How to Choose an Imaging Provider for Your Clinical Trial

Medical Imaging plays an important role in the clinical development of new drugs. In non-alcoholic steatohepatitis (NASH) specifically, it is one of the most common primary and surrogate endpoints. Liver biopsy is currently the reference standard to discriminate between hepatic steatosis and steatohepatitis, but has the inherent limitations of being invasive, expensive, and often imprecise.1 Non-invasive diagnostic methods with high sensitivity and specificity are a patient-friendly, cost-efficient, and accurate alternative for the analysis of NASH and non-alcoholic fatty liver disease (NAFLD).

Selecting the right Imaging Provider for your clinical study is an essential milestone to the success of your trial. Whoever you choose will be a crucial asset to your clinical trial team, as they will be managing all imaging related activities from study start-up to closeout and providing proper support to ensure sites are trained and qualified in the imaging procedures. Before making this choice, it is important to take the time to consider all the different options available and understand what each one can and cannot offer your trial.

So, how do you know that an Imaging Provider is the right fit for your trial? Here are some important elements to consider:

Who are the various imaging providers and what do they offer?

Most of the Imaging Providers provide the same offerings for imaging in the NASH space. The typical offerings provided are MRI-PDFF, MRE and DEXA. However, there are some important differences that should be taken into consideration when selecting an Imaging Provider for your study.

• Type of Imaging Provider: There are three major types of Imaging Providers: Full-Service CRO, Imaging CRO, and Imaging Core Lab (academic or industry). Depending on the needs of your study, it is important to select an Imaging Provider that can not only deliver the necessary imaging capabilities, but also provide you with the amount of support your study requires. If you are new to a disease space, it may be better to opt for a provider that has more specialized knowledge in that particular area. If you are looking for someone to manage the operations of your study from end-to-end, you may lean towards a Full-Service CRO. Imaging CROs will often work together with both Full-Service CRO and Imaging Core Labs to offer a compromise between specialized knowledge and end-to-end study management.
• Cost: This is a huge factor when selecting the imaging provider for a clinical trial. As more investigational products enter phase 3 trials, where a single study can sometimes cost over $100M, the economic impact that results from a failed study can be substantial for a sponsor.2 Some Imaging Providers have global or regional site network connections that can help support your trial; selecting a vendor that can directly contract with imaging centers can significantly lower imaging-related costs. Site Management Organizations (SMOs) often lump the cost of imaging and analysis into one total bill, disguising the fact that most of the upfront cost of imaging is due to unnecessarily inflated scanner time costs. By pre-negotiating scanner time costs directly with a network, imaging providers can guarantee the fairest prices are always being offered to sponsors and ensure including imaging in trials is scalable to all trial sizes at every phase of drug development. It also important to select a vendor with experience in designing study protocols that can make your trial more cost-efficient. This is a balance between operational expertise and specialized knowledge of your particular disease space. Finally, when screening patients to enroll in your trial, the diagnostic accuracy of the screening test directly impacts the screen fail rate at biopsy. Screening tests with low diagnostic accuracy lead to more false positives, which results in unnecessary and invasive patient procedures, such as a liver biopsy, that are costly to the sponsor. To ensure resources are not wasted on failed screening biopsies, it is critical to select an Imaging Provider that offers robust, reliable biomarkers and can also recommend screening strategies and eligibility criteria around these.
• Technical Capability & Flexibility: Selecting an imaging provider with the right technical capabilities and the ability to adapt to the needs of your specific study will help your trial stay flexible. For example, some Imaging Core Labs offer customizable metrics, data analytics and scientific support that enhance your clinical trial data and are better suited to streamline data management. This will also determine the time needed to have the data analyzed and the report available.
• Metrics: Although most Imaging Providers offer to analyze the same type of data, they do not all deliver the same quality data. Be sure the metrics you are using have well-validated repeatability and reproducibility. Furthermore, some Imaging Providers have initiated collaborations with academic researchers and key opinion leaders to develop validated or FDA-approved biomarkers for NASH. These biomarkers may offer additional insight into patient response to treatment.
• The Image Analysis Method: It is important to select an Imaging Provider that uses an accurate and reliable data analysis method that results in minimal variability of the biomarker data collected. The lower the variability is, the fewer number of patients you will need to have statistically significant results. This means fewer patients need to be enrolled, which can significantly speed-up enrollment and reduce trial costs.

Finding the right fit for your clinical trial

An Imaging Provider is a crucial asset to your clinical trial team. It is essential to select an Imaging Provider that has both a deep knowledge and understanding of the NASH space and can also offer you continuous support throughout the study. If you are new to a disease space, it may be better to opt for a provider that has more specialized knowledge in that area.

Although cost is an important factor, it is also essential to consider the quality of data acquired, accuracy of imaging metrics, and reliability of the biomarker within the NASH space. Unreliable data that does not correlate to histological outcomes will end up costing more time and resources in the long term. Non-invasive biomarkers with high diagnostic accuracy for NASH patients, particularly NAS ≥4 F≥2, can be used as part of a screening strategy ahead of confirmatory biopsy to reduce the screen fail rate on the costlier procedure. Typical histological screen fail rates in NASH trials are 50-60%,3 which leads to a large number of unnecessary biopsies and high expenditure that could have otherwise been saved. By using a combination of imaging and blood-based biomarkers with high positive predictive value (PPV) for NAS ≥4 F≥2, histological screen fail rate can be significantly lowered to the point where the cost savings realized help to offset the upfront imaging budget.

Remember, you will be working very closely with your Imaging Provider throughout the trial so it is important that you have confidence and trust in them. Your Imaging Provider should make a commitment to your business and not de-prioritize you. Although larger organizations are often more prepared to handle any issue because of how they are organized, this also means they have very standardized, inflexible procedures and more frequent changes of project management team. Smaller to midsize organizations often have a more focused expertise and can provide your trial with more attention and support. Another benefit of a smaller organization is that the Project Management Team assigned to your study will stay with you over a longer period and are typically quite responsive and easy to get in contact with.

Imaging CROs generally offer the best balance between specialized knowledge and end-to-end study management. They are small enough to give the specialized support you need and large enough to have the available project management and research personnel to do so. An Imaging CRO can work collaboratively with the Sponsor and the Full-Service CRO throughout the entirety of the study and bring ongoing project management to ensure sites are trained and qualified in the imaging procedures.

Why Perspectum is the right fit for your trial

Perspectum is a global expert in medical image analysis and software development with specialized Imaging CRO capabilities for clinical studies. Perspectum has deep medical and scientific understanding of NASH, paired with extensive operational and imaging experience, allowing them to work with Sponsors across multiple aspects of their clinical development program. They have provided imaging services for over 30 NASH trials from Phase 1 to 3 and have experience working with biotech, mid-, and large pharmaceutical sponsors. This experience enables them to easily customize and scale their services to meet requirements of trials in different phases and of different sizes. Additionally, they have proven experience and existing relationships with many different Full-Service CRO’s and Imaging Core Labs gives you access to many of the benefits of both large and small imaging providers. With offices across the US, UK and Singapore, Perspectum can provide around the clock support 365 days a year.

Perspectum has a global imaging site network with over 300 sites equipped with their LiverMultiScan technology. In addition, their partnerships with large site networks enable sponsors to run multi-center clinical trials around the globe. Based on previous experience on working with sites in NASH trials, they are able to provide information to help Sponsors quickly identify and select high-performing sites. MRI scan time prices are always being pre-negotiated with imaging centers on behalf of the sponsors to ensure the fairest prices are being offered.

Perspectum is highly flexible in its offerings. Their in-house imaging services can be customized to specific clinical trial needs which allows us them to quickly and efficiently identify problems and design solutions. They offer the traditional imaging metrics (MRI-PDFF, MRE and DXA) and proprietary ones. Perspectum’s IDEAL-PDFF improves on the more conventional MRI-PDFF methods making it the gold standard MRI-PDFF method for assessment of hepatic fat. In addition, due to the constant innovation in the NASH/NAFLD arena, Perspectum also offers a proprietary biomarker to measure fibroinflammation, called “corrected T1” (cT1), which correlates to histological markers for liver disease and predicts clinical outcomes.4-8 This novel biomarker offered by Perspectum offers additional insight into disease progression and has superior repeatability and reproducibility compared to other biomarkers currently available on the market such as Transient Elastography.9  Due to the large scientific R&D team Perspectum employs, they can quickly adjust their offerings based on Sponsor needs and requirements. This same team is constantly publishing new data that showcases the reliability of their available biomarkers. All in all, Perspectum is a turn-key medical imaging solution ready to handle all aspects of your clinical trial from study start-up to close-out.

Authors:

• Charlotte Erpicum, PhD
• Emily Bray, MBA
• Jack Vidani

References

1. Castera, L. et al. (2010). Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango?. Gut, 59(7), 861–866. https://doi.org/10.1136/gut.2010.214650
2. Aspril, J. (2018, September 24). Cost of Clinical Trials For New Drug FDA Approval Are Fraction of Tota. Johns Hopkins Bloomberg School of Public Health. https://www.jhsph.edu/ news/news-releases/2018/cost-of-clinical-trials-for-new-drug- FDA-approval-are-fraction-of-total-tab.html
3. Ratziu, V., et al. (2020), Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study. Hepatology. doi:10.1002/hep.31108
4. Banerjee, R., et al. (2014). Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. Journal of Hepatology, 60(1), 69-77. doi: 10.1016/j.jhep.2013.09.002.
5. Pavlides, M., et al. (2016). Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. Journal of Hepatology, 64(2), 308-315. doi: 10.1016/j.jhep.2015.10.009.
6. Pavlides, M., et al. (2017). Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity. Liver International, 37(7), 1065-1073. doi: 10.1111/liv.13284.
7. Idilman IS et al. (2013) Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology, 2013;267:767–75. doi: 10.1148/radiol.13121360.
8. Caussy C, Reeder SB, et al. (2018) Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in NASH Trials. Hepatology, 2018;68:763-72. doi: 10.1002/hep.29797
9. Jayaswal, A.N., et. al. (2020), Prognostic value of multiparametric magnetic resonance imaging, transient elastography and blood-based fibrosis markers in patients with chronic liver disease. Liver International. Accepted Author Manuscript.