Front and centre: handling complexities of clinical trials

Central laboratories have long been a staple part of the clinical trials chain. Unlike many of the other services offered by CROs, central lab services are almost entirely outsourced, with few sponsor companies performing these activities in house. Sponsors, then, have gained valuable experience in partnering with central labs, along with a litany of subcontractors further down the line.

That said, this familiarity should not be taken for granted. As trial protocols become more complex, outsourcing practices are evolving rapidly and expectations are changing. This means central labs are now being called upon to offer an array of value-added services.

“Sponsors have traditionally relied on central labs for vital safety testing, endpoint analyses, and confirmation of patient inclusion and exclusion criteria,” says Angela Berns, director and head of vendor management at UCB Biosciences. “In the future, laboratories will have to maintain these basic services globally, but the expectations for enhanced efficiency in terms of set-up times, reliable delivery of data and seamless integration with data from other vendors will continue to increase.”

Having worked in the clinical research arena for 25 years – including a six-year stint at Amgen – Berns is well placed to note how service models are changing. She feels that the mark of a strong central lab is its ability to adapt.

“As we continue to innovate and look for disruptive models to target the unmet needs of patients, we strive to work with partners and vendors that are agile and continually advancing,” she says. “Laboratories must be moving beyond the routine analysis to support the development of targeted therapies, precision medicine, and investigation of new biomarkers and genomic assays.”

So, what is the role of the central lab in today’s pharma landscape, and what does a successful laboratory need to do to meet the shifting demands of sponsors?

Multiservice offering

At the most basic level, central labs are there to analyse patient samples and provide standardised results across the globe. Contrary to what the name might imply, a central lab is rarely a single brick-and-mortar institution. While such an approach may have sufficed in the 1990s, today’s globalised trials require a wide spread of facilities. Lab services, then, tend to take the form of virtual networks, spanning the geographic regions where trials are conducted.

Covance, for instance, which manages the world’s leading central labs network, has a reach of more than 60 countries, while Q² Solutions (formerly Quintiles) has locations dispersed as far afield as South Africa and Singapore. This trend is replicated across the board, with a particular move towards emerging pharma regions such as China in recent years.

In some cases, central lab services are run by a company geared specifically towards this purpose, while, in others, a CRO will operate labs as part of a full-service model. It should be noted that labs are not an essential part of a CRO’s service offering, and that most CROs, like sponsors, maintain their preferred vendor relationships. However, when CROs do offer multiple services – as is commonly the case today – there can be benefits for all concerned.

“These multiservice CROs can offer easier integration of data from various services, including the electronic datacapture system at the investigator site, the clinical trial management system, the interactive voice or web-response system and, of course, the central laboratory,” says Berns. “They may also have the added benefit of facilitating review through cross-functional dashboards, allowing review of the data from the various systems in real time.”

Whichever operational model is in place, the procedure is likely to be broadly the same. After lab results are collected, they are sent to the doctors overseeing the clinical trials, as well as to the sponsor for submission to the regulatory authorities. This service is vital at every stage of the trial, from patient accrual onwards.

“Laboratory parameters are key safety data in most clinical trials, but results that are outside of the normal standard reference ranges may be a flag to exclude a patient from participation,” says Berns. “Alternatively, results that are indicative of, or a marker for, a particular disease state may be used as inclusion criteria for a patient wanting to enrol in a clinical trial.”

She adds that, in addition to providing results, central labs also contract with courier companies to deliver the necessary materials for sample collection.

“These kits are built specifically for the clinical study and the materials are barcoded to allow immediate identification of the patient and ordering results automatically. This increases efficiency in sample receipt, processing, analysis and release of results,” she says.

An eye on compliance

While different central labs will take different approaches, they are usually able to perform about 80% of the necessary sample analysis on their own steam. However, certain types of tests may be subcontracted to specialist laboratories, especially if the work is highly esoteric, rarely requested or otherwise not practical to conduct in house.

In these instances, the central lab will need to conduct due diligence reviews of its potential partner, making sure it has the appropriate technical skills and quality management systems in place.

“These reviews should include financial, technical and quality assessments or audits,” says Berns. “Generally, these referral laboratories, once assessed, become established as qualified subcontractors, and the outsourced testing can be set up quickly and efficiently.”

If the speciality lab tests require any particular materials, such as specific collection containers for samples, the central lab will take charge of these and they will be included in the kits shipped to the investigator. Later, the speciality samples are shipped back to the speciality lab through the central lab, supporting a seamless supply chain.

“The laboratory information system of the central lab should enable integration of data coming from esoteric or speciality labs, and allow streamlined reporting to sites and sponsors,” adds Berns.

Sponsor companies, then, don’t have to worry too much about these subcontracted parties from a logistical standpoint. That said, it is critical that they do keep a close eye on the lab activities as a whole.

“ICH GCP E6 Revision 2 has specific language to ensure that sponsors maintain adequate oversight of the vendors that they contract with directly, as well as any vendors subcontracted by these primary vendors,” says Berns. “As part of the sponsor’s qualification activities for the central lab, the sponsor should ensure that the central lab has robust subcontracting procedures in place to ensure that they audit and qualify any potential subcontractors.”

Aligned values

While Berns can’t talk about UCB’s own outsourcing strategy in depth, she explains that it has evolved to be fit for the company’s purpose, combining a primarily strategic partnership model with functional service providers and a selection of technical vendors.

“This structured and, at the same time, agile arrangement allows UCB to focus on company strategy and direction,” she says. “The partnerships in place are supported by strong alignment and governance models, allowing UCB to dedicate internal resources to innovation and respond rapidly to an evolving research ecosystem.”

For UCB, the partner selection process came down in part to the principles they embraced. In effect, the partner needed to accord with UCB in its drive to develop solutions for unmet needs.

“Our partners embrace the same principles as UCB, based on our passion for science, and our desire to engage with and serve our patients,” says Bern. “In order to manage the handover between in-house and outsourced activities, we work closely with our strategic partners through established governance, streamlined processes with clear designation of roles and responsibilities, and open, transparent communication to ensure that we work as a single dedicated team.”

Each partner is trained to pay attention to their individual core metrics – budget, key performance and quality indicators. There are also systems in place to facilitate continuous feedback, allowing the teams to change tack where necessary. Clearly, effective outsourcing hinges on strong communication and managing the potential culture clash.

When it comes to future requirements, Berns feels that faster turnaround times will be key.

“This applies at the front end, when the samples are submitted by the investigator site, and in-process, as the samples are being analysed and results made available,” she says. “In this space, we are starting to see electronic requisitions, where the investigators complete their order for the individual patient sample analysis online, thus preventing the typical data entry errors and omissions.”

As the clinical trial outsourcing landscape continues to evolve, it seems clear that central labs will sink or swim based on their ability to offer such services, adapting to the complexities of today’s research environment and staying attuned to the sponsor’s needs.