EDC Focus: CROs & EDCs

Uneasy alliance or a match made in heaven?

By Anne Zielinski

Contract Research Organizations (CROs) and Electronic Data Capture (EDC): are they a match made in heaven or an uneasy alliance contrived by overly anxious relatives? More than half of clinical trials today are conducted using EDC, and more than half of trails are conducted by CROs, so it’s increasingly important to understand how CROs and EDC can best work together.

Under the business model traditionally followed by many CROs, client fees are calculated based on the estimated time required to provide the necessary services. A technology that actually reduces the number of hours CROs need to spend in the conduct of a trial would, in theory, cause no small amount of consternation for many CROs and deter many from moving to EDC.

However, when EDC was introduced, some brave CROs adopted initial incarnations in the belief that meeting client sponsors’ desires for higher data quality was not only the right thing to do, but also made good long-term business sense. The higher the data quality and the earlier a CRO could provide meaningful insight to the progress of a trial, the more likely a sponsor was to choose that CRO again. With this in mind, a few CROs in the 1990’s actually built their own EDC systems. An early endorsement of the concept, these EDC solutions did not reflect their organizations’ core competencies and were almost universally abandoned.

Today, CROs that understand the value of EDC have had to choose between two types of commercial applications: full-featured EDC systems that are scalable to fulfill all the requirements of bio/pharma companies’ complete portfolios, or niche applications mostly appropriate for a particular type of trial. Similarly, CROs tend to fall into two categories: large, global organizations that can provide comprehensive trial services across multiple geographies, therapeutic areas and trial types, and providers that address a particular niche or offer a small set of specialized services. Frequently, these organizations have different approaches to the use of EDC.

Playing in the Big Leagues Means Using EDC

Most of the major CROs that initially resisted EDC have, over time, accepted the technology in response to the growing adoption of EDC by global bio/pharma companies. As a result, all of the largest CROs and many of the mid-sized and small ones have expertise in at least one system, which they use to varying degrees. At the most basic level, they perform site monitoring and/or data management on an EDC system. To perform more than basic roles using EDC, CROs typically enter into a partnership or vendor relationship with an EDC provider. (Note: EDC vendors and CRO partners are independent companies and not liable for each other’s business activities. The term “partnership” and its derivatives refer to close business relations collaborating on certain clinical study projects, not an actual business partnership or J.V..)

At the basic levels, CROs may train investigator sites in the use of an EDC system. CROs with deeper EDC relationships may provide investigators’ the rights and access to an EDC system. At the most sophisticated levels of partnership, CROs may configure and design trials in an EDC system, integrate the EDC system with other software applications, configure custom reports, maintain global libraries of items and forms and configure other EDC-specific capabilities. The sponsor, CRO and/or the EDC vendor may share responsibility for the set-up and conduct of the EDC system for a particular trial within a single system.

Close collaboration between the EDC vendors and their CRO partners makes for flexible outsourcing options. In some cases, sponsors can contract directly with CROs to license an EDC system. Enabling a CRO partner to be a one-stop solution to a sponsor’s EDC needs makes the process faster and easier, with less potential for misunderstandings, ill-defined responsibilities and unclear communications.

Incorporating therapeutic expertise and knowledge of the investigator environments and practices, CROs add value when they design EDC systems for particular trials, as well as when they train investigator site personnel in the use of the EDC system. A holistic approach to the design of an EDC trial and the training of site users in the EDC system increases the likelihood that the EDC system will be used to its fullest potential, and ensures that users will have a positive experience with it.

Over time, many large bio/pharma companies have standardized on one primary EDC technology. Establishing and maintaining a library of standard terms and/or forms within the EDC system allows sponsors to reuse their study assets to help drive consistency across trials as well as to streamline study setup time and shorten time-to-database lock, when data can be reported upon and analyzed more readily and completely. For sponsors that have standardized on an EDC platform, it is critical to choose a CRO trained and qualified in their chosen EDC system in order to enforce use of their library of standards and realize the benefits of enterprise EDC adoption.

Sponsors that choose to use EDC through a CRO can take advantage of the inherent capability to view up-to-date trial data. Whether viewing relevant safety information for an ongoing trial or information on project progress, sponsors can use EDC to keep track of their outsourced clinical trials.

EDC Shrinks the Challenges of Global Trials

For the majority of bio/pharma companies that conduct large, global clinical trials, there is no choice but to use a CRO, simply because most sponsors do not have the resources or expertise to deal with the multitude of issues that often arise in global trials. Conducting large trials in many countries introduces countless challenges, as global trials can

• involve a wide diversity of geographically dispersed investigators who have varying technology skills, access and infrastructure,
• represent a multitude of languages and cultures, and
• require compliance with a variety of country-specific regulations and laws.

Clearly monitoring global trial data and overall trial progress can be challenging without the proper technology to support timely review of data and visibility into trial metrics (such as recruitment rates). Properly chosen and implemented, EDC can help minimize and control a number of these challenges.

• Some EDC systems can be accessed from any computer and do not require the download of any application, applet or object.
• Select EDC systems are designed to minimize the bandwidth needed to transmit data via the Internet.
• Systems can be provided in each user’s native language, so that investigator recruitment no longer needs to be limited based on language, and data in various languages from investigator sites can be stored in the same database. This means that all study data is available in one place for review, reporting and tracking. Furthermore, reviewers can view the system in a different language than the one used by the investigators who entered the data.
• Systems that provide eLearning — and provide it in various languages — allow investigator site users to access the learning they need when they need it and in their own languages.

Helping Niche CROS Leverage Expertise in Smaller, Specialized Studies

But what about CROs that don’t conduct large global trials? CROs that focus on one therapeutic area — or perhaps on early or late phase trials — can leverage their particular expertise by using an EDC system. Applying the knowledge of how to conduct a specific type of trial, these CROs can adapt flexibly-configurable EDC systems to meet the needs of unique trial types. In-depth knowledge of the capabilities of an EDC system allows CRO personnel to optimally make use of a system’s capabilities to enhance the quality of data collected and to increase study conduct efficiency.

Consider the case of trials for which patient-reported outcomes are primary endpoints. Knowing that an EDC system, with little or no additional work required, can easily integrate with tools used to collect electronic patient outcomes so that all clinical trial data is viewable and reportable from one interface, a CRO can set up a trial to provide tremendous additional value to a sponsor.

Late phase observational studies usually do not have a visit structure, nor do they usually require source document verification. A CRO’s knowledge of and training in the capabilities and flexibility of an EDC system can equip it to set up an EDC system to reflect the way these trails are conducted, adding value to the sponsor that uses that CRO to provide EDC for an observational trial.

Golden Opportunities

Using EDC offers CROs an opportunity to implement both new technologies and new business processes. Many CROs layer EDC use over the traditional roles of the clinical research associate (CRA) and data manager. Some organizations have successfully defined business processes using EDC without simply retooling traditional roles, creating new roles directly tailored to EDC environments in order to maximize trial efficiency and quality. For instance, the responsibility to perform data locking and data freezing may differ in an optimized EDC model compared to in paper-trial environments. Software tools can do much of the data review that was done by humans before EDC. New role definitions offer efficiencies to CROs and job satisfaction to the personnel involved, while ensuring that the sponsor and CRO are fully exploiting the benefits of the EDC technology.

Using EDC also provides CROs an opportunity to conduct trials using adaptive trial designs. These phase-bridging designs rely on realtime data availability and the ability to rapidly change treatment allocations. Many sponsor organizations would find it difficult and unwise to assemble the infrastructure needed to administer a single adaptively designed trial. Working with a CRO can provide an opportunity to try out an emerging practice without making a change in an internal organization. A cutting-edge approach that can decrease the duration and cost of drug development, adaptive trial design holds great promise for our industry and great opportunity for CROs using EDC.

The Chicken or the Egg?

For clinical trial sponsors, which should come first: a decision to use EDC or a decision to use a CRO? As with many of life’s questions, it depends.

If a sponsor first chooses an EDC system, the EDC vendor should be able to indicate which CROs are adequately trained, enabled and supported on the EDC system. Any recommended organization must have had adequate, documented training in the services it is going to provide using the EDC software, appropriately qualified personnel and appropriate procedures in place to ensure the system is used in a regulatory-compliant manner.

Furthermore, the CRO should have audited the EDC vendor to ensure that the application meets regulatory requirements and has been developed in accordance with an appropriate software development lifecycle. The CRO should also have an ongoing relationship with the EDC provider so that product updates, training and help desk are available to the CRO as needed.

A sponsor that has chosen an EDC system may choose to work with a CRO that has not previously used the system. Most EDC providers would not authorize an untrained and unqualified organization to use their system. EDC vendors should be willing to share with sponsors the qualifications they require of CROs that will use their software to provide services.

Sponsors that feel more strongly about their preference of a CRO than an EDC system may not have the opportunity to choose which EDC system they will use. Whether or not a sponsor has a particular EDC preference, the qualification of any organization that uses an EDC system should include those items noted above, and any CRO that uses an EDC system must be qualified and trained to do so.

How many EDC systems a CRO can use is a different question than how many EDC systems a CRO can optimally use. While there are certainly similarities among systems, the differences will likely require separate processes, procedures, audits, training and more. It seems reasonable that the best CRO/EDC experience would be from an organization with significant experience in a technology at the core of its offering.

Working Together

Relationships are never perfect, whether between sponsors and CROs or between CROs and EDC vendors. A multi-party relationship requires vigilant attention to communication.

A sponsor using a CRO to implement an EDC system for a trial must encourage, if not ensure, that all three parties communicate regularly. Open communication among the parties curbs the all-too-human temptation to assign blame to the party that is not present. Strong communication channels across parties help guard against mistakes and ensure consistency, ultimately driving trial efficiency and quality while helping to contain costs.

A written communication plan that includes all parties and that defines trial planning, conduct, issue resolution and escalation, and progress review is a key starting point. The proper demeanor and regular interactions of the participants from each organization will bring the written plan to life.

With the growth of niche CROs, it’s possible to have more than one CRO working on a trial. A data-management specialty CRO may manage the EDC system, while a clinically-focused CRO may provide monitoring services. This same model — qualified, trained providers working together with the vendor and the sponsor under a written communication plan — can be equally effective in delivering a high-quality, efficiently run clinical trial.

Happily Ever After

CROs that embrace EDC do so because of a belief in the promise of increased trial efficiency and data quality, because they want to be responsive to their clients, or more likely, both of these reasons. Over the past four years, EDC vendors have made it easier for CROs to adopt their tools, providing increased functionality and scalability and, in some cases, sophisticated partner programs that train and guide CROs to beneficial implementation of these EDC tools.

Successful partnership requires careful selection by all parties involved, with aligned goals and compatible cultures. An EDC vendor that accepts every CRO as a partner may not be qualifying them adequately. Conversely, a CRO that uses too many EDC systems many not be realizing the full capabilities of any one of the systems.

Even marriages that appear to be made in heaven often encounter rough patches. Similarly, CROs and EDC vendors that partner to implement sophisticated projects requiring high-performing tools and teams need to work through the inevitable challenges that arise in a clinical environment to sustain a productive relationship for the benefit of their sponsor clients. Careful selection of partners can help ensure that the relationship that appears to have been made in heaven does, in fact, provide a “happily ever after” ending to sponsors’ clinical trials.

Anne Zielinski is vice president of alliances at Medidata Solutions Worldwide.