Editor's note: Corrections have been made in the final paragraph.

By Deborah Borfitz

May 29, 2019 | In many respects, High Point Clinical Trials Center (HPCTC) is not your run-of-the-mill phase I study site. It is one of less than a handful of clinical pharmacology facilities in the US capable of running technical metabolic studies, including those involving de novo lipogenesis and glucose clamping. It runs a mobile unit with strong brand recognition in the community, rolling to a new location on an almost weekly basis, and has close relationships with local referring physicians for highly collaborative access to patients for early proof-of-concept studies. HPCTC also offers the largest isolated smoking area in the country for combustible cigarette and vaping research.

President Lorraine Rusch, provides consultative, technically-focused advice to study sponsors and is an avid proponent of sponsor-driven involvement in the patient community. Patients who give freely of their time and data as study participants should understand the study outcomes and potential future benefits of those studies on their conditions, she says.

Under Rusch's leadership, High Point, North Carolina-based HPCTC transitioned from an internal clinical pharmacology unit of a local biotech into a commercial, dedicated facility focused on complex clinical pharmacology research. It is today a standout in the early-phase study space by virtue of its metabolic scientific expertise specific to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The experts include Vice President of Pharmacology Services Clayton Dehn, a key opinion leader in the metabolic area who spoke to research leaders at the recent NASH Summit in Boston.

The trials center has over 100 beds, in addition to a clinical pharmacology unit purposefully built for early-stage clinical development, says Rusch. HPCTC also houses cutting-edge technologies, including point-of-care ultrasound test FibroScan and instrumentation developed by YSI Life Sciences, which are key to its metabolic-focused research capabilities.

Adaptive Clinical Trials

Biopharma companies of every size now shortlist their lead compounds via adaptively designed studies, which are a big book of business for HPCTC, says Rusch. These studies typically involve healthy normal participants and patients dosed with an experimental drug long enough to show an effect or proof of principle. In many cases, they also include extra arms to evaluate other early-phase questions related to food effect, cardiac safety, and drug-drug interactions, she adds. While adaptive trials provide modest cost savings, their real benefit is in allowing proactive changes to dosing routes, regimens, and endpoints to expedite learning about an investigational drug under one protocol rather than several studies, she notes.

HPCTC is a reliable source of patients along the metabolic spectrum—from obesity and diabetes to NAFLD and NASH—because it has all the necessary relationships to provide imaging and lab tests to stage patients appropriately, including access to MRI and liver biopsy providers, says Rusch. Its technical expertise in designing appropriate endpoint testing, including de novo lipogenesis and glucose clamping technologies, is in high demand.

High Point Clinical Trials Center is currently negotiating an exclusive relationship with a leading contract research organization that would add eight to 10 new adaptive clinical trials to the roster each year, says Rusch. The project will entail a large, database-building exercise whereby lab values are used to predict the best patients to funnel into different study arms.

Community Outreach

General and study-specific community screenings rely on a mobile unit that gets driven to remote locations and popular local events, says Rusch. It is essentially a screening center on wheels, able to add high-tech extras as needed. Stops at two locations were responsible for about 40% of enrollment in one recent study, and at one event 300 people signed up to learn more.

This type of community outreach is wholly unique, says Rusch. "We're very grassroots about this—we saw the need, bought a van, wrapped it and put it on the road." In a slow-moving industry, "change and educational access for patients is long overdue."

Among the places the van has traveled is the Piedmont Triad International Airport, which hosts an annual charity run on its runway. "We do a lot of testing and general education there and it drives patients back to the facility or one of our remote sites," Rusch says.

Recruiters, physicians, and other staff of HPCTC also volunteer at the Community Clinic of High Point, which serves the local uninsured population, Rusch adds. Patients can get free testing (e.g., pulmonary function and EKG) and, if interested and qualified, opt to participate in an enrolling trial. Added benefits for participants include other medical screenings as well as stipends, she says.

Useful Technology

Recent technology investments have been game-changers for High Point Clinical Trials Center. This includes FibroScan, which noninvasively measures fibrosis (scarring) and steatosis (fatty change) in lieu of the "gold standard" diagnostic tool—liver biopsy. "Many physicians will not subject their patients to this procedure to diagnose NASH, a disease which currently has no cure," Rusch says.

FibroScan images from more than 1,000 patients, along with their lab values and demography, now populate a database being used to better characterize potential patients for studies, says Rusch.

As part of HPCTC's community service, the FibroScan device is loaned out to local physicians (including a gastroenterologist, endocrinologist and liver surgeon) so they can proactively test their patients and support referrals to the research facility.

Other technologies speed manual processes, Rusch continues. Tablet-based cognitive assessment software from Cambridge Cognition is being used as an alternative to paper questionnaires. Many drugs elicit cognitive effects as they cross the blood-brain barrier and FDA guidance "outlines the [agency's] expectations that the effects to be assessed in a scientifically rigorous manner. However, manually measuring, transferring and quality-checking vast amounts of data obtained from any sort of pen-and-paper cognitive test is unnecessarily labor-intensive," she adds. Even in a small study population, the typical 15-question survey tool generates thousands of data points that need to be verified. Using a tablet, patient responses can be quickly calculated and transferred into a database.

High Point Clinical Trials Center has primarily used tablet-based cognitive testing for tobacco and electronic nicotine device studies, as required by the FDA's premarketing tobacco application process.

A Few Cautions

When designing phase I studies, sponsors should remember that "patients can experience technology fatigue which will affect data quality," says Rusch. User acceptance testing in the real world can also yield differing results, so sites and sponsors need to carefully monitor technologies used in protocols to ensure they work in the field as expected.

Before adding too many apps and wearables into clinical trials, Rusch advises sponsors to consider the necessity and reliability of the data being generated. Studies often presume participants will have an appropriate phone, superior wireless connection, and the wherewithal to download and routinely use new applications—and this is not always the case.

"As client engagement and technology oversight needs increase, budgets for such studies will need to increase for this additional coverage," she points out. Her advice for keeping budgets reasonable, patients engaged, and data quality high is for sponsors to avoid "scope creep" by adding endpoints beyond a study's original intent.

Rusch also believes sites can and should be advocating for sponsors to share early trial results with participants, including those in phase I studies where the drug is still many years from market. "Patients need to know that their contribution matters," she says. "I look forward to the day when our industry updates these 'clients' in the same manner we update our investment communities—that would show commitment to patients in a very tangible manner."