Clinical Researcher—December 2022 (Volume 36, Issue 6)

TRIALS & TECHNOLOGY

Brad Vince, DO

Phase I clinical trials are unique in the drug development process in that they require overnight confinement of study participants to a research facility for days and sometimes weeks at a time. Furthermore, instead of patients who are afflicted with the disease or condition being studied, Phase I trials typically use participants who do not have any significant medical conditions, known as “normal healthy volunteers.” Lastly, while late-stage trials have flexible windows for study visits and procedures, Phase I trials are the exact opposite; their visits follow narrowly defined schedules, and their procedures must be performed at exact timepoints relative to the administration of the investigational product, all of which adds up to a very labor-intensive process. These stringent requirements give rise to unique challenges during Phase I study conduct.

Perhaps the most significant challenge that contract research organizations (CROs) face when conducting Phase I trials is the lack of updated, purpose-built facilities for them. In many cases, Phase I sites are placed in antiquated buildings that have been repurposed to conduct early-phase trials. Unfortunately, these facilities do not invite the same level of innovation or efficiency found in modern building design and construction.

Fortunately, even the most outdated buildings can benefit from several innovative modalities that can propel them into the modern era of research. The following is an overview of challenges faced in early-phase studies and the corresponding technologies that help overcome and eliminate these issues.

The Quality Conundrum

Many clinical research sites still utilize paper source documents, recording data manually and then transcribing it into a database sometime later. At minimum, this presents two instances where manual entry can cause data errors. What’s more, if there is a mismatch between the information captured on the source document versus the information entered in the database, a query may be issued. Given the large number of datapoints captured in a Phase I study, query resolutions can cause considerable delays in achieving database lock, which will impact the timeline of nearly every downstream deliverable.

Phase I CROs should consider leveraging an electronic source (eSource) platform to significantly reduce the potential for error by automatically transcribing the data into a database. This technology can save even more time and yield even more powerful insights when integrated with additional equipment, such as vital signs machines, ECGs, and barcode scanners. When properly deployed, this equipment allows real-time transcription with no manual data entry or human calculations of any kind. This can significantly reduce the time spent on query resolution and provide even greater efficiencies when trial investigators can review and sign off on data remotely at any time of day.

The Paper Trap

Continued reliance on paper documentation creates numerous issues that cause challenges for research sites across the board. Paper records require wet ink signatures, which can create a bottleneck for completing study-related activities and require the documents to be physically stored onsite for the duration of the trial and beyond. Again, this invites the possibility of human error when records are moved or modified, creating a significant obstacle in producing complete datasets and finalizing trial closeout activities. Furthermore, when the time comes to monitor your data, tracking down paper records for clinical research associates requires significant resources that could otherwise be used to support clinic activities.

To solve these issues, Phase I sites should adopt a digital and cloud-based investigator site file for document management. These systems offer signatures that are compliant with 21 CFR Part 11 in the Code of Federal Regulations for long-term records with remote monitoring and the ability to automatically redact specific parts of documents to maintain blinded data and participant privacy during sponsor review. In addition, all document audit trails can be reviewed and downloaded.

The Trouble with Temperature

Early-phase trials often require extensive onsite storage for investigational products (IPs) and pharmacokinetic samples collected from participants. Storage requirements are outlined in established procedures, pharmacy manuals, and laboratory handbooks, and they specify the acceptable ranges that still allow for taking precise measurements, such as those for the temperatures found in freezers, refrigerators, and ambient spaces. If these environmental settings fluctuate outside the permissible ranges, drug products and samples could be rendered unusable, resulting in unnecessary waste and additional delays to trial activities.

To prevent significant excursions, 24/7 cloud-based environmental monitoring should be utilized in all pharmacy and sample storage areas, as well as in temperature-controlled equipment. The most effective environmental monitoring platforms will send alerts to relevant site staff via phone calls, text messages or e-mails, and these alerts will be accessible remotely from any browser or web-based application. Typically, a dashboard will provide an overview of all environmental conditions being tracked, displaying real-time readings and graphical representations of the data gathered by each sensor over time. Best of all, these platforms allow for 21 CFR Part 11–compliant data logging with clear audit trails and secure user access.

Inventory Management

As labor-intensive as Phase I trials are, they also require large volumes of supplies and materials. A Phase I site must avoid inadequate or expired inventory at all costs, as either scenario can be problematic for a study. Using expired test tubes can result in protocol deviations, potentially compromising study data and demanding attention through a corrective and preventive action (CAPA) plan. As such, having a system in place to provide visibility into inventory levels and track lot numbers and expiration dates is of considerable benefit to both the site and sponsor.

The Little Things Matter

Often, the adoption of technology in clinical pharmacology studies has been resisted due to caps on capital expenditures, limited overall budgets, and a lack of adequate training. The unfortunate truth is that many facilities are not profitable enough to fully invest in technology, and even if the funds were available, post-pandemic realities coupled with the strain of the “Great Resignation” has created an environment where clinical research sites are too busy and too short-staffed to challenge the status quo. As a result, systems in clinical pharmacology studies will remain antiquated as long as “good enough” remains the prevailing mentality across Phase I sites.

Fortunately, sites do not need to make substantial investments across the board to improve their operations. The little things matter, and minor expenditures can have a significant impact on a site’s results. For example, having the technology to contact study volunteers via their preferred method of communication, such as a text message, can decrease no-show rates for study visits. Transitioning a participant database away from spreadsheets to a cloud-based system can allow investigators to make real-time updates. Biometric security controls for pharmacy areas can help ensure that IPs are not handled by anyone other than approved staff.

Implementing these functions is fairly cost-effective, and training researchers to use them is quick and easy. Ultimately, small updates like these can alleviate the burden on staff and better optimize their time. In doing so, Phase I sites may find it possible to make even greater investments with a truly meaningful impact on clinical pharmacology studies as they progress into the future.