS Research Policy highlights (4) “Failure of the Principal Investigator to follow these requirements may result in the suspension of permission to continue the research with VPS data, including denial of future requests for VPS data for research purposes, notification of a PI’s institutional privacy officer and/or of the U.S. Department of Health and Human Services, and/or civil or criminal prosecution.” 28

29. START Researcher interested in using VPS data for study Affiliated with a PICU participating in VPS? Review VPS Research Policy available at www.myvps.org Is there an active VPS study with same question? Secure IRB approval/ exemption from your local IRB Complete VPS Research Request form available at www.myvps.org Submit signed VPS Research Request form and project proposal to Christine Gall at cgall@myvps.org Review Data Use Agreement prior to signing form Research Committee Reviews Research Request Options: Select another topic or request collaboration with PI of active study Need to have a co- investigator from an ICU participating in VPS Respond to questions/ comments from Research Committee and resubmit Committee Approves Study? Request sent to VPS Data Manager- Processing time depends on # of studies in queue The VPS Data Manager will contact you for preferences on file format and data file delivery Data File Received: Commence Research Submit quarterly status updates to VPS Research Committee Will project be finished in one year? Apply for an extension from the VPS Research Committee Extension Granted? Do you intend to publish or present findings? Complete research by original study end date Following completion of the analysis and publication/ presentation of the findings, the data file should be destroyed and may not be used for other purposes Researchers may be contacted in the future by PI’s interested in studying the same question. Inform VPS research coordinator if you have concerns. The VPS maintains a library of all publications and presentations- Please resubmit accepted abstracts/ publications in final form along with the reference citation. The VPS Research Committee will forward any comments to you for consideration and incorporation into final work. Submit final abstract, manuscript or presentation to VPS Research Committee >= 10 business days prior to deadline for submission Provide rationale regarding decision not to publish/ present results to VPS Research Committee PROCESS FOR USE OF VPS DATA FOR RESEARCH END No Yes No Yes

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38. Research Staff and Committee VPS – RoxAnne Dent – Nancy Brundage – Casey Lauer Committee – Matt Scanlon MD – Howard Jeffries MD, MPH, MBA – Ron Dechert PhD – Tom Rice MD – Ramesh Sachdeva MD, PhD, MBA 38

39. Questions? bmarkovitz@chla.usc.edu or RoxAnne Dent (rdent@myvps.org) 39