Integration of Point-of-Care Devices in Clinical Trials

Laboratory point-of-care (POC) testing at investigator sites has been part of clinical trials for many years. Perhaps the most obvious example is pregnancy testing. Investigators also perform glucose tests and oxygen concentration tests, via pulse oximeters, at their sites. More recently, these tests can be performed at patient homes via innovative “connected” medical devices.

Over the past few years, there has been growth in the use of more complex POC laboratory devices in clinical trials. For example, devices have been deployed at investigator sites to screen and enroll a patient in a single visit, help reduce screen failure rates via a pre-screening step, and provide for results more rapidly than local labs.

• Screen and enroll in a single visit. A therapeutic influenza study required patients to be diagnosed with influenza prior to enrollment. The sponsor was concerned that if patients went home after the screening visit to wait for lab results prior to enrollment, those patients who became sick might not be able to go back to the site to become enrolled. To solve this dilemma, an influenza A/B POC laboratory device was utilized at each investigator site to enable screening and enrolling in a single visit.
• Reduce screen failure rates. A global chronic kidney disease trial used POC laboratory devices to test for estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) in a pre-screening step, which enabled subjects to be ruled out of a higher-cost screening process, ultimately reducing the screen failure rate.
• Faster results. A rare disease study used a POC laboratory device to test for C-reactive protein (CRP) in order to rapidly identify patients who experienced “heart-attack-like” symptoms but were not having a myocardial infarction. As soon as symptoms were experienced, the patients went to the investigator site for an assessment. The availability of faster results via the POC device helped reduce medical risks and provided a screening approach for the study.

In each of these cases, the POC laboratory devices were used for screening, but device data was not submitted to regulatory authorities. Instead, samples were sent in parallel to the central laboratory company (central lab), a clinical trial laboratory with globally harmonized laboratory systems and processes. The central lab produced lab reports for the clinical trial investigators and performed the data transfers to sponsors, who need the data for regulatory filings.

Why don’t sponsors utilize data from the POC laboratory devices in regulatory filings?

Historically, regulators and sponsors were concerned that investigator site staff, even with ample training, may not operate, calibrate, and maintain devices in a manner that would assure consistent results. This perception varies greatly by geography, indication, and individual investigator site. As POC laboratory devices become easier to use, in part due to regulatory scrutiny, and with expanded training and accreditation for sites, this concern should dissipate.

In addition to concerns around the operation of POC laboratory devices, these devices do not enable sponsor study team members (e.g,,. medical monitors) to view lab reports or receive alerts regarding out-of-range results. In addition, the devices by themselves don’t enable clinical trial study teams to receive and process laboratory data needed for regulatory filings.

Integrating POC laboratory device data with clinical trial laboratory systems

In the patient care space outside of clinical trials, POC laboratory devices are routinely connected to hospital laboratory and physician systems and electronic medical records (EMR) systems. The same concept has been applied to the clinical trial laboratory testing environment by connecting these devices to clinical trial laboratory systems.

There are at least two methods of integrating POC laboratory device data into central lab systems to enable viewing of lab reports and centralizing data transfers. First, POC laboratory device lab reports (print outs) can be manually entered into the central laboratory system. Central labs use a similar approach for local lab data entry. (Local labs are laboratories used in clinical trials that are near the site and may be able to provide results faster than central labs, due to reduced transportation time.)

The drawback of manually entering lab report data is the time it takes for investigator sites to provide the lab reports (with reference ranges) to the central lab, and the time spent by lab personal on data entry and quality control checks. This may result in a delay in study team visibility to POC laboratory device results. Machine learning can be used to partially automate the data entry process, but there is still a reliance on the site personnel to provide the lab report in a timely manner.

A second approach is to adapt what is done in the healthcare space to the clinical trial ecosystem. Instead of connecting the POC laboratory devices to a hospital lab system, or EMR system, the devices can be connected directly to clinical trial laboratory systems.

The POC connectivity solution takes a POC laboratory device, like those available for chemistry analysis or complete blood count (CBC), and connects them to a cellular internet of things (IoT) router. This enables transmission of the device data via a virtual private network (VPN) to a middleware, which then sends the data to the central lab.

The central lab enables visibility of laboratory reports, alerts for out-of-range results, and centralized data transfers.

Will POC laboratory devices replace brick and mortar labs?

The elimination of brick and mortar labs does not seem to be on the horizon. Many tests can’t be performed by POC laboratory devices today. In some cases, sample processing may require experienced laboratory professionals or additional equipment, which may not be available in all settings. Even if technology overcomes the hurdles associated with specific tests and processing requirements, the high-volume capacity and automation at commercial labs, hospital labs, and clinical trial labs may create a barrier to acceptance of POC laboratory device testing due to cost concerns.

However, in certain situations, POC laboratory devices may have advantages. For example, if a patient is undergoing surgery in an operating room, a faster result may provide better patient care even in a hospital with a lab. Within clinical trials, investigator sites in remote locations may make it challenging to get samples to laboratories in a timely manner, assuring sample stability, or like the hospital example mentioned, require a more immediate result. As such, connecting POC laboratory devices to clinical trial laboratory systems may be advantageous. It is interesting to note that in clinical trials today, the need for faster results sometimes drives investigators and study teams to utilize local laboratories. Perhaps a similar connectivity model will be developed to connect local labs with central labs. Of course, combinability of local lab data may still be a challenge, since local labs working on a given study or program may not use the same instrumentation, SOPs, reference ranges, etc. It would be particularly challenging related to biomarker testing, especially in cases where sponsor-specific biomarkers are utilized.

The future of POC laboratory devices and home-based testing

Many companies are developing and honing POC laboratory devices, so test menus may continue to expand, and instrumentation may continue to be easier to use. For more information, consider Select Science1 for a list of 130+ devices, the American Association for Clinical Chemistry (AACC)2, and Point of Care Search3, which provides a test-based interface. Note that you will need to request information from the website proprietors.

Today, many companies are racing to develop complex POC devices, which someday may be used by patients to generate lab results at home, perhaps via their mobile phones. These more sophisticated devices aim to enable a fast-at-home CBC, chemistry analysis, or biomarker test with data and reference ranges analogous to those available at brick and mortar laboratories. While devices like this have not yet achieved regulatory approvals, this approach could be the way lab testing is performed in the future.

References

1. https://www.selectscience.net/point-of-care/product-directory
2. https://www.aacc.org
3. http://www.pointofcaresearch.com

Chuck Drucker, MBA, Head of Alliance Management and Marketing; Guy Rachmuth, PhD, Vice President, Strategy and Corporate Development; and Jian Wang, PhD, Vice President, Head of Digital Innovation; all of Q2 Solutions