Databases trial data collection

In 1968 an international collaboration to identify rare adverse events not detected in clinical trials was set up under the auspices of the WHO in Uppsala, Sweden. The Uppsala Monitoring Centre maintains an international database with data collected from 58 official member countries (those with a formally recognised national ADR monitoring centre) and six... 

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 (Koop et al. [19]) to increase data quality and shorten the time needed to close the database. They have also been used for mobile interviewing [20] and for bedside data collection [21]. In patient-directed data entry, subjects are given handheld computers to answer the trial s questions (Clarke et al. [22]). 

Web-based data collection and management systems provide a mechanism for remote data entry, where entered data are added to a centralized database once the submit button is pressed. They can be designed to automate the various aspects of clinical trials such as eligibility evaluation, data collection, and tracking specimens. They also serve as a resource site for participating sites to access trial-specific information, facilitate communication, track data queries and their resolutions, and allow administrative management of trials [28, 29]. For these reasons, they play an important role in facilitating the conduct of international clinical trials. 

This method is also being used at the Hines VA CSPCC for a number of trials. It appears to be superior to the paper data collection with centralized interactive data entry. It is not time consuming because data are entered with high-speed double-key data entry, which expedites processing of received forms and thus the accumulation of the master database. Another major advantage is that only one person is needed to run the system. 

Various issues must be considered before deciding on the type of the data collection and management system. The wide range of computer programming languages, database management, proprietary software, and hardware provide for the ability to select the most appropriate system design for a trial. 

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 (1) participating sites are not be able to modify retained data (2) data are presented in a way that allows sites to easily locate any data form for any subject at any trial visit and (3) the site PI is solely responsible for the retained data. 

If the empirical approach is chosen, an empirical disease progression model can also be developed based on data collected during clinical trials or from public databases. A general empirical disease progression model has the following components ... 

There have been numerous advances in the area of remote data acquisition. Data can be collected at the site via an electronic CRF or a hand held electronic device. These data can then be transmitted back to the sponsoring company and batch loaded into the sponsor s clinical trial database. Remote data entry technology currently allows for the easy definition and distribution of the electronic CRFs to the investigator site. Some online cleaning can be performed as the data are entered before transmission to the sponsor site, where additional quality checks are applied and transmitted back to the investigator site. This iterative process allows for collection and generally... 

Clinical teams should design database before the trial begins, reduce the amount of data collected, use standardized CRFs and complete the review process on an ongoing basis. The philosophy is do it right, first time at the source. 

Systems audits in this late phase in clinical trials aim at assessing related procedures to ensure that capable procedures exist for managing and cleaning clinical trial data, for conducting statistical analyses and for preparing the final study report which represents properly the data collected and reported in the clinical trial. Such systems audits are performed across functional boundaries. Such systems audit can be combined with a database audit and/or an audit of the final study report. 

There are a number of design principles that facilitate the use of CRFs in clinical trials. These principles include the concepts of standardization and minimization. The sponsor standardizes the design of CRFs in one consistent international format. This permits uniform databases, consistency in collection and more rapid data entry. In addition, standardization facilitates the monitoring process and therefore increases accuracy of the data. While efficiency is an important variable in the design process, the systems must also be sufficiently flexible to account for the variances between projects. Finally, an important principle of both protocol and CRF design is to collect only the data needed to satisfy the objectives of the protocol. The inherent temptation to collect more data must be resisted. 

Data collected from U.S. National Institutes of Health public database on clinical trials. 

Usually a separate CRF is used to capture serious adverse events, as those must be reported to the FDA within 24 hours. That often means that the serious adverse events CRF data and the regular trial CRF adverse events are collected in different data tables, if not entirely different software systems. Pharmaceutical companies often want to reconcile the two databases to ensure that all serious adverse events appear in the regular-trial CRF adverse events database and that any event in the serious adverse events database is flagged properly as serious in the regular CRF adverse events database. 

Cochrane Library. The Cochrane Library [44] includes The Cochrane Database of Systematic Reviews, a collection of regularly updated, systematic reviews of the effects of health care. It is maintained by contributors to the Cochrane Collaboration. Cochrane reviews are reviews mainly of randomized controlled trials. To minimize bias, evidence is included or excluded on the basis of explicit quality criteria. Data are often combined statistically, with meta-analysis, to increase the power of the findings of numerous studies, each too small to produce reliable results individually. Database of Abstracts of Reviews of Effectiveness is also included. It consists of critical assessments and structured abstracts of good systematic reviews published elsewhere. The Cochrane Controlled Trials Register with bibliographic information on controlled trials and other sources of information on the science of reviewing research and evidence-based health care are part of the Cochrane Library. It is commercially available on CD-ROM or the Internet. 

The availability of both comprehensive SNP databases (10) and a plethora of technologies available to determine DNA variants at ever-decreasing costs has enabled the pharmaceutical industry to begin to incorporate germline DNA collection and testing into clinical trials (II). This allows for hypotheses to be developed and tested from the start of phase I testing in humans, when a direct correlation can be made between toxicity, efficacy, and pharmacokinetic variables. Furthermore, this allows the sponsor to pool data Irom several studies to significantly increase the statistical power. 

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