The DIMACS Working Group on Disease and Adverse Event Surveillance Henry Rolka and David Madigan Background • WG Objective: Bring together researchers in adverse event monitoring and disease surveillance • Part of a 5-year special focus on computational and mathematical epidemiology • 50+ WG members: epidemiologists, public health professionals, biostatisticians, etc. • Focus on analytic/statistical methods • Two WG meetings plus week-long tutorial (02-03) • Coordinated closely with National Syndromic Surveillance Conferences Areas of Common Interest Disease Surveillance Vaccine Safety Surveillance Drug Safety Surveillance Syndromic Surveillance Representation • Carnegie-Mellon University • FDA • Quintiles Inc. • CDC • Rutgers University • Emergint, Inc. • AT&T Labs • NJ State • • • • • • • • NYC Dept. of Health University of Pennsylvania Aventis ATSDR University of Connecticut Los Alamos National Lab Lincoln Technologies SAS Institute Background, cont. • WG conceived before September 11, 2001 • Surveillance landscape has changed drastically • Major public health effort directed at bioterrorism detection • Proliferation of novel surveillance projects in response to national threat • “Good for detecting outbreaks of various kinds” New Data Types for Public Health Surveillance • Managed care patient encounter data • Pre-diagnostic/chief complaint (text data) • Over-the-counter sales transactions – Drug store – Grocery store • • • • • • 911-emergency calls Ambulance dispatch data Absenteeism data ED discharge summaries Prescription/pharmaceuticals Adverse event reports New Analytic Methods and Approaches • • • • • • • Spatial-temporal scan statistics Statistical process control (SPC) Bayesian applications Market-basket association analysis Text mining Rule-based surveillance Change-point techniques ANALYTIC METHODS IN USE • Scan statistics (e.g., Kulldorff ’s SaTScan) • Statistical process control (e.g., Hutwagner’s EARS) • Association rule mining (e.g., Moore’s WSARE) • Bayesian shrinkage (e.g., DuMouchel’s MGPS) • Generalized linear mixed models (e.g., Kleinman) • Sequential probability ratio tests (e.g., Spiegelhalter, Evans) SCAN STATISTICS • Martin Kulldorff ’s SaTScan Spatial and Space-Time Scan Statistics - software. • e.g., spatial scan – using Poisson model computes likelihood of all possible circles compared with likelihood under the null distribution • Picks the circle with the biggest likelihood ratio • P-value computed via Monte Carlo • Big literature on disease clustering: Besag & Newell, Diggle, Moran test, Turnbull’s method, Cuzick & Edwards, etc. • Need methodology for multiple sources Farzad Mostashari BAYESIAN SHRINKAGE ESTIMATION • DuMouchel’s GPS/MGPS • Compares observed counts of “market baskets” to expected counts under some (simple) model. For example, saw 30 cases in the ER today with G.I. syndrome AND fever AND work in Newark compared with an expectation of 3 cases • 30-to-3 is more convincing than 3-to-0.3 but less convincing that 300-to-30. Idea: shrink the smaller ones towards one. 6 GPS SHRINKAGE – AERS DATA number of reports 3 2 1 0 log EBGM 4 5 1 2 3 5 10 50-100 0 1 2 3 log RR 4 5 6 BAYESIAN SHRINKAGE ESTIMATION • Issues: Appropriate amount of shrinkage? Where do the expected values come from? Temporal dimension? Covariate information Simpson’s paradox (“innocent bystander”) SEQUENTIAL PROBABILITY RATIO TESTS • Classical much-studied statistical method dating back to Wald (1948) NATURAL LANGUAGE • Important sources of health data begin life as free text “chief complaints” (ED visits, primary care encounters, adverse event reports, e-mail, etc.) “Approximately 5 minutes after receiving flu and pneumonia vaccine pt began hollering, "Oh, Oh my neck is hurting. Feels like a knot in my throat, a medicine taste." Complained of chest pain moving to back and leg numbness.” • Some (successful) work on automated coding of free text. • Little work on direct surveillance of text data CONCLUSION • Analytic methods for surveillance have a long history in Statistics but currently attract substantial new interest from researchers in both CS and Statistics • Urgently need new methods for multivariate, multi-data type streams • Data availability a bottleneck; simulation non-trivial. • DARPA currently staging a competition THE IDEA OF A COMPETITION Thesis: Rapid growth in the number of deployed health surveillance systems and increasing complexity require new analytic methodologies Goal: Stimulate mainstream Computer Science and Statistics researchers to focus on this area How: A signal detection competition Examples: the Message Understanding Conferences (MUC), Text Retrieval Conferences (TREC), KDD Cup, M3 Time Series competition COMPETITION STATUS •DIMACS Working Group on Adverse Event and Disease Reporting, Surveillance, Analysis •Subgroup focused on competition; applied for funding; identified data sources •Key challenge: appropriate methods for inserting signals into real data (“spiking”) •Other groups face the same challenge (e.g. BioStorm) ANALYTIC METHODS IN USE • Scan statistics (e.g., Kulldorff ’s SaTScan) • Statistical process control (e.g., Hutwagner’s EARS) • Association rule mining (e.g., Moore’s WSARE) • Bayesian shrinkage (e.g., DuMouchel’s MGPS) • Generalized linear mixed models (e.g., Kleinman) • Sequential probability ratio tests (e.g., Spiegelhalter, Evans) SCAN STATISTICS • Martin Kulldorff ’s SaTScan Spatial and Space-Time Scan Statistics - software. • e.g., spatial scan – using Poisson model computes a likelihood ratio for all possible circles comparing event counts inside and outside • Picks the circle with the biggest likelihood ratio • P-value computed via Monte Carlo • Big literature on disease clustering: Besag & Newell, Cuzick & Edwards, Diggle, Moran test, Pagano, Turnbull’s method,, etc. • Need methodology for multiple sources Farzad Mostashari BAYESIAN SHRINKAGE ESTIMATION • DuMouchel’s GPS/MGPS • Compares observed counts of “market baskets” to expected counts under some (simple) model. For example, saw 30 cases in the ER today with G.I. syndrome AND fever AND work in Newark compared with an expectation of 3 cases • 30-to-3 is more convincing than 3-to-0.3 but less convincing that 300-to-30. Idea: shrink the smaller ones towards one. 6 GPS SHRINKAGE – AERS DATA number of reports 3 2 1 0 log EBGM 4 5 1 2 3 5 10 50-100 0 1 2 3 log RR 4 5 6 BAYESIAN SHRINKAGE ESTIMATION • Issues: Appropriate amount of shrinkage? Where do the expected values come from? Temporal dimension? Covariate information SEQUENTIAL PROBABILITY RATIO TESTS • Classical much-studied statistical method dating back to Wald (1948). Mostly univariate. NATURAL LANGUAGE • Important sources of health data begin life as free text “chief complaints” (ED visits, primary care encounters, adverse event reports, e-mail, etc.) “Approximately 5 minutes after receiving flu and pneumonia vaccine pt began hollering, "Oh, Oh my neck is hurting. Feels like a knot in my throat, a medicine taste." Complained of chest pain moving to back and leg numbness.” • Some (successful) work on automated coding of free text. • Little work on direct surveillance of text data THE IDEA OF A COMPETITION Thesis: Rapid growth in the number of deployed health surveillance systems and increasing complexity require new analytic methodologies Goal: Stimulate mainstream Computer Science and Statistics researchers to focus on this area How: A signal detection competition Examples: the Message Understanding Conferences (MUC), Text Retrieval Conferences (TREC), KDD Cup, M3 Time Series competition HOW CAN THIS BE ACCOMPLISHED • Definitions of signals. • Test data sets for refining signal detection procedures. • Modular, interoperable signal generation algorithms. • Computing efficiencies for Monte Carlo simulations of signal detection events in large complex data. • Multidimensional graphical displays to interpret results and evaluate algorithms. • Multivariate statistical techniques for evaluating signal detection profiles across multiple data sources. COMPETITION STATUS •DIMACS Working Group on Adverse Event and Disease Reporting, Surveillance, Analysis •Subgroup focused on competition; applied for funding; identified data sources •Key challenge: appropriate methods for inserting signals into real data (“spiking”) •Other groups face the same challenge (e.g. BioStorm) CONCLUSION • Short-term goals/benefits: •Promote coordination and collaboration • Long-term goals/benefits • Stimulate methodological research • Provide objective evaluation of competing algorithms • Produce high quality spiking algorithms ANALYTICAL METHODS FOR HEALTH SURVEILLANCE DAVID MADIGAN DEPARTMENT OF STATISTICS RUTGERS UNIVERSITY Novel Surveillance Applications Methodologies • Early Aberration Reporting System (EARS), CDC • What’s Strange About Recent Events? (WSARE), U of Pittsburgh and Carnegie-Mellon U • Spatial and Space-Time Scan Statistics (SaTScanTM – Kulldorff) • Web Visual Data Mining Environment (WebVDME), Lincoln Technologies, Inc. Novel Surveillance Applications Projects • Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE I&II), DOD • Real-time Outbreak and Disease Surveillance (RODS), U of Pittsburgh • Biological Spatio-Temporal Outbreak Reasoning Module (BioSTORM), Stanford U • Rapid Syndrome Validation Project (RSVP), Sandia NL, NM • Alternative Surveillance Alert Program (ASAP), Health Canada • Syndromic Surveillance Project, NYC • Bioterrorism Syndromic Surveillance Demonstration Program, CDC/Harvard Conceptual Taxonomy Public Health Surveillance Adverse event (to intervention exposure) Drug Vaccine Disease Syndromic Traditional Infectious disease Birth defect Other Injuries Etc.