Using DS2TREE Macro to Create Interactive Treeview Diagrams for Clinical Adverse Experiences Records

Transcription

1 Using DS2TREE Macro to Create Interactive Treeview Diagrams for Clinical Adverse Experiences Records Shi-Tao Yeh, GlaxoSmithKline, King of Prussia, PA. ABSTRACT The SAS DS2TREE macro uses the Treeview applet to generate an interactive node or link diagrams for hierarchical data. The applet is designed to visualize large hierarchical data, focusing on some of specific nodes of interest while retaining the context of the data hierarchy. The applet places the root node at the center of the view and the successive level of child nodes around the root node in circles of increasing radius. This is useful because some data sets collected from clinical trials are in hierarchical structures. These types of data are well-suited for the Treeview display. This paper discusses the application of the DS2TREE macro to clinical AE data and illustrates the interactive graph features provided by the Treeview applet. The SAS products used in this paper are SAS BASE and SAS/GRAPH 9.1 on a PC Windows platform. INTRODUCTION In clinical trial studies, the investigators are responsible for recording the subjects AE at each clinical office visit or assessment. An adverse experience is defined as: any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs, symptoms, and/or laboratory, changes occurring in any phase of the clinical study whether associated with the study drug, active comparator or placebo, and whether or not considered drug related. In other words, an adverse experience is some unplanned, unwanted event which occurs to a subject and which is possible related to the study medication and therapy. The instructions for the investigator in the Case Report Form (CRF) are: Have there been any adverse experiences observed or elicited by the following direct question to the subject: "Have you felt different in any way since the last assessment? " If the answer is 'Yes', please record details in the Adverse Experiences section. The study team has responsibilities to review and report the adverse reactions and unexpected experiences involving risks to subjects. The following AE summary table is a sample display of AE report. Summary of All Adverse Events Body System Dose A Dose B Preferred Term (N=314) (N=326) ANY EVENT 283 (90%) 274 (84%) EAR NOSE & THROAT Any Event 82 (26%) 90 (28%) Upper respiratory tract infection 39 (12%) 37 (11%) Throat irritation 11 (4%) 11 (3%) Upper respiratory inflammation 5 (2%) 10 (3%) Nasal congestion/blockage 5 (2%) 6 (2%) Rhinitis 5 (2%) 5 (2%) Sinusitis 5 (2%) 4 (1%) Rhinorrhea/post nasal drip 4 (1%) 1 (<1%) Hoarseness/dysphonia 1 (<1%) 3 (<1%) Ear nose & throat signs & symptoms 0 3 (<1%) Epistaxis 1 (<1%) 2 (<1%) Table 1. Sample AE Report 1

2 Table 1 depicts a standard AE summary report with the AE terms of Body System / Preferred Term by treatment group which are shown on the table. The data used through out the paper are from a hypothetic clinical trial and are for illustration purpose only. SAS/GRAPH 9.1 provides a SAS macro DS2TREE with the Treeview Applet for creating interactive Treeview diagrams. The Treeview applet provides multi-scale viewing as well as user choice interaction properties. It implements the concept of a Space-Scale diagram. The information objects are organized in space and scale. The users interact directly with information space, mainly through the user interfaces. The user interfaces are controlled by using a mouse, buttons, and menus. Zooming techniques are often used to change the object s scale. Zoomable interfaces come in two types: 1) Geometric zooming where the zoom scale is linear with the zoom multiplier, 2) Semantic zooming where objects may change shape at different zoom levels. The semantic zooming is a distortion technique that displays a fisheye view to change object scale in a single view. By moving around and changing the scale, the user can get integrated context and focus of the large information space. The interactive menus available are: pop-up data tips, drill-down links, and interactivity via pop-up menus. The Treeview applet places the root node at the center of the view and places successive levels of child nodes around the root node in circle of increasing radius. Child nodes of an intermediate parent node are grouped close to the parent. An exponential view transformation is used to display the tree. Regardless of the view, the whole tree is always displayed. These interfaces include an overview, often called overview + detail interfaces illustrate the details of an information space together with an overview of the entire information space. Nodes and links at the center of the view port are displayed with normal magnification, while nodes, and links near the edge of the tree are compressed or to be displayed with reduced details. The overview + detail strategy allows users to interact with the tree in more detail in any area while still retaining overview of the tree. The Treeview applet is well-suited for the display of a large hierarchical data set. The features provided from the Treeview Applet are: 1. Scroll across the diagram by selecting off-center nodes or by searching nodes. 2. Move over a node can display optional data tips. 3. Access a pop-up menu by right-clicking the mouse. The menu enables the viewer to highlight or hide subtrees or drill-down to an optional URL. The menu also enables the viewer to select all nodes, display all previous hidden nodes, reset the view, display applet help, and search for nodes using various search parameters. 4. The fisheye distortion factor, coupled with extensive node selection features, enables a single node/link diagram to accommodate large data sets. 5. The thickness and various colors of the connection lines between the nodes provide a visual illustration of weighed relationships or summation of occurrences between the nodes. 6. The Treeview can generate an optional external XML file. DATA FILE A sample data file containing AE records is used in the SAS macro program for illustration purposes. The output from PROC CONTENTS is shown as follows: # Variable Type Len Pos Format Label AE_C Char AE: Dictionary Code 3 AGE Num Age 10 BDAT Num 8 16 DATE9. AE: Onset Date 8 BODY1 Char AE: Body System Level 1 12 EDAT Num 8 24 DATE9. AE: End Date 13 GIAE_C Char AE: GI Event of Concern Code 2

3 14 INTENS Char AE: Intensity 1 PID Char Patient ID 9 PREF Char AE: Preferred Term 2 RAND Char Randomization 15 RELAT Char AE: Relationship 16 RELT_FD Num 8 32 AE: Rel Time First Dose 17 RELT_LD Num 8 40 AE: Rel Time Last Dose 18 SER_C Char AE: Serious Code 6 SESSION Char Session 5 SES_ID Num 8 8 Session ID 4 SEX Char Sex 7 TRX Char Treatment 19 WITHAE_C Char AE: Withdrawal Code AE records from the clinical trials are in a hierarchical structure with different levels of AE terms. It is an ideal data structure for the Treeview display. SAS MACRO FOR AE DISPLAY I The type I AE display uses AE variable RAND as a tree root with the hierarchical structure of variable BODY1 as the first level nodes and the variable PREF as the child nodes from parent of the Body System node. DS2TREE macro arguments used in the sample program are as follows: Argument Description Default Value NDATA Specifies the SAS data set that contains the node data. CODEBASE Specifies the path of the SAS Java archives. The CODEBASE argument is required. You can specify CODEBASE=file:///c:\xxxx if the HTML file and Java archive are in the same directory. HTMLFILE Specifies the name and storage location of the HTML output file. If the external file does not exist, then it is created for you. NID Specifies the name of the variable in the nodes data set whose values are illustrated as the nodes in the diagram. The node ID variable can be either numeric or character. NLABEL Specifies the name of the variable that represents the node labels. The variable type can be either numeric or character. NTIP Specifies the name of the variable that provides the data or text that is displayed in the pop-up data tips window. NFNTNAME Specifies the name of the variable that determines the text The default node font is font for the node labels. The variable value can be SERIF, specified by the SANSSERIF, DIALOG, DIALOGINPUT, MONOSPACED. FNTNAME = argument. NCOLOR Specifies the variable in the nodes data set that determines the background color of the nodes, using HTML 3.2 color names or 6-digit hexadecimal RGB values. NCOLFMT Specifies the name of a user-defined SAS format that converts the values in the variable named in the NCOLOR= argument to valid HTML color names. HEIGHT Specifies the height of the applet window. The unit of 600 measure is pixels unless changed by the AHUNITS=argument. WIDTH Specifies the width of the applet window. The unit of 800 measure defaults to pixels unless specified by the AWUNITS=argument. 3

4 LWIDTH Specifies the name of the variable in the data set that determines the width of the link lines. LCOLOR Specifies the name of the variable that determines the color of the link lines. LCOLFMT Specifies the name of a user-defined SAS format that converts the values in the variable named in the LCOLOR = argument to valid HTML color names. CBACK Specifies a background color for the Treeview Applet. The value must be a valid HTML 3.2 color name. CNODE Specifies the node background color. The value must be a valid HTML color name. CSELECT Specifies a color for nodes that are selected by the mouse or as the result of a node search. The value must be a valid HTML 3.2 color name. BG Specifies the background color or image, based on the value of the BGTYPE= argument. BGTYPE NONE COLOR IMAGE NONE TTAG Specifies a text string that the macro translates into one or PREFORMATTED + more tags that will enclose the SAS TITLE. HEADER 3 TCOLOR Specifies the color of the text in the SAS TITLE, using an HTML 3.2 color name or a six-digit hexadecimal RGB value. FTAG Specifies a text string that the macro translates into one or PREFORMATTED + more tags that will enclose the SAS FOOTNOTE. HEADER 3 FCOLOR Specifies the color of the text in the SAS FOOTNOTE, using an HTML 3.2 color name or a six-digit hexadecimal RGB value. Table 2. DS2TREE Macro Arguments Used in the Sample Code I The argument CODEBASE specifies the path of SAS Java Archive(JAR). The JAR file format enables you to bundle multiple files into a single archive file. Typically a JAR file will contain the class files and auxiliary resources associated with applets and applications. The Treeview applet uses three JAR files; treeview.jar, j2d.jar and nld.jar. If you specify that the HTML file and JAR file are in the same directory, you need to copy all three JAR files into that directory. The light colors for background color of node and applet are recommended. Solid colors are better for link lines. Data tips, one of the interactive features, allows the user to graphically access information about any graphical elements shown on the screen. This is a mouse action feature, by hovering the mouse pointer over the desired entities on the graph a pop-up text box will display information about the object. In this AE application, the following information will be displayed: AE Treatment (root) Node: number and percentage of subject with AE events, AE Body System Node: body system label with body system code, number, and percentage of subject with this body system AE events. AE Preferred Term Node: preferred term label with preferred term code, number, and percentage of subject with this preferred term AE events. Data tips used in this application convert all the AE event count and percentage count information on each cell in Table 1 into data tips text. %macro runtree(trt=, where=); libname sa 'c:\nesug05'; data mstone; set sa.mstone; sdur=ltdat - ftdat +1; count=1; 4

5 if rand="&trt"; keep pid rand race sex age sdur count; proc sort;by rand; proc summary data=mstone; by rand; var count; output out=p0(keep=rand total) sum=total; data mstone; merge mstone p0; by rand; proc sort data=mstone;by pid; data ae; set sa.ae; &where; data ae; set ae; count=1; if ses_id=1 and rand="&trt" ; keep pid rand body1 pref body1_c pref_c count relt_fd; proc sort;by pref_c relt_fd pid; data ae; set ae; by pref_c relt_fd pid; if first.pid; proc sort data=ae ;by pid ; data ae; merge ae(in=a) mstone; by pid; if a; %macro setdata(var1=, var2=); data ae&var2; set ae; proc sort;by rand &var1 pid; data ae&var2; set ae&var2; by rand &var1 pid; if first.pid; proc summary data=ae&var2; by rand &var1; var count; output out=p&var2(keep=rand &var1 scount) sum=scount; proc sort data=ae&var2 nodupkey;by rand &var1; proc sort data=p&var2;by rand; proc sort data=p0;by rand; data ae&var2; merge ae&var2 p&var2 p0 ; by rand; length pref1 $90.; spct=round((scount/total)*100,.01); pref1='0a'x ' Subjects with Event: ' compress(scount) ' (' compress(spct) '%)'; 5

6 keep body1 body1_c pref pref_c scount spct rand pref1; %mend; %setdata(var1=pref_c, var2=p); %setdata(var1=body1_c,var2=b); %setdata(var1=,var2=a); proc sort data=aep;by pref_c; proc sort data=aeb;by body1_c; data aea; set aea; length pref_c body1_c $4. pref $35.; pref_c='0000'; body1_c=' '; pref="&trt ADVERSE EVENTS"; data aeb; set aeb; pref=body1; pref_c=body1_c; body1_c='0000'; data final; set aea aeb aep; tname='sansserif'; fnwt='bold'; lscount=round(log(scount),.2); pref1= left(trim(pref)) '(' left(trim(pref_c)) ')' '0A'x trim(pref1); title1 "&t1 - &trt"; footnote1 "&f1 "; proc format; value $body = 'cxffff00' = 'cxffff00' /* more color specification */ = 'cxff33ff'; proc format; value lcola ='cx333333' ='cx33ffff' ='cx3333ff' ='cxcc6600' ='cxcc00cc' ='cxff0000'; ods listing; %ds2tree(ndata=final, codebase=file:///c:\nesug05, htmlfile=c:\nesug05\g9aetr05.htm, nid=pref_c, nparent=body1_c, nlabel=pref, ntip=pref1, nfntname=tname, nfntstyl=fnwt, ncolor=pref_c, ncolfmt=$body., height=500, width=980, lwidth=lscount, lcolor=lscount, 6

7 lcolfmt=lcola., cback=cxccffff, cnode=yellow, cselect=red, bg=cxffaaff, bgtype=color, ttag=header 3, tcolor=navy, ftag=header 5, fcolor=navy ); ods _all_ close; %mend; SAS MACRO INVOCATION: AE DISPLAY I %let t1=treeview of First Onset AE; %let f1=c:\nesug05\g9aetr05.sas &sysdate &systime; %runtree(trt=dose A); Figure 1. Treeview Diagram for AE Data You can move the cursor to the position of interest, hold the cursor, and drag the diagram to create a fish-eye distortion to view the second level nodes. You can also move the cursor over a node to view the data tips. The following figure shows the pop-up menu that a user can invoke by right-clicking a Treeview diagram in a browser. The pop-up menus illustrates all the options that are available for interacting with the diagram. For a description of these options, right-click on any Treeview diagram and select Treeview Applet Help from the pop-up menu. Figure 2 shows the fish-eye distortion, data tips, and interactive menus of the diagram. 7

8 SASMACROFORAEDISPLAYII Figure 2. Interactive Features of AE Treeview The type II AE display uses AE variable BODY1 as the tree root with the hierarchical structure of variable PREF as the parent node and variable PID as the child node. In this AE application, the following information will be displayed: AE Body System (root) Node: body system label with body system code, number, and percentage of subject with this body system AE events. AE Preferred Term Node: number and percentage of subject with this preferred term AE events. Subject Node: Subject ID, Race, Gender, Age, First AE on set relative to the first dose, and Study duration days. %macro runtree(trt=,where=); /* data preparation steps */ ods listing; %ds2tree(ndata=final, codebase=file:///c:\nesug05, htmlfile=c:\nesug05\g9aetr02.htm, nid=pid_c, nparent=apref_c, nlabel=apid, ntip=pref1, 8

9 nfntname=tname, nfntstyl=fnwt, height=520, width=980, lwidth=lscount, cback=aqua, cnode=yellow, cselect=red, bg=aqua, bgtype=color, tcolor=navy, fcolor=navy); ods _all_ close; %mend; SAS MACRO INVOCATION: AE DISPLAY II %let t1=treeview of First Onset AE at Subject Level; %let f1=c:\nesug05\g9aetr02.sas &sysdate &systime; %runtree(trt=dose A,where=%str(if body1_c='1100')); Figure 5. AE Treeview at Subject Level 9

10 SASMACROFORAEDISPLAYIII Figure 6. Subject Information Are Shown as Data Tips The type III AE display combines type I and II together to create a three level hierarchical structure. It uses AE variable RAND as the tree root with the hierarchical structure of variable BODY1 as the first level node, variable PREF as the second level node and variable PID as the third level node. %macro runtree(trt=, where=); libname sa 'c:\nesug05'; data mstone; set sa.mstone; sdur=ltdat - ftdat +1; count=1; if rand="&trt"; keep pid rand race sex age sdur count; proc sort;by rand; proc summary data=mstone; by rand; var count; output out=p0(keep=rand total) sum=total; data mstone; merge mstone p0; by rand; proc sort data=mstone;by pid; data ae; 10

11 set sa.ae; &where; data ae; set ae; count=1; if ses_id=1 and rand="&trt" ; keep pid rand body1 pref body1_c pref_c count relt_fd; proc sort;by pref_c relt_fd pid; data ae; set ae; by pref_c relt_fd pid; if first.pid; proc sort data=ae ;by pid ; data ae; merge ae(in=a) mstone; by pid; if a; %macro setdata(var1=, var2=); data ae&var2; set ae; proc sort;by rand &var1 pid; data ae&var2; set ae&var2; by rand &var1 pid; if first.pid; proc summary data=ae&var2; by rand &var1; var count; output out=p&var2(keep=rand &var1 scount) sum=scount; * proc print data=p&var2; proc sort data=ae&var2 nodupkey;by rand &var1; *proc print data=ae&var2; proc sort data=p&var2;by rand; proc sort data=p0;by rand; data ae&var2; merge ae&var2 p&var2 p0 ; by rand; length pref1 $90.; spct=round((scount/total)*100,.01); pref1=' Subjects with Event: ' compress(scount) ' (' compress(spct) '%)'; keep body1 body1_c pref pref_c scount spct rand pref1; *proc print data=ae&var2 (obs=30); %mend; %setdata(var1=pref_c, var2=p); proc sort data=aep;by pref_c; %setdata(var1=body1_c,var2=b); proc sort data=aeb;by body1_c; %setdata(var1=,var2=a); data aea; set aea; length apref_c abody1_c $10. pref $35.; apref_c='0000'; 11

12 abody1_c=' '; pref="&trt ADVERSE EVENTS"; data aeb; set aeb; length apref_c abody1_c $10.; pref=body1; apref_c=body1_c; abody1_c='0000'; proc sort data=mstone;by pid; proc sort data=ae;by pid; data aepid; merge ae(in=a) mstone(in=b); by pid; if a and b; data aepid; set aepid; length pref1 $68. apref_c abody1_c $10. ; scount=1; abody1_c=pref_c; body1=pref; apref_c=compress(pid) '_' compress(_n_); pref1=compress(pid) ' ' compress(race) ' ' compress(sex) ' Age:' Compress(age) ' First Onset(d): ' compress(relt_fd) ' St. Dur.(d): ' compress(sdur) ; pref=pid; data aep; set aep; length apref_c abody1_c $10.; apref_c=pref_c; abody1_c=body1_c; data final; set aea aeb aep ; pref1= left(trim(pref)) '(' left(trim(pref_c)) ')' trim(pref1); data final; set final aepid; tname='sansserif'; fnwt='bold'; lscount=log(scount); *proc print data=ae(obs=30); title1 "&t1 - &trt"; footnote1 "&f1 "; ods listing; %ds2tree(ndata=final, codebase=file:///c:\nesug05, htmlfile=c:\nesug05\g9aetr03.htm, nid=apref_c, nparent=abody1_c, nlabel=pref, ntip=pref1, nfntname=tname, nfntstyl=fnwt, height=520, width=980, lwidth=lscount, cback=aqua, cnode=yellow, cselect=red, bg=aqua, 12

13 bgtype=color, tcolor=navy, fcolor=navy ); ods _all_ close; %mend; SAS MACRO INVOCATION: AE DISPLAY III %let t1=treeview of First Onset AE; %let f1=c:\nesug05\g9aetr03.sas &sysdate &systime; %runtree(trt=dose A); Figure 7. Three Level AE Treeview Diagram 13

14 Figure 8. Different AE Subset Treeview Diagrams CREATE AN EXTERNAL XML FILE The type III program creates the Treeview with XML embedded in the HTML file. Several additional macro arguments are added to create an external XML file. Argument Description Default Value xmltype Specifies the name and storage location of the XML output file. makexml Specifies whether or not an XML file is to be generated. If you specify Y MAKEXML=N and MAKEHTML=Y, then only an HTML file will be generated. Note that under these circumstances, you may specify a value for the XMLURL= argument. xmlurl Specifies the URL of the existing file that contains the XML tags that define the node/link disgram. This argument is required if you specify XMLTYPE= EXTERNAL. xmlfile Specifies the name and storage location of the XML output file. If the external file does not exist, then it is created for you. This argument is required if you specify MAKEXML=Y and XMLTYPE= EXTERNAL. Note: Do not use the XMLFILE=argument if you use the XMLFREF= argument. Table 3. Additional Macro Arguments Used to Generate an External XML File 14

15 SAMPLE CODE IV: GENERATING AN EXTERNAL XML FILE ods listing; %ds2tree(ndata=final, codebase=file:///c:\nesug05, htmlfile=c:\nesug05\g9aetr08.htm, xmltype=external, makexml=y, xmlurl=file:///c:\nesug05, xmlfile=c:\nesug05\g9aetr08.xml, nid=apref_c, nparent=abody1_c, nlabel=pref, ntip=pref1, nfntname=tname, nfntstyl=fnwt, ncolor=apref_c, ncolfmt=$body., height=500, width=980, lwidth=lscount, lcolor=lscount, lcolfmt=lcola., cback=cxbbffff, cnode=yellow, cselect=red, bg=cxffaaff, bgtype=color, ttag=header 3, tcolor=navy, ftag=header 5, fcolor=navy ); ods _all_ close; The following partial XML document is generated from sample SAS Code IV. Figure 9. Partial XML Document Generated from Sample Code IV. 15

16 You can use the SAS XML Mapper to create an XML map, SAS code, table view, and contents. SAS XML Mapper is available in SAS version It is a Java-based application that allows users to create XMLMaps for use by the XML engine. SAS XML Mapper provides a graphical interface that you can use in order to generate the appropriate XML elements. SAS XML Mapper analyzes the structure of an XML document or an XML schema and generates basic XML syntax for the XMLMap. Figure 10 illustrate the SAS XML Mapper panes. Figure 10. SAS XML Mapper Panes CONCLUSION The clinical trials collect AE data. The AE data are converted to a hierarchical structure with different levels of AE terms based on the AE dictionary used. The interactive Treeview diagram is well-suited for the illustration of clinical hierarchical AE data. The interactive features provided from the Treeview applet allow users to do the following: 1. Select off-center nodes by clicking any node so that the applet moves that node to a focal position 2. Search for nodes, or drag any node to a desired position 3. Set any parent node as the root node of its descendant tree 4. Select, display, or hide any parent node s subtree 16

17 5. Position the cursor over a node for displaying data tips 6. Right-click the mouse to access a pop-up menu 7. Customize menu for highlight or hide subtrees, select all nodes, display hidden nodes, reset the view, display applet help, and search for nodes using various search parameters. 8. Generate an external XML file. REFERENCES [1] Patel, H., S. Matange,(2000): New Visualization in V8.2, Proceedings of the 26 th SAS Users Group International Conference, Paper [2] SAS Institute Inc.,(2003): SAS OnlineDoc 9.1, Cary NC. ACKNOWLEGMENTS The author would like to thank Lelia McConnell from SAS Institute Technical Support group for resolving my technical questions. TRADEMARKS SAS is a registered trademark of SAS Institute Inc., Cary, NC, USA indicates USA registration. Author Shi-Tao Yeh, Ph. D. (610) (W) Shi-Tao.Yeh@gsk.com 17