Table 2 Original SAS ASCII output Table 3 From SAS to Excel using DDE

STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Device Statistic mm ------------------------------- Easyhaler Mean 80.2 Median 84.0 Min 36.0 Max 100.0 SD 17.5 N 69.0 Turbuhaler Mean 69.5 Median 74.0 Min 3.0 Max 100.0 SD 23.5 N 69.0 B. Wilcoxon signed rank test for the paired differences between the devices Test Comparison statistic p-value -------------------------------------------------- Easyhaler - Turbuhaler 465.500 0.0010 STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Device Statistic mm Easyhaler Mean 80,2 Median 84 Min 36 Max 100 SD 17,5 N 69 Turbuhaler Mean 69,5 Median 74 Min 3 Max 100 SD 23,5 N 69 B. Wilcoxon signed rank test for the paired differences between the devices Comparison Test statistic p-value Easyhaler - Turbuhaler 465.500 0.0010 Table 2 Original SAS ASCII output Table 3 From SAS to Excel using DDE

STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Treatment Statistic mm Easyhaler Mean 80.2 Median 84.0 Min 36.0 Max 100.0 SD 17.5 N 69.0 Turbuhaler Mean 69.5 Median 74.0 Min 3.0 Max 100.0 SD 23.5 N 69.0 B. Wilcoxon signed rank test for the paired differences between the devices Comparison Test statistic p-value Easyhaler - Turbuhaler 465.500 0.0010 STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Device Statistic mm ------------------------------- Easyhaler Mean 80.2 Median 84.0 Min 36.0 Max 100.0 SD 17.5 N 69.0 Turbuhaler Mean 69.5 Median 74.0 Min 3.0 Max 100.0 SD 23.5 N 69.0 B. Wilcoxon signed rank test for the paired differences between the devices Test Comparison statistic p-value -------------------------------------------------- Easyhaler - Turbuhaler 465.500 0.0010 Table 4 From SAS to Word using RTF Table 5 From SAS to HTML using SAS macros

-XQHWK 6(8*,0LND/HLQRQHQ

/* opening Excel from SAS */ options noxwait noxsync; x cd \progra~1\micros~1\office ; x excel ; /* waiting for a while for excel to open: */ data _null_; x=sleep(2); run; -XQHWK 6(8*,0LND/HLQRQHQ

/* opening the ascii file to excel */ filename command dde excel system ; data _null_; file command; put [APP.MINIMIZE()] ; put [OPEN("c:\temp\table.lst")] ; -XQHWK 6(8*,0LND/HLQRQHQ

/* formatting the table */ data _null_; file command; put [SELECT("R1C1:R5C1")] ; put [STYLE(true,false)] ; put [FORMAT.FONT("Times New Roman")] ; put [SELECT("R6C1:R50C1")] ; put [FORMAT.FONT("Courier New")] ; -XQHWK 6(8*,0LND/HLQRQHQ

/* saving as an Excel sheet */ data _null_; file command; put [SAVE.AS("c:\temp\table.xls",1,"", FALSE,"",FALSE)] ; /* closing excel */ put [QUIT()] ; run; -XQHWK 6(8*,0LND/HLQRQHQ

filename command dde winword system'; data _null_; file command; put '[ToolsMacro.Name="formtab",.Run]'; run; -XQHWK 6(8*,0LND/HLQRQHQ

/* output to HTML format */ %out2htm(capture=on, window=output, runmode=b); proc report...; /* saving the HTML file */ %out2htm(capture=off, window=output, runmode=b, openmode=replace, htmlfile=c:\temp\table.html); -XQHWK 6(8*,0LND/HLQRQHQ

HIGH-QUALITY SAS REPORTING - WHICH IS THE OPTIMAL OUTPUT FORMAT? Mika Leinonen Dept. of Biostatistics and Data Management, Orion Pharma, Espoo, Finland Abstract A clinical study report includes a huge amount of listings and tables produced by the SAS System. One of the worst bottlenecks in the process of creating a study report is the management of the SAS output: the ASCII output produced by SAS has to be exported to a more convenient format. The four frequently applied output formats in the pharmaceutical industry are MS-Word, MS- Excel, HTML and PDF. Various methods for creating documents in these formats using Base SAS have been published. A review of the methods will be presented, along with the main tools utilised by these methods (Proc Report, Dynamic Data Exchange, Rich Text Format, visual basic macros, HTML code). Pros and cons of the four major formats will be compared. The forthcoming release 7 of SAS is expected to make the output management easier by offering a set of new formats. Therefore, also future prospects of output management using SAS will be discussed. Introduction The data flow in clinical trials can typically be divided into three parts. Firstly, the data collected from the patients will be cleaned for errors and entered to a clinical data management system. Secondly, the data will be transformed to SAS datasets for analysis and reporting. Thirdly, the output created by the SAS System (tables, listings and figures) will be imported to a document management system. The focus of this paper will be on the third part, the management of SAS output. In release 6.x of the SAS System for Windows, ASCII is in practise the only output format created automatically by the system. Conversion of ASCII output to a more convenient format is very time-consuming, if it is done manually. In addition, there is a risk of typing errors, if the output will be further edited. Therefore, there should be a way to produce the output needed in the final documentation directly with the SAS System. At the moment, there is no global standard for the output format in pharmaceutical industry. Microsoft Word is often used as the main tool for creating documents. That being the case, a natural choice would be to export the SAS output to Word. Microsoft Excel documents can easily be integrated with Word documents and hence SAS output is sometimes exported to Excel. Two other output formats, HTML (HyperText Markup Language) and PDF (Portable Document Format) have recently become more popular. Especially important feature with these two formats is the excellent linking capability, which makes the management of files easier. In this paper, output management options by using Base SAS are discussed. In addition, there are many tailor-made SAS solutions available. Creating high-quality reports can be made easier by using Enterprise Reporter. SAS/PH-Clinical is a work-group application for reviewing and

analyzing clinical trials data. The SAS PharmaTechnology Process is a technology architecture and a suite of products trying to optimise the whole data flow in clinical trials. These solutions will not be discussed in this paper. All examples presented in this paper were produced in the following environment: Microsoft Windows 95 SAS System for Windows release 6.12 Microsoft Office 97 (MS-Word, MS-Excel) Microsoft Internet Explorer 3.0 Adobe Acrobat Distiller 3.01 Case I: From SAS to Excel using Dynamic Data Exchange Dynamic Data Exchange (DDE) is a method for exchanging information between Windows applications. The concept is based on a client/server relationship. DDE can only be used between two applications that both have a support for DDE. In release 6.12 of SAS System for Windows, SAS always has the role of client. From SAS, you can invoke and close applications, send commands to applications and exchange data between applications. In this case, a table produced by Proc Report in SAS will be sent to Excel, editing is done to the table and finally the table is saved as an Excel worksheet. Part 1: To invoke Excel from SAS, the following code is submitted: /* opening Excel from SAS */ options noxwait noxsync; x cd \util\office\ ; x excel ; /* waiting for a while for Excel to invoke */ data _null_; x=sleep(2); System option NOXWAIT causes the command prompt window to close automatically when the application is finished, without having to type EXIT. System option NOXSYNC allows the SAS System to continue processing while Excel is still running. Excel will be invoked from its own installation directory, which typically is not the current default directory. Though computers nowadays are very quick to process, it is useful to wait a couple of seconds for Excel to invoke. Part 2: To export a table (ASCII file) produced by SAS to current Excel worksheet, the following code is submitted: /* opening the ascii file to excel */ filename command dde excel system ; data _null_; file command; put [APP.MINIMIZE()] ; put [OPEN("c:\work\table.lst")] ; To specify the use of DDE in SAS, FILENAME statement of the following form is used. Firstly, a valid name is given for the file reference, in this case COMMAND. Secondly, the keyword DDE tells the SAS System that you would like to use DDE. The third part, a DDE

triplet, specifies the actual DDE task. DDE triplet is an application-specific list of the following form: application-name topic!item. Application name is the executable name of the server application, in this case Excel. Topic defines the topic of data exchange between the SAS System and the server. This can be, for example, a full path filename of a document. In this case, the SYSTEM topic enables you to execute commands within Excel. Item specifies the range of conversation between the SAS System and the server. For example, this could include a range of cells of a document specified as a topic. In this case, for SYSTEM topic there is no item. Because DDE triplets are application-specific, correct syntax is often difficult to find. Sometimes you can get help by using the DDE Triplet command in the Options Menu in the SAS AWS menu bar. Otherwise, you should refer to the DDE server application s documentation. In the documentation of the SAS System for Windows [1], there is a more complete discussion about the DDE triplet. However, finding the correct syntax of the DDE triplet can often be laborious. After the filename containing the DDE triplet has been defined, you can issue commands to the application in a data step by using PUT statement. In release 6.12 of the SAS System, when Excel is used as a server, the commands have to be issued by using the macro language of version 4.x of Excel. In this example, first the application is minimised by issuing the command APP.MINIMIZE( ) and after that, the ASCII file is opened to the current sheet by the OPEN( ) command. Part 3: The SAS table has now been exported to the Excel worksheet. To enhance the lay-out, the following code is submitted: /* formatting the table */ data _null_; file command; put [SELECT("R1C1:R5C1")] ; put [STYLE(true,false)] ; put [FORMAT.FONT("Times New Roman")] ; put [SELECT("R6C1:R50C1")] ; put [FORMAT.FONT("Courier New")] ; Again, the macro language of version 4.x of Excel is used. First, 5 first rows and the first column of the sheet are selected (command SELECT). The text in the selected area is then bolded (command STYLE) and the font is changed to Times New Roman (command FORMAT.FONT). After that, the font in rows 6-50 is changed to Courier New. Part 4: The table is now ready. It will be saved as an Excel worksheet. After that, Excel is closed. The following code is submitted:

/* saving as an Excel sheet */ data _null_; file command; put [SAVE.AS("c:\work\table.xls",1,"", FALSE,"",FALSE)] ; /* closing excel */ put [QUIT()] ; run; It is often quite difficult to find all the correct options to the commands. In this example, you would like to save the file as an Excel 6.0 worksheet without Excel prompting for anything. The final Excel table is presented in Table 3. From version 5.x of Excel onward, Visual Basic is used instead of the old Excel macro language as the tool for writing macros in Excel. Unfortunately, Visual Basic is not supported in the DDE link between release 6.12 of the SAS System and Excel. However, Excel Visual Basic macros can be used via DDE by invoking them using the old Excel macro language. Case II: From SAS to Word using WordBasic Macros Another application, that can be used as a server for the SAS System by using DDE is Microsoft Word. WordBasic macros of the current versions of Word are supported in DDE of the release 6.12 of the SAS System. Because the WordBasic code is not too compact, it is often more convenient to record and edit macros in Word and save them. From SAS, these macros can be invoked using DDE. A typical macro designed to format a table first opens the file to Word, formats the lay-out and finally saves the file in Word format. Following is an example on how to invoke a WordBasic macro from the SAS System using DDE. filename command dde winword system'; data _null_; file command; put '[ToolsMacro.Name="formtab",.Run]'; run; It is even possible to convert the ASCII tables to Word table format. An excellent example is presented by Gary Cunningham in [2]. ASCII tables are created by using Proc Report and delimiters are inserted between cells. The tables are exported to Word using DDE. In Word, Convert-Text-to-Table command is utilised to convert the ASCII tables to Word tables. Case III: From SAS to Word using Rich Text Format Rich Text Format (RTF) is a publicly available document format maintained by Microsoft. For example, Word 97 uses RTF as a default document format. Also various other applications have the ability to import RTF files. Peszek & Peszek [3] have published a SAS macro, which converts ASCII output produced by the SAS System to RTF format. The idea is first to insert unformatted text (cells of the table, headers and other related information) to a file. After that, appropriate control words and symbols are inserted to the file. A table produced using this macro can be found from Table 4.

Using the SAS macro by Peszek & Peszek is relatively easy, you need not to be a SAS or a programming specialist. If you would like to expand the macro, you need to be familiar with the RTF language and with SAS macro language. Also other SAS macros using same kind of approach have been published in Internet. You need to be careful when producing files including RTF code. If you open a RTF file with errors in the code to Word, Word will probably crash down. Case IV: From SAS to HTML using SAS macros SAS Institute has produced a set of macros called Web Publishing Tools [4]. These macros convert SAS output or SAS datasets to HTML format. The tables produced by these macros are static and the purpose is only to convert tables to a different output format. The three basic conversions are: SAS dataset to HTML Output of any SAS procedure to HTML Output of Proc Tabulate to HTML. The first and third options (dataset or Proc Tabulate) provide more options regarding lay-out. However, the second option (any output) is discussed here, because of the ease of use: it is often quite difficult to save the output of a SAS procedure to a SAS dataset, and the syntax of Proc Tabulate is very complicated. The following example converts the output of Proc Report to a HTML file: /* output to HTML format */ %out2htm(capture=on, window=output, runmode=b); proc report...; /* saving the HTML file */ %out2htm(capture=off, window=output, runmode=b, openmode=replace, htmlfile=c:\work\table.html); A table produced by this program is presented in Table 5. Case V: From SAS to PDF Adobe Portable Document Format (PDF) is an open standard for electronic document distribution. PDF files can be shared, viewed, navigated, and printed exactly as intended by anyone with a free Adobe Acrobat Reader. The U.S. Food and Drug Administration (FDA) has released guidance on use of electronic documents in pharmaceutical industry [5]. At the moment, PDF is a preferred format type for text and images reviewed by the FDA. According to author s knowledge, there is currently no easy solution available to produce PDF files directly from SAS. However, you can create PDF files using the DDE link between SAS and Excel or Word. One solution would be first to change your current printer in Excel or Word to print to a PDF file and after that, simply send the print command to Excel or Word using DDE. To be able to do this, you need to have the complete Adobe Acrobat program installed. You cannot create PDF files with the free Adobe Acrobat Reader.

What next? The forthcoming releases 7 and 8 of SAS seem to have a lot to offer, regarding output management. Output Delivery System (ODS) will be introduced to almost all SAS procedures, making the customisation of output much more flexible. With ODS, you can select specific components from the output, define output and style templates and format fonts, colors and other visual aspects of your output. There are three main formats for the output: ASCII, SAS data set and HTML. In addition, RTF and Postscript files are included as experimental alternatives. Much emphasis has been put on creating HTML files, including options to create links between different objects. Conclusions The need to produce documents in the final format directly with the SAS System is obvious. The tools currently available in the SAS System are incomplete. Too much programming work is needed to create customised output in the formats presented in this paper (Word, Excel, HTML, PDF). Pros and cons of the methods presented in this paper are summarised in Table 1. The selection of the output format depends on various aspects, but there are two especially important questions: Which is the format of the body document (SAS output will be integrated to the body document)? Should linking / navigation be possible? Concerning the first question, Word is often the tool, which is used for writing the body document. Also, Word is often the final output format for the body document, although, because of the guidance from the FDA [5], PDF is becoming increasingly popular. Thus, Word would be a desirable selection for this purpose. The final documentation of a drug development process consists of a huge number of documents. Management of these documents is much easier, if navigation is possible. For this purpose, HTML and PDF would be ideal formats. At the moment, creation of HTML documents is easier from the SAS System. There are great expectations on the forthcoming releases of the SAS System. The support for creating output directly from the SAS System in the desired formats will be considerably better. The focus of the SAS Institute seems to be in HTML. Also Word documents should be easy to produce, because the option to create RTF output will be added to the SAS System. However, for pharmaceutical industry, better tools to produce PDF documents with the SAS System would still be needed.

Trademark notice: SAS is a registered trademark of SAS Institute Inc. Other brand and product names are registered trademarks or trademarks of their respective companies. References: [1] SAS Institute Inc. (1996). SAS Companion for the Microsoft Windows Environment, Version 6, Second Edition. Cary, NC: SAS Institute Inc. [2] Cunningham G. (1998). An Easy-to-Use SAS Macro for Use with Microsoft Windows That Converts Existing Text Tables to Microsoft Word Tables. Proceedings of PharmaSUG 98 Conference. San Fransisco, CA. [3] Peszek I. & Peszek R. (1998). Automate the Creation and Manipulation of Word Processor Ready SAS Output. http://www.sas.com/service/doc/periodicals/obs/obswww13/index.html. SAS Institute Inc. [4] SAS Institute Staffs. Web Publishing Tools. http://www.sas.com/rnd/web/publish.html. SAS Institute Inc, 1998. [5] FDA (1999). Guidance for Industry: Providing Regulatory Submissions in Electronic Format - General Considerations. U.S. Food and Drug Administration, Rockville, MD. Author: Mika Leinonen Orion Pharma, Department of Biostatistics and Data Management Orionintie 1, P.O. Box 65 FIN-02101 Espoo, Finland Phone: +358-9-4293072 E-mail: Mika.Leinonen@Orion.Fi

Case Pros Cons Case I: From SAS to Excel using Dynamic Data Exchange SAS System release 6.12 and Excel 97 are compatible with regard to DDE The DDE link seems to be very stable, crashes of the system are rare Excel is not very commonly used as an output format There is no support for the current Excel macro language (Visual Basic) Customisation of the table lay-out can be laborious Excel does a lot of automatic formatting, which can cause trouble Case II: From SAS to Word using WordBasic Macros Word is a commonly used output format RTF format used by Word will be better supported by SAS in the future The DDE link between SAS and Word does not seem to be stable Customisation of the table lay-out can be laborious Case III: From SAS to Word using Rich Text Format Word is a commonly used output format You can relatively easily produce customised layouts Various applications can import RTF files Errors in RTF code can crash applications Writing SAS macros to produce RTF requires good knowledge of both RTF code and SAS macro language Case IV: From SAS to HTML using SAS macros HTML files can be read with various applications in different platforms Excellent and easy-touse linking capabilities In releases 7 and 8 of SAS, very much emphasis is put on HTML HTML is not yet commonly used as a general output format Case V: From SAS to PDF PDF files can be read with various applications in different platforms Excellent linking capabilities Creation of PDF documents is difficult with SAS No direct support for PDF in SAS has been promised (except for Postscript files) Table 1 Summary of Pros and Cons of the methods

STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Device Statistic mm ------------------------------- Easyhaler Mean 80.2 Median 84.0 Min 36.0 Max 100.0 SD 17.5 N 69.0 Turbuhaler Mean 69.5 Median 74.0 Min 3.0 Max 100.0 SD 23.5 N 69.0 B. Wilcoxon signed rank test for the paired differences between the devices Test Comparison statistic p-value -------------------------------------------------- Easyhaler - Turbuhaler 465.500 0.0010 STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Device Statistic mm Easyhaler Mean 80,2 Median 84 Min 36 Max 100 SD 17,5 N 69 Turbuhaler Mean 69,5 Median 74 Min 3 Max 100 SD 23,5 N 69 B. Wilcoxon signed rank test for the paired differences between the devices Comparison Test statistic p-value Easyhaler - Turbuhaler 465.500 0.0010 Table 2 Original SAS ASCII output Table 3 From SAS to Excel using DDE

STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Treatment Statistic mm Easyhaler Mean 80.2 Median 84.0 Min 36.0 Max 100.0 SD 17.5 N 69.0 Turbuhaler Mean 69.5 Median 74.0 Min 3.0 Max 100.0 SD 23.5 N 69.0 B. Wilcoxon signed rank test for the paired differences between the devices Comparison Test statistic p-value Easyhaler - Turbuhaler 465.500 0.0010 STUDY 0142022 Table 11.2 Assesment of the device: Visual analogic scale (VAS) A. Descriptive statistics Device Statistic mm ------------------------------- Easyhaler Mean 80.2 Median 84.0 Min 36.0 Max 100.0 SD 17.5 N 69.0 Turbuhaler Mean 69.5 Median 74.0 Min 3.0 Max 100.0 SD 23.5 N 69.0 B. Wilcoxon signed rank test for the paired differences between the devices Test Comparison statistic p-value -------------------------------------------------- Easyhaler - Turbuhaler 465.500 0.0010 Table 4 From SAS to Word using RTF Table 5 From SAS to HTML using SAS macros