Data Mining Consultant GlaxoSmithKline: US Pharma IT Integrating Discovery, Development, and Commercial Data into Data Mining Jennifer Sloan Data Mining Consultant GlaxoSmithKline: US Pharma IT 15 September 2004

Data Mining Definition Data Mining is a process that uses a variety of data analysis tools to discover patterns and relationships in data that may be used to make valid and accurate predictions.

Data Mining is a tool that allows us to Identify problematic areas Control process variability Make concrete decisions on business needs Develop a model which can aid in future business decisions

Analyzing Multivariate Data Managing Data Usage Model Building Commercial Data Analyzing Multivariate Data Managing Data Usage Model Building

Multivariate Data Sets Data are multivariate in nature Large data sets containing multiple criteria within each observation Comparing multiple vectors is nearly impossible without reducing to a single point

Here we view 5-dimensional information on one observation Here we view 5-dimensional information on one observation. Each point represents a prescriber and the color represents a Market Share increase or decrease. Overlapping distributions make this difficult to interpret and further analysis is required. Over 200K observations are represented in this graph.

The same observations are observed but now two-way interactions between the variables help us determine which variables are affecting market shifts and lead to constructing models which will predict prescriber behavior.

Drug Development

Drug Development Issues Adverse Event Reporting System (AERS) Over 2 million AE reports and approximately 2000 drugs and biologics submitted to the FDA since 1968 Creates Extremely Complicated Matrix of Data Recently, Data Mining methods have helped address this issue with the development of a method used to examine large databases for associations between drugs and AEs

Data Mining Algorithm Multi-Item Gamma Poisson Shrinker (MGPS) Developed by William DuMochel (AT&T) Through statistical modeling, this Empirical Bayesian method identifies higher-than-expected reporting relationships of drug-event combinations Automated, web-based system with rapid drill-down capability MGPS runs using all event terms and drugs in the AERS database and produces results for all drug-event combinations

MGPS: Significance Handles Complex Stratification (age, gender, year of report > 945 categories) Performs complex computations in minimal amount of time: Much MORE EFFICIENT Real World Example:

Membership: PhRMA-FDA Working Group Chair: June Almenoff (GSK) FDA Involvement Involved PhRMA companies: Abbott, Allergan, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Lilly, Merck, Novartis, Schering-Plough, Pfizer, Roche, Wyeth

Drug Discovery

SCAM—Statistical Classification of Activities of Molecules Recursive partitioning customized for chemistry Creates a structure activity relationship (SAR) mode7l Handles large numbers of descriptors (> 1 million)

SCAM : Data Structure Biological Activities Y1 1 0 1 0 1 1 1 0 1 0 0 0 0 0 0 0 0 0 0 0 0 1 Y2 1 0 1 0 0 1 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 1 Y3 1 0 1 0 1 1 1 1 1 0 0 0 0 1 0 0 0 1 0 0 0 1 Y4 1 0 1 0 0 1 1 0 1 0 0 0 0 0 1 0 0 1 0 0 0 1 ... ... 1 0 0 0 1 1 1 1 0 1 0 1 0 0 0 1 0 0 0 0 0 1 Yn > 2 million >100K

SCAM’s Recursive Partitioning Ave = 0.34 SD = 0.81 Feature n = 1614 ave = 0.29 sd = 0.73 n = 36 ave = 2.60 sd = 0.9 rP = 2.03E-70 aP = 1.30E-66 AID, Automatic Interaction Detection, is a simple statistical method for finding interactions in large data sets. It is recursive. One variable and a split point is selected to divide the data set into two or more groups. Each group is divided in turn. When the groups become too small or are homogeneous, the splitting is stopped. A tree results and the sub-grouping rules are read off the tree. NB: It is possible to separate off different groups that are following different mechanisms. There are serious multiple testing questions. Also at issue is the statistic to use for splitting. Signal 2.60 - 0.29 t = = = 18.68 Noise 0.734 1 1 36 1614 +

SCAM Tree

Advantages of SCAM Works for complex situations, mixtures and interactions. Output is easy to understand and explain High statistical power Produces a valid answer

SCAM Drawbacks Data greedy Only one view of the data Binary descriptors may be too “crude” Disposition of outliers is difficult Highly correlated variables may be obscured Higher order interactions may be masked The are of course disadvantages to any algorithmic method used to analyze large data sets.

Concluding Remarks Data Mining enables us to efficiently handle LARGE amounts of data Data Mining allows us to perform analyses IN REAL TIME Data Mining covers a wide array of topics in drug industry and its benefits are plentiful

References Almenoff, June S, et al. “Disproportionality Analysis Using Empirical Bayes Data Mining: A tool for the Evaluation of Drug Interactions in the Post-Marketing Setting.” Pharmacoepidemiology and Drug Safety,12, 517-521 (2003). Donahue, Rafe. “An Overview of Data Mining in Drug Development and Marketing.” http://home.earthlink.net/~rafedonahue. May 2003. Hawkins, D.M. and G.V. Kass, “Automatic Interaction Detection.” Topics in Applied Multivariate Analysis, ed. Hawkins, (1982). Hawkins, D.M., S.S. Young and A. Rusinko. “Analysis of a Large Structure-Activity Data Set Using Recursive Partitioning.” QSAR, 16, 296-302 (1997).