Monday, August 29, 2016

Preventing Inconsistencies in Study Conduct and Protocol Noncompliance Across Sites

by Shree Kalluri

Clinical trials are more complex than ever and it’s important to make sure a study is being conducted in the same manner across sites. However, ensuring consistency across multiple sites for any aspect of a clinical trial can be more difficult than one would expect. Some inconsistencies at the site-level are unknown to many sponsors, resulting in both efficiency and quality problems in the industry.

One example of this industry challenge stems from having each research site transform the schedule of events, also known as the time and event schedule, into their local clinical trial management system (CTMS). This transcription requires sites to review and interpret the protocol document and build it out as a protocol calendar in their CTMS. The protocol calendar, a schedule of treatments and tests to be completed by a participant on a study, is one of the most important aspects of a clinical trial, and any deviations from the calendar can have detrimental consequences. The calendar is connected and tied to other downstream activities and uses within the site’s CTMS, making it more powerful than a static spreadsheet or PDF.

This process can be replicated from ten to a hundred times based on the size of the trial and the number of participating sites. With so much duplicated effort, this method is unnecessarily complicated, administratively expensive, and fraught with the potential for costly errors.

The problems with each site building the same calendar

Sponsors often underestimate the challenges associated with sites building protocol calendars. Calendar creation is the cornerstone of activating a trial for some sites, as it’s the first step they take to initiate a trial. Thus, the sooner the site gets the calendar, the sooner the coverage analysis is completed, the sooner the budget and contract are negotiated, and the sooner they can open the study to accrual. Given the amount of manual effort and large volume of trials being conducted concurrently by research institutions, it’s not uncommon for sites to have a backlog of calendars that need to be built. It can take months to build these out.

Additionally, building a protocol calendar is no mindless task. It takes a lot of time and knowledge to complete the document review alone. Protocol documents often have unstructured representations of the schedule of events and procedures, instructions buried in the footnotes, and modifications reflected elsewhere. This requires sites to put a lot of effort into understanding and breaking down each protocol and what it takes to actually implement it.

With subtle and large-scale intricacies associated with the increasing complexity of clinical trials, there are many details that can slip through the cracks. Given how critical the protocol calendar is, one would expect it to be created with scientific rigor, including checks, balances and best practices to ensure it carefully reflects the sponsor’s intent. However, if you ask any study coordinator from a given research site, they will readily admit that the calendar is more of an art than a science. Any two coordinators may interpret the same protocol very differently.

Even more, the same person isn’t always building calendars at a given site, nor do all sites have the in-house resources or expertise to do so. Between full workloads, employee turnover, and training new employees, it can be an activity that is postponed or completed by people that aren’t proficient in building calendars. When individual staff make judgment calls on the protocol independently, misinterpretation, confusion, and human error are bound to occur across sites. When a sponsor has no direct oversight to double-check or verify what the sites are using is correct, the likelihood of inconsistency increases.

Simply hoping each site will interpret the protocol document the same way and that the protocol calendar will come out perfectly every time won’t be enough in today’s complex research landscape; there will inevitably be errors.

Quality control

Having each calendar builder at every site interpret the protocol in his or her own unique way can have a negative impact on quality. The consequences of variations in protocol calendars can lead to deviations and violations during the participant lifecycle on the trial. Such deviations from the calendar can result in missed visits and inaccurate treatments, which create non-trivial safety concerns for participants and regulatory compliance challenges for the site and sponsor. This can negatively impact the quality of data and trial outcomes. In order to get all sites on the same page and using the same protocol calendar – one that exactly reflects the sponsor’s intent – there must be a single source of truth.

One version, one interpretation

Sponsors have an opportunity to take a more hands-on approach and be more directly engaged with sites. Creating a calendar once so that it can be used multiple times across sites shortens timelines and limits duplicate effort. This increased reuse helps achieve economies of scale to make clinical trials more efficient and systematic. Additionally, using a sponsor-approved calendar that defines exactly how a protocol should be executed removes guesswork for sites and helps ensure a consistent representation to improve quality. This will inevitably lead to increased compliance and productivity of protocols, creating a win-win for all.

About the author: Shree Kalluri is the Founder & CEO of Nimblify, a company he formed in August 2015 to pursue new, targeted technologies that make great strides in improving operations. Dedicated to improving trial outcomes by connecting stakeholders in clinical research in innovative ways, Nimblify’s technologies include Participant Payments, the Protocol Calendar Exchange, Research Resonance Network and Research Insights. For more information, visit

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