March 10, 2003
| SURVIVAL IN THE drug development industry, let alone success, is a complex juggling act. Biopharmaceutical companies must develop medical innovations ever faster, while balancing heightened regulatory pressures with an unrelenting drive to control rising costs and improve quality. Once an investigational new drug reaches the market, there are no guarantees. New therapies entering the market face difficult economic conditions and intense competition.
It is widely believed that the adoption and use of information technology is critical to helping companies do a better job juggling the demands of the drug-development operating environment. "E-clinical" technologies, in particular, have the potential to reduce data collection and management inefficiencies, improve development planning and management, and accelerate the filing of drugs with regulatory agencies.
Many e-clinical technologies are more than 10 years old, but biopharmaceutical companies have been slow to include anything perceived as risky in standard operating procedures. For example, research professionals currently report that paper-based data capture remains the typical approach for the majority of their clinical research studies. In addition, only one in four professionals is routinely using Web-enabled and voice-response technologies.
Currently data collection and management activities account for about 60 percent of the total time within which Phase I-III programs are conducted. Recently published estimates hold that the global pharmaceutical industry could achieve dollar savings of more than $2 billion — and nearly a 65 percent reduction in cycle time — by implementing electronic data capture and management technologies. No wonder industry professionals expect e-clinical technologies to play a much larger role in the coming 24 months.
Solutions for the CT Continuum
Indeed, e-clinical technologies have the potential to accelerate and improve each of the three primary areas that make up the overall clinical research process:
- Development planning and initiation, which includes designing the protocol, identifying and selecting physician investigators to conduct the clinical trial, initiating the clinical trial, and engaging and receiving approval from an ethical review board.
- Study conduct and management, which includes managing the clinical trial; identifying and enrolling study volunteers; managing subject participation; and collecting, monitoring, and processing data.
- Study completion and NDA filing, which includes analyzing the data, reporting the results, preparing the new drug application (NDA), and then submitting the application for FDA review.
E-clinical products are now available for each core area. In development planning and initiation, for instance, more sophisticated electronic authoring and document management solutions are emerging for organizing and standardizing the protocol development process. A number of simulation technologies are designed to arm researchers with more powerful feasibility assessment and predictive capabilities. These simulation technologies can help improve clinical study design before costly trials are initiated.
For investigative site selection, biopharmaceutical and clinical research organizations (CROs) have long used relatively simple database applications to archive site information for selection purposes. During the past several years, however, e-clinical technologies have provided more sophisticated databases and user interfaces offering more robust comparative information. Ideally, these solutions may save time and offer researchers the ability to make more informed and strategic site-selection decisions.
Once a clinical trial is initiated, drug companies, research organizations, and investigative sites typically use fairly simple in-house systems to track contracts, document review and approval activity, initiate payments, and monitor clinical trial milestones. But e-clinical solutions are emerging that offer a more convenient, interactive, and responsive approach — many based on Internet technology — to automate, centralize, and streamline trial initiation activities.
In the area of study conduct and management, drug companies have often used project management and trial management software developed either in-house or by vendors. Experienced investigative sites have also used either proprietary or off-the-shelf trial management applications. Emerging third-party e-clinical technologies, however, are striving to integrate trial management applications with those of electronic data management activities. Such integration will create opportunities to automate and streamline three important process areas:
- The input of information used for study tracking purposes
- The accessibility of management information
- The analysis of business information that pertains to those operations involved with conducting the trial
Simple databases and management applications to maintain and access study volunteer information are likewise being supplanted by e-clinical technologies that provide robust patient-recruitment information in a more efficient and centralized manner. These new solutions are often based on call-center technology and processes, and population demographic and psychographic information once affordable to only major corporations is now more broadly accessible.
For example, site personnel have traditionally collected patient demographic information, medical histories, and trial-specific information such as volunteer participation metrics and logistics. Today, with the financial assistance of drug companies and CROs, investigative sites can draw from a variety of Internet-based and offline applications to identify, select, and even contact volunteers from much larger and more comprehensive databases containing patient information.
EDC: The Biggest Opportunity
Historically, drug firms have used back-end software called clinical data management systems (CDMS) to support in-house data management functions such as edit checking, query resolution, and auditing. The front-end systems for data collection, however, are newer to the scene.
|Warming Up to E-Clinical Products
|Below are the percentages of survey respondents who agree that e-clinical technologies are a major strategic initiative to accelerate drug development.
Source: CDISC-CenterWatch, 2002
Typically deployed at the investigative site, these electronic data collection (EDC) systems have evolved greatly over the past decade. A wide variety of EDC technologies — including optical character recognition, interactive voice response, graphical interfaces, handheld devices, and central laboratory interfaces — promise to improve three key processes:
- Collecting clinical study data with or without human involvement
- Verifying original source documents
- Tracking electronic signatures
Changes made to the electronic data are recorded as part of an audit trail.
However, EDC involves more than streamlining data entry. It also integrates functionality that allows more of the overall clinical trial process to be managed electronically. For example, many EDC solutions offer better data checks and improved access for systematic review. Relative to other e-clinical technologies, EDC solutions offer perhaps the largest opportunity to streamline drug development cycle times.
EDC-based data entry may also be monitored in real time to alert investigative site personnel to possible errors. By itself, this immediate feedback can significantly shorten the resource-intensive error-resolution process. Project managers can also review and evaluate data in near-real time, enabling streamlined project oversight and better safety of clinical trial patients.
Most clinical trial sponsors currently use a mix of EDC and paper-based source documentation, so the full benefits of EDC have yet to be realized.
The third and final area of clinical trials — study completion and NDA filing — is perhaps the most fully automated. Statisticians within drug companies have been using computer-based applications to analyze data and present their findings for 30 years. Here, the key issue is how quickly in-house statisticians can begin their analyses and interpretation of the study findings. The sooner a clinical study database is cleaned and locked, the sooner statisticians can do their jobs.
New e-clinical technologies mainly offer process improvements to accelerate this cycle. For example, data analyses and reports can now be created and updated in parallel with an ongoing clinical trial. As such, once that trial has ended, the time to complete data analysis and reporting can be compressed.
As for filing with the FDA, the agency has weighed in during the past 18 months with guidance on electronic submissions for drug companies. E-clinical technologies are starting to address this guidance and may indeed streamline regulatory review, as well as foster adoption of data standards across the industry.
But despite the promise of e-clinical technologies, the outlook for adoption is decidedly mixed. First, the good news: A recent survey, conducted by the Clinical Data Interchange Standards Consortium (CDISC) and research firm CenterWatch, of several hundred biopharmaceutical companies revealed that drug development sponsors are using e-clinical technologies for 24 percent of their Phase I-IV trials — up from 12 percent in 2000. And companies report that they anticipate using these technologies for almost half of all clinical projects by 2004.
Every survey respondent reported using e-clinical technologies in 2002 on an average of four clinical research studies. Moreover, more than 80 percent of biopharmaceuticals and CROs view e-trial technologies as essential to shortening development cycle times and improving data quality.
Now, the bad news: These clinical trials players also see barriers to rapid e-clinical adoption. "Solutions," for example, typically aren't integrated. Instead, they're used largely on a per-project basis, creating islands of data and trained personnel. As such, most research professionals report mixed experiences after working with e-clinical technologies.
Companies also perceive a high level of uncertainty, given the absence of clear regulatory direction from 21 CFR Part 11. Moreover, they see a highly fragmented vendor market and the need for data interchange standards. Nearly two-thirds of companies surveyed believe that current e-clinical technology solutions offer inadequate functionality at this time.
As for standards, more than 90 percent of biopharmaceutical companies and CROs believe that data interchange standards should be extended to facilitate data collection at the investigative site level. This will help reduce variability among data collection requirements, as well as consolidate training requirements across data systems.
The CDISC-CenterWatch survey also indicated that clinical research professionals want drug companies to take the lead. Specifically, researchers want sponsor companies to play a more active role in shaping standards, setting higher levels of accountability among project teams and contract service providers, and narrowing the relevant set of standards-supporting technology solutions.
It's equally clear that research professionals are eager to leverage the benefits of e-clinical technology, but not at the expense of reinventing the entire drug development process — and not if it means replacing critical human interactions with impersonal, automated systems. Researchers want technology solutions to accommodate existing development process strengths, to preserve important human interactions (e.g., between research professionals and patients), and to match these solutions with scientific and business requirements.
Kenneth Getz is the founder, president, and publisher of CenterWatch, a research, consulting, and publishing firm that focuses on all aspects of the clinical research enterprise. He may be reached at firstname.lastname@example.org.