Like all new technologies, e-based technologies to speed clinical trials have been neither the panacea that proponents originally promised nor the minefield that skeptics had forecast. Proponents promised a total revolution in speeding clinical trials, and there are many vendors today who make that claim, while extolling the virtues of their technologies and hyping their putative benefits.

The impact of EDC on a trial’s efficiency varies widely from trial to trial, so that it is not yet possible to lay out a cookbook approach to success in this area. A complicating factor in understanding the impact of EDC is that a large percentage of the many positive articles that appear in Applied Clinical Trials, R&D Directions, The Monitor, and similar publications are authored by vendors who are hoping to sell their products and services. Some articles report case studies by highly sophisticated technology experts who have mastered this area and have had success in the case study that is published. Even the titles of many articles appear promotional (e.g., “Promoting clinical trials in country X,” “Taking computers into the next X,” “The inevitability of X”). The author is not questioning the veracity of these reports but suggests that one needs to determine which of the technologies available today can actually produce the desired results for a specific clinical trial by the current staff of an average clinical trial team [both at the company or contract research organization (CRO) and investigators’ sites], as opposed to sophisticated “techies” and vendors who are promoting the technology.

In several areas, the use of e-based clinical trials has already been productive and has helped to speed drug development. One benefit is the ability to have data entered into the sponsor’s (or CRO‘s) computers directly from the investigator’s site. This process saves data transmittal time to the sponsor or CRO and eliminates the step of having it double-entered. This approach does not per se affect the accuracy of data entered into databases, nor would it per se lead to fewer queries of the data or, in many cases, decrease the amount of paper that has to be stored.

Some articles tout many additional benefits for EDC such as better data quality, improved performance, enhanced productivity, and reduced costs in clinical trial management. While these benefits are goals that can be sought in a trial using EDC, it is unlikely that each of these will accrue in any one trial.

Some people anticipate that, as technology improves further, implementing a clinical trial will routinely be done almost entirely with e-trial techniques. Others remain more skeptical and see e-technologies as an adjunct to the current methods of planning, implementing, and conducting trials and analyzing their results. When viewing the periodic “crashing” of computers and computer systems, it is difficult to foresee a day when at least some paper back-up methods are not used.

However, because many edit checks are built into the EDC system to prevent illogical values from being entered or to allow missing values from occurring, there is less need for queries to the site for corrections or to complete CRFs. This should lead to reducing the time to database lock.

Welker (2007) has identified the following barriers to implementing EDC systems. He is not a skeptic about the value of e-clinical trials because he also provides useful solutions to each of these barriers. Those barriers identified are the following:

The issue of costs is a highly contentious one because there are strong proponents who claim the use of electronic systems reduces costs and others who claim that costs are not reduced and, in many cases, increased when e-systems are used. It is clear that each situation must be carefully assessed to determine the financial implications of using each particular electronic module or tool in that specific clinical trial.

Some consulting companies have focused on creating large databases of investigators. These databases include far more information than is listed in the investigators’ 1572/1573 regulatory forms and include data on the investigators’ past performances and details of their site. These databases are made available online and can be transmitted to a client. Whether a company uses one of these vendors (e.g., Acurian, Fast Track Systems) or finds investigators through its own internal database, the result is likely to locate qualified and competent investigators more rapidly and effectively than previously.

E-mail communications from fixed computers, laptops, and handheld devices are a fast and generally efficient means of communication. A large time savings will not necessarily be realized by other even more sophisticated techniques. This is because the many types of interactions and communications with sites, Institutional Review Boards, and other groups in order to process the details needed to initiate a clinical trial are already efficiently conducted in the majority of companies. This occurs using currently available electronic methods (e.g., e-mail) that almost all professionals and staff are comfortable with.

Drug accountability, reconciliation of returned drug, and destruction of unused drug are some of the activities needed to manage the drug supply chain, beginning with packaging the drug according to the randomization code, assuming that one is to be used with the drug packaging. This occurs after the active substance is synthesized, the drug is formulated and mixed and placed into vials or pressed into tablets, or other dosage forms are made. It is necessary to document the complete chain-ofcustody information for the drug under test.

E-based approaches have been successful in this area. Numerous companies are active in the patient recruitment area and usually work by providing information directly to patients who have indicated an interest in being informed about clinical trials in a specific therapeutic area. The US government’s website (www.clinicaltrials.gov) and that of Centerwatch (www.centerwatch.com) provide information about ongoing or planned clinical trials for patients, as do the individual company websites.

There are e-recruiters such as Acurian, AmericanDoctor, HopeLink, and Veritas Medicine that reach potential patients via the Internet and have patients opt-in to seek information on future trials or to encourage patients to contact the sites in their area for ongoing or planned trials. The overall success of such firms has been relatively modest at best.

Certain obvious aspects, such as monitoring, adverse event reporting, and data collection, have been early focal points for e-based approaches in the conduct of trials. The number of onsite monitoring visits will not be decreased, but the monitor should benefit from earlier and more efficient access to patient data and information. Greater efficiency allows faster processing and would allow the monitor to spend more time on potentially more productive matters when onsite, such as having discussions with the investigator and other staff, rather than being overwhelmed with routine audit-type issues.

CRFs are changing from paper format to computer screens for web-based computer entry and transmission of data from the investigator’s site. CRFs can also be transferred to small handheld devices for the investigator to complete while interviewing or examining the patient. The data can be transmitted directly to the sponsor’s database. The handheld electronic instruments can be used in some situations to expedite greatly the collection of data and are quite useful in related areas such as patient diaries.

E-techniques have long been used in this regard, and their usefulness over traditional methods (e.g., fax, mail, courier, telephone) is well demonstrated in many situations. E-techniques for transmitting data include not only fixed computer PCs using the World Wide Web (i.e., Internet), but also handheld devices that transmit directly to the CRO or sponsor. Internet-based trials are discussed later in this chapter.

Problems with subject diaries using paper have been well known since they began to be used. These are primarily poor compliance by subjects, long delays to achieving data lock, and poor quality of data. Electronic diaries can help with each of these problems. Dutton (2003) describes the technology and instruments that may be used as electronic diaries.

The use of computer-based methods for entering and processing data from clinical trials and other areas of a pharmaceutical company’s activities has been developed over a period of more than 20 years. The state today is of a highly automated and efficient operation. Nonetheless, important progress is being made today.

E-based techniques facilitate a number of steps within data entry and data management. A recent development has been the increased use of handheld PDAs and other devices to obtain real-time data from subjects and to reduce the time and expense involved in data management, as described in the previous section. In some cases, this has actually eliminated the need for a separate data entry step for some types of data to be transmitted to the sponsor’s site.

Some of the steps to improve data management in the e-process are as follows:

The ideal system for a given trial should allow for the efficient use of paper when EDC is impractical.