Technology in clinical trials
pharmafile | October 15, 2003 | Feature | Research and Development |Â Â clincial testing, technologyÂ
The major drive for the pharma industry is the pressure to reduce drug development times and costs. Although paper-based processes have continued to improve, the industry is reaching the point of diminishing returns and the time has come to fully integrate with electronic trial technology. However, the other major factor influencing the rate of conversion to electronic trial management is cost/benefit. Claims about potential savings have not yet been substantially validated or proven.
Embracing the new technology
The new technology can be used in two ways. Firstly, it can improve communications with key opinion leaders and investigators via a website, and, secondly, technology can be used to improve the stages of the trial process. This can be achieved by electronic transfer of trial documentation to investigators, ethics committees, regulatory authorities and on-line training to facilitate centre set-up. Validation and monitoring should be achievable on-line. Project management is also facilitated by on-line access to real time data, interactive randomisation systems and access to laboratory data. Software is also available for clinical pharmaceutical management systems and adverse event tracking and reporting systems. In a recent survey carried out by the American Company Waife & Associates, nearly 100 biopharmaceutical companies and research organisations were asked which software they used. According to the findings, Clintrial (from Clinsoft Corporation) had a 48% share of the market sample with Oracle Clinical (from Oracle Corporation) second with 32%. Nine per cent of the sample used other products. Other vendors – primarily SAS Institute and eResearch Technology – had 6%, while in-house systems represented 5% of the market. Using these on-line management systems greatly facilitates the tracking of patient recruitment, one of the major reasons why clinical research takes longer than anticipated.
Electronic data capture
Electronic data capture (EDC) can be web-enabled or web-based. Web-enabled data capture is where the investigator enters data off-line and downloads it via the website when it has been cleaned. This has the advantage of speed, flexibility and lower costs but has drawbacks as the local hardware needs to be project-dedicated and downloaded software needs local validation. Web-based data capture, on the other hand, is sent on-line to a central server, which removed the need for local validation. The need for dedicated software is also lessened and software can be pre-validated and protected. The impact of new technology compared with paper-based processes has ramifications on other parts of the process of clinical trial management. The resolution of data queries is speeded up and other costs reduced as the data resolutions can be made at the study site, with the clinical research associate working in tandem with data management. Pop-up data warnings at the data entry level reduce errors significantly, although training requirements of site staff in data capture and validation will have an impact on the cost. A continuing assessment of training requirements and technical ability of the sites is expensive and needs continued management regarding staff turnover.
The Internet and patient recruitment
The recruitment of patients into clinical trials is frequently the rate-limiting step to completing a study to schedule.
Historically, pharmaceutical companies in the US have used the public media (via newspaper advertising and the radio) to recruit patients by making available to the patient information about clinical trials for which they may be eligible. The concept of patient recruitment via the Internet provides means for patients to be pro-active in 'proposing' themselves for participation. There are US companies that run such websites, for example, CenterWatch, Acurian and Veritas Medicine. Although the use of the Internet in the US in this way is already a reality, it is in its early days. This is predicted to rise significantly as more information becomes available such as disease specific information, patient communities and direct to physician and consumer advertising. There are also a number of sites providing clinical trial information including commercially-sponsored trials.
The European sites so far are based around publicly-sponsored trials that offer predominately trial searching, trial matching (to the medical profile of the patient), background information and publication-style editorials. Traditionally, in Europe, the target patient numbers recruited at each site has been investigator led according to the disease profile of their practice. Numbers are often unrealistically inflated thus prolonging the length of the study when targets are not met.
However, there are some drawbacks to using the Internet for recruitment. There will be patients who are ineligible and these will require a greater input from site staff, thus increasing their workload. A pre-screening questionnaire that matches a patients medical profile accurately may need to be introduced. Sponsors also need to be satisfied that the use of the Internet shows that patent recruitment into trials is completed more quickly than previously, with high rates of retention of patients, implying that the recruitment process has screened out unsuitable patients. There are figures available that show the number of patients visiting a clinical trials-related website but no information to determine efficacy of the process. A straw poll conducted at a recent Clinical Research Meeting for the Pharmaceutical Industry asked how many people had used the Internet recruitment in Europe. Only one hand was raised, with the person mentioning that the experience was not good.
How secure is the Internet?
The FDA has guidelines that impact on the use of open systems (ie, the Internet) that requires that security complies with FDA regulations (CFR 21 part 11). Their main concerns are authenticity, data integrity, audibility, confidentiality and quality. The International Conference on Harmonisations (ICH) guidelines on Good Clinical Practice (GCP) also has regulations regarding the security of data, and whose principles are in line with those of the FDA. The vulnerabilities of a computer system are physical security, data integrity and availability. Other areas of concern are the audit trial within the database. According to the FDA industry guidelines 'Computerised Systems used in Clinical Trials', published in April 1999, 'clinical investigations' should retain either the original or a certified copy of all source documents sent to a sponsor or contract research organisations or a certified copy of the audit trial. Is this a return to the paper trail?
Interactive voice response systems
Interactive voice response (IVR) is a new technology. Electronic trial management company ClinPhone Group provides both web and telephone-based IVR technology, which can provide a variety of services, such as:
- clinical trial supplies management
- patient eligibility screening, including identification of placebo-responders during ashout
- measurement of treatment effects, eg, in depression trials
- identification of early onset of action
- tracking patient recruitment.
The system is flexible and versatile and can be accessed from anywhere using a telephone system. The system is multi-lingual and has a world-wide toll-free telephone network capable of running clinical trials on a global scale. However, whether the industry will embrace such a system and 'contract out' with the obvious cost implications remains to be seen. Evidence of cost savings has not been defined. Perhaps when more surveys have been conducted and cost-effectiveness assessed such systems will be generally accepted.
The Data Protection Act 1998 impact on electronic data transfer
Companies that fail to comply with the Act and its enforcement provisions will be committing a criminal offence and in certain circumstances, company directors may incur a personal liability. As data controllers, pharmaceutical companies have ultimate responsibility for ensuring the privacy of each trial subjects clinical trial data as long as the trial subject's data can be identified. If clinical trial data is being transmitted via the Internet the data needs to be encrypted. The sponsor is required to make sure the country to which the data is being transferred has "adequate levels of protection" and contracts that have been approved by the Data Protection Commissions for the purposes of such data transfer.
Conclusion
The biggest hurdle to electronic trial management is regulatory compliance. Processes and operating procedures will need to be developed that allow the best use of technology and conform to GCP.
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