The purported benefits of decentralized clinical trials (DCT) include accelerated enrollment, reduced patient burden and improved retention rates, among other efficiencies. Incorporating virtual elements into the traditional trial model requires a clear vision for the technologies, platforms and other “site-less” elements that support these efforts; however, the potential challenges of managing multiple vendors are often overlooked. This article discusses key considerations for vendor management, auditing and scalability in today’s evolving clinical trial landscape.
Tracking vendor viability in the decentralized clinical trial (DCT, aka hybrid and virtual trial) models
In the DCT models, vendors cannot be considered static elements. Like the trials they support, vendors must remain flexible and responsive as they adjust to their sponsor’s specific requirements. Given that their services can represent major components of a study, such as overseeing patient safety and privacy, data collection and ensuring the investigational product chain of custody, vendors can have a significant impact on study conduct.
When a CRO contracts with a vendor to support a sponsor’s DCT elements, the CRO must perform due diligence and provide appropriate vendor oversight on the vendor’s performance. To ensure a vendor can meet regulatory standards and follow best practices, the CRO will perform an audit and ensure alignment, as applicable, to the following guidance documents:
- ICH Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2)
- FDA Guidance for Industry, Computerized Systems Used In Clinical Investigations, May 2007
- The General Principles of Software Validation; Guidance for Industry, January 11, 2002
- FDA Code of Federal Regulations (21 CFR Parts 11, 50, 54, 56, 312)
While some of these documents are U.S.-centric, many trials also include global study sites. Vendors need to understand how specific regulations can affect their work across different countries and regions.
Realizing the benefit and limitation of audits
Vendor auditing is a detailed process carried out with appropriate due diligence to ensure that the vendors have the appropriate capabilities, skills and quality systems necessary to perform the services required. Following guidance documents can provide a good baseline for ensuring quality results, but in reality, an audit cannot cover all aspects of the vendor’s operations – it is only a snapshot at a single point in time.
The auditing process must also account for vendors that operate in multiple global locations. If a vendor utilizes the same Quality Management System in each location, this can assist the CRO to assess risk when overseeing global DCTs.
As DCT services continue to evolve, CROs will gain experience with these types of trials, but must keep pace with technological advances and align with input from regulatory agencies. CROs must also remain nimble to respond to ongoing assessments of vendors as they develop new systems, services or update current ones. Once qualified, a vendor can be requalified via questionnaires or remote auditing tools, but a CRO needs to determine which factors influence decisions to audit/assess onsite for any new vendor service.
Finding a balanced approach to auditing
A balanced approach for auditing can apply risk-based management principles that add efficiency to the auditing process by categorizing the risk categories of vendors.
- High-risk vendors have direct interaction with study subjects/patients; they are responsible for collection of data that contributes to primary and secondary efficacy or safety variables
- Medium-risk vendors have the potential to influence study conduct (e.g., translation vendors, equipment suppliers)
- Low-risk vendors do not engage with patients or provide data for the trial. They support ancillary tasks (e.g., meeting planners, advertisers)
A high-risk vendor would typically require an in-person audit. A low- to medium-risk vendor could be evaluated with a remote audit or questionnaire to help verify that the proper processes, procedures and document control system(s) are in place.
Even if a vendor is considered low-risk, components of a Standard Operating Process system, a training program and quality management system are still important. For those vendors that do pass an audit, it does not mean that future follow up is unnecessary. Any performance issue or complaint from the project team could trigger additional audit activities.
Meeting increasing demands for services
As DCTs have gained acceptance and popularity, the demand for vendor services has increased. Study sponsors and CROs must consider the ongoing availability of their qualified vendors. Some businesses have been acquiring vendor groups for their exclusive use, which can create a temporary gap in services as others must find and assess new vendors.
Even with a reliable vendor, scalability is another consideration as the market grows. Some vendors handle their increased volume of work by hiring third-party groups, for example, to provide home health nursing or mobile phlebotomists.
Is the CRO then responsible for verifying the work of the third party as well and assuming the oversight and due diligence on behalf of the study sponsor? Will the CRO know if the vendor appropriately qualified their own vendors? To ensure milestones and deliverables are met, CROs need to understand the level of oversight taking place and determine if the depth of auditing performed within the layers of sub-contractors presents an inherent risk to the sponsor, the clinical trial and even the study subjects.
Looking ahead for the growing decentralized clinical trials landscape
Sponsors expect that when they work with a CRO, all contracted aspects of their trial are managed, including any vendors and their third-party contractors. CROs need to find a manageable way to evaluate aspects of all the parties contributing to the decentralized elements of their trial while considering risks. As DCTs become more commonplace, our industry will need to be prepared to adjust to the demands of finding qualified vendors and ensuring that these vendors can align with global regulations, generate quality data, scale with demand and contribute to a successful trial.
We have invested in developing a rigorous vendor ID, qualification and oversight program. Our mission is superior execution in the trials we manage for sponsors. Our rigorous approach blends our deep experience as a DCT thought leader and partner in working with you to identify and mitigate risks to your programs.
Learn more about how we can help you build efficiencies into decentralized clinical trials.
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