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EZ-Entry: A clinical data management system
Computers in Biology and Medicine 38 (2008) 1042 – 1044 www.intl.elsevierhealth.com/journals/cobm
EZ-Entry: A clinical data management system Qing-Bin Gao a,1 , Yu Kong a,b,1 , Zheng Fu a , Jian Lu a , Cheng Wu a , Zhi-Chao Jin a , Jia He a,∗ a Department of Health Statistics, Second Military Medical University, Shanghai 200433, China b Department of Computer Science, Second Military Medical University, Shanghai 200433, China
Received 19 July 2007; accepted 23 July 2008
Abstract In this paper, a new data management system named EZ-Entry is introduced. Five major functions are enclosed in this system: (1) user authentication; (2) database construction; (3) double data entry with instant alignment; (4) revision tracking; (5) query management. The practical application performed on two clinical trials indicates that EZ-Entry meets the requirements of clinical data management with high efficiency and security. This software is freely available on request from the authors for academic purposes. 䉷 2008 Elsevier Ltd. All rights reserved. Keywords: Clinical trial; Clinical data management system; Double data entry; Revision tracking; Query form
1. Background Management of data in clinical trials is a valuable work for anyone involved in any type of clinical trial, from large multicenter trials to small single-investigator studies [1–3]. Nowadays, most clinical trial data are recorded on paper, such as the case report forms (CRFs). These materials need to be stored in digital formats and normalized for further analysis. Therefore, it is essential for us to develop an effective clinical data management system (CDMS) to address these problems [4,5]. According to the good clinical practices (GCP) [6–8], a good CDMS usually has a user-friendly interface, through which users can create electronic-CRFs (e-CRFs) conveniently on the basis of paper-CRFs. The system must have the ability to assure the accuracy and integrity of the data. The present operator would receive a system message if a mistake occurred in the process of data entry. Moreover, to improve the speed and quality of data entry, the system may have the function of generating query form timely. Another function that a CDMS can perform is the guarantee of system security; only authorized user can log in to the system and revise the data set in the database. When the
revision takes effect, the user, original data, revision time and revision reason should be recorded in a log file simultaneously. According to the log file, users can easily check out who has made the revision, what the revision is and when it takes effect. As a free software for clinical data management, EpiData is now popular for its convenience and good power in data entry and data management [9,10]. EpiData is distributed by the EpiData Association Denmark and freely available at http://www.epidata.dk/. The main functions of EpiData include: (1) setting up e-CRFs by simple syntax; (2) data entry with checkout theory; (3) data check after double input; (4) exporting data in multiple formats. However, EpiData has a very low system security. Everyone can log in to the database and make revisions to the data set, and these revisions cannot be recorded. On the other hand, EpiData cannot generate the query form in time. Query form is a good way to improve the data quality. According to the considerations mentioned above, we extend the functions of EpiData and develop a new software named EZ-Entry for clinical trial data management, which improves the security and efficiency of data management in comparison with EpiData. 2. Systems and functions
∗ Corresponding author. Tel.:/fax: +86 21 25070418.
E-mail address: [email protected] (J. He). 1 Contributed equally.
0010-4825/$ - see front matter 䉷 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.compbiomed.2008.07.008
EZ-Entry is written in Microsoft Visual Basic 6.0 and uses Microsoft SQL Server 7.0 to manage the data set. Fig. 1
Q. Gao et al. / Computers in Biology and Medicine 38 (2008) 1042 – 1044
User Interface
Program
1043
Database
Fig. 1. Schematic architecture of EZ-Entry.
Fig. 4. Revision record.
Add a user account
Delete a user account
User management
data entry, revision tracking, query management, data import and export. Here we only focus on two major functions different from Epidata.
Modify user account
2.1. Security protection Administrator Assign key field
Data scanning
Data management
Data locking
Generating Query form
Data output
Fig. 2. Administrator module.
e-CRF design
e-CRF modification e-CRF management
Security is an important issue for system and database maintenance. In the present system, system security depends on the following two aspects: (1) User authentication: Only authorized user is granted the privilege of accessing the system and database. When a user attempts to get into the database, the system will pop-up a window and ask him to supply the user name and password. If the user name or password entered is incorrect three times the system will halt automatically. (2) Revision tracking: When an authorized user enters a new entry or makes revisions to the original data, the system can record these operations automatically and generate a log file. The contents in the log file consist of the no. of e-CRFs, field name, original field value, revised field value, user name and operating time. Fig. 4 gives an example of such log files, in which ‘No’ is the key field and its field value is ‘25’. In this case two fields were revised: field ‘END’ was changed from ‘1’ to ‘0’ and field ‘KTIME’ was changed from ‘202005’ to ‘27/07/2005’. The two revisions were done by user ‘11’ and the operations were recorded at ‘2006–9–8, 11:23:58’.
Set Value range Print e-CRF e-CRF output
User
Generate e-CRF file
First entry
Data management
Second entry
Query form generating
Fig. 3. User module.
illustrates the schematic architecture of this system. This program consists of two modules, i.e. the administrator module (Fig. 2) and the user module (Fig. 3). Each module contains multiple sub-modules that implement a specific function encapsulated in the CDMS, such as the database creation, double
2.2. Quality control To reduce the possibility of errors due to human entry, EZEntry employs different means to verify the entry and improve its quality. (1) Field value check: During the phase of data entry, data can be validated to check for logical errors. This system uses the range of field value to check for such errors. If field value entered by a user is not within the range for a study, the system will pop-up a system message to inform the user to determine if there is an error in the data. (2) Query form: When the field value on the paper-CRFs cannot be recognized by the system, such as the value is out of the normal range or illogical, the user can communicate with the investigator by a query form. The system can generate the query form automatically if necessary, which is recorded on a Microsoft Word file and is convenient for e-mail and printing. (3) Data entry alignment: Independent double data entry with full discrepancy management is one of the most reliable methods for data entry. In this way users can minimize the data
1044
Q. Gao et al. / Computers in Biology and Medicine 38 (2008) 1042 – 1044
errors. Two persons enter the same data independently, then a third person runs a program to compare the two data sets. All discrepancies reported by the comparison program are corrected based on the CRF data. The comparison process is continued until all data errors are resolved. However, this method is time-consuming. Based on the fact that the probability two people make the same mistakes in the process of data entry is very small, EZ-Entry suggests a new method called double data entry with simultaneous alignment to improve the speed of data entry. When the second person enters the data, the system compares the new entry value with the original value in database. If any discrepancy is detected, the system will inform the user to check the errors. 3. Conclusions In this paper, a new CDMS named EZ-Entry is introduced, which use Microsoft Visual Basic 6.0 as the programming language and SQL server 7.0 as the database and works on Microsoft Windows platform. EZ-Entry has a user-friendly interface and extends EpiData’s functions by incorporating security management, double data entry with instant alignment, revision tracking, query management and data import and export. This system has been applied in two clinical trials and the results demonstrate its effectiveness. It is anticipated that EZ-Entry will be a powerful tool for the effective and flexible management of clinical trial data. This software is freely available on request from the authors for academic purposes. Conflict of interest statement None declared. Acknowledgements This work was partly supported by the Foundation of WHO (APW A50883), the National Natural Science Foundation of China (Nos. 30671821, 30471502) and the Natural Science Foundation of Shanghai (No. 04ZR14049). The authors are grateful to the anonymous reviewers for their helpful comments on this work. References [1] E. McFadden, Management of Data in Clinical Trials, Wiley, New York, 1997. [2] Good Clinical Data Management Practices, Society for Clinical Data Management, Inc., 2005.
[3] P.M. North, Ensuring good statistical practice in clinical research: guidelines for standard operating procedure (an update), Drug Inf. J. 32 (1998) 665–682. [4] R.A. Greenes, A.N. Rappalardo, C.W. Marble, G.O. Barnett, Design and implementation of a clinical data management system, Comput. Biomed. Res. 2 (1969) 469–485. [5] B.C. Tai, J. Seldrup, A review of software for data management, design and analysis of clinical trials, Ann. Acad. Med. Singapore 29 (2000) 576–581. [6] R.K. Rondel, S.A. Varley, C.F. Webb, Clinical Data Management, second ed., Wiley, New York, 2000. [7] Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products, WHO Technical Report Series, No. 850, Annex 3, 1995. [8] Handbook for Good Clinical Research Practice (GCP): Guidance for Implementation, World Health Organization, 2005. [9] J.M. Lauritsen, M. Bruus, EpiTour—An Introduction to EpiData Entry, Epidata Association, 2005. [10] S. Bennett, M. Myatt, D. Jolley, A. Radolowicz, Data Management for Surveys and Trials: A Practical Primer Using Epidata, EpiData Association, 2001. Qing-Bin Gao was born in Gansu, China, in 1977. He received a Bachelor degree from the National University of Defense Technology, China, in 1999 and a PhD, from the same University, in 2006. Since 2007, he has been with the Second Military Medical University, China, where he is a lecturer in health statistics. His research interests focus on bioinformatics, health statistics and biomedical engineering. Yu Kong was born in Jiangsu, China, in 1975. She received a Bachelor degree from the Nanjing Normal University, China, in 1998 and a MM, from the same University, in 2007. Now she is a lecturer in computer science. Her research interests focus on computers in biomedical engineering. Zheng Fu was born in Zhejiang, China, in 1981. He received a Bachelor degree from the Second Military Medical University, China, in 2004. His research interests focus on health statistics and biomedical engineering. Jian Lu was born in Shanghai, China, in 1968. He received a Bachelor degree from the Second Military Medical University, China, in 1993 and a MM, from the same University, in 2006. Now he is associate professor in health statistics. His research interests focus on biomedical engineering and health statistics. Cheng Wu was born in Ningxia, China, in 1979. She received a Bachelor degree from the East China Normal University, China, in 2001 and a MM, from the Second Military Medical University, in 2004. Now she is a lecturer in health statistics. Her research interests focus on bioinformatics, health statistics and biomedical engineering. Zhi-Chao Jin was born in Zhejiang, China, in 1982. He received a Bachelor degree from the Second Military Medical University, China, in 2008. His research interests focus on health statistics and biomedical engineering. Jia He was born in Jilin, China, in 1963. She received a Bachelor degree from the Second Military Medical University, China, in 1986 and a MD, from the Shanghai Second Medical University, in 1999. Now she is professor in health statistics. Her research interests focus on bioinformatics, health statistics and biomedical engineering.
EZ-Entry: A clinical data management system Qing-Bin Gao a,1 , Yu Kong a,b,1 , Zheng Fu a , Jian Lu a , Cheng Wu a , Zhi-Chao Jin a , Jia He a,∗ a Department of Health Statistics, Second Military Medical University, Shanghai 200433, China b Department of Computer Science, Second Military Medical University, Shanghai 200433, China
Received 19 July 2007; accepted 23 July 2008
Abstract In this paper, a new data management system named EZ-Entry is introduced. Five major functions are enclosed in this system: (1) user authentication; (2) database construction; (3) double data entry with instant alignment; (4) revision tracking; (5) query management. The practical application performed on two clinical trials indicates that EZ-Entry meets the requirements of clinical data management with high efficiency and security. This software is freely available on request from the authors for academic purposes. 䉷 2008 Elsevier Ltd. All rights reserved. Keywords: Clinical trial; Clinical data management system; Double data entry; Revision tracking; Query form
1. Background Management of data in clinical trials is a valuable work for anyone involved in any type of clinical trial, from large multicenter trials to small single-investigator studies [1–3]. Nowadays, most clinical trial data are recorded on paper, such as the case report forms (CRFs). These materials need to be stored in digital formats and normalized for further analysis. Therefore, it is essential for us to develop an effective clinical data management system (CDMS) to address these problems [4,5]. According to the good clinical practices (GCP) [6–8], a good CDMS usually has a user-friendly interface, through which users can create electronic-CRFs (e-CRFs) conveniently on the basis of paper-CRFs. The system must have the ability to assure the accuracy and integrity of the data. The present operator would receive a system message if a mistake occurred in the process of data entry. Moreover, to improve the speed and quality of data entry, the system may have the function of generating query form timely. Another function that a CDMS can perform is the guarantee of system security; only authorized user can log in to the system and revise the data set in the database. When the
revision takes effect, the user, original data, revision time and revision reason should be recorded in a log file simultaneously. According to the log file, users can easily check out who has made the revision, what the revision is and when it takes effect. As a free software for clinical data management, EpiData is now popular for its convenience and good power in data entry and data management [9,10]. EpiData is distributed by the EpiData Association Denmark and freely available at http://www.epidata.dk/. The main functions of EpiData include: (1) setting up e-CRFs by simple syntax; (2) data entry with checkout theory; (3) data check after double input; (4) exporting data in multiple formats. However, EpiData has a very low system security. Everyone can log in to the database and make revisions to the data set, and these revisions cannot be recorded. On the other hand, EpiData cannot generate the query form in time. Query form is a good way to improve the data quality. According to the considerations mentioned above, we extend the functions of EpiData and develop a new software named EZ-Entry for clinical trial data management, which improves the security and efficiency of data management in comparison with EpiData. 2. Systems and functions
∗ Corresponding author. Tel.:/fax: +86 21 25070418.
E-mail address: [email protected] (J. He). 1 Contributed equally.
0010-4825/$ - see front matter 䉷 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.compbiomed.2008.07.008
EZ-Entry is written in Microsoft Visual Basic 6.0 and uses Microsoft SQL Server 7.0 to manage the data set. Fig. 1
Q. Gao et al. / Computers in Biology and Medicine 38 (2008) 1042 – 1044
User Interface
Program
1043
Database
Fig. 1. Schematic architecture of EZ-Entry.
Fig. 4. Revision record.
Add a user account
Delete a user account
User management
data entry, revision tracking, query management, data import and export. Here we only focus on two major functions different from Epidata.
Modify user account
2.1. Security protection Administrator Assign key field
Data scanning
Data management
Data locking
Generating Query form
Data output
Fig. 2. Administrator module.
e-CRF design
e-CRF modification e-CRF management
Security is an important issue for system and database maintenance. In the present system, system security depends on the following two aspects: (1) User authentication: Only authorized user is granted the privilege of accessing the system and database. When a user attempts to get into the database, the system will pop-up a window and ask him to supply the user name and password. If the user name or password entered is incorrect three times the system will halt automatically. (2) Revision tracking: When an authorized user enters a new entry or makes revisions to the original data, the system can record these operations automatically and generate a log file. The contents in the log file consist of the no. of e-CRFs, field name, original field value, revised field value, user name and operating time. Fig. 4 gives an example of such log files, in which ‘No’ is the key field and its field value is ‘25’. In this case two fields were revised: field ‘END’ was changed from ‘1’ to ‘0’ and field ‘KTIME’ was changed from ‘202005’ to ‘27/07/2005’. The two revisions were done by user ‘11’ and the operations were recorded at ‘2006–9–8, 11:23:58’.
Set Value range Print e-CRF e-CRF output
User
Generate e-CRF file
First entry
Data management
Second entry
Query form generating
Fig. 3. User module.
illustrates the schematic architecture of this system. This program consists of two modules, i.e. the administrator module (Fig. 2) and the user module (Fig. 3). Each module contains multiple sub-modules that implement a specific function encapsulated in the CDMS, such as the database creation, double
2.2. Quality control To reduce the possibility of errors due to human entry, EZEntry employs different means to verify the entry and improve its quality. (1) Field value check: During the phase of data entry, data can be validated to check for logical errors. This system uses the range of field value to check for such errors. If field value entered by a user is not within the range for a study, the system will pop-up a system message to inform the user to determine if there is an error in the data. (2) Query form: When the field value on the paper-CRFs cannot be recognized by the system, such as the value is out of the normal range or illogical, the user can communicate with the investigator by a query form. The system can generate the query form automatically if necessary, which is recorded on a Microsoft Word file and is convenient for e-mail and printing. (3) Data entry alignment: Independent double data entry with full discrepancy management is one of the most reliable methods for data entry. In this way users can minimize the data
1044
Q. Gao et al. / Computers in Biology and Medicine 38 (2008) 1042 – 1044
errors. Two persons enter the same data independently, then a third person runs a program to compare the two data sets. All discrepancies reported by the comparison program are corrected based on the CRF data. The comparison process is continued until all data errors are resolved. However, this method is time-consuming. Based on the fact that the probability two people make the same mistakes in the process of data entry is very small, EZ-Entry suggests a new method called double data entry with simultaneous alignment to improve the speed of data entry. When the second person enters the data, the system compares the new entry value with the original value in database. If any discrepancy is detected, the system will inform the user to check the errors. 3. Conclusions In this paper, a new CDMS named EZ-Entry is introduced, which use Microsoft Visual Basic 6.0 as the programming language and SQL server 7.0 as the database and works on Microsoft Windows platform. EZ-Entry has a user-friendly interface and extends EpiData’s functions by incorporating security management, double data entry with instant alignment, revision tracking, query management and data import and export. This system has been applied in two clinical trials and the results demonstrate its effectiveness. It is anticipated that EZ-Entry will be a powerful tool for the effective and flexible management of clinical trial data. This software is freely available on request from the authors for academic purposes. Conflict of interest statement None declared. Acknowledgements This work was partly supported by the Foundation of WHO (APW A50883), the National Natural Science Foundation of China (Nos. 30671821, 30471502) and the Natural Science Foundation of Shanghai (No. 04ZR14049). The authors are grateful to the anonymous reviewers for their helpful comments on this work. References [1] E. McFadden, Management of Data in Clinical Trials, Wiley, New York, 1997. [2] Good Clinical Data Management Practices, Society for Clinical Data Management, Inc., 2005.
[3] P.M. North, Ensuring good statistical practice in clinical research: guidelines for standard operating procedure (an update), Drug Inf. J. 32 (1998) 665–682. [4] R.A. Greenes, A.N. Rappalardo, C.W. Marble, G.O. Barnett, Design and implementation of a clinical data management system, Comput. Biomed. Res. 2 (1969) 469–485. [5] B.C. Tai, J. Seldrup, A review of software for data management, design and analysis of clinical trials, Ann. Acad. Med. Singapore 29 (2000) 576–581. [6] R.K. Rondel, S.A. Varley, C.F. Webb, Clinical Data Management, second ed., Wiley, New York, 2000. [7] Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products, WHO Technical Report Series, No. 850, Annex 3, 1995. [8] Handbook for Good Clinical Research Practice (GCP): Guidance for Implementation, World Health Organization, 2005. [9] J.M. Lauritsen, M. Bruus, EpiTour—An Introduction to EpiData Entry, Epidata Association, 2005. [10] S. Bennett, M. Myatt, D. Jolley, A. Radolowicz, Data Management for Surveys and Trials: A Practical Primer Using Epidata, EpiData Association, 2001. Qing-Bin Gao was born in Gansu, China, in 1977. He received a Bachelor degree from the National University of Defense Technology, China, in 1999 and a PhD, from the same University, in 2006. Since 2007, he has been with the Second Military Medical University, China, where he is a lecturer in health statistics. His research interests focus on bioinformatics, health statistics and biomedical engineering. Yu Kong was born in Jiangsu, China, in 1975. She received a Bachelor degree from the Nanjing Normal University, China, in 1998 and a MM, from the same University, in 2007. Now she is a lecturer in computer science. Her research interests focus on computers in biomedical engineering. Zheng Fu was born in Zhejiang, China, in 1981. He received a Bachelor degree from the Second Military Medical University, China, in 2004. His research interests focus on health statistics and biomedical engineering. Jian Lu was born in Shanghai, China, in 1968. He received a Bachelor degree from the Second Military Medical University, China, in 1993 and a MM, from the same University, in 2006. Now he is associate professor in health statistics. His research interests focus on biomedical engineering and health statistics. Cheng Wu was born in Ningxia, China, in 1979. She received a Bachelor degree from the East China Normal University, China, in 2001 and a MM, from the Second Military Medical University, in 2004. Now she is a lecturer in health statistics. Her research interests focus on bioinformatics, health statistics and biomedical engineering. Zhi-Chao Jin was born in Zhejiang, China, in 1982. He received a Bachelor degree from the Second Military Medical University, China, in 2008. His research interests focus on health statistics and biomedical engineering. Jia He was born in Jilin, China, in 1963. She received a Bachelor degree from the Second Military Medical University, China, in 1986 and a MD, from the Shanghai Second Medical University, in 1999. Now she is professor in health statistics. Her research interests focus on bioinformatics, health statistics and biomedical engineering.