A Case Study in Redefining Regulatory Binder Management

Hether Seifert headshot

Hether Seifert, MSM, CCRP, Mayo Clinic Cancer Center

Paperless regulatory document management is a hot topic today among personnel at study sites, contract research organizations (CROs), and sponsors facing what is often overwhelming paperwork that seems to grows exponentially with each new trial. Many institutions are starting to invest in regulatory document management solutions to increase staff productivity, speed study start-up, and improve inspection readiness.

However, simply going “paperless” does not solve the core document management issues of workflow, change, and signature management, especially in a complex environment. Understanding how others have identified and addressed these issues can help an organization examine its own operations.

Framing the Problem

Clinical trials require regulatory documents to capture the activities performed before, during, and after the accrual of participants. These documents may vary depending upon the type of trial and regulatory requirements, but typically contain the study protocol, institutional review board (IRB) approvals, informed consent forms completed by participants, copies of curricula vitae and medical licenses of study investigators, financial disclosures, package inserts (in device studies), the Form FDA 1572 (“Statement of Investigator” required by the U.S. Food and Drug Administration in drug studies) or Investigator Agreements (required by FDA in device studies), the site’s delegation of authority log, and many more. This collection of essential documents is referred to as the regulatory binder.

When an individual at a site is responsible for one regulatory binder, and all staff are based at the same location, document management is not complex. However, when the person managing the binder is not located at the same location as the investigators and the files need to be shared across locations, the problem starts to make itself evident.

A popular solution at this point is to move to a paperless or electronic shared server environment, in which documents are scanned and uploaded to a shared server space for easy electronic access, and then manually tracked via spreadsheets. The person responsible for the electronic binder ensures that document updates, for example staffing changes, are scanned and uploaded to the server. This procedure via a shared server with manual document management can meet the needs of small to midsized research organizations.

However, as the number of trials conducted simultaneously at a site increases, the existing individual or team managing regulatory binders may no longer be able to handle the mounting workload. Document management becomes much more complex due to the volume of trials, locations, staff, and updates, as well as the complexities of document coordination across supporting staff. Lost documents, missing document updates, and spreadsheet discrepancies are inevitable within even the most tightly run organizations. It now becomes clear that a manual or hybrid process of document management does not support the fast-paced study environment of a large research operation.

Case Study: Facing Confusion, Seeking Clarity

Let’s consider the case of a research center that used to have just one person managing trial documentation by keeping paper copies in binders that were shipped to monitors at different physical locations for each visit. It was time consuming for the staff member to manage such clunky binders, and for the monitors to manually go through the paper documents to determine what had already been reviewed and what was new.

As the research center grew, the number of trials and supporting staff increased. Sharing and managing paper documents across an increasing number of staff and physical locations was challenging. It had become evident that regulatory binders could no longer be maintained efficiently in the paper format, so the decision was made to move to an electronic format on shared server space. It was assumed that this tactic would deliver improvements in study efficiency and reduce staff workload by simplifying document sharing, storing, and updating.

Under the new process, documents were routed for physical signature via e-mail, scanned, and uploaded into a standard set of folders using an agreed-upon naming convention, in an attempt at standardizing the tasks. Trial statuses were tracked by each staff member using personal spreadsheets. When monitor visits were scheduled, rather than sending a physical binder of documents, a disk with copies of all relevant documentation from the shared server was created; monitors then spent time deciphering the organization of files on the disk and reviewing all documents to find new and updated information.

This hybrid electronic solution with manual tracking, while an improvement over the former, completely paper-based process, did not deliver the anticipated workload efficiency benefits. It did not solve, but exposed, what proved to be the root issues driving staff workload—document change management, tracking, retention, and preparing for monitor visits.

This hybrid electronic solution with manual tracking, while an improvement over the former, completely paper-based process, did not deliver the anticipated workload efficiency benefits. It did not solve, but exposed, what proved to be the root issues driving staff workload—document change management, tracking, retention, and preparing for monitor visits.

The research center continued to grow—as did the number of trials—to the point that additional staff were required to support the volume of activity and cross-coverage of duties. Each basic regulatory binder had a minimum of 179 documents [(2 labs per trial x 2 documents per lab) + (50 staff per trial x 3 documents per staff) + (25 study docs)]. With more than 650 trials, the staff was supporting more than 100,000 documents.

At this point, the document management task was overwhelming. The electronic shared server solution was not adequate; however, it did uncover the root issues that needed to be addressed.

The Search for a Solution

Simplifying the management and sharing of thousands of regulatory documents across multiple trials, locations, and staff would require an automated solution that addressed the core issues driving staff workload—document change management, tracking, retention, and preparing for monitor visits. The new solution needed to:

  • Enable staff to submit a document update once, then automatically update all trials using that document
  • Streamline the visibility of trial and document statuses
  • Electronically capture 21 CFR Part 11–compliant signatures in adherence to the Code of Federal Regulations
  • Replace paper documents with online documents that met regulatory retention requirements
  • Securely share trial documents online anywhere, anytime, from any device As with any large problem, the standard barriers existed in terms of funding, staffing and expertise, viable solutions, implementation time, and availability of internal information technology (IT) resources.

The search began with “off the shelf” solutions. The evaluation found challenges with packaged solutions in that, first, the cost of such solutions evaluated were prohibitive; second, in terms of the need to adapt business processes to the software; and third, regarding the requirement for integration resources from the internal IT team. These challenges added to the overall expense with the hidden costs of adaptation and process updates, internal IT costs, and implementation delays based on the internal IT queue.

The next option explored was a “home built” system developed by internal IT staff. The evaluation found this could be more expensive, and would still require business processes changes to adapt to the developed solution. The traditional software development process would require significant time from the trial staff and internal IT staff. With the large IT workload queue, a solution was anticipated to be years away.

The third option was to collaborate with a custom software expert to develop a custom solution. This was the least expensive and quickest strategy to implement. Utilizing an iterative and incremental development methodology, less time was required from trial staff to define and develop the solution. The resulting solution was developed in four months and rolled out in phases, to allow the staff time to adjust to a fully automated solution. While the system was designed by the users, there was a bit of adjustment required, as old manual processes were no longer needed, and staff gained capacity to do more.

The final solution delivered the advantages of centralized document management via a single master source of documents, eliminating duplicate documents with mismatched updates. When document updates are entered, such as a CV with new details, the change is submitted once and all related documents and trials automatically and instantly have the updated information.

The solution is a cloud-based approach with anywhere, anytime, any device access. It incorporates e-signatures and e-forms, allowing investigators to sign documents from anywhere in the world using their tablets or phones. Monitors now log in remotely to access up-to-the-minute documents, and can easily identify and review new or changed documents. Regulatory document retention requirements are satisfied and paper binders have been eliminated.

A key lesson from this experience was the importance of selecting the right software development partner. With trial management expertise and no IT background, we benefited from a partner with comprehensive technology expertise that could understand our objectives, help us dig deep into the details to ensure all of the automation opportunities were being considered, and present multiple options with cutting-edge technology. The collaboration expanded our view of how to solve the workload issues, resulting in a solution that was more valuable than originally envisioned.


Redefining regulatory document management can deliver new levels of efficiency by focusing on core process improvements in terms of automating and simplifying change management, tracking, document retention, and preparing for monitor visits.

For the research center in this case study, the move to an automated document management process took four months (design, development, implementation) and demonstrated quantifiable results:

  • All told, 200 regulatory binders are now managed by each full-time employee (FTE). In addition, each FTE provides cross-coverage for five peers. Significant efficiency increases were achieved by implementing a single master source of documents with updates applied once then available across all trials, as well as the capability of electronic signature capture and secure document sharing.
  • There has been a 92% reduction (from an average of 50 hours to just four hours) in the amount of trial start-up time devoted to regulatory document management. No more waiting on documents in transit, lost on desks, or waiting for investigators to return from travel.
  • The time that monitors spend on each trial visit was reduced from an average of 90 minutes to 10 minutes.

Members of the regulatory document management staff have experienced tremendous workload reduction. Principal investigators like the ease of managing and completing online approvals versus paper documents and e-mails. Monitors have responded with comments like “best system yet!” and “I wish everyone had this system. It sure would make life easier!” The system allows all of these trial stakeholders to stay organized and know what documents need review. Even sponsors have responded positively to the system by accepting electronic versions of paper document requests.

Whether an organization manages a dozen or many hundreds of trials, automating binder management can improve efficiency, study start-up times, and inspection readiness. It is hoped that this article helps organizations identify their core issues and potential benefits of an automated solution.

Hether Seifert, MSM, CCRP, (seifert.hether@mayo.edu) is a program manager with the Protocol Development Unit at Mayo Clinic Cancer Center in Rochester, Minn.

Becky Bosch (bbosch@vacava.com) is a client engagement manager with VACAVA Inc.


[DOI: 10.14524/CR-16-0026]