News article Archives

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PSI FAQs: How do PSI CRAs support clinical site relationships?

At PSI, your last patient in is our first priority. Keeping this goal in mind is only possible with dedicated Clinical Research Associates (CRAs) that support your trial from end to end. This stability not only streamlines communication and transparency with your team but also with the sites who are critical to the success of your trial.

Each site on your study will have a single point of contact with one of our highly qualified CRAs, who serves as a site manager. This CRA’s responsibilities include:

• Ensuring sites are up to date and have all the essential documents
• Maintaining a deep working knowledge of the latest protocol version
• Confirming standards of care and investigator interest
• Ensuring a streamlined process of reporting
• Liaising with investigators and clinical research personnel
• Responding to site questions and providing regular remote follow-up in between visits

With experience working with 4,000 sites worldwide, we recognize that building relationships with investigators and site teams takes time. To ensure the success of each site relationship, our CRAs receive extensive project-specific and soft skills training. This difference between managing site relationships and simply monitoring sites can have a direct impact on the success of your current trial as well as a site’s willingness to work with a sponsor or CRO again in the future.

At PSI, we recognize that every patient counts. That’s why our CRAs go the extra mile to ensure our sites receive the support they need so that your study enrolls on time. Contact us today to learn more.

“I would like to thank you from the bottom of my heart for working so diligently for this patient. I know it was a lot of hard work by everyone but if you could have seen the patient’s face when I told her our site was activated it was worth it.”

Lead Certified Clinical Research Nurse Tweet

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral.

Case Study

A sponsor of a pivotal Phase 3 prostate cancer study investigating a radiopharm product approached PSI for support based on our experience and established network of 300 global radiopharmaceutical sites.

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience.

The PSI Advantage

For the sixth year in a row, PSI CRO has been named a CRO Leadership Award winner in the categories of Expertise, Quality, and Reliability in the Overall (combined Big and Small pharma) respondent group. The CRO Leadership Awards are presented by Life Sciences Leader and Clinical Leader based on research conducted by ISR Reports. The awards recognize CROs that are voted by sponsors to meet or exceed expectations.

blurred female scientist using a dropper and test tube

Demystifying Biosimilar Development Regulations: Key Considerations for Sponsors

News article / By Ashley Stufano

Biosimilars – biological medicines highly similar to another already approved biologic – have emerged in recent years as an area of rapid development activity, especially for Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC). While these drugs have historically faced the common misconception that they are less safe and less effective compared to the original biologic product, biosimilars undergo very rigorous and extensive testing before receiving regulatory approval, and public perceptions are starting to shift. As these drugs continue to grow in popularity with physicians and patients alike, it is crucial for sponsors to understand what these changes mean for current and future IBD development activity.

In our new white paper, Similar But Different: Regulatory and Operational Considerations for Biosimilar Clinical Development in IBD, we discuss how biosimilars have transformed the treatment landscape for IBD in the past decade, their current therapeutic uses in CD and UC, and global regulatory considerations for running biosimilar clinical trials in IBD. This post reviews some of the regulatory factors that are evaluated for biosimilar medications during the course of a trial. The list of full regulatory requirements varies by country; however, these factors are common parts of the evaluation process by many regulatory bodies.

Comparability

Even licensed biologics undergo changes in relevant molecular attributes over time.¹ In a study of biologics licensed for use in rheumatology, all reported changes to the production process over time, including change of cell culture supplier and modification of the protein purification procedure.² The original medicines available today are therefore not identical but comparable to those available in previous years. 

Biosimilars must demonstrate clinical comparability with the reference drug (the original biologic) in order to receive regulatory approval. The following table outlines the properties and methods used to demonstrate comparability in a biosimilar for infliximab (IFX).^3,4 

Properties	How was similarity determined?
Protein structure and production quality	Detailed laboratory analysis of the structural characteristics of different batches of the drug
Pharmacokinetic, pharmacodynamic and toxicological tests on animals	"In vitro" and "in vivo" tests on different species
Pharmacokinetic, pharmacodynamic and toxicological tests on humans	Initial clinical trials
Clinical efficacy and safety	Major clinical trials
Safety in everyday practice	Risk management plan , Post-marketing trials (Phase 4),  Routine reporting of side effects,  Pharmacovigilance

Extrapolation

The initial comparability tests are conducted in the indication and population that are considered the most sensitive to detect clinically significant differences in safety, immunogenicity, and efficacy between the original and biosimilar drug. If the biosimilar product is highly similar to the reference medicine and has comparable safety and efficacy in this therapeutic indication, safety and efficacy data may then be extrapolated to indications already approved for the reference medicine.⁵

Extrapolation must be supported by all the scientific evidence generated in other comparability studies. In these cases, clinical trials are often not required to be repeated for all indications; instead, changes are approved based on data from quality and in vitro comparability studies. The possibility of extrapolation is dependent on the regulatory landscape of the particular country or countries in which the clinical trial is being conducted. In the EU, which pioneered biosimilar regulation by establishing a solid framework for approval, decisions based on extrapolation are dependent on a number of criteria:^5,6

Mechanism of action: The mechanism of action of the active substance should be mediated by the same receptor in both the initial and extrapolated indication. If the mode of action is complex, involving multiple receptors or building sites, additional studies may be needed to prove that the biosimilar and reference medication will behave similarly.
Study population: Comprehensive comparability studies must demonstrate that the biosimilar is highly similar to the reference medicine in a “key population” in which potential differences can be detected.
Clinical setting: Data from one indication may not be directly applicable to an indication within another therapeutic area where the mode of action, posology, or pharmacokinetics may be different. Additional studies may be needed in this case.
Safety data: A comparable safety profile for the proposed indication must be established in one therapeutic indication before extrapolation. Comparability must be shown at the structural, functional, pharmacokinetic, and pharmacodynamic levels, and efficacy must be comparable.
Immunogenicity data: Extrapolation of immunogenicity data always requires justification as immunogenicity is determined by more than product-related characteristics. Factors relating to patient (age, immune status), disease (comorbidities, concomitant treatments) and treatment-related factors (route of administration, length of exposure) must be considered.

Meet the challenges of your IBD trial with confidence

Understanding each country’s regulatory intricacies of biosimilar development is crucial for the success of your trial. With a network of more than 3,900 global IBD sites, and a regulatory team with local regulation expertise, PSI specializes in delivering studies on time and with quality data.

Discover the full white paper here, or contact us to learn more about running your pivotal Phase 2 and 3 IBD trials with PSI.

References

¹ Schiestl M, Stangler T, Torella C, Cepeljnik T, Toll H, Grau R. Acceptable changes in quality attributes of glycosylated biopharmaceuticals. Nat Biotechnol. 2011;29(4):310-312. doi:10.1038/nbt.1839. https://www.ema.europa.eu/en/human-regulatory/overview/biosimilar-medicines-overview

² Schneider C. Biosimilars in rheumatology: the wind of change. Annals of the Rheumatic Diseases. 2013;72(3):315-318. doi:10.1136/annrheumdis-2012-202941

³ European Medicines Agency. Assessment report Inflectra. European Medicines Agency. June 27, 2013. https://www.ema.europa.eu/en/documents/assessment-report/inflectra-epar-public-assessment-report_en.pdf

⁴ Krznarić Ž. Biosimilars in Inflammatory Bowel Disease: From Theory to Practice. Presented at: PSI Internal Training; June 27, 2023.

⁵ European Medicines Agency, European Commission. Biosimilars in the EU – Information Guide for Healthcare Professionals. European Medicines Agency. 2019. https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf.

⁶ European Medicines Agency. Biosimilar Medicines: Overview. European Medicines Agency. April 26, 2023. Accessed July 3, 2023. https://www.ema.europa.eu/en/human-regulatory/overview/biosimilar-medicines-overview.

african american doctor standing in front of other doctors

PSI FAQs: How does PSI reduce CRA staff turnover on your project?

News article / By Ashley Stufano

Project team turnover can have a severe impact on your study’s timelines, leading to delays in everything from patient recruitment and site activation to data collection and study management. Clinical Research Associate (CRA) turnover rates in particular have climbed in recent years due to the COVID-19 pandemic and shifting economies, being reported as high as 30% in the US.

Despite this, PSI’s turnover has remained historically low with a company-wide staff turnover rate of only 14%. This kind of employee retention doesn’t just happen – it’s part of our commitment to stability for our biotech partners over the past 25 years.

While PSI offers competitive benefits and opportunities for employee recognition, we also support our CRAs in a number of other ways. We launched a CRA Academy to provide to help our team members develop therapeutic expertise as well as soft skills to manage key relationships with sites.

PSI also ensures that your study is effectively resourced by CRAs with manageable workloads by being selective about the projects take on. We are a specialized global CRO committed to pivotal Phase 2 and 3 clinical trials in select therapeutic areas, including oncology, hematology, gastroenterology, multiple sclerosis, and many rare diseases. This allows a more focused approach to resourcing, including providing additional study-specific training for CRAs on all new projects.

To learn more about how PSI ensures stability on your pivotal trial, contact us today.

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral.

Case Study

PSI managed to demonstrate swift feasibility and start-up ahead of schedule, leveraging site relationships, and fostering team consistency and stability.

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience.

The PSI Advantage

Case Study: How VISIONAL™ is Helping to Accurately Predict Study Enrollment Timelines

Case Study, News article / By Ashley Stufano

At a Glance: AI and ML-powered insights for your next trial

A sponsor of a challenging breast cancer study needed to identify the optimal mix of countries and sites with similar experience and access to a hard-to-recruit subpopulation of breast cancer. Using internal and external data sources, PSI’s VISIONAL™ platform compared thousands of feasible country-site combinations and recommended the optimal enrollment scenario to meet the sponsor’s timelines and cost constraints.

Trial Enrollment Recommendations from VISIONAL™

Sponsor Challenges

The study targeted patients pretreated with recently approved drugs. Our key criteria for country and site selection included local standards of care, historical performance in the indication, and current competition. After the initial planning had begun, the sponsor also requested 20% of patients from Latin America.

How VISIONAL™ Helps Make Strategic Decisions

Working with internal and external data sources and KOLs, PSI feasibility team quickly pulled all available data on standards of care, site performance, and historical enrollment rates, carefully curated for similarity. The dataset included 40+ countries in North America, South America, Europe, Asia-Pacific, and Africa. Using this trove of data, VISIONAL™ compared hundreds of country/site combinations, taking into account study costs and probability of success.

We were able to easily adjust the constraints for regional patient quotas as well as additional requirements from the FDA and EMA after two rounds of protocol review.

Results

1. Optimal Enrollment Scenario

VISIONAL™ recommended the most optimal combination of sites, countries, and timelines based on the current landscape and historical benchmarks, while taking into account all constraints set by the sponsor and the FDA.

2. Cost vs. Speed
The system recommended the fastest and most cost-efficient scenario within the sponsor’s budget range and timelines. We were also able to quickly evaluate alternative options:

Faster scenarios with an acceptable risk level
Longer but less expensive scenarios
Scenarios that buffer for unexpected delays

3. Customizable and Adaptive Reports
The initial work done during the planning stage also provided the sponsor with peace of mind during the study launch with the ability to rapidly model new scenarios based on additional constraints/new requirements.

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral.

Therapeutic Areas

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience.

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience.

up close image of a small clear vial, a CT scan of a brain and a stethoscope

Case Study: Phase 3 Radiopharmaceutical Clinical Trial in Oncology

Case Study, News article / By Ashley Stufano

At a Glance: FDA Approval in 4 Years

Radiopharmaceutical clinical trials face a host of logistical challenges from startup through the clinical phase. A sponsor of a pivotal Phase 3 prostate cancer study investigating a radiopharm product approached PSI for support based on our experience and established network of over 400 global radiopharmaceutical sites. By working closely with our sites and vendors, PSI met or beat all critical milestones, helping our client secure FDA approval for their radiopharmaceutical product in under four years.

Patient Screening and Enrollment Numbers

Sponsor Challenges

The major challenges in global nuclear medicine trials include the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. The investigational product in this study had a half-life of three days, necessitating diligent time management and site engagement to deliver the study on schedule.

PSI Strategy

To make sure eligible patients didn’t miss these three-day windows, PSI’s CRAs encouraged sites to maintain frequently updated pre-screening logs and regularly discuss the pool of potential patients with the investigators. We also worked closely with sites and the manufacturing facilities to time the inclusion of each patient appropriately, especially around local bank holidays when a manufacturing facility would not be available.

Results

1) Expedited Study Timelines
PSI met or beat all critical milestones during the study, including achieving FPI in the US in less than 3 months and completing NDA submission one month ahead of schedule.

2) 99% Enrolling Sites
Only one out of all initiated sites did not enroll a patient.

3) Successful Regulatory Approval
After passing three FDA inspections without major findings, PSI’s regulatory experts helped our client secure FDA approval in under four years.

“I would personally like to acknowledge and thank the entire PSI team and leadership for the dedication, perseverance and determined support that supported the early completion of the study. Your team have showcased all the capabilities and attributes of a best-in-class CRO for project delivery.”

--Global Head

External Relationship Management

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral.

Therapeutic Areas

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience.

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience.

red blood cells under a microscope viewing with a purple dye contrast

Case Study: Optimizing Feasibility and Start-Up for a Phase III HemOnc Clinical Trial

Case Study, News article / By Ashley Stufano

At a Glance

No trial is ever easy. But with the continued effects of the global pandemic and the war in Ukraine, the sponsor had larger than average challenges. Nonetheless, PSI managed to demonstrate swift feasibility and start-up ahead of schedule, leveraging site relationships, and fostering team consistency and stability. In the end the study completed enrollment of nearly 900 patients on time at as many as 370 sites all around the world. Italy and Australia showed up as the top enrolling countries.

Patient Enrollment Numbers

Sponsor Challenges

Enrolling over 900 patients and in a clinical trial of this complexity would pose a challenge even in the most mundane of years. Add to that continual pandemic consequences and a global conflict, the stage is set for every possible delay and communication breakdown. The sponsor needed a CRO willing to tackle an aggressive recruitment plan and provide a solid partnership in order for the trial to succeed.

Start-Up in Sync

Staying on time means starting on time. Working closely with sites to understand how the pandemic affected their ability to meet site activation, PSI offered them several technical options that allowed for remote site selection visits. PSI managed to identify over 3000 sites and select about 500 sites 3 months ahead of schedule.

Additionally, feasibility projections were actually reflected in enrollment, not merely a best-case scenario or wishful thinking. This is due in large part to knowing the sites. Today, PSI would have also added machine-learning-powered tool, VISIONAL™, to generate the most optimal enrollment scenarios that could potentially further reduce the study time and cost.

Racalibrating the Geo-mix

Not every CRO can offer flexibility and adaptability, especially in a short amount of time. During enrollment, a change of strategy on the sponsor side called for more sites, and swiftly. In order to do this, countries with initially smaller projected sites and patients had to ramp up with little to no interruption. The only way this could be accomplished was with previously established solid global site relationships and coordination and stellar communication on every level of the study team.

Managing Motivation, Staffing, & Velocity

To motivate teams on a country level, PSI staff focused on maintaining a sense of competition between teams. This helped create a friendly sense of excitement as countries saw their recruitment numbers grow.

Continuity of the study team also played an enormous role in the study’s success. This not only helped keep the study on track when the client had changes to their own staff but provided a sense of consistency and reliability throughout the course of the trial at every level. Key roles project supervisor, project manager and other key staff stayed on for the whole of two years of study duration, something almost unheard of in this ever-changing industry. They are still with PSI running the trial as we write these lines.

The PSI Advantage

icon of philadelphia skyline with five years in a row

King of Prussia Office Receives Prestigious Best Places to Work Award for 5th Year in a Row

Life at PSI CRO, News article / By Stephanie Kim

PSI CRO is excited to announce that its King of Prussia office has been recognized as one of Philadelphia Business Journal’s Best Places to Work for 2023. This prestigious accolade acknowledges PSI’s exceptional company culture, strong leadership, and unwavering commitment to its employees, as voted on by the dedicated professionals within the organization.

This achievement marks the fifth consecutive year that PSI’s King of Prussia team has been honored with this esteemed award, reflecting the office’s consistent dedication to fostering an environment where employees can thrive and excel.

“We are very proud to be named one of Philadelphia’s Best Places to Work for a fifth year in a row,” says Tom Flud, Director of Operations in PSI’s King of Prussia office. “During the last five years, PSI’s King of Prussia office has experienced substantial growth and transformation, while overcoming challenges posed by a global pandemic. Throughout this journey, our dedicated employees have continued to flourish, demonstrating unwavering resilience and a commitment to our belief that Every Patient Counts.”

The selection process for the Best Places to Work award involves a partnership between Philadelphia Business Journal and Quantum Workplace. The public nominates companies, and employees at these nominated companies are then invited to complete an online survey that assesses various aspects of company culture, including compensation, benefits, and trust in senior leadership.

At PSI CRO, cultivating a strong culture is a top priority, both in the King of Prussia office and across all global locations. The company’s foundation is built on stability and longevity, with a group of managers who founded PSI a quarter of a century ago still actively involved in the organization today. This enduring stability has fostered a unified global culture that spans six continents.

The company adheres to seven core values that guide its business practices, and serve as the bedrock of PSI’s growth and unwavering commitment to providing exceptional customer service for more than 25 years. With a workforce of more than 2,700 employees worldwide, these values ensure that PSI maintains its unique path of organic growth and customer-centric dedication.

For more information and to explore opportunities to join the dynamic PSI team, please visit our careers page.

radiopharmaceutical molecules, glass-like on an light blue background

Operationalizing Radiopharmaceutical Clinical Trials: Opportunities and Challenges

Leave a Comment / News article / By Ashley Stufano

When PSI published a blog post on the current state of radiopharmaceutical clinical trials in 2019, we had no way of knowing of the changes that would transform the clinical trial industry – along with every other one on earth – just a few months later.

Of course, managing global nuclear medicine trials has never been easy due to the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. However, travel restrictions and supply chain challenges have only exacerbated these obstacles. While some of these issues are starting to ease, the need for an experienced, global perspective toward managing these studies has only increased.

Success starts with understanding the risk factors that can impact your radiopharmaceutical trial from startup through the clinical phase. Drawing on our experience as we continue to run radiopharm studies in multiple oncology indications, we’ve highlighted some of the most common challenges to consider below – and how to overcome them.

1. Country-specific Regulatory Requirements for Radiopharmaceutical Agents

As development interest in this new class of agents has continued to grow, so has the complexity of the regulatory landscape. Additional approvals should be considered for studies in both the United States and the United Kingdom, as outlined in the table below:

Country	Consideration
USA	Radiation Safety Committees approvals typically obtained before submissions to IRBs
UK	HRA radiology review prior to submission is needed, as well as approval of Administration of Radioactive Substances Advisory Committee (ARSAC). ARSAC review goes in parallel to the ethics/regulatory review

The European Union’s Clinical Trial Regulation has streamlined the process for submitting clinical trial applications in the EU, but many countries still encourage or require additional approvals. An in-depth understanding of each specific country’s requirements in your trial is essential to proactively anticipate requirements and potential questions that can delay approvals. Drawing on our experience with these studies, PSI maintains a library of country-specific radiopharmaceutical requirements and regulations within VISIONAL™, our machine-learning-powered system for data-driven feasibility and enrollment forecast. This pairing of regulatory expertise and technology allows us to accurately predict timelines and model hundreds of country and site combinations, their budgets, and probability of success within minutes.

2. Site Imaging Qualifications and Other Common Delays in Site Activation

Site qualification can be time-consuming for sites, so sponsors should confirm timelines during the feasibility process and ensure that sites are well-trained and supported with any study-specific calibration or camera requirements. PSI created the role of Site Support Specialist to help support sites in the qualification and camera process as well as during the study, saving them time and frustration. An example of the site imaging qualification process is shown below.

This is a simplified example, and the process can be much lengthier if dosimetry is included as part of the study. We have found having a dedicated Site Support Specialist assigned to work one-on-one with each site during the qualification process significantly decreases delays in site activation due to camera qualification.

Issues with technical transfer, or IND amendments (if the drug will be manufactured on-site), can also lead to delays. In some instances, choosing a central procurement facility may be effective, allowing one facility to execute the contract and technical transfer independent of site startup and activation.

3. Logistical Issues During Clinical Phase

As noted in our previous article, cooperation and coordination are imperative every step of the way for the successful delivery of radiopharmaceutical trials: from the facilities and procedures that produce the nuclear material to their handling and storage to the transportation of the drug and dispensation. Understanding the patient journey and which procedures must be completed at each step, including when the investigational product should be ordered, is recommended as a proactive foundational tool. At PSI, we have developed a detailed and unique visual patient journey utilized at the site and project levels.

In addition, other tools for clinical staff, such as a patient visit and MRI/whole brain PET scan tracker calendar, biopsy procedure schedule, source template, and automatic calculator for time-dependent procedures, will help provide additional clarity and compliance. We also recommend tracking key steps via Interactive Response Technology.

4. Central Radiology Review and Delays in Submitting Scans

It is critical to manage and track all steps in the imaging process at each site, including navigating the technical dialogue between nuclear medicine technologists, nuclear physicians/radiologists, investigators, and other stakeholders. Sponsors should ensure clear communication and receipts from the central reader for all scans received and that the appropriate project team members are copied on any queries to the site. PSI’s Site Support Specialist is key in ensuring every stage is performed accurately and on time, including monitoring site submissions in real time and assisting sites with submissions when needed. This role has also proven beneficial in managing and providing oversight of all site queries, cutting the site team’s time spent on imaging queries in half.

5. Development and Implementation of Site-Specific Enrollment Plans

Solid tumor oncology trials represent one of the most competitive markets in clinical research, with over 3,000 trials ongoing or planned, according to data from clinicaltrials.gov, Citeline, and GlobalData. With additional obstacles presented by sites’ limited proximity to manufacturing centers, sponsors and their partners should have detailed site-specific enrollment plans that consider the patient journey at each site, from identifying prospective patients to scheduling the needed imaging assessments and surgeries or biopsies. Walking through this patient journey helps both the site and the CRA to identify all the involved team members so that potential risk factors can be mitigated. PSI’s dedicated Site Support Specialists may meet with sites as soon as they’re selected by clients to understand this patient journey and put together a tailored site enrollment strategy based on site referral patterns, facilities, capabilities, and other key factors.

Meet the challenge of your radiopharmaceutical pivotal trial with PSI

Every study is different, and there is no one-size-fits-all solution for ensuring success. With an established and proven network of almost 300 global radiopharmaceutical sites, PSI specializes in delivering radiopharm studies on time and with quality data. Seventy-nine percent of PSI CRAs have oncology experience, and PSI has developed therapeutic-specific training and resources for radiopharmaceutical trials to achieve the highest level of quality for your study. In addition, PSI’s Site Support Specialist role has led to a dramatic improvement in site activation and enrollment.

IBD Clinical Trial Landscape: 3 Greatest Unmet Needs in IBD Clinical Development in 2023

Leave a Comment / News article / By Ashley Stufano

With the steady increase in the prevalence of inflammatory bowel disease (IBD) worldwide and the discovery of new disease pathways, there has also been a renewed interest in IBD drug development. During the ten years from 2010 to 2020, the number of clinical trials in the IBD therapeutic area almost doubled due to a combination of factors, including the continuous development of biologics, the discovery of new pathways, and, consequently, the introduction of new classes of medications such as JAK–STAT pathway inhibitors.

Our new white paper Inflammatory Bowel Disease: Current Status and Future Perspectives offers insights into recent trial and research developments that will most impact study design and operationalization for various IBD therapies and indications. In our previous post, we discussed the common challenges in IBD patient enrollment. In such a competitive landscape, it is also critical for drug developers to understand the major unmet needs in IBD management.

1. Lack of Predictive Biomarkers for Early Diagnostic Testing

There are a number of biomarkers, divided into two groups based on their application, currently used in clinical practice, but there is no single one that can help with an accurate diagnosis of IBD. The first group, aimed at diagnosis and monitoring of IBD, contains blood-based biomarkers of inflammation (C-reactive protein and erythrocyte sedimentation rate) and stool-based biomarkers (e.g., fecal calprotectin, fecal lactoferrin, fecal neopterin, and polymorphonuclear neutrophil elastase). The second group of biomarkers, aimed at the subclassification of IBD between UC and CD, includes blood-based biomarkers such as antineutrophil cytoplasmic antibodies (ANCAs), anti–outer membrane protein C (Anti-OmpC), anti–S. cerevisiae antibodies (ASCA), and anti-I2, anti-carbohydrate, and pancreatic antibodies.ⁱ These biomarkers can only be used as supporting data secondary to clinical data and endoscopic examination. Another limitation of biomarkers is their inability to predict response to therapy in patients with IBD.

2. Lack of Drugs with Minimal Side Effects

Conventional therapy methods, including 5-aminosalicylates, corticosteroids, thiopurines, anti-TNFs, and others, are generally effective in controlling symptoms, but adverse side effects such as immunosuppression, systemic fungal infections, and possible cancer development may have an overall negative impact on the disease outcome. There continues to be an unmet need for long-term treatments with minimal side effects, one of the greatest motivators for driving new IBD biologic development. For instance, all anti-TNF-α drugs in the US carry a boxed warning due to the increased risk of infections in 25–30% of patients, with limited treatment options afterwards. Etrolizumab was a potentially promising drug that was thought to close this gap, but as of November 2022, etrolizumab met its primary endpoint of inducing remission versus placebo for patients with UC in only two out of five studies and failed to meet its primary endpoint versus placebo as maintenance therapy.ⁱⁱ

3. Lack of Oral Drug Formulations

Based on the literature analysis and feedback from clinical trial investigators (and indirectly from the patients), the primary unmet need in management of moderate to severe IBD is lack of oral drug formulations: patients would prefer an oral formulation over the subcutaneous or intravenous administration. If the disease progresses further, requires hospitalization and IV corticosteroids, treatment options are limited with options of infliximab or cyclosporin, that in turn have significant side effects and they are at risk of toxic megacolon or bowel perforation with subsequent surgery. Prevention of this outcome is another focus of drug development – finding effective drugs for a late-stage disease.

Key Takeaways

IBD therapeutics and biologic developments have, thus far, not been able to provide substantial holistic solutions that improve a patient’s quality of life. More than that, limitations in testing, serious side effects, recalls and a lack of convenient therapeutic options have made minimal improvements upon current therapies. With the growing number of IBD studies, it is essential to consider and choose the right partner to help your IBD clinical trial stand out.

Despite the competition, PSI continues to deliver higher enrollment rates than typical across the industry due to our relationships with more than 3,900+ IBD sites around the world. Our studies are successful due to our long-term relationships with recruiting sites; we know the investigators on a personal level and they are motivated to work with us. Visit us online to learn more about our IBD therapeutic experience.

References

ⁱ Soubières, A. A., & Poullis, A. (2016). Emerging Biomarkers for the Diagnosis and Monitoring of Inflammatory Bowel Diseases. Inflammatory Bowel Diseases, 22(8), 2016–2022. https://doi.org/10.1097/MIB.0000000000000836 

ⁱⁱ M. Agrawal, B. Verstockt. (2021) Etrolizumab for ulcerative colitis: beyond what meets the eye. Lancer Gastoenterology and Hematology 7(1): P2-4. https://doi.org/10.1016/S2468-1253(21)00369-1 

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