MPH07 Computers in clinical development.pptx

My topic is computers in clinical development. There are various ways pf collecting data like pure paper based system, electronic based system and communication.

1. Computers in Clinical Development NAME : BHUMIN N. JAIN M. PHARM FIRST YEAR DEPARTMENT OF PHARMACEUTICS GUIDED BY – DR. H. S. MAHAJAN DR. N. B. KULKARNI ROLL NO- MPH07 1

2. CONTENTS : Introduction Data Collection and Data Management Communication Pure Paper-Based System Electronic- Based System Hybrid System Processes Before Data Collection Processes During Data Collection Processes after Data Collection Regulation of Computer System Conclusion References 2

3. INTRODUCTION : Clinical development- Also called Drug Development, is a term used to define entire process of bringing a new drug or device to market. It includes drug discovery, pre-clinical trials and clinical trials. Clinical Research- In order to analyze the efficacy of treatment, after administration of new treatment to patients and observing responses over time. Clinical Trials- It involves evaluation of effectiveness and safety of medications or medical devices by monitoring their effects on large groups of people. Clinical Data Collection- From trial’s participating sites, it consists of process of collecting reliable clinical, control and administrative data. 3

4. Clinical Data Management- It involves a set of process that must be executed successfully to turn out reliable clinical, control and administrative data to a central location such as a coordination center, a data center and a resource center. In the literature,these processes merged together under the name clinical data management or clinical trial data management. These aspects are accomplished and coordinated through a set of communication tools, a central ingredient of any clinical trial, used to develop a data collection and management system. With ongoing and rapid advancement in computer hardware and software technology,clinical trial data collection have become widely attainable, much easier, less time consuming,more reliable,more secure, and more scalable than ever. 4

5. 5 Figure illustrates the integration of communication aspect before data collection begins, during data collection, during data management, and after data collection.

6. Data Collection Data collection in clinical trials consists of the processes of collecting reliable clinical, control, and administrative data from trial’s participating sites with agreed-upon methods and procedures to record the collected data and send them to a central location. Data Management The official definition given by Data Management Asssociation (DAMA) is “The development and execution of architectures, policies, practices and procedures that properly manage the full data lifecycle needs of an enterprise”. A layperson’s definition of data management is, “The process of accumulating collected data into a master database in a central location while ensuring their security, validity, and completeness by generating quality assurance reports to monitor the progress of the trial”. 6

7. Communication Communication is the process of sending information from one location to another or from one person to another by means that enable the sender to send the information to the intended recipient and the intended recipient to receive, retrieve and interpret the information. Planning, conducting, and ultimately reporting the results of a clinical trial require that trial personnel be connected throughout the duration of the trial to ensure successful completion. Examples of types of communications include Direct contact meetings, Mail carrier, Telephone, Fax, E-mail, Web sites, File transfer protocol (FTP), Videoconferencing. 7

8. i . Direct Contact Meetings- 8 Once a trial is approved, the principal investigator (PI) meets with appropriate coordinating center staffs, they include- the biostatistician, computer programmer, and project manager, to review and finalize the drafted data collection forms and their data points before they are sent to form designer for production. The programmer at the coordinating center meets with biostatistician to get answers to questions regarding the trial’s protocol and to set up a development plan, assign tasks, and resolve problems. The protocol, the Manual of Operations (MOP),drug-dispensing procedures,and any other important issues are presented, using various presentation packages such as MS Powerpoint through a projection device.

9. ii. Telephone- The telephone is still one of primary means of communication for clinical trial personnel for transmission of digital data from one location to another. Various software packages have been developed for this purpose. Using a voice modem connected to telephone, a user on a local computer can connect to another remote computer that has a modem connected to a telephone and download or upload data files. The telephone is also utilized in development of interactive voice response (IVR) systems that support touch-tone or speech recognition responses. IVR systems have been developed for subject randomization, drug assignment, and survey data collection. 9

10. iii. Fax - With fax technology , documents can be easily transmitted to trial participants either from hard copies with a fax machine or as an electronic file directly from a computer. Fax technology is also used to fax data collection forms as an image to a computer equipped with OMR or OCR software that can receive the image, interpret recorded data, flag bad entries and add data to a centralized database. 10

11. iv. E-Mail - It is used as stand-alone software or integrated within a data collection and management system. With e-mail, text messages and attachment files can be sent to the trial’s personnel instantaneously. When integrated in a data collection and management system, it can be programmed to send messages automatically. E-mail as a communication tools has a number of drawbacks, it is vulnerable to being intercepted, Intended recipients may not access their e-mail on a timely basis, there is probability of sending files inadvertently to wrong recipient. 11

12. v. Web Sites - The widespread acceptance and use of internet as a means for communication in clinical trials has revolutionized way clinical trials information is disseminated among various individuals. A trial’s website provides trial personnel an easy, secure, real-time access to information that includes operational issues, clinical procedures, data collection, phone directories, contact lists, calenders, reference documents, policies, protocol, MOPs, meeting agendas, and meeting minutes. 12 vi. File Transfer Protocol – File transfer protocol (FTP) technology is a data communication tool that allows sending, accessing, and sharing files quickly and easily through secure environment. The user logs onto FTP site with valid account name and a valid password.

13. vii. Videoconferencing- In a videoconference, two or more people in different locations can see and hear each other at the same time, sometimes even sharing computer applications for collaboration. The visual communication provides a feeling of direct contact that enhances understanding and helps participants feel connected to each other. 13

14. Pure-Paper Based System - They are still being used by many CROs either because of financial constraints or because they deal with small clinical trials that do not justify that investment. Suitability and Hardware/Software Requirements: Their advantages are that no computer hardware or software is needed because data are recorded manually on paper forms that are transferred to centralized location in batches. A major drawback is that participating sites do not have real-time access to their data. However, both hardware and software are needed at centralized location for data management system. The most commonly used platforms include Open VMS, Unix, or PC, and one of most widely used software packages is SAS. 14

15. Design and Implementation – Pure paper-based data collection systems use paper forms that can be designed with any graphical or word processing software such as Adobe PageMaker, Microsoft Word, or MS PowerPoint. Forms consisting of records of 80 columns long are standard, but they can be longer. A header is repeated for every record that contains identifying information. These identifiers must contain sufficient information to uniquely identify each line or record of data entered into database. Each collectable data element exists in a specific record of specific form and can be further identified by column or space number within the record. 15

16. Managing Data 16 Pure paper-based data collection require large data editing overhead. Personnel at the central location must perform visual inspection of forms and compare them and visually inspect for completion and legibility, log the received forms, and send received forms that pass visual inspection to data entry staff. The data entry staff enters the data into electronic text files with Double key data entry software. Then these files are released to trial data management programmer. The trial programmer develops customized programs to read the text files, perform data checking for accuracy and consistency, rectify data errors, and add edited data to master database.

17. Electronic-Based Systems- The hallmark of electronic-based data collection and management system is elimination of paper data collection forms. Instead of recording data on paper forms, data collectors enter data directly into a computer system. The advantages of such systems over traditional pure paper-based data collection system include their ability to, Provides data cleaner faster, thus significanty reducing query rates and eliminating double data entry. Provide up-to-date interim progress reports in a timely fashion, Reduces the time. 17 Centralized Systems- Centralized systems reside at a central location and are accessed through a local area network(LAN), a wide area network(WAN), or a virtual private network(VPN). The user logs into system with valid user id and password. This system enables direct entry of data into a centralized database.

18. Distributed Systems- 18 In distributed systems, each participating site must be equipped with a desktop or a laptop computer loaded with distributed data collection system software to collect and enter data locally. In addition, each site is provided with necessary storage devices such as tapes, zip diskettes, and cds and printers. Collected data are transferred periodically to central location as files saved on storage devices, via phone modems, by FTP, or through wireless communications, where they are managed by a centralized data management system. Various software packages are available to transfer data from participating sites to central location. One example of this software is PCAnywhere32 from semantic, which allows for downloading and uploading data from participating sites in addition to remote control sessions.

19. Wireless Systems- 19 The use of wireless computer systems has gain popularity in data collection for clinical trials. They have been used as a substitute for normal paper-based patient diaries to increase data quality and shorten time needed to close database. In comparison to laptops and desktops, hand-held computers have much smaller screens. They have limited memory space and computational capability. For these reasons they cannot be used to enter large amounts of text data or perform sophisticated edit checks. They are prone to loss or damage, but they have an advantage over laptops and desktops in their ease of mobility. Pdf-Based System- This method of data collection uses Portable Document Format(PDFs) forms. This approach is flexible and inexpensive. A number of commercial software packages such as adobe acrobat, latext , and Microsoft word and free software such as python and R are used to create PDF forms.

20. Hybrid Systems- Hybrid system are those systems that employ various strategies to collect data. In such systems, data may be collected on paper forms as patient self administered questionnaries, while additional data may be download from centralized databases where data coordinators enters them directly into centralized data system. Paper data collection with centralized batch data entry- In this approach data are collected on paper forms. Completed forms are mailed to coordinating centers, where they go through visual inspections. Forms that pass visual inspection are sent to data entry department, where they are entered with high-speed double-key data entry. It is not time consuming because data are entered with high-speed double-key data entry. Major advantage is that only one person is needed to run the system. 20

21. Processes Before Data Collection- Choosing a data collection and management system- Depending on size of CRO and nature of trial, the system may be acquired in one of the following ways:- Developed in-house by organization’s staff with off-the-shelf commercial software, Outsourced to outside contractors With open source/free software (OSS/FS), and Purchased from e-clinical proprietary vendors. 21

22. Hardware and Software Selection- The type of system chosen determines the types of hardware and software needed. It also determines the processes for aquiring necessary hardware and software. The hardware selection may include desktops, laptops, printers, scanners, fax machines, and storage devices. The software selection includes system development software, the database management software, the data communication software, the data conversion software, specialized proprietary software, servers, and firewalls. 22

23. System Validation- Before a data collection and management system is implemented, it has to be validated. For a newly developed application, the validation processes consist of various layers of testing. The first layer is testing components of system as it is being developed. This validation ensures that programming segments of system are error free and work as expected. The next layer of validation takes place after the system is completed and before it is put into production. 23

24. System Evaluation- Evaluation ensures that system is working as intended, and that end users understand it and are comfortable with it. It also provides feedback from end users to correct any glitches and enhance system. Data Quality Assurance- From the moment data collection begins to closing of trial, monitoring the progress of trial is essential for maintaining its integrity and successful completion. Various computer software and programs have been developed for that purpose, to enable the trial staff to be aware of every single development and indicate how to respond to it throughout the trial. Handling Unexpected Events- Unexpected events may occur that need to be taken care of during clinical trial. Some of these events may require actions to be taken with regard to data collection and management system. 24 Processes During Data Collection-

25. Processes after Data Collection- Data Lockout- Relatively little has been written about practicalities of closeout of large, multicenter clinical trials, but this aspect of trial conduct and design is important and requires careful planning to be accomplished in a timely and orderly fashion. Data Retention- Data collected at each participating site must be stored in a read-only format at that site for future reference.The institutional review board (IRB) at each participating site requires that the site retain its local database after trial closeout. Data retention can be achieved in various ways.However the method should ensure that participating sites are not be able to modify retained data; data are presented in a way that allows sites to easily locate any data form for any subject at any trial visit and the site PI is solely responsible for retained data. 25

26. Data Archiving- After the data collection phase of clinical trial is completed and its collected data are analyzed, collected data are archived centrally, usually at coordinating center, for future reference. In paper-based data collection system, the physical paper forms may need to be archived for a specified period of time. Scanning technology allows for storing paper forms as images. The computerized database is archived. Data Sharing- Computers facilitate data sharing among researchers. The internet provides, an effective method for designing and implementing data repositories of completed clinical trials. 26

27. Regulation of Computer System- The Federal Drug Administration describes Biopharmaceutical industries as “Self regulated” retaining for itself the responsibility of assuring and check on that self regulatory process. 21 CFR Part 11- 21 CFR Chapter 11 is a standard that deals with requirement for use of electronic signatures and archives. 21 CFR Part 11- Regulatory Requirements- The procedures and controls of system should be able to generate accurate and complete copies of records in both human readable and electronic form which is suitable for inspection, review and copying by regulatory agency. The software should have procedures which limit access to authorized personnel only. Identification code should be unique for each user, should be periodically checked,recalled,revised or changed. 27

28. Conclusion- Clinical trial processes involves set of processes which is expensive and time consuming. The development of computers and reliable data collection in clinical trials helps to reduce time and also supports to use less number of participants. New developments in computer hardware and software technology have made clinical trial data collection and management timely and effective and also with help of computers in clinical trials can be done quickly. Regulation of computer systems in part 11 serves as a guideline for industry control of all computer systems and as a requirement for high-risk systems directly affecting human health and safety. 28

29. References- Wang B. Computer applications in pharmaceutical research and development. John Wiley & Sons; 2006 Jul 11. Doolan DF, Bates DW, James BC. The use of computers for clinical care: a case series of advanced US sites. Journal of the American Medical Informatics Association. 2003 Jan 1;10(1):94-107. Balakin KV. Pharmaceutical data mining: approaches and applications for drug discovery. John Wiley & Sons; 2009 Nov 19. Lane SJ, Heddle NM, Arnold E, Walker I. A review of randomized controlled trials comparing the effectiveness of hand held computers with paper methods for data collection. BMC medical informatics and decision making. 2006 Dec;6(1):1-0. Abdellatif M. Clinical Data Collection and Management. Computer Applications in Pharmaceutical Research and Development. 2006 Jul 14:591-632. 29

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