BY CHRIS BAKER - SENIOR VICE PRESIDENT AND GLOBAL HEAD OF FSP, PAREXEL
JOANNE SULLIVAN - GLOBAL HEAD OF SAFETY AND REGULATORY OUTSOURCING, PAREXEL
LISA FEENEY, VICE PRESIDENT, CLINICAL OPERATIONS FOR EXECUPHARM
YUN HARDIMAN, VICE PRESIDENT, BIOSTATISTICS FSP, PAREXEL
In an already challenging clinical trial environment, the COVID-19 era has exacerbated uncertainty on an unprecedented scale. In a matter of days, biopharmaceutical companies faced the challenges of harnessing all available resources and expertise at warp speed to begin development of potential vaccines and treatments for COVID-19, while also keeping mission critical non-COVID trials moving.
The functional service provider (FSP) outsourcing model enables sponsors to efficiently and cost-effectively manage workforce needs across clinical portfolios. FSP models proved to be a strategic asset during the coronavirus pandemic when the ability to increase resource flexibility and provide targeted access to specific expertise became critical to clinical trial continuity.
Staff augmentation FSP models helped many biopharma companies mitigate COVID-19 era challenges, including the ability to manage unpredictable work volumes, and access highly skilled professionals rapidly to help document scores of protocol and process deviations. Three main areas where FSP models are making a significant impact are clinical operations, drug safety and biostatistics.
The required shift to remote working catalyzed the importance of flexibility and scalability to meet timelines and keep clinical trial activities moving. As sponsors, sites, CROs and regulators all adjusted to working from home, an important global challenge centered on how to remotely monitor patient data. Institutions that haven’t traditionally been open to remote review of electronic medical records (EMR) were forced to accept and implement remote processes to maintain clinical trial continuity. Despite past resistance, EMRs are now more widely available for monitors to review remotely. These successes in clinical operations will activate positive change, increasing acceptance of remote monitoring and source data going forward.
For many sponsors, the ability to quickly and flexibly shift clinical resources across different studies or programs is also an effective strategy to deliver results with limited resources. For example, one Parexel customer quickly re-deployed resources within an FSP model and early clinical development CRAs from other clinical trial programs to monitor a high priority clinical study that evaluated the safety and efficacy of an FDA-approved prescription medicine in patients with COVID-19. The approach was accelerated with the U.S.-based team and the team was trained in less than a week. The experienced monitors were able to quickly pivot to a nontraditional monitoring approach, which was conducted entirely remotely and focused on patient safety, protocol compliance and targeted source data verification of critical data points.
Other unexpected, but positive outcomes from alternative approaches forced teams to rethink the rationale behind traditional timelines. Some activities, such as internal approval of a protocol, have seen a dramatic timeline compression from months or weeks to literally hours, which will no doubt extend into the post-COVID era.
Within drug safety, safety data are still being reported, but not in the traditional ways. COVID-19 disruptions at the site level have contributed to many incomplete and/or incorrect reports. Access to skilled safety specialists is essential to correct these issues and fill important gaps with the data. In Parexel’s case, we provided safety FSP resources with deep foundational knowledge. We relied on more experienced team members for problem solving to meet regulatory timelines and ensure the quality of the filings. We also tapped into internal resources and used more generally skilled resources to help with case processing and the full-time effort required for documenting deviation notes to file.
In one case, Parexel’s safety team was called upon to assist in a (literal) overnight transition over from a transactional outsourcing relationship to provide business continuity. The team was quick to map out worst case scenarios and develop alternative strategies to ensure regulatory timelines were still met by adding more trained sources as well as increasing work hours through split-shift schedules.
Since drug safety is a traditionally an office-based function, another major challenge involved ensuring a rapid and stable transition to remote-based working. While continuity plans and infrastructure requirements were already in place, additional quick actions included confirmation of adequate internet connectivity as well as assurance of the appropriate remote working environment for employees accustomed to office work through frequent staff outreach and pressure testing optimal use cases for video and audio formats.
Biostatistics and Statistical Programming
COVID-19 caused disruptions which significantly impacted data quality and integrity, and consequently, the credibility of study results. Statistical analysis plans can be amended based on how protocol deviations related to COVID-19 will be handled for the prespecified analyses by either adding a modified full analysis set or implementing sensitivity analyses. The FDA provided guidance in March 2020 on how to address challenges due to COVID-19 for data quality and integrity due to missing data, lack of consistency, and increased variability.
For sponsors, the biggest statistical consideration is to address missing information that arises from changes in study visit schedules, missed visits, or patient discontinuation due to COVID-19. The FDA guideline indicates specific information in the case report form (CRF) that explains the basis of how the missing data and the relationship to COVID-19 should be captured and summarized in the clinical study report to help the sponsor and the FDA.
Maintaining consistency in assessment methods should be balanced against the need to minimize missing data and variability in the data. The decision to use different methods should be justified in study documentation.
As a part of best practices, Parexel biostatisticians follow guidelines to amend statistical analysis plans (SAPs) that may include various sensitivity analyses by analyzing pre vs. post COVID-19 data separately.
The Importance of Culture Mapping
Before COVID upended clinical trials all over the world, FSP outsourcing was already on the rise. The discussion shifted to how to access the right talent and maintain project continuity. Sponsors often struggle to find the right people – not only with the right domain expertise, but also to find talented people who can be quickly trained on their SOPs and also fit into their specific company's culture.
To find the best match, we use a methodology we call the Parexel FSP Culture Map™ process, designed to match both the skill set and the cultural fit of candidate to the biopharma customer. Honed by years of recruitment and placement experience, it’s a methodology that looks beyond a candidate’s professional skills and background to evaluate how their personality, adaptability and soft skills will fit in a specific customer’s environment. In some cases, it can go down to the personality at the project level. It may be important to consider who the project lead is, or who the candidate may interact with the most. Finding the right talent through culture mapping helps increase retention and decrease disruption from staff turnover.
Staff retention is major concern of any outsourcing initiative. Training is a significant investment and for many clinical roles it can take a full six months to ensure staff members are proficient in the customer systems and processes. A range of initiatives, from formal mentorships, career development approaches and staff support programs provide tangible examples of successful retention efforts.
Looking forward, there are several plausible legacies of COVID-19 on outsourcing behavior. The global trend of remote working has proven successful in clinical trial management and product lifecycle support and will continue to accelerate. As COVID-19 provided a dire reminder of the power of uncertainty, more comprehensive upfront planning between FSP providers and biopharma companies is another near-term positive outcome. Finally, today’s unpredictable environment requires new levels of nimbleness from all stakeholders to enable better preparedness for any event. As more organizations now have the luxury of time to look ahead, key questions for sponsors are whether they can access targeted resources and expertise and operate with execution choice and flexibility under new and ever-changing circumstances.
For additional insights, click here to watch a recent roundtable discussion on this topic.