ASCO 2022 – Standing ovation and hope.
Astra Zeneca and Daiichi Sankyo’s Enhertu is the first targeted treatment prolonging progression-free survival of HER2-low breast cancer patients.
Presented in the @NEJM and at #ASCO2022 (Phase 3 Destiny-Breast04 clinical trial), Enhertu almost doubled median progression-free survival to 10.1 months over chemotherapy (5.4 months) in women with HER2-low, estrogen receptor-positive breast cancer, equivalent to a 49% reduction in the risk of progression. Around half of all breast cancers are considered HER2-low (IHC score 1), meaning that a major life-changing drug is on its way for hundreds of thousands of patients.
Trastuzumab deruxtecan (formerly DS-8201), an antibody–drug conjugate consisting of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload through a tetrapeptide-based cleavable linker, has been approved for the treatment of patients with metastatic HER2-positive breast cancer who have received prior anti-Her2 based treatment and relapsed. It binds to and blocks the signaling of the epidermal growth factor reception 2 (Her2).
Once it is bound to Her2, it is internalized and the payload (deruxtecan) interferes with DNA replication during mitosis, ultimately resulting in DNA damage and cell death. A main adverse event caused by Enhertu is interstitial lung disease (ILD), which will need to be carefully monitored in Her2 low breast cancer patients during the administration of this drug.
At Cerba Research, we pride ourselves on providing state-of-the art histopathology services, alongside our global central lab footprint. With a biobank of over 3,000 samples and Her2 as a validated marker, we are ready to take on the challenge to expand our capacity and support the development of more breast cancer drugs that will undoubtedly come to light on the tails of this fantastic new development.”
How Cerba Research Helped Advance a Phase IIb Study in the Middle of a Pandemic and Brexit
by John Hinton, project manager, Cerba Research USA
A two-country clinical trial that involves a nasopharyngeal swab and two assays sounds relatively straightforward. But when you’re conducting a study during a global pandemic and Brexit, nothing is simple.
A combination of creative logistics, careful planning, and a strong customer relationship allowed Cerba Research to keep sample processing for a novel COVID-19 treatment on track in the middle of extraordinary upheaval.
The case: A randomized, controlled Phase IIb clinical trial to evaluate the safety and efficacy of the sponsor’s drug for high-risk subjects with mild COVID-19. The subject population enrolled a total of 600 men and women aged 18 years and over, recruited in the U.S. and the U.K., and initially included 25 U.S. sites and 10 U.K. sites. However, as COVID-19 continued to impact investigator and site availability and patients’ willingness to visit sites, the sponsor moved to a decentralized model.
Once the sponsor randomized patients into the trial, a “COVID in a Box” kit was delivered to patients’ homes. Patients could then decide whether to participate on-site or remotely using telemedicine. Most chose the latter.
Once the patient supplied the sample and repacked the box, an agent from Marken, the preferred courier, arrived within the hour to collect the sample. Both agent and patient followed a strict process using physical distancing and personal protective equipment (PPE) during the handoff.
The challenge: The sponsor had an ultra-quick turnaround time. For example, it requested a fully executed contract one week after the award. It also had a three-month window to ship supplies and bring sites online.
According to our stability testing, samples had a maximum room temperature stability of 72 hours between collection and testing. Samples had to move fast, and shipments coming through U.K. ports were at their peak due to Brexit concerns.
How we responded: Cerba Research had a strong preexisting relationship with the sponsor. The high level of established trust allowed us to obtain approval and execute all contracts quickly.
Kit production for the U.K. sites took place at Cerba Research’s central lab in Ghent, Belgium. Kit production for the U.S. sites occurred at our New York facility. Staff from other departments came in to help manually assemble kits. Others worked evenings and weekends. With teamwork, the necessary collection materials, requisition forms, and PPE were kitted into each COVID in a Box in as short a time as possible. Necessary random batch QC checks were performed before we forwarded the kits to the U.K. investigator sites in bulk.
Concerned about the short stability window, our lab in Johannesburg, South Africa, conducted an additional long-term stability experiment on the Abbott m2000sp sample preparation platform using the Seegene Allplex 2019 kit. Based on this data, we were able to extend the stability of the samples from 72 to 96 hours. Marken managed all inbound shipments. No samples were lost to stability issues.
Get all legal and vendor onboarding agreements in place early, perhaps prospectively. Even with necessary agreements in place, responsiveness and goodwill will help smooth the process.
Find practical solutions to sponsor challenges. Cerba Research experts in two different continents came together to find a way to overcome Brexit-related logistical challenges and execute within a tight timeline.
Bring in your central lab partners early. During preliminary conversations, we can evaluate assay stability, lab capacity, logistics, screening timelines, and other important aspects of your study. Early involvement helps us develop strategies to advance your research sooner.
Build a relationship of trust. Cerba Research’s reputation — built on robust governance paired with open, transparent conversation and a commitment to do whatever it takes to keep studies on time and on budget — allowed us to get the rapid client buy-in required to deliver under challenging circumstances.
For more than 35 years, this commitment is why organizations worldwide choose Cerba Research: the central lab centered on you.
Integrate IHC Biomarkers for More Effective Clinical Development in IO
by Amanda Finan
Immuno-oncology (IO) research carries a low probability of success. The likelihood-of-approval rate for oncology in general falls well below average — 5.3% vs. 7.9% for all indications.
Biomarkers can improve the clinical trial success rate for pharma and biopharma drug developers by allowing for the selection of patients more likely to respond to a potential new therapeutic, by enhancing safety, and by serving as surrogate clinical endpoints. Statistically, the use of biomarkers for patient stratification increases approval rate five-fold (Wong et al., Biostatistics, 2019).
The integration of biomarkers — and the process of choosing from the lengthy number of candidates — into a comprehensive clinical development plan to increase the effectiveness of your clinical trial is always a quandary. The less-invasive approach is to look at systemic protein or genomic biomarkers in bodily fluids or circulating tumor or immune cells.
In oncology, however, pathologists can obtain critical information from tissue biopsies that they cannot observe at the systemic level. Using classic techniques such as immunohistochemistry (IHC) and in situ hybridization (ISH), they can observe not only the presence of an antitumoral response, but also information on its presence and actual engagement at the tumor level. For these reasons, biopsies are a must when monitoring the effectiveness of anti-blockade treatments in clinical trials.
Histology (IHC) Helps Us Understand Biomarker Mechanisms in the Tumor Environment
Immunohistochemistry technology has historically been, and remains today, the gold standard of clinical pathology. It is a simple (Fig. 1), cost-effective, readily available method for profiling biomarkers to individualize a patient’s therapy.
How IHC Works
IHC offers very different information compared with other types of biomarker approaches. In flow cytometry, for example, individual cells in suspension are evaluated, with no fixed relationship. In genetic screening (e.g., NGS), the sample corresponds to a homogenization of the tissue. With IHC, you can appreciate the context of the target within the tumor micro-environment. The possibility of spatial analysis — learning where types of cells are located or where the target is in relation to other structures — is a key advantage of IHC.
IHC allows a greater understanding of the following:
- Tumor microenvironment
- Tumor structure
- Spatial relationships between cells of tumor, stroma, and immune origin
- Status of immune response at the tumor site
The Value of Multiplex IHC
It has become increasingly apparent that with the complexity of immuno-oncology, a single biomarker may not be sufficient and has thus led to a need for multiplexing techniques in
preclinical and clinical studies. Multiplex IHC allows for the detection of multiple biomarkers (up to eight) on a single tissue section, broadening mechanistic investigations. Harnessing the power of multiplex IHC can expand your biomarker research by allowing for a myriad of analyses, including in-depth immune cell phenotype analysis (e.g., regulatory T cell — CD3+/CD4+/CD25+/FoxP3+) and target localization (e.g., Ligand in relation to a receptor, protein expression on specific cell types).
Multiplex IHC is particularly useful in preclinical and early and retrospective clinical studies. These early investigations can have more flexibility to study a panel of candidate biomarkers that could (Fig. 2) accomplish the following:
- Detect a specific drug target of interest, look at its level of expression, and determine its localization. Is it expressed in the healthy tissue or is it within the tumor? Is it expressed on a certain cell type?
- Examine the mechanism — the biology of interactions in the tumor microenvironment between the tumor, the infiltrating immune cells, and the stromal cells that are supporting the tumor.
- Profile immune cells and understand where different subtypes are within the tissue, such as CD8 T cells. For example, are these immune cells within the tumor (hot) or do they stay on the periphery (cold)?
- Look at interactions between different cell types: are they within proximity of one another and possibly communicating?
Combining the multiplex and clinical data can then be used to identify a more focused biomarker approach that is more applicable in later phase clinical trials.
Having had one of the first multi-spectral imaging systems in Europe, Cerba Research has years of multiplex IHC experience and has developed off-the-shelf panels with a number of common immuno-oncology targets. We have the expertise and technology to help you understand the neighborhoods of your tissue sections, always with respect for the patients behind the samples.
Fit-for-Purpose IHC Assays Must Be Validated for the Intended Use
Once the basics have been determined — which biomarkers are relevant, what tissues are being studied, the intended use (e.g., proof of principle, mechanism), what type of analysis is relevant — we can generate a fit-for-purpose assay.
A robust biomarker validation process is crucial for the successful integration of biomarkers into a clinical trial. It requires collaboration between you and your specialty lab at each stage of preclinical and clinical development with special attention to the protocol optimization, specificity, sensitivity, and precision.
At Cerba Research, our IHC expert scientific team is flexible in their approach and delivery to providing timely and cost-effective solutions to meet your clinical and commercial objectives.
Cerba Research solutions include:
- A catalog of available protocols
- Development of custom IHC assays and validations for preclinical and clinical studies
- Access to numerous indications in our tissue biobank to facilitate target detection in multiple disease areas
- Guidance by IHC experts
- Support technologies (imaging mass cytometry, Nanostring, cell culture, antibody target screening)
Shape Your Immuno-Oncology Research With IHC
Detection of specific antigens in tissue sections by IHC is a unique tool in cancer and immunotherapy research. It can provide far more detailed insights than standard histopathology. With special techniques such as multiplex IHC and ISH, tissue biomarkers can yield crucial insights for diagnosis, patient stratification, or mechanistic evaluation. Proper validation is required for regulatory acceptance, provides confidence in the results, and improves the chances for success in I/O clinical trials.
Together, Lowering the Global Tuberculosis Burden
On World Tuberculosis Day, we raise our voices to increase awareness of the indication that is still one of the top ten causes of death worldwide and the leading cause of death from a single infectious agent. While curable and preventable, research is still needed to reduce tuberculosis (TB) incidence worldwide.
Research Breakthroughs and Clinical Trials Are Key
TB treatments have been used for decades, and strains that are resistant to one or more therapeutics have been documented worldwide. The evolution of the strains requires innovative breakthroughs in the prevention and treatment of the illness. Looking at the clinical trial landscape, we can see that at the moment there are 183 ongoing clinical trials on tuberculosis worldwide, 83 planned clinical studies on tuberculosis worldwide, and that the majority of studies are run in the Asia-Pacific and African regions, where TB incidence is highest.
At Cerba Research, we are committed to shaping patient’s lives. When it comes to battling TB, our experts and laboratories worldwide support drug and vaccine developers in their effort to reduce TB prevalence. Our strong presence in South Africa, one of the eight countries that account for two-thirds of new TB cases, highlights our commitment to lowering the global TB burden.
P3 Labs and TB Testing
TB testing requires a P3 laboratory and, often, the use of GeneXpert machines, which have mainly been reallocated in 2020 as a global response to the COVID-19 pandemic.
Our affiliate in South Africa, BARC SA, has one of the largest TB P3 laboratories in Africa, consisting of a P3 facility and a separate area for MGIT analyzers and microscopic analyses. This lab, combined with our network of laboratories in Europe and North America, has the testing capacity and capabilities needed to support TB clinical trials on an international scale.
Furthermore, we understand the need to develop TB testing to support the research agenda of quantitative detection and further characterization (Targeted Next-Generation Sequencing for resistance detection, species determination [RFLP, TB Fingerprinting, whole-genome sequencing]) of TB.
Together, let’s lower the global tuberculosis burden.
- World TB Day 2021. (2021, March 22). WHO. https://www.who.int/campaigns/world-tb-day/world-tb-day-2021
- Global Data. (2021, March 22). Global Data. https://pharma.globaldata.com/ClinicalTrialsPartial/Search
- WHO. (2020). Global Tuberculosis Report. https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdf
5,000 Liver Biopsies? What It Took to Support the Largest Global Phase III NASH Study
At Cerba Research, previously Barc Lab, comprehensive central lab services are at our core. When you partner with us for global central laboratory services, our 35 years of experience, and industry-leading laboratories spanning five continents, our sights are centered on your trial success.
That’s why, in 2016, a midsize biotech engaged our services for the largest Phase III nonalcoholic steatohepatitis (NASH) study to date. NASH affects almost 12% of people in developed countries, with a growing number of patients progressing to end-stage liver disease. The need for NASH therapeutic agents is urgent, so we were eager to help.
Central lab services we provided for this study included:
- Global liver biopsies, slide handling, and processing for KOL investigator
- Safety analysis, patient monitoring for response to drug and placebo
- Biomarker testing
- Project management
- Site support
- Unified global study database
In NASH Screening, the Liver Biopsy Is the Gold Standard
Managing global clinical trial testing can be challenging, and NASH is an indication with real operational complexity. To succeed, we had to leverage all our experience — and a large number of NASH-knowledgeable local affiliates — to manage the scores of sites, countries, and patients involved.
Between 2016 and 2019, our work included:
>5,000 liver biopsies
>2,000 patients randomized
NA, EU, AUS, AF
NASH Study Complexity Extends Beyond Liver Biopsy Collection
Liver biopsy results are often the primary endpoint in monitoring NASH disease progression and remain the gold standard for diagnosis. In NASH clinical trials, biopsy processing, staining, and reporting are all crucial. Through experience, flexibility, and attention to detail, we were able to apply robust quality processes at every step of the complex biopsy workflow for over 5,000 patients screened at more than 600 sites in 31 countries. Our teams leveraged expertise in:
- Liver biopsy performance
- Logistics around biopsy blocks and slides
- Custom staining
- Digital imaging and software analysis of stained samples
- In-house NASH testing
- Flexibility to adjust processes toward agency updates/requirements
- Relationship building with key opinion leaders (KOL)
Reading the subtle histological changes that characterize NASH biopsies is practically an art form, mastered by only a handful of KOLs worldwide. Excellent cooperation with these top pathologists paired with skilled slide preparation — including digital imaging and analysis — ensured the consistent biopsy readings delivered in this successful study.
The Right In-House Validated Biomarker Testing Makes All the Difference
From noninvasive tests for fibrosis scoring to biochemical urine markers to liver tissue tests, NASH trials can require a vast range of validated testing, from basic to exploratory options. And with a global trial like this one, study teams rely on comparability of results and easy data access.
Because Cerba Research offers guidance and a vast portfolio of biomarkers required for NASH and other trials, our client had no difficulty obtaining what was needed. Even assays we don’t normally carry can be added and validated in-house. Generally, our biomarker testing covers:
- Genetic predisposition
- Inflammatory biomarkers
- Glycemic and lipid biomarkers
- Safety and serology
Lab Support for NASH Studies Has a Definite Learning Curve
The processes and logistics for supporting a study of this type are far from simple. However, NASH is a key indication for Cerba Research, so our quality processes and experience were primary factors for successful conduct in a global trial this large. The team established detailed operational workflows and internal monitoring with a focus on the primary endpoint liver biopsy.
Our worldwide affiliates’ regional project managers supported local requirements and helped maintain global consistency and standardization. Cerba Research’s proactive site training and monitoring reinforced sites’ compliance with protocol expectations, including quality slide production and correct blinding practices. Furthermore, a unified global study database enabled study teams around the globe to access all trial data via our online portal.
Cerba, the Central Lab Centered Around You
We believe customer-focused project management is essential to conducting a smooth trial. It took a lot of collaboration to manage every component of this project. Our SMEs and PMs communicated openly and proactively with our client throughout to optimize processes and services. Generally, the Cerba Research team is able to help with optimal biomarker selection given the study requirements, molecule, and budget. We can also help ensure the proposed protocol will be compliant with evolving FDA, EMA, or other regulatory body suggestions or regulations.
Additionally, we partner effectively with CROs offering them our NASH expertise. For instance, a joint CRO-lab offering, integrated seamlessly, can be a win-win and deliver great results and efficiencies for sponsors.
At the same time, NASH studies are notorious for high screen-failure rates and ballooning costs. At Cerba, we monitor the budget closely throughout the trial, tracking expenditures and flagging any outliers or excesses right away to address potential overages proactively.
Learnings From This Trial Help Us Anticipate Future Needs
Change is a given in clinical research, especially in indications as new as NASH. We have applied insights from this Phase III NASH trial to develop an improved suite of offerings that increases efficiency for our clients and addresses forthcoming regulatory updates. In particular, we were inspired by the new requirement for multiple biopsy readers and the expected progression to digitalization and evaluation by AI. Our liver biopsy services will soon or already include:
- Digitalized slides
- Integrated platforms
- Next-generation image analysis
- An app to improve processes
Other novel offerings are:
- Metabolomics, whereby a mass spec profile of serum metabolites is analyzed against a NASH/steatosis database. This method can be used to evaluate short interval responses to therapy, investigate a drug’s mechanism of action, or tailor a companion diagnostic.
- BioKortex, a patient-centric recruitment solution that uses the vast Cerba HealthCare patient database to save sponsors time and expense through customized digital tools, patient-enriched data, and partnership with strong medical laboratory networks.
- Richer resources for site training and site performance management along with a site performance database to gauge the likelihood of success.
We expect these newer options will provide added value for our clients.
Cerba Means Certainty
Reaching a global patient base can be challenging — but across continents to rural villages, through language and customs barriers and regulatory requirements — Cerba gets the job done. Through close partnership, we provided this midsize biotech company with global access to the industry-leading laboratories, scientific experts, and skilled project management needed to support this challenging NASH trial successfully. As part of our comprehensive lab support, we processed more than 5,000 liver biopsies and had them certified by a KOL.
When you partner with Cerba Research for global central laboratory services, our sights are centered on your clinical trial. Rely on more than 35 years of experience, industry-leading laboratories spanning five continents, and six-week standard startup time. You’ll experience seamless efficiency and excellence in central lab support for your trial from The Central Lab Centered Around You.
3 Central Lab Capabilities Mandatory for I/O Clinical Trial Success
In the exploding field of immuno-oncology (I/O), delivering the right treatment to the right patient at the right time requires expert, integrated clinical laboratory and diagnostic solutions delivered by top scientists who will help you assess needs and generate early insights that optimize your protocol. Along with access to a sizable patient database, impeccable performance across the globe, and I/O experience, three main testing capabilities are nonnegotiable when selecting a lab partner for the challenging journey from translational research to commercialization.
Biomarkers make all the difference in immunotherapeutic and personalized medicine
For a drug developer, the value of obtaining early biological insights that help identify the right patients, treatments, dosages, and durations and streamline complex trials cannot be overstated. Biomarker development and validation are key to:
- Guide dose selection
- Characterize mode of action or resistance
- Stratify patients/determine inclusion-exclusion
- Predict drug efficacy and safety profiles
- Aid in prognosis
- Monitor disease
At Cerba Research, where half of our studies are in oncology, access to biobanked human specimens provides a clear advantage when identifying novel and existing I/O-related pathways including tumor morphology, tumor genetics, tumor protein and gene expression, and tumor infiltrating lymphocytes (TILs). Related biomarkers can then be developed further to stratify patients into treatment groups, gauge efficacy, formulate hypotheses, and increase the trial’s probability of success.
3 types of test support a wide variety of biomarkers
For precision medicine in immuno-oncology, a complete program enabling a 360˚ view of patient status and tumor susceptibility demands experienced guidance and customization for three types of testing: flow cytometry, tissue immunohistochemistry (IHC), and genetic screening (next-generation sequencing, NGS).
Flow cytometry is a powerful technique that rapidly detects and measures thousands of cells with high sensitivity and specificity, providing a snapshot of the immune response. Beyond cell surface markers, flow cytometry can also detect intracellular antigens such as cytokines and phosphorylated signaling proteins. This methodology allows functional analysis and helps with therapeutic strategies and prediction of therapeutic response. The simultaneous use of many biomarkers generates data that is multifaceted, highly complex, and dimensional.
Immune profiling by flow cytometry produces a large amount of information from a single blood sample. The result is a very granular breakdown, for example, of lymphocytes and subtypes, down to T cell memory subsets and activated-versus-nonactivated markers. Clinical researchers can utilize this technology to understand how patients are responding and what kind of therapies are suitable for patient-specific treatment plans.
These studies demand highly skilled staff scientists to develop and validate both off-the-shelf and novel biomarkers. Therefore, the lead time for assay development to validation must be considered. Further, for global trials, a standardized approach is critical, including instrument standardization and assay process standardization (same SOP).
Immunohistochemistry (IHC) is a cost-effective assay that profiles tissue biomarkers to individualize a patient’s therapy. It is an antibody-mediated approach that allows detection of the target of interest in the tissue through fluorescent or chromogenic revelation for quantification and cellular localization. This technique has typically been used for the diagnosis and classification of tumors such as lymphomas and breast cancer. In addition, IHC conveys structural information about the tumor and the tumor microenvironment, demonstrating the localization of immune cells in relation to the tumor or other immune cell populations. It can also reveal the expression of activation/deactivation biomarkers as part of immune cell profiling and oncogene evaluation. Cerba Research offers sponsors an ever-increasing number of novel I/O biomarkers, including hard-to-develop, customized IHC assays for the preclinical phase, with subsequent validation for use in clinical trials.
Multiplex IHC, the combination of several biomarkers on a single slide/section, is an advanced version that allows for the detection of up to eight biomarkers in one precious tissue section. The ability to detect more biomarkers per slide is increasingly important as:
- Demand for more biomarkers is growing.
- Accurate phenotyping requires several markers.
- Biopsy size limits the number of sections.
- Some data cannot be obtained from circulating markers, such as spatial context and organization and distances between populations of cells.
NGS for genetic screening
Genetic screening measures changes in nucleic acid sequences associated with disease susceptibility or resistance. Next generation sequencing (NGS) enables a wide range of new applications and investigations in genetics, including analysis of solid and hematologic tumor genomes as well as in-depth analysis of the patient’s immune repertoire pre- and post-treatment, including T cell receptor (TCR) analysis.
Cerba Research’s capacity for high throughput, with the ability to sequence 1,000+ whole human genomes in a week — coupled with one of the largest catalogs of clinical NGS genetic and genomic testing — helps ensure that sponsors reach milestones and preserve development timelines, whether they need whole exome sequencing or gene panels customized to suit their protocol.
Applications of genetic insights to look for:
- Biomarker discovery, with comprehensive genomic profiling and customized assays that link mutation to disease
- Prospective patient stratification screening with NGS, PCR, and other assays
- Companion diagnostics development on NGS-based or CHIP-based multiplex qPCR platforms to assess therapeutic suitability
- Cyto- and molecular-genetic diagnosis of constitutional and acquired disorders, including developmental disease, predisposition factors, and clotting malfunctions
As an example, the tumor mutational burden (TMB) is a genetic biomarker currently receiving some attention. Cancer is the result of a series of mutations, and cancer cell lines each have between one (1) and around 10,000 coding mutations, or .1 to 100 mutations per megabase — the tumor mutational burden. TMB is associated with antitumor response and is a good predictor of response to cancer immunotherapy drugs in some cases, such as melanoma, cutaneous squamous cell carcinoma, and certain colorectal and noncolorectal GI cancers. The reason may be that tumor cells with high TMB have high neoantigen loads, leading to greater T cell reactivity and an enhanced antitumor T cell response. Although the gold standard for TMB analysis has been whole exome sequencing, recent advances in NGS tumor panels have provided consistent results.
Support for immuno-oncology trials depends on experience and commitment
With ever-expanding possibilities for specificity and design, immune-based therapies are pouring into the clinical research funnel. In immuno-oncology clinical trials, finding the proper resources to achieve your goals can be a challenge. Three main testing methodologies are needed for immuno-oncology: multiplex immunohistochemistry (IHC) for solid tumors, flow cytometry for cells in suspension, and genetic studies (NGS).
Partnering with a high-performing global central lab like Cerba Research for patient- and science-driven insights can help you optimize your protocol, then seamlessly ramp up to commercial scale. You will be able to minimize expenditures while keeping timelines intact — and bring groundbreaking therapies to patients sooner. With over 35 years of experience, Cerba Research is a leader in immuno-oncology clinical trials, providing global solutions that include a vast array of biomarker assays and expert validation services. Start with Cerba Research. As your partner, we empower you to bring new life-changing therapies to patients worldwide.Together, we’ll change the shape of your clinical development.
How We Put Patients First On a Daily Basis
September 17th marks World Patient Safety Day, an initiative created by the WHO to bring awareness to the safety of patients all around the world. As a clinical laboratory whose mission is to help shape and advance clinical trials and ultimately improve patients’ lives, their safety lies at the core of our business. We’re also proud to have directly supported Health Worker safety through our various COVID-19 testing projects across the world and support the WHO’s slogan of “Safe health workers, Safe patients’.
So, how as a leading, global clinical trial laboratory service provider, do we put patients first on a daily basis?
Every employee at Cerba Research, no matter the job function, completes the Good Clinical (Laboratory) Practice training. We ensure our entire organization is, aware of our responsibilities regarding the conduct of clinical trials in order to meet GCP’s objective; ensuring that the rights, safety and well-being of human subjects are protected. This is also reinforced in our company culture whereby patient safety supports our core values and mission.
While perhaps not the most obvious in terms of patient safety, data security is paramount to the well-being of patients in clinical trials. It is vital to secure the privacy of subjects, to guarantee that people cannot be identified based on the samples and (medical) data. Similar to our GCP training, all employees attend mandatory training on data security and GDPR compliance. Further still, our CISO and DSO ensure that our IT infrastructure remains secure and that we have the appropriate systems and checks in place to maintain data security at all times.
Sites and Sample Collection
As a clinical trial laboratory, we have a fundamental role to play in patient safety as the data we produce are critical to health care decisions that will be made affecting diagnosis or treatment. Any analytical or diagnostic error therefore has the potentially to significantly affect patient safety and drives our unrelenting focus on quality all the way through our processes.
These processes begin even before any samples are taken, whereby careful measures are taken to minimize discomfort and pain for the subjects and guarantee the health worker’s safety. Our in-house kit-building team and project management team are instrumental in this. Through them, the sites receive both instructions on how to take samples and the necessary equipment to do so thus creating an informed and protected environment for both.
Through accreditation by the major bodies, we ensure that testing is always done to the highest standards, ensuring accuracy and reproducibility of results. Our deep scientific, technical and operational expertise mitigates any risk during the journey from sampling through to reporting, thus ensuring certainty of results.
Towards the future
Clinical trials continue to evolve, bringing new requirements but always with a focus on the patient to ensure their safety. As 2020 has proven through the COVID-19 pandemic, clinical trials and their processes need to be flexible enough to adapt and overcome unforeseen disruptions. That’s why we are constantly looking for ways to support these new developments, and proactively create solutions that will help support patients’ lives across the globe by enabling them to participate in research in a flexible way that’s centered around them..
The major challenge during the pandemic was the inability of patients or healthcare works to visit sites. Decentralized trials, whereby some or all of the study visit is performed in a patient’s home, is one way around this. Home sampling is therefore an important initiative that we are developing to tackle this obstacle. A combined package of sampling materials and clear instructions that can be sent to the patients themselves, allows them to take their own samples. Guided step-by-step through the process with videos and manuals, patients will no longer need to leave the comfort of their own home in order to participate in trials. Not only does this increase the safety of the patient, it also allows us to involve patients in studies who might have been unable to before. This enables those patients that live in hard-to-reach areas, with little infrastructure, or those who simply do not possess the time or means to go to the collection site, to participate.
How We Started an Infectious Disease Trial in Ten Days
COVID-19 changed the shape of clinical development. But you can be certain with Cerba Research: This blog describes a trial for a COVID-19 prophylactic medication. In the spring of 2020, we initiated complete central laboratory support for a substantial virology study in just 10 days. A typical timeline for a project like this would be eight weeks.
Phase III Infectious Disease Trial
A Friend in Need
A long-standing pharma client wanted to evaluate a previously approved drug for safety and efficacy in a new indication — as post-exposure prophylaxis for a viral respiratory illness. The FDA had granted rapid protocol approval for a Phase III study, which our client was anxious to initiate. For rapid study startup, the sponsor needed complete central laboratory support, including custom test kits distributed to various North American locations — and the associated database build — in 10 days.
Here’s how it went:
Time from project kickoff to collection kits received at sites
Typical Timeline for Similar Project — Eight Weeks
Services We Provided
We hit our target! And within that breathtaking timeline, we handled protocol changes, logistics challenges, and more.
How Infectious Disease Preparation Along With Communication, Flexibility, and Resourcefulness Made It All Work Out
Cerba Research is highly capable, with extensive global experience in infectious disease. Our cutting-edge laboratories provide the full portfolio of harmonized laboratory testing services required in infectious disease research including vaccine immunogenicity and efficacy, neutralization assays, immunoassays, viral load, and BSL 3 environments. Our seven centers in Ghent, Johannesburg, Montpellier, New York, Paris, Shanghai, Sydney, Taiwan, and Tokyo enable you to target disease populations even in the most remote locations with results easily cross-referenced via our unified global clinical data management platform.
In fact, our industry-leading expertise was called on at the start of the pandemic by the Belgian government, which invited Cerba Research to join an elite consortium task force of leading pharma, biotech, IT, and academia to scale up COVID-19 testing. Our teams worked at risk and over evenings and weekends to ensure rapid testing of the most exposed populations within Belgium.
But even the best resources and pedigree cannot make up for human elements like grit, cooperation, and good sense. In this study, paired with our top laboratories and full portfolio of testing services, the following factors made all the difference and were key to our successful service.
Communication and transparency
To meet this timeline, the Cerba Research team knew it would take dynamic organization, collaboration, adaptability, and understanding. Multiple daily meetings kept hurdles in sight and gave the team space to brainstorm solutions. Daily internal calls included project, trial setup, sample handling, and logistics staff along with associate trial managers, scientific liaisons, and regional heads of project management in disparate time zones. In addition, daily teleconferences with client representatives ensured key milestones were met. Even the contracts and proposal team completed their work within the collapsed timeline.
Flexibility and persistence
During this time, ramped-up border controls were causing delays and uncertainty in international shipping. And with demand for hospital PPE outstripping availability, supplies for both sample collection and testing were scarce. Yet initially, despite these ongoing shortages and supply chain interruptions, the Cerba Research team worked with suppliers and obtained everything needed — with one exception.
At 5 p.m. on a Friday, word came that a shipment of swabs from Belgium was held up in customs, indefinitely. This was a major setback, as the site supplies were to be shipped the following Tuesday. Swabs sourced locally did not pass validation with the assay being used.
Finally, the Cerba Research facility in Belgium shipped the supplies as a series of smaller-value lots to expedite their passage through customs. By building our test kits in-house, we ensure rapid, accurate production and quick reorder turnaround times. In this case, the kit-building team received the swabs late afternoon on Monday, QC’d them, and started shipping complete kits that evening.
Expertise and initiative
Protocol amendments can wreak havoc with any timeline — especially with one as truncated as this. In response to a last-minute client request to fulfill an updated FDA requirement, we added stool PCR testing and located a lab with a validated process to perform the assay. Other amendments our team negotiated successfully included a change from ambient to refrigerated shipping and its resultant cascade of adjustments to the related database, supplies, and manuals. Cerba Research also added value by tapping our network to help recruit health care workers for the study and connected the sponsor with a nonprofit able to assist with funding.
Motivation and Accomplishment Yield Insights
With infectious disease, timing is critical. Inspired by our long-term client and eager to go above and beyond to solve a global dilemma, our team was wholeheartedly determined to achieve this timeline. Because we have partnered with clients in key areas such as influenza, tuberculosis, malaria, HIV, and arboviruses as well as many other indications, we were confident we could get the job done. What we learned was that close collaboration overcomes the highest hurdles. We succeeded because of:
- Tireless and transparent internal and external communications
- Outstanding organization and management
- Flexibility to adapt to changing needs
- Global scientific experts and logistics network
- In-house kit production
- Highly capable team for building a unified global study database
Despite today’s changeable landscape, you can think outside the box. Or you can change it. Cerba Research has the expertise, assets, and optimal timing to empower our clients to bring new life-changing therapies to patients worldwide sooner. Even as the shape of clinical development changes, you can be certain with Cerba Research.