January 20, 2015 | Clinical trial design has become more complex and the demands of the regulators ever more stringent, but clinical automation tools can make life easier on both counts. Clinical automation is a centralised software tool implemented within a clinical unit that supports volunteer recruitment, automates workflow through an electronic trial design schedule, drives operations at the clinical floor, and enables study data to be captured electronically (eSource), streamlining the clinical process. It also enables high quality data to be shared online, in real time, with the sponsor.

The Clinical Pharmacology Unit of SGS Life Science Services in Antwerp, Belgium, is equipped with an automated solution to support the management of Phase I trials. This automated solution efficiently collects all data types (trial execution, safety lab, and medical device data) directly into an electronic format (eSource).

Paper & EDC 

Prior to the implementation of the clinical automation in SGS’ Antwerp Unit, collection of individual patient data was done on paper Case Report Forms (CRFs), a tedious method that could result in data errors and wrong conclusions. The data collected on the paper CRFs were then entered directly into the clinical database. Inconsistencies in the database were queried using paper Data Clarification Forms (DCFs), which had to be tracked manually leading to increased administrative work at both the site and the Data Management department. Consequently, this process resulted in a significant delay in the availability of high quality, clean data to the clinical team.

Over the last five years, the pharmaceutical industry has embraced web-based electronic data capture (EDC) systems as the preferred means for research sites to input, share, and store trial data.  Despite widespread adoption of EDC systems, this solution has failed to significantly reduce the time and cost of conducting clinical research because EDC does nothing to address the most critical step in the data collection process – the initial point of capture with the patient.  When the initial source documentation is done via paper, data collection remains error-prone, time consuming and insecure.

eSource 

In a September 2013 guidance, the FDA promoted capturing source data in electronic form, ensuring the reliability, quality, integrity, and traceability of data, from electronic source, all the way through to electronic regulatory submission. eSource provides the opportunity to engineer accurate data with boundary and edit checks for missing and/or out of range data, devoid of contradicting information often represented by subjective reporting in an unstructured format. The source data should be attributable, legible, contemporaneous, original, and accurate (ALCOA) and must meet the regulatory requirements for recordkeeping.

The use of eSource is key to achieving the full efficiency benefits of automation at the clinical unit. Checks, time-alerts, and tube barcode verification improve quality during collection. Transcription is eliminated and data are available for review in real-time. Using the eSource as the electronic Case Report Form (eCRF), rewards the sponsor with important additional efficiencies by eliminating source document verification from the process flow, thus allowing a Centralized Risk-Based Monitoring approach, as well as retaining the classic benefits of Electronic Data Capture (EDC) tools. These benefits include an earlier database lock and online availability of clean data in real-time allowing dose-escalation decisions.

The latest advance is the ability to create a workflow in the system that guides the staff at the trial site through all the different steps of the process. It will indicate to the nurse that it is time to take a blood sample from the trial subject, for example, or to measure their blood pressure.

What are the benefits? 

There are many key benefits of implementing clinical automation. Quicker recruitment of trial subjects results from an easy-to-use scripted data collection wizard which, in conjunction with appointment scheduling tools, greatly assists in trial planning. An efficient and configurable inclusion and exclusion rules process uses data on demographics and medical history to select potential trial participants.

Once the panel of subjects has been identified, the trial protocol is faster to set up than traditional EDC systems – taking days rather than weeks. It can draw on libraries with adaptable elements, including test panels and tests.

Then, when the trial is actually being conducted, there are further benefits. Software follows the operational workflow of the nurses and lab technicians involved in the trial, providing the ‘what, where, whom and when’ information that is essential to run the study. The handheld devices used to collect data are also wireless, increasing the mobility of the nurses.

Direct data capture leads to a dramatic reduction in the need for paper records, either by nurses entering data directly into the system, or devices automatically providing readings. The devices, such as ECG and blood pressure monitors, interface with HL7, as promoted by the FDA. Sample management is also automated. A barcode-driven-system captures data and controls each sample’s progress. The results of the safety lab data are also automatically integrated into the database.

Consequently, a key advantage lies in the optimisation of data management. The eSource system can act as an eCRF platform, eliminating the need to design the eCRF. It allows data to be visualised and verified, reviewed and approved, complete with metrics. Queries are also managed within the system.

Furthermore, flexible data transfer options are a real advantage. SGS’ Data Management department can deliver CDISC SDTM datasets or CDISC operational model extract, for example, or a fully customised format as required by the sponsor. Sponsors can also access subject data on line, with real-time subject data monitoring enabling faster query resolution. And, of course, the system can automatically generate comprehensive reports.

Cleaning of the clinical data can start as soon as it is captured by the eSource software that is at the heart of the system, and they are immediately available for import into the clinical database, with no requirement for data extracts. No additional monitoring time is necessary, as these queries can be raised in parallel with cleaning. Limited source verification is required, and the monitoring can be done remotely. As a result, the database lock will be earlier.

As with all new technology, challenges have been encountered. Internal learning curves may be longer than expected, and the implementation needs to be supported by standard operating procedures and work instructions. There are learning curves that need to be overcome within the sponsor companies, too, as it will influence their in-house structures and processes. But once these learning curves are overcome, the advantages of moving to a clinical automation system are clear, with time saved, costs cut, and errors eliminated.

Wim Verreth is project director, biometrics and medical affairs, SGS Life Science Services. He can be reached at wim.verreth@sgs.com