Clinical Development

Our goal is your goal – bringing new drugs to the people who need them. For more than 30 years, we have been supporting phase II-III clinical development for sponsors across a range of compounds, from niche treatments to blockbuster drugs and biosimilars treatments. Through our global reach and using our innovative technologies, flexible approach and scientific expertise, we help you navigate your R&D dilemmas by skillfully executing complex, global studies across a range of therapeutic areas.

THE INDICATION EXPERIENCE OF OUR PEOPLE AND OUR DEEP UNDERSTANDING OF THE SPONSOR’S PROTOCOL IS AT THE CORE OF OUR DEVELOPMENT PROCESS

Michael Brooks – Sr. Vice President, Product Registration

Flexible Approach

A work culture characterized by flexibility, integrity and transparency and a commitment to proactively anticipate challenges and communicate creative solutions, allowing our clients’ clinical programs to progress quickly, safely and cost-effectively.

Innovative Technologies

Leveraging Clinical Informatics, we combine a strategic approach with state-of-the-art technologies and the power of data-driven decision making to deliver high-quality clinical development. Our methodology for study feasibility, protocol validation, site selection and patient access enable optimal study start-up.

Scientific Expertise

From our scientific and medical experts to therapeutically aligned project managers and monitors, we provide the expertise needed for today’s complex studies. Our project teams possess deep therapeutic knowledge, understand clinical development plans and can interact seamlessly across borders—sharing and benefiting from a collective experience.

Global Reach

We never forget that every global study is executed locally. At PRA, global presence is more than just dots on a map. With global offices providing service in 80+ counties, our team harnesses practical knowledge of local regulations, standards of care and cultural customs to maximize safety and efficiency for your studies.

We are committed to the drug development process because we understand how it impacts the lives of patients and their families. At the end of the day, we are not just researchers; we are patients, survivors or family members too.

01
Risk-Based Monitoring

The key to success in Risk-Based Monitoring (RBM) is to incorporate a holistic evaluation of each individual study, the right organizational structure to support both central and on site monitoring; and the analytics to review the data trends real time. A number of factors are leading to a paradigm shift in the way that clinical research is conducted. Regulatory agencies are demanding smarter, more efficient risk-based methodologies to improve the quality of data. The increasing cost of research and the adoption of EDC technologies that provide real-time access to data have forced the industry to look at optimized methods of conducting clinical studies. In addition, several studies have shown that 100% SDV may not result in higher data quality. Together, these factors have led to an increased interest in incorporating RBM strategies which were traditionally utilized in late phase and mega trials into a variety of study designs and phases. Pioneers in RBM methodology, PRA team members have been utilizing RBM approaches for more than 20 years. Our RBM philosophy and strategy aligns with the regulatory/industry guidance’s (FDA, EMA, TransCelerate) and has a strong foundation in successful implementation. As a result, PRA has remained at the forefront of the RBM community, utilizing proven best practices for RBM within our own studies.
Flexible Approach: There’s No “One Size Fits All” RBM Strategy PRA understands that individual sponsors have various experience and comfort-level with RBM. Our flexible approach allows PRA and our clients to identify the best study-specific monitoring strategy that aligns with the study-specific risks identified during the Risk Assessment & Planning phase. A variety of factors can influence the overall RBM approach, including:
  • Study Phase and Design
  • Primary and secondary study objectives
  • Safety profile of product/device
  • Treatment paradigm and standard of care
  • Complexity of study-specific requirements
  • Number of sites/patients
  • Site profile (i.e., research naïve)
  • Study duration (patient retention requirements)
  • Geographic regions
Considering the number of factors that determine the best type of monitoring strategy—there is no “one size fits all.” As a result, there is not a set ratio of on-site monitoring versus centralized monitoring. Traditionally, monitors are 100% onsite to review the data every four to six weeks. With RBM, risks and parameters are discussed at the beginning of the study with our clients to understand what the best approach for each protocol. The below graph depicts the evolution that sponsors typically experience as they transition from 100% SDV to full RBM: Solutions_Clinical_Development_Risk_Based_Monitoring_Graphic Risk Assessment and Planning The risk assessment process is an evaluation of risk of each individual study, beginning with a multi-disciplinary team. This process is not only conducted at the onset of a study, but also reevaluated and modified as needed due to changes in study design or standard of care. There are a number of considerations that should be evaluated during the risk assessment and planning phase. It is especially important to consider the study's critical data points, including the primary study objectives and safety data, as well as the critical processes that impact patient safety and support data quality. The plan should then be developed across functional areas and stakeholders to ensure that all findings of the risk assessment are addressed:
  • Identify critical study Data and Processes
  • Perform a risk assessment to identify risks to these critical data and processes
  • Design a monitoring plan tailored to identified important and likely risks
True RBM employs various approaches to evaluate key data and processes from various sources of a study and take action when required. The key is to ensure it is clearly documented and trigger points are clearly defined and an action plan in place to address each. Successful Operational Approach Centralized Monitoring is a key component of any RBM approach and involves the review of data without source documents and completion of other monitoring tasks off-site. When effectively implementing RBM, there is a site management shift from the regional onsite CRA to the highly trained Central monitoring team. This may consist of checks for completeness and consistency of data, analysis of data trends and distribution, identification of protocol violations, evaluation and management of risks, site management and administrative, site training and retraining, and regulatory tasks. The growing consensus among clinical researchers and regulatory authorities is that RBM is more likely to ensure patient protection and overall study quality and allows for monitoring that can be more effective than the traditional model of routine visits to all sites with 100% source data verification (SDV).
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02
Clinical Operations

PRA’s Clinical Operations group provides clients with highly trained, locally based project teams that develop a strong relationship with each study site, ensuring consummate quality and timely receipt of clinical deliverables. PRA's experienced clinical research professionals lead the study to ensure a successful site start-up, maintenance and closeout for each trial. This group's key competencies include:
  • Local regulations and country-specific expertise
  • Medical practices
  • Safety
  • Critical therapeutic and research areas (e.g., CNS, oncology, biosimilars, rare diseases)
PRA's project start-up services include:
  • Recruiting investigational sites
  • Supporting PRA Regulatory Affairs group with regulatory authority submissions
  • Coordinating ethics committee approvals
  • Collecting and reviewing initial essential documents
  • Closing investigator contracts (clinical trial agreements)
PRA clients benefit from a strong support structure for clinical teams. Our in-house clinical research associates are responsible for site management activities and logistics, enabling field CRAs to focus on the most critical aspects of their monitoring visit. In-house site management includes:
  • Reviewing and processing site documents in eTMF
  • Assisting with site queries
  • Tracking clinical activity status in the PRA Clinical Trial Management System
  • Tracking and assisting with data queries
  • Providing support to CRAs and lead CRAs

03
Scientific Affairs

PRA’s Scientific Affairs is a unique group of highly recognized scientific and medical experts offered by PRA to support our clients, project teams and investigators throughout the clinical development process. These experts often come into play well before a project is even awarded to PRA and stay engaged well after the study start-up process. Board-certified physicians and industry experts, they bring decades of functional and therapeutic expertise across a broad range of indications, including cardio-metabolic, oncology/hematology, infectious diseases, neurology/psychiatry, rare disease, respiratory and biosimilars. Additionally, they have built strong relationships with worldwide thought leaders, offering access to opinion leader-level therapeutic advice, support and leadership in translational medicine and access to study-specific target populations. PRA’s Therapeutic Expertise service provides:
  • Support across the entire drug development continuum, including and specifically, in clinical medicine, biostatistics and regulatory submission strategy
  • Life-cycle management
  • Data-driven feasibility assessments
  • Clinical development program and protocol design
  • Project team training and support during operational delivery of clinical services
  • Integration of scientific/clinical, regulatory and economic development needs
  • Scientific Advisory Board formation and memberships
  • DSMB membership, setup, coordination and charter writing
PRA’s Scientific Affairs guides the development of drugs and biologics from the late pre-clinical phase to marketing across all of PRA’s core therapeutic areas.

04
Feasibility

Early planning for an upcoming clinical program requires careful consideration of a multitude of factors essential to study success. Performing a comprehensive study feasibility assessment is an important first step too often overlooked. PRA’s Feasibility group provides comprehensive study feasibility assessments for clinical trials and drug development programs worldwide. With an excellent track record of success, we use real-time feasibility surveys and data from our Medical Informatics group in conjunction with PRA’s operational experience to better position our sponsors’ trials for success. Through an evidence-based methodology and well-planned approach, each feasibility assessment is led by a doctoral level feasibility manager - in collaboration with our medical, clinical, regulatory and therapeutic experts - to help our sponsors plan for study success. Feasibility Group’s Services
  • Identify protocol design concerns/constraints
  • Determine availability of appropriate patient population
  • Understand potential investigators’ overall interest in the trial design
  • Target optimal regions or countries
  • Determine disease prevalence/incidence
  • Understand regional standards-of-care
  • Identify investigators who best fit study needs
Solutions_Clinical_Development_Feasibility_Graphic

05
Site Identification and Selection

Research suggests that 80% of all clinical trials fail to meet their enrollment goals and that in most trials at least 50% of sites enroll either one or no patients. For this reason, selecting the right investigative sites is one of the most important factors in successfully completing a clinical trial. Unfortunately, selecting the right sites is not always easy, as much of the information required to identify and select the best sites is not readily available. To address this challenge, PRA formed the Site Intelligence and Strategic Development (SISD) group to provide an industry-leading, data driven approach to site selection that takes into account the need for both timely enrollment and high quality data. Working across all therapeutic indications, the SISD group uses both proprietary and public data sources to evaluate potential trial sites, including:
  • Commercial site databases
  • PRA’s internal site-specific enrollment and data quality metrics from prior studies
  • PRA’s knowledge of each site’s start-up process and timelines
  • Professional and pharmaceutical claims data
  • Previously conducted feasibility studies
  • Study sponsor input
Using these data sources, the SISD group employs a weighted algorithm that evaluates each potential site according to the following key factors: Solutions_Clinical_Development_Site_Identification_and_Selection_Evaluation Once potential sites have been evaluated according to this algorithm, the SISD group provides the study team with a prioritized list of sites that are desirable for the trial. Local country experts also provide input at this stage to ensure that there are no ongoing issues that might affect the ability of specific sites in their region to participate in the planned study. The highest priority sites identified during this evaluation process are then contacted by the study team to assess interest in study participation and to initiate the site start-up process. PRA has consistently demonstrated that this data-driven site selection process saves time and money by contacting only the sites that are most likely to be interested in study participation and capable of meaningfully contributing to enrollment, ultimately producing faster overall study enrollment and better data quality! Investigative Site Ratings According to the 2011 CenterWatch Global Survey of Investigative Sites, PRA is one of the top 5 CROs worldwide for fostering quality relationships with investigational sites. CenterWatch’s first-ever global survey - based on feedback from clinical research professionals from more than 1200 sites - rated PRA number 4 across all relationship attribute categories, including project management, grant payments, staff professionalism and study start-up. Respondents rated CROs that they had worked with over the past 2 years. Solutions_Clinical_Development_Site_Identification_Global_Investigative_Site_Survey_Graphic

06
Investigator and Site Engagement Program

Modern drug development’s aggressive timelines have made timely enrollment and high-quality data more critical than ever to clinical research. The pressure on biopharmaceutical companies to both educate investigators on the trial’s scientific background and help them enroll the appropriate patients continues to grow. PRA Investigator and Site Engagement (PRAISE) will help our clients overcome these challenges. Modeled after the Medical Science Liaison role in the pharmaceutical industry, the PRAISE program employs Clinical Trial Liaisons (highly trained PhDs or PharmDs) to assist clients with investigator engagement throughout site selection and the clinical trial. Our CTLs utilize proven strategies to cultivate productive relationships across key functions, including:
  • Principal investigators
  • Sub-investigators
  • Study coordinators
  • Additional research staff
The PRAISE program’s goal is to increase participation and enrollment in our clients’ clinical trials, while ensuring they receive the high-quality data critical to successful drug development. Key Features & Benefits Solutions_Clinical_Development_Site_Investigator_Patient_Access_Graphic PRA is committed to providing innovative programs and solutions, such as PRAISE, to help our clients introduce new drugs and improve lives.

07
Medical Informatics

PRA’s Medical Informatics group leads the industry in advancing evidence-based approaches for the ranking of candidate investigators and sites, protocol validation, study feasibility and patient access. To enhance global accrual rates for clinical trials, PRA mines public and private databases and applies a proprietary methodology for patient and site access. In greater than 60% of instances, our clients have adjusted their protocol design and/or country and site selection based on our evidence-based data and therapeutic experts’ recommendations. Data Driven Approach Solutions_Clinical_Development_Medical_Informatics_Graphic Evidence-Based Methodology PRA’s therapeutic experts conduct scientific and medical reviews of the site-selection process in cooperation with our Medical Informatics team. Together, they work cross-functionally with our global feasibility, patient access, site intelligence & strategic development and investigator and site engagement groups to create comprehensive clinical trial strategies for site selection as well as patient recruitment/retention and accrual. Leveraging PRA’s evidence-based methodology, a stepwise approach overseen and directed by our medical and scientific experts, we are able to target the appropriate geographic areas for disease prevalence and identify a targeted list of investigators suited to a study and with the highest likelihood of accrual. Our evidence-based approach includes:
  • searching our databases for information relevant to the specific protocol
  • researching local treatment patterns to confirm their compatibility with the target population
  • reviewing countries’ existing approved and marketed drugs
  • examining this data in the context of our Medical Informatics suite of searches to identify sites with the highest number of actively treated patients
Solutions_Clinical_Development_Medical_Informatics_Evidence_Based_Planning_Graphic Client Benefits: Sample Medical Informatics Data PRA’s Medical Informatics group originated with infectious diseases research and has since expanded to all other therapeutic areas. The sample below demonstrates the type of invaluable data we utilize to guide our clients’ studies. MI Sample: Country Selection – HCV Genotype 2 and Genotype 3 by Country Solutions_Clinical_Development_Country_Concentration_Graphic We believe this methodology is the best in the industry and is critical in transforming the current drug development paradigm from an inefficient and costly model to a more efficient and cost-effective one.

08
Patient Recruitment and Retention

Patient recruitment is the most challenging aspect of the clinical trial process, consuming approximately 30% of the clinical timeline and often leading to trial delays. Clinical teams should employ the following critical success factors to achieve enrollment goals and other key study objectives. Critical Success Factors Solutions_Clinical_Development_Patient_Recruitment_Retention_Critical_Success_Factors_Graphic
PRA’s Patient Access and Retention Services (PARS) group liaises directly with PRA’s therapeutic experts and Medical Informatics group to offer our clients the best possible blend of services in patient recruitment and retention by:
  • Partnering with best-in-class patient recruitment organizations based on the study’s needs, indication-specific work and global experience.
  • Developing customized program campaigns.
  • Conducting project assessments, identifying patient pathway(s) and determining the target patient pool.
  • Serving as liaisons between our clients’ clinical operations team, the PRA study team and the patient recruitment partner.
This synergistic approach is the essence of our success, ensuring the full integration of services, maximum recruitment and retention campaign adoption, clear communication and recruitment/retention metrics collection throughout the project. Approach to Patient Recruitment & Retention In an ever-changing and highly competitive drug development environment where sponsors compete for a limited pool of patients and healthcare information continues to increase exponentially, patient enrollment becomes increasingly more challenging. A strong study identity along with clear patient-focused communication tools are the keys to successfully reaching and engaging patients. Our capabilities allow us to offer a customizable and robust strategy based on the following proven patient recruitment and retention tactics: Solutions_Clinical_Development_Patient_Recruit_Retention_Tactics_Graphic Why Choose PARS? Through our strategic recruitment specialists and integrated partner model, PARS can deliver industry-proven patient recruitment and retention strategies by expert providers with extensive therapeutic and indication-specific global experience. Whereas some companies provide in-house patient recruitment services limited to their internal capabilities, PARS is able to quickly assess a study program utilizing our partners’ resources and our internal experience. Furthermore, we utilize our extensive background in data-driven, evidence-based methodologies to develop effective, customized patient recruitment and retention programs that cater to the study’s specific needs. Recent Experience and Expertise PARS’ experience ranges from consulting services to full patient recruitment and retention programs deployed globally. Our therapeutic experience and global expertise can offer an unprecedented approach to our clients’ patient recruitment and retention needs. Through PRA, PARS benefits from the size infrastructure and process standards of a major CRO to run complex campaigns and support global needs. At the same time, our PARS group retains a small feel with the ability to remain flexible to ensure a consultative service attitude that helps us understand the individual needs of each of our clients and studies. PARS Global Study Experience Solutions_Clinical_Development_Patient_Recruitment_Retention_TherapueticIndication_Graphic Contact PARS today to learn more about our results-driven solutions or to schedule a lunch-and-learn presentation with our experts.
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09
Regulatory Affairs

PRA’s global Regulatory Affairs group provides regulatory consulting and strategy development services for the approval and registration of our sponsors’ pharmaceutical, biologic, generic, biosimilar and medical device products. Our experts are experienced working with Regulatory Authorities, Competent Authorities (CAs) and Ethics Committees (ECs) around the world and providing regulatory support across all phases of development from product development planning and rapid study start-up consultation to end-of-study activities. We provide submission strategies that support early clinical development, product registration and late-phase trials. Our regulatory services include:
  • Agency liaison and meeting coordination and representation
  • Sponsor support for all interactions with regulatory authorities
  • Global regulatory intelligence
  • Preparation and coordination of Clinical Trial Applications
  • Consultation and support for Orphan Drug, Fast Track and Pediatric Applications
  • Consultation and support for Marketing Applications, including CTD format
  • Clinical supplies labeling consultation
  • Labeling support: physician and patient text
  • Import license applications
  • Maintenance of applications
  • Gap analyses and assessment of scientific and technical data for various submissions/applications
  • Due diligence assessments
Our dedicated global Regulatory Affairs centers in the US, Canada and Europe are supported by an internal network of local, native-speaking experts in countries across Latin America, Western and Eastern Europe, Africa and Asia Pacific. Our global regulatory team members and local experts act as clients’ representatives for submissions and direct communications with Regulatory Authorities and ECs in all regions. IND Submission Services The regulatory landscape continues to evolve and present fresh challenges for the submission of investigational new drug applications (IND). PRA’s regulatory and early phase teams help clients prepare and deliver their applications with confidence, providing reliable, centralized support throughout the entire project life cycle. Backed by 20+ years of industry experience, our global, fully integrated IND teams develop customized submission strategies designed to save clients time and money. PRA’s IND Services include:
  • Tailored and flexible solutions
  • Fully integrated project teams
  • Extensive phase I experience across 4 US clinics
  • Global regulatory support
  • Regulatory publishing excellence and sophisticated tools

010
Project Management

PRA’s Project Management Methodology supports project teams in every project-related objective. Within the Project Management Group (PMG), PRA’s Service Delivery Model ensures sponsors’ needs are met by utilizing best-in-class project management solutions coupled with senior operational oversight and therapeutic leadership. This dual focus allows us to achieve a high quality of service and exceed expectations. Solutions_Clinical_Development_Project_Management_Graphic PRA employs a distinctive approach to project management that has a foundation in the Lean Six Sigma paradigm which enhances our ongoing commitment to innovation and operational transparency. By applying the proven principles of Lean Six Sigma, PRA has developed a project management framework focused on standardized quantitative and qualitative performance metrics dedicated to continuous process improvement. This allows us to provide our partners with a project management solution not only focused on high quality execution and efficiency but also dedicated to accountability in lifecycle management and communication as well as real time identification and management of key risks. Importantly, the PRA methodology allows for flexibility and customization while still maintaining the ability to efficiently produce reliable and repeatable results.

011
Medical Affairs

PRA’s Medical Affairs group supports the planning, conduct and evaluation of global clinical studies with a primary focus on patient safety. Our Medical Affairs group consists of experienced physicians with expertise in nearly all areas of medicine. They provide contracted medical and liaison services in relation to:
  • Implementation and conduct of clinical trials, including inclusion/exclusion criteria
  • Primary medical contact to the sponsor, investigative sites and project team
  • Connections to clinical specialists and thought leaders
Medical Affairs oversees the safety activities for our sponsors’ studies. It is our philosophy that these activities must not be separated, so that the responsible MD has a concise and global overview of all medical and safety aspects of the trial. Our Medical Affairs team protects each patient's safety by continually reviewing the following:
  • Laboratory and ECG review
  • Serious Adverse Events and Adverse Drug Reaction (SAE/AE)
  • SAE/AE Coding
  • CRFs / data review
These reviews are an important component for detecting safety issues from the outset in a clinical trial. For medical monitoring and clinical trial support, 24 hour / 7 day toll-free phone lines direct calls to the PRA Medical Support Center. Medical monitoring associates staffing the support centers serve as high-level interface between PRA's medical directors and/or client medical directors and clinical monitors (and other staff) on questions from investigative site personnel, ensuring that all issues and requests are handled in an expedited fashion.

012
Clinical Monitoring

PRA’s clinical monitoring services are second to none. Our CRAs monitor the progress of clinical trials at the investigative sites and ensure that our sponsors’ studies are being conducted in accordance with the protocol (SOPs), ICH-GCP and all applicable regulatory requirements. With country-level experts based across 80+ countries, your site and data will be protected and validated throughout your study. PRA monitors investigator sites across the globe using clinical research associates who receive expert training to:
  • assess sites for ability to conduct study
  • activate sites on completion of start-up activities
  • monitor recruitment, eligibility and informed consent procedures
  • validate and verify data collected at site
  • review IP and accountability records
  • review adverse events and serious adverse event reporting procedures
  • monitor Investigator site files
PRA also provides customized risk based monitoring services aligned with the FDA, TransCelerate and the EMA’s recommendations. These alternative strategies:
  • consider protocol requirements and investigational products to better identify risks, outliers, noncompliance and poor performance
  • increase project team awareness of critical study issues, such as subject protection, data integrity, regulatory compliance and more
  • provide efficient methods for remote data review, modified visit frequencies and targeted Source Data Verification

013
Quality Assurance

PRA's global, independent Quality Assurance (QA) group is staffed by a team of experienced QA professionals in North America, Latin America, Europe and Asia Pacific. The QA group is entirely separate from and independent of the personnel engaged in the direction and conduct of clinical trials. With the goal of promoting ongoing quality awareness and continuous improvement of PRA’s processes, the QA team serves our clients by:
  • Providing a benchmark for PRA operations ensuring the highest level of service
  • Conducting auditing services in compliance with GCP (Good Clinical Practice), GLP (Good Laboratory Practice), GMP (Good Manufacturing Practice) and 21-CFR § 11 standards.
PRA’s global QA group has performed audits for a wide range of medical indications across all phases of clinical research and conducted audits on six continents. We work in close collaboration with the FDA and the EMA.