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Putting the Focus Back on Site Relationships Part 3: The Patient Journey

This is the third in a series of posts based on PSI’s new white paper, Putting the Focus Back on Site Relationships in Clinical Trials. Part 1 focused on the common challenges sites encounter while running clinical trials, while Part 2 discussed strategies to help ease the burden of sites, which ultimately supports sponsors in meeting trial timelines and milestones. In this final post in the series, we’ll explore why considering the patient journey first is an essential – and often overlooked – element of the relationship between CROs, sponsors and sites..

Considering the patient journey

Evaluating study procedures from the perspective of the patient can help minimize patient burden and the overall impact on sites. Providing site training and materials to smooth patient transitions and processes can improve the likelihood of meeting enrollment and retaining patients. These materials offer guidance and reassurance to patients after they leave the site. This makes it easier for sites to develop meaningful and valuable relationships with patients because less time is spent on repetitive tasks such as reviewing basic study information and processes.1

PSI charts out the patient’s journey for each study, allowing site teams to understand the needs of the patient and study requirements more clearly. For example, suppose the patient needs to have a lab specimen taken eight hours after the investigational product administration. In that case, the site team can plan for the patient needs, such as space for the patient or food vouchers. In turn this reduces the potential protocol deviations, ensuring the quality of the study endpoints.

psi patient journey chart

Concluding thoughts: Why site relationships really matter

In addition to boosting engagement, making sites feel heard, and reducing turnover, there are many other benefits to building strong site relationships. As PSI has learned, when we can understand and even predict the needs of each site, we can provide sites with self-awareness about which trial programs are right for them. In turn, this allows us to provide our future sponsors with insight into how to identify the optimal sites for their particular trials, further reducing operational waste.

When it comes down to it, sites want to work with CROs and sponsors with whom they have positive experiences. Making them feel heard, reducing project team turnover, optimizing change management, and providing support are all part of improving site relationships.

If you’re looking to expand the horizon of your next clinical trial, partner with the CRO with global reach, Swiss quality, and on-time delivery. At PSI, we understand your needs and what it takes to help your product achieve global success. Learn more about how PSI prioritizes our sites by downloading the full white paper or get in touch with our team to discuss your feasibility needs.

1WCG CenterWatch. (2023). 2023 WCG CenterWatch Global Site Relationship Benchmark Survey Report for Sponsors. Falls Church, VA. WCG CenterWatch.

About Us

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

Case Study

When a small biotech approached PSI to run a complex UC study, the sponsor’s concerns were clear: streamline initial set-up, avoid complex vendor management, and overcome multiple operational challenges.

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. 

Putting the Focus Back on Site Relationships Part 3: The Patient Journey Read More »

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Putting the Focus Back on Site Relationships Part 2: 3 Strategies for Mitigating Trial Site Burden

This is the second in a series of posts based on PSI’s new white paper, Putting the Focus Back on Site Relationships in Clinical Trials. In Part 1, we discussed three of the most common challenges sites encounter while running clinical trials with sponsors and CROs. A lack of communication, resources, training and support can impact sites’ ability to enroll patients, in addition to complicating the patient journey. In this post, we share three of PSI’s strategies to help ease the burden of sites, which ultimately supports sponsors in meeting trial timelines and milestones.

When aiming to improve site relationships, there is no better place to start seeking feedback than the sites themselves. In a recent survey by WCG CenterWatch,1 the top 10 CRO attributes most valued by sites are:

  • Quality of communication with study team/site staff
  • Responsiveness to site staff inquiries
  • Organization and preparedness
  • Professionalism, knowledge, and training of monitors/CRAs
  • Access to staff for escalation and resolution of issues
  • Professionalism of staff in clinical operations functions
  • Ongoing help/support provided in running the study
  • Ability to effectively work with sponsors
  • Professionalism and efficiency of administrative staff
  • Efficiency in contract and budget negotiation
While the list of attributes has remained largely consistent over the past few years, attributes seven through ten were added this year, reflecting a shift in site priorities when working with CROs toward “overall project support, study monitoring, and contracts and budget handling.”1

Strategies for successful site relationships

When considering how to build strong site relationships, look to the qualities considered most important to sites, yet which received low actual rankings in terms of delivery.

Flexibility and openness when dealing with protocol and budget modifications, practicing open communication, and reducing staff turnover are among the top concerns for sites.2

Prioritizing technology and process integration can ease the technology burden of site staff, keeping training and retraining to a minimum.

A key reason for enrollment slow-down at the site level (as well as overall timeline delays and additional costs for sponsors) is excessive protocol amendments. To help guard against this risk, sponsors should seek to optimize protocols as much as possible during the trial design phase.2

Scientific Advisory Boards are often valuable for assessing patient burden and suggesting improvements to study design and inclusion criteria during early review. Through PSI’s SAB protocol review and recommendations, future protocol amendments are minimized. When protocol and budget amendments occur, there should be thorough guidelines and clear communication of all necessary changes and processes to the site.

The patient journey is another element to consider during trial design and implementation. We’ll dive into this further in our third and final post in this series.

Site support solutions for pivotal Phase 2 and 3 trials

Understanding how to navigate the needs of individual trial sites is crucial for the success of your trial. With a global database of more than 4,000 sites and a unique approach to site support, including our dedicated Site Support Specialists, PSI excels in delivering studies on time and on budget.

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

1 WCG CenterWatch. (2023). 2023 WCG CenterWatch Global Site Relationship Benchmark Survey Report for Sponsors. Falls Church, VA. WCG CenterWatch. https://www.centerwatch.com/products/587-2023-wcg-centerwatch-global-site-relationship-benchmark-survey-report-for-sponsors#:~:text=The%202023%20Global%20Site%20Relationship,more%20than%203%2C600%20site%20representatives.

2 Malloy, M., & Cammarata, N. (2022, July 18). Tips For Clinical Trial Sponsors To Cultivate Meaningful Relationships With Sites. Clinical Leader. Retrieved November 21, 2023, from https://www.clinicalleader.com/doc/tips-for-clinical-trial-sponsors-to-cultivate-meaningful-relationships-with-sites-0001

About Us

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

Case Study

When a small biotech approached PSI to run a complex UC study, the sponsor’s concerns were clear: streamline initial set-up, avoid complex vendor management, and overcome multiple operational challenges.

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. 

Putting the Focus Back on Site Relationships Part 2: 3 Strategies for Mitigating Trial Site Burden Read More »

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Putting the Focus Back on Site Relationships Part 1: Top Site Challenges 

Solid site relationships are the backbone of successful clinical trials. Without happy, supported sites, enrollment simply cannot happen predictably or within budgetary constraints. Yet fostering deep site relationships is often overlooked because many CROs are simply unable or unwilling to put in the effort, resources, and time necessary to do so.   

While historic challenges like staffing shortages, trial complexity, and issues related to site startup have intensified, they are now joined by the need to often learn and implement unfamiliar new technologies with little support and training. Our new white paper, Putting the Focus Back on Site Relationships in Clinical Trials, digs deeper into the evolving challenges sites face as well as PSI’s real-world strategies for supporting our site partners – and our sponsors in turn. 

3 Top Challenges for Sites

Site relationship management is challenging no matter what, whether managing dozens of sites for a global trial with tight enrollment timelines, providing support and training for complex molecules, or building site-specific patient pathways. Understanding each site’s pain points is often a monumental task requiring a highly tailored approach, yet doing so is essential to overcoming these obstacles. It’s likely that many CROs neglect this critical step due to what is often perceived as a time-consuming and costly process. 

In addition to hands-on experience, there is a growing collection of existing data and real-time feedback from sites to help sponsors and CROs make more effective decisions about site support from the beginning. Sites report similar challenges across therapeutic areas, including: 

1. Lack of Resources

In a recent survey, sites identified staffing, study budgets, and protocol complexity as the top areas that have become increasingly difficult over the last five years.1 Specific challenges sites may encounter in the current clinical trial landscape include navigating vendor arrangements, the impact of the COVID-19 pandemic, and addressing regional conflicts that affect normal operations and the patient population. 

2. Lack of Communication

Sponsors often wonder what they can do to help sites struggling to meet patient enrollment goals. While the answer may seem simple, executing it is anything but: communication. Establishing clear lines of communication and providing the space for open conversation and feedback, including regular calls and face-to-face meetings to address questions and concerns, helps sites mitigate waste and handle change management more effectively. In addition, sites consistently mentioned a lack of communication before, during, and after the close of a trial as directly impacting their optimism and willingness to work with a sponsor or CRO again.2 

3. Lack of Training and Support

CROs and sponsors should aim to create as seamless an experience as possible for sites. Many sites have shared that they often feel they are participating in a “pilot” mode where sponsors or CROs are testing new combinations of technology tools or processes without consistency across the organization or even the therapeutic team, often leading to additional workflow disruption due to retraining and unfamiliarity. 1 A lack of support during trial operationalization, including training on study design (and redesign), budgets, and data management and handling, can add further complexities.

Learn more from PSI’s site relationship experts

The success of clinical trials hinges on the quality of the relationship between CROs, sponsors, and sites. At PSI, we know a thing or two about providing site support and meeting enrollment goals. With more than 4,000 sites worldwide that love working with us, we specialize in providing sites with the tailored resources, training, and support they need to deliver our sponsors’ pivotal Phase 2 and 3 studies. Stay tuned for tips on how to mitigate site burdens in part 2 of our series. Discover more about how to navigate these challenges and the value of site relationships by reading the complete white paper here. To learn how PSI can support your next study, contact us today.

1 Clinical Leader. (2023, April 18). Strengthening the Sponsor-Site Relationship in Clinical Trials . Clinical Leader. https://www.clinicalleader.com/doc/strengthening-the-sponsor-site-relationship-in-clinical-trials-0001

2 Hosely, M. (2021, March 23). Improving site-sponsor relationships leads to transparent clinical trials. Advarra. https://www.clinicalleader.com/doc/strengthening-the-sponsor-site-relationship-in-clinical-trials-0001

About Us

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

Case Study

When a small biotech approached PSI to run a complex UC study, the sponsor’s concerns were clear: streamline initial set-up, avoid complex vendor management, and overcome multiple operational challenges.

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. 

Putting the Focus Back on Site Relationships Part 1: Top Site Challenges  Read More »

Benefits of PSI Global Support for Chinese Biotech Sponsors  

Deciding where to run your study can determine the success of a trial; from meeting patient enrollment and providing a positive patient journey to ensuring site expertise and a broad eligible patient population, choosing the right sites and countries to run clinical trials is crucial.

For Chinese biotech sponsors running global trials, the US is an obvious choice for running clinical trials due to the ability to collect vast amounts, and in some cases, the majority of study data, very quickly and in one place. In addition, the US is often a top choice for smaller biotechs seeking potential investors due to the visibility of trials.

However, sponsors should also consider the benefits of adding European countries to their geomix. Because many European countries have startup timelines similar to the US, adding these sites can further enhance overall timelines due to faster recruitment over a wider geographical area with additional patient populations.

PSI is a full-service CRO based in Switzerland that’s ready to support your global clinical trials with over 3,000 team members across 55 countries, spanning Asia, Europe, Africa, and the Americas. PSI has been continually recognized for excellence, including receiving CRO Leadership Awards in the categories of Expertise, Quality, and Reliability* for the past six years in a row.

Below are some additional ways PSI can provide support for Chinese sponsors as you plan your next trial:

  • Minimizing your budget: Many countries in Europe may be less expensive to run trials, with timelines just as fast as US sites. PSI uses VISIONAL™, our advanced feasibility tool, to harness the power of machine learning to provide accurate enrollment forecasting, comparing hundreds of country and site combinations and their probability of success within just a few minutes.
  • Overcoming regulatory hurdles: With our expansive European footprint and local teams, PSI can assist in navigating language and regulatory concerns such as data privacy (GDPR) from the European Union that may impact data robustness across international lines. Our regulatory experts in US and Europe have successfully supported more than 20 drug approvals in the last five years.
  • Trial design and protocol review: Designing clinical trials with the patient journey in mind and providing a plan for globalizing a trial is crucial to mitigate slowdowns further in the process. PSI’s Scientific Advisory Board can help sponsors gather detailed feedback on the overall trial design and protocol to minimize protocol amendments down the line.
  • Facilitating startup and recruitment: PSI’s Patient Recruitment and Site Support Specialists, along with our extensive vendor and site relationships, ensure tailored startup and enrollment plans at every site, especially when managing patient recruitment materials.
  • Ensuring the quality of clinical data: PSI strictly follows Good Clinical Practice (GCP) principles to run clinical trials, ensuring high quality clinical data as well as the protection of subjects. We exhibit validated quality with more than 130 FDA and EMA inspections to PSI sites, with additional successful inspections this year.

Learn more about how working with trial sites in China can help support your upcoming global study or contact us today to learn how PSI helps support sponsors around the globe.

* Overall (combined Big and Small Pharma) respondent group.

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.

Applying for Multiple Phase Studies in China With Lisa Lu

Did you know you may be able to run Phase 1 and Phase 3 studies in China in parallel, particularly for urgent medical needs?

Benefits of PSI Global Support for Chinese Biotech Sponsors   Read More »

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PSI FAQs: How does PSI use Robotic Process Automation (RPA) to support sponsors’ clinical trials?

Recent years have spurred the clinical trial industry to embrace innovative new solutions and technologies as a way to streamline processes and continue bringing trials to patients. However, the digital transformation started long before then. PSI CRO has consistently been a leader in applying sophisticated digital solutions to pivotal phase 2 and 3 clinical trials to optimize study modeling, budgeting, and operationalization, including developing our proprietary cloud-based suite of clinical trial planning tools, INTELIA™.

This forward-thinking approach also led to PSI’s early adoption of Robotic Process Automation (RPA) as a digital solution to standardize high-volume tasks and conduct them efficiently in an error-free manner. “While doing so, it builds quality control and compliance into the processes, cutting costs by 35 to 70%,” explained Doug Shannon, RPA Technology Lead at PSI CRO, in an interview with Labiotech.

PSI uses RPA to reduce processing time, human error rate, and the amount of routine work in several areas. For instance, automating the querying of abnormal laboratory values in EDC increased on time query processing by 100%. Other functions where RPA can support clinical trials include tasks that are heavy in documentation management, such as finance and accounting, supply chain, inventory management, and back-office processes like human resources and information technology services.

RPA offers several benefits for you as a sponsor, including:

  • Freeing up PSI team members’ time to focus on your trial’s most critical tasks
  • Capturing a sequential record of each step in every process, streamlining regulatory and drug safety data, and easing the burden of regulatory submissions preparation
  • Supporting PSI’s therapeutic area subject matter experts as part of a cross-functional approach to clinical data collection, analysis, and management

To learn more about how PSI incorporates RPA and other industry-leading technologies into our global CRO services, 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

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.

PSI FAQs: How does PSI use Robotic Process Automation (RPA) to support sponsors’ clinical trials? Read More »

Iv drip with gray overcast sky in the background

7 Challenges for Sponsors of Biosimilar Clinical Trials

This is the second of two articles based on our new white paper on biosimilar development in Inflammatory Bowel Diseases (IBD). In our previous article, we discussed some of the common regulatory considerations for biosimilar clinical trials. In this article, we focus on some of the greatest design and operational challenges. In the highly competitive IBD landscape, understanding the unique obstacles that biosimilar development can pose can help sponsors predict potential challenges and pivot effectively.

Designing biosimilar clinical trials to support comparability and future extrapolation requires careful planning from the outset to ensure these and other criteria are met. Sponsors should consider working with a partner experienced in understanding and overcoming the challenges of these studies. Key challenges include:

  • Endpoint selection: Ulcerative colitis, Crohn’s disease, and other IBDs are multifactorial diseases with highly subjective manifestations. When determining endpoints for biosimilar trials in IBD, it is important to select endpoints that capture relevant aspects of the disease and are sensitive enough to provide clinically meaningful results.
  • Ethical considerations: Sponsors must balance the need for clinical research with the wide availability of effective treatments for IBD. Convincing patients with established treatment regimens to participate in a biosimilar clinical trial often requires providing supporting educational materials and clear messaging to ensure informed consent.
  • Study design: Availability of existing treatments also impacts study design considerations such as blinding and the use of placebo. In cases where administration routes of the biosimilar and reference biologic vary, maintaining blinding may be challenging or impossible.1 The long half-lives of many biologics can also impact the determination of an appropriate washout period for patients who have been previously treated with the reference medicine.
  • Variability: Microheterogeneity is a common characteristic of all biologic drugs.2 Sponsors must have plans for controlling variability of manufacturing processes and raw materials to ensure that the biosimilar’s product quality remains within an acceptable range, particularly as the proprietary technology used to develop the original molecule will be unknown.3 An iterative process is therefore necessary to “guide” the fingerprint of the biosimilar towards that of the original medicine.4
  • Long-term safety: Due to the shorter length of biosimilar trials compared to the real-world treatment duration of IBD, there is a need for long-term safety and immunogenicity data. Assessing long-term safety requires resource allocation and planning for additional studies or post-marketing surveillance.
  • Patient bias: The “nocebo effect” is a negative effect of a pharmacological or non-pharmacological medical treatment induced by patients’ expectations and unrelated to the physiological action of the treatment.”5 Several studies investigating a switch to IFX biosimilar have reported higher discontinuation rates in transitioned patients than in patients continuing treatment with IFX, and it has been suggested that may be influenced by a negative perception of biosimilars.6,7,8
  • Lack of clinical and scientific interest: Investigators may be hesitant to participate in clinical trials with biosimilars compared to studies involving new biological molecules or novel pathways. Such clinical trials may be of little interest to patients who already have access to the reference product as part of the standard of care. This has led to a trend towards conducting trials in countries where the reference drug is unavailable or not covered by insurance plans.

Success starts with the right partner

Designing effective IBD trials requires careful planning from the outset to ensure these and other criteria are met. Sponsors should consider working with a partner experienced in understanding and overcoming the challenges of these studies. Sponsors that understand the unique challenges that come with IBD development can set themselves up for success.

With the help of PSI’s VISIONAL™, challenges with IBD patient enrollment and site selection can be predicted and mitigating, allowing sponsors to pivot quickly saving valuable time and money. With a network of more than 3,900 global IBD sites, and an expert team, PSI specializes in delivering pivotal Phase 2 and 3 IBD trials. Download the full white paper here, or contact us to learn more.

1 Lai ZV, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open. Published online February 1, 2016. doi:10.1136/rmdopen-2015-000154

2 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

3 Caldwell B. Variability of Biologics and its Impact on Biosimilar Development. European Medical Journal. Published online September 12, 2019:22-30. doi:10.33590/emj/10312818

4 Vulto AG, Jaquez OA. The process defines the product: what really matters in biosimilar design and production?. Rheumatology (Oxford). 2017;56(suppl_4):iv14-iv29. doi:10.1093/rheumatology/kex278

5 Pouillon L, Socha M, Demoré B, et al. The nocebo effect: a clinical challenge in the era of biosimilars. Expert Review of Clinical Immunology. 2018;14(9):739-749. doi:10.1080/1744666x.2018.1512406

6 Bressler B. Is there an optimal sequence of biologic therapies for inflammatory bowel disease?. Therap Adv Gastroenterol. 2023;16:17562848231159452. Published 2023 Apr 5. doi:10.1177/17562848231159452

7 Bernard EJ, Fedorak RN, Jairath V. Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease. Dig Dis Sci. 2020;65(8):2354-2372. doi:10.1007/s10620-019-06036-0

8Scherlinger M, Germain V, Labadie C, et al. Switching from originator infliximab to biosimilar CT-P13 in real-life: The weight of patient acceptance. Joint Bone Spine. 2018;85(5):561-567. doi:10.1016/j.jbspin.2017.10.003

About Us

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

GI Experience

We match theory to practice, making sure that our teams know what’s going on right now with IBD around the globe.

Demystifying Biosimilar Development Regulations

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. 

7 Challenges for Sponsors of Biosimilar Clinical Trials Read More »

doctor speaking with pharmaceutical sales rep, blurred background, shaking hands

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.”

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.

PSI FAQs: How do PSI CRAs support clinical site relationships? Read More »

blurred female scientist using a dropper and test tube

Demystifying Biosimilar Development Regulations: Key Considerations for Sponsors

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.

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.

Demystifying Biosimilar Development Regulations: Key Considerations for Sponsors Read More »

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

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

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.

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

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

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™
key metrics for VISIONAL case study. 520 patients with heart in hand symbol. 126 trial sites with a target in a human head symbol. 7 countries with a world symbol. all in white text.

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. 

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