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Top 4 Sponsor Challenges in IBD Patient Enrollment

Leave a Comment / News article / By Ashley Stufano

The number of IBD clinical studies grows each year; however, the number of patients enrolling in these studies has not increased proportionally. Instead, patient enrollment rates for IBD trials in recent years have shown a significant decline: from 1998 to 2018, the average recruitment rate in moderate-to-severe UC decreased from 0.32 to 0.13 patients per site per month, while the average recruitment rate in moderate-to-severe CD decreased from 0.65 to 0 to 0.10 patients per site per month.ⁱ

In PSI’s white paper Inflammatory Bowel Disease: Current Status and Future Perspectives, Senior Medical Advisor Maxim Kosov breaks down recent trends in IBD clinical research, including insights into patient recruitment and retention. Read on to discover the top four challenges to consider when enrolling IBD patients for your next trial.

1. Availability of Existing Treatments

The success of FDA-approved treatments, particularly vedolizumab in 2014, ustekinumab in 2016, and tofacitinib in 2018, often leads to a decreased patient enrollment rate in placebo-controlled randomized controlled trials. When the currently approved drug provides effective treatment with minimal side effects, patients will often opt for this method instead of enrolling in a study where they may receive a placebo drug. This is often a leading factor contributing to slow enrollment.

2. Competition Between Trials

When it comes to site choices and geomix, many sponsors and their partners approach larger academic centers first, assuming that these sites will have more experienced staff and equipment. One study found patients followed at academic centers are almost twice as likely to have participated in randomized clinical trials. However, the study also found over half of enrolled patients were followed in private practice settings.2 Focusing on large institutions leads to higher competition rates. For instance, as of October 2022, in the University of California San Francisco alone, there were 29 active IBD clinical trials, and 9 of them were enrolling.ⁱⁱ

3. Country and Site Selection

Additional factors may influence low enrollment potential, including site choice and geomix. When choosing the right geomix of sites, sponsors must consider the incidence of the disease, treatment standards, and availability of the medications. The incidence of IBD is increasing in Asia, Africa, and Latin America, driving interest in shifting clinical trials to these regions.ⁱⁱⁱ Additional factors to consider when selecting sites include the health insurance environment (the likelihood that insurance companies will approve less efficient generic medications over specialty ones) and the presence of preferred study sites (sites with whom the CRO has a long history of cooperation and appropriately trained study teams).

4. Screen Failure Rates

Over the past decade, screen failure rates in IBD trials have grown, approaching 50% in UC and 70% in CD, primarily due to failure to meet minimal endoscopic or biomarker criteria for active disease and a growing list of exclusionary concomitant medications. In PSI studies, we’ve seen a screen-out rate of 26-48% in UC and up to 64% in CD.

Some general recommendations to minimize screen failure and aid in patient enrollment rates include higher drug-to-placebo rates (such as a ratio of 2:1 or 3:1 rather than 1:1), broader use of patient-reported outcomes as the primary study endpoint, and optimization of study visits’ duration and complexity (including fewer procedures and endoscopies). Additional options for trial design include adding a long-term open-label extension for patients responding to therapy, and more involvement from the patient’s primary GI physicians at local hospitals and private practices. Primary care doctors see patients at the earlier stages of the disease course. There is a better chance that such patients are more likely to meet eligibility criteria than those admitted to larger hospitals or academic institutions, where the disease is often more severe and potential complications more frequent.

Conclusion

IBD patient recruitment and retention depends on the study protocol criteria and complexity, which must be scientifically sound to achieve the goals of the study as well as being attractive to patients. PSI provides a thorough review of the protocol by internal therapeutic area experts and harnesses the power of AI and machine-learning through our INTELIA ™ platform, combined with strong site relationships around the globe, to ensure your study meets enrollment goals. If you’d like to learn more about PSI can support your global Phase 2 and 3 IBD trials, click here.

References

ⁱ Harris, M. S., Wichary, J., Zadnik, M., & Reinisch, W. (2019). Competition for clinical trials in inflammatory bowel diseases. Gastroenterology, 157(6), 1457–1461. https://doi.org/10.1053/j.gastro.2019.08.020

ⁱⁱ Heyman, M., Terdiman, J., Lewin, S., Verstraete, S. G., & Mahadevan, U. (2022, November 7). UCSF inflammatory bowel disease clinical trials – San Francisco Bay Area. UCSF Clinical Trials. Retrieved November 21, 2022, from https://clinicaltrials.ucsf.edu/inflammatory-bowel-disease

ⁱⁱⁱ Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Tang, W., Benchimol, E. I., Panaccione, R., Ghosh, S., Wu, J. C., Chan, F. K., Sung, J. J., & Kaplan, G. G. (2017). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st Century: A systematic review of population-based studies. The Lancet, 390(10114), 2769–2778. https://doi.org/10.1016/s0140-6736(17)32448-0

Clinical Research Breakthroughs Defining the Future of Oncology

Leave a Comment / News article / By Ashley Stufano

The 2022 American Society of Clinical Oncology (ASCO) Annual Meeting is one of the largest events for those professionals working in oncology in both clinical practice and research. While there was a significant focus on providing positive outcomes from trials, there were a few major ongoing or recently concluded studies that provided significant research discoveries based on their continued or lack of success.

Preparing for the Future of Oncology Clinical Research, co-authored by PSI’s Dr. Maxim Kosov, Senior Medical Advisor, Operations, and Dr. Victor Zenzola de Toma, Medical Monitor, provides essential insights for sponsors into the trends with the greatest potential to affect clinical trial design and operationalization. Read on to learn more about the general oncology trends to be aware of in 2023.

New insights into the influence of concomitant medications on immune checkpoint inhibitors

Immune checkpoint inhibitor (ICI) therapy is currently a standard of care for many malignancies. Recent findings suggest that the outcomes of ICI therapy may be influenced by concomitant medications that also have immunomodulatory properties, such as corticosteroids and antibiotics. Two study teams presented findings that explored the effects of concomitant use of acetaminophen and the live bacterial product CBM588 on ICI efficacy in cancer patients.

Antoine Italiano (Institute Bergonié, France) assessed the impact of acetaminophen use on immunotherapy efficacy in patients with different types of cancer.ⁱ The study showed that detectable plasma acetaminophen levels at treatment onset were associated with a worse clinical outcome in ICI-treated cancer patients and reduced treatment efficacy. Important unanswered questions remain, including the nature of the influence of the previous acetaminophen exposure, whether there is a difference between sporadic and chronic acetaminophen use, and whether there is any influence of acetaminophen on ICI-related toxicity.

The negative association between ICI response and concomitant antibacterial therapy is well defined. Nazli Diman (City of Hope Comprehensive Cancer Center, California, USA) investigated whether concomitant use of the live bacterial product CBM588 (a probiotic strain of bacteria that can restore species of Bifidobacterium to the microbiome) with ICI therapy could facilitate an improved response.ⁱⁱ The study enrolled patients with newly diagnosed metastatic renal cell carcinoma and showed that adding CMB588 to the standard treatment scheme with nivolumab/ipilimumab increased the objective response rate from 20% to 58%. The investigators suggested that CBM588 decreases antibiotic resistance, which is significant given the common use of antibiotics in cancer patients to treat infections.

ctDNA as an Emerging Biomarker

Circulating tumor DNA (ctDNA) was first described in 1948, but the first clinical validation happened only when next-generation sequencing (NGS) technology was introduced in the 2000s.ⁱⁱⁱ The symposium “ctDNA: Dawn of a New Era” at the 2022 conference discussed how this methodology is transforming the field of oncology.

During the past several years, liquid biopsy (detection of ctDNA through a simple blood draw) has gained much attention in clinical practice and clinical research. In May 2022, the U.S. Food and Drug Administration (FDA) released industry guidance on ctDNA testing when developing drugs for early-stage tumors.^iv The guidance describes three potential uses for ctDNA:

Selecting patients for treatment based on molecular alterations
Monitoring tumor response at the molecular level via minimal residual disease to identify risk of recurrence
Acting as an early surrogate measure of long-term outcomes

The biggest challenge with ctDNA testing is that researchers still do not know whether intervening after a positive ctDNA result will improve patients’ outcomes like survival or quality of life. Multiple clinical trials aim to address this question, particularly what should be done in the case of a positive (or negative) ctDNA result.

Another therapeutic research focus was on ctDNA testing across multiple tumor types, including head and neck cancer, non-small cell lung cancer (NSCLC), breast cancer, soft tissue sarcoma, and oropharyngeal cancer. Based on the findings from these papers, we can conclude that:

ctDNA can be used for molecular profiling in patients with advanced solid tumors to guide therapeutic decisions
ctDNA has the potential to identify patients who have a molecular response to therapy at an early timepoint
Detection of ctDNA after curative therapy across many tumor types is strongly predictive of the likelihood of recurrence in many cases, and importantly, it occurs before radiographic or clinical progression.

The interpretation of ctDNA-negativity must follow the same pattern as for many diagnostic tests — ctDNA-negativity does not mean the disease is cured, but ctDNA-positivity does mean it is not cured.

Conclusion

While breakthrough technology and therapies drive much of the conversation in research, it is important to highlight the long-term effects of current treatments and therapies year-over-year. If you are interested in learning more about PSI’s in-depth experience with various oncology indications, check out our oncology therapeutic expertise page or contact us to learn how PSI can help you propel your phase 2 or 3 oncology study forward.

References

ⁱItaliano, A., lsambert, N., Metges, J.-P., Toulmonde, M., Cousin, S., Pernot, S., Spalato, M., Grellety, T., Auzanneau, C., Lortal, B., Kind, M., Le Loarer, F., Sellan-Albert, S., u Bellera, C. A. (2022). Caire: A basket multicenter open-label phase 2 study evaluating the EZH2 inhibitor tazemetostat in combination with durvalumab in patients with advanced solid tumors. Journal of Clinical Oncology, 40(16_suppl), TPS2703-TPS2703 https://doi.org/10.1200/jco.2022.40.l6_suppl.tps2703

ⁱⁱDizman, N., Meza, L.A., Bergerot, P. G., Dorff, T. B., Lyou, Y., Frankel, P.H., Llamas, M., Hsu, J., Zengin, Z. B., Malhotra, J., Govindarajan, A., Castro, D. V., Gillece, J. D., Reining, L. J., Trent, J.M., Takahashi, M., Oka, K., Higashi, S., Highlander, S. K., u Pal, S. K. (2022). Characterization of the microbial resistome in a prospective trial of CBM588 in metastatic renal cell carcinoma (MRCC) offers mechanism for interplay between antibiotic (abx) use and immune checkpoint inhibitor (ICI) activity. Journal of Clinical Oncology, 40(16_suppl), 4510-4510. https://doi.org/10.1200/jco.2022.40.l6_suppl.4510

ⁱⁱⁱMandel, P. and Metais, P. (1948) Les acides nucl, eiques du plasma sanguin chez l’homme., C. R Seances Soc.Biol. Fil.142, 241-243.

^ivOncology Center for Excellence. (2022, May). “Use of Circulating Tumor Deoxyribonucleic Acid for Early-Stage Solid Tumor Drug Development; Draft Guidance for Industry; Availability. U.S. Food and Drug Administration.” Retrieved July l, 2022, from https://www.fda.gov/regulatory-information/search-fda guidance-documents/use-circulating-tumor-deoxyribonucleic-acid-early stage-solid-tumor-drug-development-draft-guidance

^vLipsyc-Sharf, M., De Bruin, E., Santos, K., McEwen, R, Stetson, D., Patel, A., Kirkner, G. J., Hughes, M. E., Tolaney, S. M., Krop, I.E., Knape, C., Feger, U., Marsico, G., Howarth, K., Winer, E. P., Lin, N. U., u Parsons, H. A. (2022). Circulating tumor DNA (ctdna) and late recurrence in high-risk, hormone receptor-positive, HER2-negative breast cancer (CHIRP). Journal of Clinical Oncology, 40(16_suppl). https://doi.org/10.1200/jco.2022.40.l6_suppl.103

3 Innovations Impacting Oncology Clinical Trials in 2023 & Beyond

Leave a Comment / News article / By Ashley Stufano

Each year, the American Society of Clinical Oncology (ASCO) Annual Meeting is held, bringing together professionals working together in oncology in both clinical practice and research. This year’s conference focused on innovations from a variety of oncologic therapeutic disciplines, highlighting research that has the greatest potential to change current clinical and therapeutic practices. PSI’s Dr. Maxim Kosov, Senior Medical Advisor, Operations, and Dr. Victor Zenzola de Toma, Medical Monitor, reviewed the abstracts presented to develop a comprehensive overview of the trends with the greatest potential to affect oncology clinical trial design and operationalization. Read on to learn about three of the most significant oncology innovations to be aware of from ASCO 2022. For the full report, download Preparing for the Future of Oncology Clinical Research, available now.

1. Breast Cancer Breakthrough: Doubling Progression-Free Survival in "HER2-low" Patients

Breast cancer is the most frequent malignancy in women, with an estimated 291,000 new cases expected in the United States in 2022.^I While breast cancer is curable at early stages, advanced or metastatic cancer is still a significant therapeutic challenge.

As a rule, patients with advanced breast cancer featuring low human epidermal growth factor receptor 2 (HER2) expression levels are diagnosed with HER2-negative disease because HER2-targeted therapies are typically ineffective in this setting. The DESTINY-Breast04 trial upends this paradigm, opening the door to a new treatment option for the approximately 60% of patients referred to as “HER2-low” (IHC score of 0-1).ⁱⁱ In this double-blind Phase 3 trial, patients with HER2-low metastatic breast cancer treated previously with one to two prior lines of chemotherapy for metastatic disease were randomized to receive trastuzumab deruxtecan (a HER2-directed antibody and topoisomerase inhibitor conjugate) or the physician’s choice of standard chemotherapy.

The study showed that progression-free survival (PFS) was nearly double for trastuzumab deruxtecan versus standard chemotherapy (9.9 versus 5.1 months), and the overall survival (OS) was significantly better with trastuzumab deruxtecan compared with standard therapy (23.4 versus 16.8 months). Safety analysis did not identify new safety concerns and showed fewer treatment-emergent adverse events (TEAE) with trastuzumab deruxtecan than with standard chemotherapy (52.6% versus 67.4%).

These practice-changing findings establish patients with HER2-low metastatic breast cancer as a targetable population with trastuzumab deruxtecan as a new standard of care in this setting. DESTINY-Breast04 is the first randomized clinical trial to show that targeting HER2 provides clinically meaningful benefits for patients with HER2-low metastatic breast cancer.

2. Trends in Hematological Oncology Clinical Trials: Exploring Comparative Therapies for Chronic Myeloid Leukemia

Many patients with chronic myeloid leukemia (CML) experience good survival outcomes from therapy with tyrosine kinase inhibitors (TKIs). However, 40-50% of these patients may need to change therapy due to disease progression or recurrence. Importantly, TKIs have different mechanisms of action, and the treatment effect depends on matching the drug and mutation.

The ASCEMBL trial is a Phase 3, randomized, multicenter study designed to explore whether asciminib is safe and effective for patients with CML compared with a commonly used ATP-binding TKI (bosutinib).ⁱⁱⁱ Asciminib is a BCR-ABL1, first-in-class specifically targeting ABL myristoyl pocket (STAMP) inhibitor that differs from TKIs in its mechanism of action and ability to overcome mutations associated with TKI resistance. Primary analyses indicated that major molecular response (MMR) with asciminib exceeded MMR with bosutinib (25.5% versus 13.2%), and results at 48 weeks consistently favored asciminib over bosutinib in efficacy and safety. Analysis of efficacy and safety outcomes at 96 weeks showed that MMR with asciminib exceeded MMR with bosutinib by 21.7%. These results are important, as providers will likely start prescribing this medication now that it is approved.

3. Lung Cancer Clinical Trial Innovations: Finding the Ideal Therapeutic Combination for Resectable Stage IIIA NSCLC

Worldwide, lung cancer caused an estimated 1.8 million deaths in 2020.^iv In the United States, there are over 230,000 new cases of lung cancer and 130,000 deaths annually.^v

The results of the NADIM II study were presented by Mariano Provencio-Pulla, MD, PhD (Hospital Universitario Puerta de Hierro, Madrid, Spain).^vi The study enrolled 86 patients who were randomly assigned to receive nivolumab plus carboplatin-based chemotherapy or chemotherapy alone. The primary endpoint was pathological complete response (pCR). The trial found that neoadjuvant nivolumab plus carboplatin-based chemotherapy improves pCR for patients with resectable stage IIIA NSCLC compared with chemotherapy alone: 36.8% versus 6.9%, correspondingly. The addition of nivolumab to chemotherapy did not significantly increase toxicity.

This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. It means that we can expect a change in the standard of care for these patients.

Conclusion

As the need for oncology clinical trials persists and grows, PSI CRO is committed to keeping abreast of the latest scientific advances and partnering with the companies doing the most exciting work across a wide range of oncology diseases. To learn more, download Preparing for the Future of Oncology Clinical Research today.

References

^I Siegel, R. L., Miller, K. D., Fuchs, H. E., & Jemal, A. (2022). Cancer statistics, 2022. CA: A Cancer Journal for Clinicians, 72(1), 7–33. https://doi.org/10.3322/caac.21708

ⁱⁱ Modi, S., Jacot, W., Yamashita, T., Sohn, J., Vidal, M., Tokunaga, E., Tsurutani, J., Ueno, N. T., Chae, Y. S., Lee, K. S., Niikura, N., Park, Y. H., Wang, X., Xu, B., Gambhire, D., Yung, L., Meinhardt, G., Wang, Y., Harbeck, N., & Cameron, D. A. (2022). Trastuzumab deruxtecan (T-DXD) versus treatment of Physician’s Choice (TPC) in patients (PTS) with HER2-low unresectable and/or metastatic breast cancer (MBC): Results of destiny-breast04, a randomized, phase 3 study. Journal of Clinical Oncology, 40(17_suppl), LBA3-LBA3. https://doi.org/10.1200/jco.2022.40.17_suppl.lba3  

ⁱⁱⁱ Rea, D., Mauro, M. J., Hochhaus, A., Boquimpani, C., Lomaia, E., Voloshin, S., Turkina, A. G., Kim, D.-W., Apperley, J., Cortes, J. E., Sasaki, K., Kapoor, S., Allepuz, A., Quenet, S., Bédoucha, V., & Minami, Y. (2022). Efficacy and safety results from ASCEMBL, a phase 3 study of asciminib versus bosutinib (BOS) in patients (PTS) with chronic myeloid leukemia in chronic phase (CML-CP) after ≥2 prior tyrosine kinase inhibitors (TKIS): Week 96 update. Journal of Clinical Oncology, 40(16_suppl), 7004–7004. https://doi.org/10.1200/jco.2022.40.16_suppl.7004 

^iv Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660 

^v Lung cancer statistics: How common is lung cancer? American Cancer Society. (2022, February 14). Retrieved July 1, 2022, from https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html  

^vi Provencio-Pulla, M., Nadal, E., Larriba, J. L., Martinez-Marti, A., Bernabé, R., Bosch-Barrera, J., Casal, J., Calvo, V., Insa, A., Aix, S. P., Reguart, N., Carpeño, J. D., Mosquera, J., Benitez, R., Aguado De La Rosa, C., Palmero, R., Hernando-Trancho, F., Romero, A., Cruz Bermudez, A., & Massuti, B. (2022). Nivolumab + chemotherapy versus chemotherapy as neoadjuvant treatment for Resectable Stage IIIA NSCLC: Primary Endpoint Results of Pathological Complete Response (PCR) from phase II Nadim II trial. Journal of Clinical Oncology, 40(16_suppl), 8501–8501. https://doi.org/10.1200/jco.2022.40.16_suppl.8501 

PSI Publishes New Report on the Future of Oncology Clinical Research

Leave a Comment / News article / By Paul Mirek

PSI CRO AG, a full-service global CRO specializing in pivotal Phase 2 and 3 trials for oncology, hematology, and other select therapeutic areas, has published a new report on the current landscape of oncology research and its impact for future trials. Preparing for the Future of Oncology Clinical Research, co-authored by PSI’s Dr. Maxim Kosov, Senior Medical Advisor, Operations, and Dr. Victor Zenzola de Toma, Medical Monitor, provides essential insights for sponsors into the trends with the greatest potential to affect clinical trial design and operationalization.

Kosov and Zenzola de Toma reviewed data from over 2,200 poster presentations at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting to develop the comprehensive overview. Topics include:

General trends in oncology, including insights into concomitant medications’ impact on immune checkpoint inhibitors and emerging biomarkers such as ctDNA
Therapeutic advances in the most challenging indications, including “HER2-low” breast cancer and resectable stage IIIA NSCLC
Additional research highlights in gastrointestinal, gynecological, and genitourinary cancers as well as pediatric oncology and rare disease

“Oncology studies face unique challenges due to their expansive geographic footprints, lengthy screening and treatment durations, and massive amounts of clinical data,” said Dr. Kosov. “As the need for oncology clinical trials persists and grows, PSI CRO is committed to keeping abreast of the latest scientific advances and partnering with the companies and investigators doing the most exciting work across the wide range of oncology diseases.”

For the past 25 years, PSI CRO has worked with sponsors to advance their research in oncology by proactively cultivating long-term relationships with sites around the world and applying advanced technology for data-driven feasibility and enrollment forecast, including through its proprietary technology platform, INTELIA™.

VISIONAL™, the latest addition to the platform, allows project managers and sponsors to model and compare hundreds of country and site combinations, their budgets and probability of success within just a few minutes. In the end, it recommends the most optimal enrollment scenario in line with sponsor key objectives.

Preparing for the Future of Oncology Clinical Research is available now. For more information about how PSI plans and executes seamless oncology clinical trials with novel designs, click here.

Best Places to Work 2022: PSI CRO Honored for Fourth Year in a Row

Leave a Comment / News article / By Paul Mirek

As one of Philadelphia Business Journal’s Best Places to Work for 2022, PSI CRO has once again earned recognition for its company culture, leadership, and values as voted on by its employees. This is the fourth year in a row that PSI’s King of Prussia team has been honored with this award.

The Business Journal partnered with Quantum Workplace to identify Greater Philadelphia’s Best Places to Work. Companies are first nominated by the public, and employees at those companies are then asked to complete an online survey measuring the company culture and taking into consideration compensation, benefits, and trust in senior leadership.

Winning in this region is no small feat. King of Prussia is home to several of the top clinical research, healthcare, and biotech companies. In total, this year’s list includes 76 companies from across the region.

“The way many of us work has been fundamentally altered over the past two-plus years.” says Philadelphia Business Journal Associate Editor Lisa Dukart. “As work – and where we work – continues to evolve, one thing remains constant: Employees want to work for companies whose values and culture align with their own.”

Culture is something we take very seriously, both in King of Prussia and across the globe. PSI is privately owned by a group of managers who created it a quarter of a century ago and still come to work every day. This stability has helped nurture the global PSI culture that unites us across six continents.

Seven core values guide the way we do business:

Delivering Wow Service
Being a Teammate
Practicing Accountability
Delivering Results
Excelling in Communication
Being Excellent & Humble
Staying Lean

As we continue to grow each day with more than 2,600 employees around the world, these values help ensure that PSI remains on the unique path of organic growth and dedication to customer service that we’ve followed for more than 25 years. To learn about each of our values and see how you can join the growing PSI team, visit our Careers page.

PSI Named a 2022 CRO Leadership Award Champion in Three Categories

Leave a Comment / News article, Press Release / By Paul Mirek

Leading full-service, global CRO continues record of success with awards in all five core categories for the fourth year in a row

PSI CRO, 14 JUNE 2022 – PSI CRO, a leading full-service, global contract research organization (CRO), has been named a 2022 CRO Leadership Award Champion in the categories of Compatibility, Quality, and Reliability across two respondent groups (Overall and Small Pharma). This is also the fourth year in a row in which PSI CRO received CRO Leadership Awards in all five categories, also including Expertise and Capabilities, across two respondent groups.

The CRO Leadership Awards are presented by Life Science Leader and Clinical Leader based on research conducted by ISR Reports. For 2022, 50 contract research organizations were assessed on 20+ performance metrics in five core categories in ISR’s annual CRO Quality Benchmarking survey. Winners in these categories are judged by their customers as having exceeded their expectations. Those companies that scored one standard deviation or more above the weighted average in each of the core categories are also recognized as the top performers or Champions.

“ISR’s stringent screening process ensures that only highly qualified industry decision-makers participate in our CRO benchmarking market research,” says Kevin Olson, CEO of Industry Standard Research. “This is paramount as we ask the research participants to provide experiential, not perceptual, feedback on their involvement with contract suppliers over the past 18 months. The data enable users of ISR’s market research to make confident business decisions based on the experiences of their industry peers.”

When the CRO Leadership Award Champion Awards were presented in 2021, PSI was named a Champion in the category of Expertise. The company has received leadership awards in the same five categories across both respective respondent groups since 2019 and also earned four awards in 2018.

“Our mission is to be the best CRO in the world as measured by our employees, clients, sites, and vendors,” says Nick Sinackevich, President of PSI. “Our continuing success in the CRO Leadership Awards is an important benchmark for this goal and a testament to the tireless work of our teams around the world.”

About PSI: PSI CRO is a privately-owned, full-service clinical research organization (CRO) operating globally. PSI’s global reach supports clinical trials across multiple countries and continents and specializes in the planning and execution of global pivotal registration clinical trials. With an exceptionally high repeat and referral business rate combined with minimal staff turnover, PSI is committed to being the best CRO in the world as measured by its employees, customers, investigators, and vendors.

Global headquarters are located in Switzerland at 113a Baarerstrasse, Zug 6300. www.psi-cro.com

For Media Inquiries:

Ashley Stufano, Marketing Specialist

919-972-9572 |ashley.stufano@psi-cro.com

“One Huge Night” for Patients and PSI: The Gift of Life Gala

Leave a Comment / News article / By Paul Mirek

Last week, we were honored to receive the 2022 Corporate Partner Award from the Gift of Life Marrow Registry at its annual One Huge Night Los Angeles Gala at the SLS Hotel in Beverly Hills. In addition to raising funds for the organization, the Gift of Life Gala offers a chance for transplant recipients and their donors to meet in person for the first time.

At PSI CRO, we are guided by a simple, straightforward calling: every patient counts. We’re proud of our longstanding partnership with Gift of Life, a national, public, not-for-profit registry facilitating peripheral blood stem cell and bone marrow transplants for patients in the United States and abroad.

Rhonda Critchlow, PSI CRO’s Senior Director, Operations, and Jeremie Braun, Senior Director, Business Development, were in attendance to accept the award, and more importantly, to meet with the people who make the Gift of Life’s mission possible.

Jeremie was instrumental in connecting PSI to the Gift of Life organization through his involvement in the Hope4Adam campaign in 2016.

The award was presented to Jeremie and Rhonda by Jay Feinberg, Gift of Life’s founder and Chief Executive Officer as well as a 26-year transplant survivor. “It is an honor to play a small part as a corporate partner when we know we are saving lives,” said Rhonda. “PSI will remain committed to Gift of Life and the important work you are doing. I challenge all of my friends to take up the battle – by doing something so simple as joining the registry with a cheek swab, which ultimately can turn into saving a life.”

About Gift of Life

Gift of Life is accredited by the World Marrow Donor Association and is a member of the global registry, Bone Marrow Donors Worldwide. Joining the registry is simple: it requires a mouth swab, making it simple for anyone to help save lives.

The Gift of Life headquarters in Boca Raton, Florida, has been servicing donors and patients alike since 1991. The state-of-the-art apheresis center, which opened in 2019, has made it convenient for donors to donate stem cells in a relaxing and spa-like facility, and PSI is grateful to be able to sponsor a collection chair at the center to make donors comfortable during the process.

PSI CRO: A Proud Partner for Patients

From the beginning, PSI has worked alongside Gift of Life to gather cheek swabs at conferences like ASH and ASCO, and inspire global employees to get involved during World Marrow Donor Day, held annually on the third Saturday of each September.

But the partnership isn’t exclusive. To meet the needs of patients around the globe, raising more awareness is imperative. Corporate partners aren’t just appreciated at Gift of Life, they’re celebrated.

If your company is dedicated to patients and passionate about saving lives, you, too, can partner with Gift of Life, and help find matches for patients like Aiden, who is fighting a rare blood disorder right now.

5 IBD Clinical Development Trends to Watch From ECCO 2022

Leave a Comment / News article / By Paul Mirek

Last month, I had the honor of representing PSI CRO at the European Crohn’s and Colitis Organization (ECCO) 2022 Congress. Now in its seventeenth year, this is the biggest event for all those working at the forefront of inflammatory bowel disease (IBD) clinical research, with nearly 6,000 attendees representing more than 100 countries.

This year’s theme was “Navigating the Oceans of IBD,” focusing on what it takes to transform the latest science into practical approaches. The numerous sessions discussing novel treatments made it clear that IBD is an exciting therapy area with many new treatments on the horizon. While new therapies will offer more choice for patients and the potential for more personalized treatment in IBD, studies testing the efficacy and safety of novel combinations will be required. In addition, presenters highlighted the need for head-to-head comparative trials to help guide treatment decisions. I’ve identified five IBD clinical development trends to watch as you plan your next study.

#1: The potential of JAK inhibitors for improving the efficacy of ulcerative colitis (UC) therapy

The latest data on Janus kinase (JAK) inhibitors demonstrates that these therapies have a rapid onset of action, are associated with durable efficacy, and achieve stringent composite endpoints encompassing both endoscopic and histologic assessments with a favorable benefit-risk profile. The key to clinical efficacy for these therapies is selectivity. With a highly selective agent, we can suppress JAK1 with a higher dose while remaining below the threshold of JAK2 activation. Selectivity brings us to a different level of clinical efficacy, and greater JAK1 selectivity over JAK2 could potentially translate into a more favorable benefit-risk profile.

We started to see it with tofacitinib, a pan-JAK inhibitor. With selective JAK inhibition, we now see striking deltas in all endpoints, including rapid efficacy and superior mucosal healing. Efficacy must be balanced with safety. For example, consider the increased risk of herpes zoster related to certain JAK inhibitors. Filgotinib and upadacitinib, selective JAK1 inhibitors, show a much lower incidence of herpes zoster than tofacitinib, a JAK pan-inhibitor. However, even with selective JAK inhibitors, the incidence of herpes zoster is higher than with placebo.

As a systemic inflammatory disease, IBD can affect other organs, and more than 40% of patients with IBD have at least one extra-intestinal manifestation. Selective JAK inhibitors may also make an impact here. One study found that a 45-mg induction dose of upadacitinib resolved more extra-intestinal manifestations at eight weeks than placebo (40% versus 33%) with an even more striking difference in resolution of peripheral or axial arthropathies (55% versus 42%). Similar effects were observed in a maintenance phase.

#2: Tailoring each clinical trial to the drug’s individual safety profile

Patients’ top concerns when choosing treatment include the achievement of long-term remission; route/frequency of administration; and such safety considerations as risk of infections (particularly of herpes zoster and tuberculosis), cardiac toxicity, and lymphoma risk (the last one is most relevant to biologics and small molecules). Some of these safety concerns, such as the risk of serious infections, vaccination status prior to initiation, and liver function, are universal and relevant to all drugs. Some are drug-specific; for instance, viral reactivation and non-melanoma skin cancer for tofacitinib and filgotinib.

Certain safety-related inclusion criteria for clinical trials with small molecules should therefore be universal: pregnancy test, vaccination (including herpes zoster), infections (screening for viral hepatitis), blood test (lymphocytes, neutrophils, hemoglobin), ECG, tuberculosis screening, and skin assessment (risk of skin cancer). However, each study protocol’s design must also consider the individual safety profile of the drug.

#3: The need for additional research into long-term effects

Additional research is needed into the IBD therapies’ potential for long-term effects, such as progressive multifocal leukoencephalopathy (PML), which is associated with certain inflammatory disorders. PML is a rare, opportunistic viral infection of the brain caused by the John Cunningham virus (JCV), typically in immunocompromised individuals. The seroprevalence of JCV antibodies ranges between 35% and 90% in the adult population as a latent or persistent infection. PML is also seen in inflammatory disorders such as systemic lupus erythematosus (SLE), sarcoidosis, polymyositis, and myasthenia gravis. Most cases were seen in multiple sclerosis with natalizumab. Patients with IBD are also considered at risk and need to be monitored for PML.

#4: An increased understanding and treatment options for patients who don’t respond to anti-TNF therapies

A significant number of patients fail to respond to anti-tumor necrosis factor (anti-TNF) therapy. New data suggests that interleukin 23 (IL-23) may be a key driver of molecular resistance to anti-TNF therapy, and blocking IL-23 may restore the balance between pro- and anti-inflammatory responses in the inflamed gut. There are several treatment options for such patients, but there have been no attempts to compare efficacy of different drugs until recently.

Two studies were presented at the congress that addressed this gap. The first one compared tofacitinib with vedolizumab in adults with symptomatic UC with prior exposure to at least one anti-TNF treatment. Both groups met the primary endpoint of corticosteroid-free clinical remission at 16 weeks (45% for the tofacitinib group and 40% for the vedolizumab group); however, the endoscopic improvement at week 16 showed the superiority of tofacitinib with a 24% rate versus 7% in vedolizumab patients.

The second study compared vedolizumab to ustekinumab after at least one anti-TNF treatment failure in subjects with Crohn’s disease. The study’s main objective was to compare the short- and long-term treatment survival rates with efficacy and safety as secondary objectives. The study showed a statistically significant higher five-year survival rate with ustekinumab, with the safety profile being similar for both drugs.

#5: New approaches to defining treatment goals in both UC and Crohn’s disease studies

In all international guidelines, treatment goals include endoscopic parameters (normal mucosa or Mayo endoscopic score 0-1). Most recent clinical trials include endoscopic subscore 0-1 and both central reading and histology during initial trial. Mucosal healing can now also include histologic improvement, as seen in the ustekinumab program.

The upadacitinib program looked at the composite endpoint endoscopic-histological score and histologic remission defined as a Geboes score of less than 2.0, which means the absence of neutrophils both in the epithelium and the lamina propria. The Geboes score is a six-grade classification scoring system to assess inflammation in UC. The most stringent definition is Geboes score 0-1: no eosinophils, no neutrophils in lamina propria, no neutrophils in the epithelium, no erosion, and no ulceration. Achieving histologic remission may be correlated with improved patient outcomes: decreased risk of clinical relapse, decreased corticosteroids use, lower risk for colectomy, and lower risk of hospitalization. Increased mucosal inflammation in UC may be associated with an increased risk for colorectal cancer.

Another study compared endoscopic healing at one year with different biologics. The best endoscopic healing for ileal involvement was seen with the infliximab biosimilar (37% of patients) and the lowest rate with ustekinumab (23%) and vedolizumab (19%). In the case of colonic involvement, the lowest rate of endoscopic healing was observed with ustekinumab (29%) and vedolizumab (31%), and the highest for adalimumab (62%).

Final thoughts

As the need for clinical trials in Crohn’s disease and ulcerative colitis grows, CRO collaboration matters more than ever. At PSI CRO, we’re committed to keeping abreast of the latest scientific advances and partnering with the companies doing the most exciting work in the IBD space. Learn more about our IBD expertise here and how we can support your next study.

A Letter from PSI CRO AG to Teams Globally

Leave a Comment / News article / By Natania Barron

Dear all,

For several days now, full-scale military aggression against Ukraine has been unfolding. There is no rhyme or reason for it, no excuse, no justification, no exoneration.

Our friends, colleagues and teammates are in bad trouble, and we are worried sick about their wellbeing. The country is under martial law. Business operations are disrupted.

Let us now make a few specific points:

As of this writing, all our employees in Ukraine are accounted for and physically safe. Emotionally, people are understandably distressed, but many have shown remarkable resilience and bravery in the face of hostilities playing out on their doorsteps.
Our office in Kyiv is now being used as a living quarters for those employees whose apartments are too close to the frontlines. Also, we’re lucky to have an underground garage that can be used as a shelter.
The leadership team in Ukraine are showing incredible resilience. Several times a night, they are awoken by the sound of air-raid sirens and they still make themselves available since the early hours of the morning, supporting their teams, alleviating other peoples’ anxiety and making sound tactical decisions.
An task force consisting of the Country Managers of some of the neighboring countries (Hungary, Romania, Poland) have been working on several scenarios for resettling our employees and their families, if they need to leave the country. It looks like Poland will have to do most of the heavy lifting, for which we should be immensely grateful.
So far, the Internet and cellular services haven’t been disrupted, so communication hasn’t been compromised. We’re exploring various backup scenarios in case the situation deteriorates.
PSI drug supplies warehoused in the region are intact.
For obvious reasons, our ability to maintain normal operations in Ukraine is severely reduced, but, importantly, not paralyzed. Onsite monitoring is currently not possible, but our people still attend calls, file documents, write reports, stay in touch with sites and, amazingly, follow up on the status of patients whenever possible.
Needless to say, the company is providing and will continue to provide support to our staff – financial, logistical, psychological. We only wish we could do more.

Many of our team members have been asking themselves, “What can I do to help?” People have offered to donate their salaries, collect warm clothes for their Ukrainian colleagues, and many other noble initiatives. This is very sweet but unnecessary. Whatever money can buy, the company will take care of that. You can do so much more. Since our operations in Ukraine have been impeded, we need to pick up the slack elsewhere. We know that work is already being redistributed within and among project teams, but we want to drive this message home: if we all do a little more, we can reduce or even cancel out the damage. Every patient we cannot enroll in Ukraine now will have to be enrolled someplace else; every draft visit report that your teammate in Ukraine cannot review will have to be reviewed by someone else; every document that cannot be timely filed by someone in Ukraine will have to be filed by a teammate elsewhere. Every extra mile, meter, foot, inch, centimeter – counts. No extra effort is too small.

Lastly, for the sake of our collective sanity, let me offer a word of caution: whatever you hear or read on the news or social media, do take it with a grain of salt. Every kernel of accurate information is heavily intermixed with hearsay, unsupported opinions of pseudo-experts, propaganda and deliberate fabrications. Information can be and is weaponized – it’s the reality of contemporary warfare. Apply critical thinking – you’re good at this.

Thank you all,

PSI CRO AG

Complete Enrollment of IBD Studies on or Ahead of Time

Leave a Comment / Case Study, News article / By Paul Mirek

The number of IBD trials initiated per year grows every year, meaning competition for sites and patients alike. To make sure one of our longtime clients’ IBD studies stood out, we drew on our database of more than 2,800 sites in 40+ countries to find the geo-mix that worked for them—and fast. (And they’re not our only repeat clients: about 95% of our business is repeat and referral.)

To help engage sites for an IBD study in an increasingly competitive landscape, we put together a 3-step early engagement campaign, including investigator letters, 1-to-1 calls, and webinars. Within four weeks, we’d collected 170 CDAs and 150 completed e-questionnaires from 20 countries. Building great relationships isn’t easy, but at PSI, we think it’s worth it.

With the combined efforts of our feasibility, site identification, and startup teams, we were able to complete enrollment two months ahead of schedule in a highly competitive indication—and with 40 more subjects randomized than planned. In today’s crowded IBD clinical trials landscape, surprise yourself. Contact us to learn how PSI CRO can deliver your next IBD trial on time.