Coping With the Complex Clinical Trial Landscape… Lessons Learned With Valarie Higgins

Successful clinical trials are an orchestral performance

When I studied pharmacy at Rutgers University, I loved the science but I couldn’t see myself working in a lab environment. I wanted to interact with people and do something where I could apply the science in a communal setting. Clinical trials seemed to be a good fit.

I first started my career as a clinical trial monitor. At that time, clinical trials were very different to what they are today. Trial data was collected by filling NCR (carbon-copy) forms. Monitors would travel to the sites to review and bring the handwritten data back to be entered into a data management system by a data entry team member, and then reviewed and queried by data managers. It could take months to obtain and clean just a small segment of clinical trial data. Randomization occurred by pulling drug kits off  the shelf in numeric order as each new patient was enrolled. There were no systems in place to enable centralized randomization, complex stratification, or adaptive trials that can impact the quantity and order in which kits are dispensed. In fact, running a global trial was nearly impossible. The introduction of technologies like EDC (electronic data capture) and IRT (interactive response technology) were key enablers of the global trial, trial efficiency, and the more advanced trial designs that we see today.

I was fortunate to work for one of the first companies to bring IRT technology to the clinical trials industry: a startup called Interactive Clinical Technologies Inc (ICTI). ICTI developed IRT for  patient enrollment, randomization, and site inventory management. In 2000, the company was acquired by the Almac Group, which is where I’ve enjoyed working since. Almac is a contract development and manufacturing organization that provides a wide range of services, ranging from preclinical formulation all the way through to commercially-marketed product distribution.

Over the course of my career, I’ve been fortunate to witness a dramatic shift in the way biopharma thinks about its R&D activities. As a result of the advancements in clinical trial technologies and methodologies over the last 25 years, specialization has emerged throughout the industry and paved the way for contract vendors and partners to act as functional service providers for esoteric areas of clinical development. This dynamic can add to the complexity of running modern trials and highlights the essential need for strong stakeholder management and partnership development. Making sure everyone is on the same page can be one of the most challenging aspects of clinical trial conduct – especially at a time when numerous protocol amendments and adaptive trial designs are becoming commonplace. To further exacerbate the complexity, stakeholders and functional contributors often operate in a very fragmented fashion, each working in their own silo, and usually only with the information needed to ensure their section of the choir is singing in tune. I’ve come to appreciate the importance of strong leadership, project management, and communication by the clinical trial manager. To orchestrate a successful clinical trial, the clinical trial manager must be the commanding maestro of the orchestra of specialized vendors that they conduct.

It’s important to seize opportunities to broaden your perspective and pool of knowledge

When working for ICTI, I was a project manager and my job was to design and deliver the IRT systems. My role was that of a “doer” or executor, which evolved over time into management where I supported the organization’s growth. I became involved in leading and developing the project management and customer partnership aspects of the business before being offered a leadership role for technical operations.

Transitioning from the customer-facing side of the business to managing the extremely technical operations was quite daunting; I almost turned it down because I lacked the technical background! But ultimately the decision turned out to be one of the most critical decisions of my career. I gleaned a much broader understanding of the business and had a strong appreciation for the opportunities and challenges. I became better at identifying solutions and opportunities for improvement, which led to roles of increasing responsibility. Later, I was promoted to vice president and then executive vice president of operations. It has been 2 years now that I have had the pleasure of leading the entire Almac Clinical Technologies organization as president and managing director. I think my career demonstrates the value of seizing the opportunities that come your way, especially when they will broaden your perspective; I don’t think I would be where I am today if I didn’t choose to step outside my comfort zone, and take on that technical operations leadership opportunity.

I believe that it’s important to be picky about the organizations you chose to work for. Ensure they have a solid employee development program, which should include aspects such as monthly training programs, management certification programs, opportunities to move into cross-functional positions, a mentoring program, and a track record for promoting from within. I do not believe in jumping from company to company to gain your experience. I may be “old-school,” but my experience has shown me that you can gain a lot more by demonstrating patience, dedication and loyalty, as well as building solid relationships within your organization to gain the most open and honest feedback and best opportunities.

Be brave! Ask for feedback and learn from everyone

From spending time in different teams at Almac, I have had the opportunity to learn a lot about important qualities belonging to strong managers and capable leaders. I learn from everyone that I have the pleasure of working with, at all levels. From business development to platform architecture, from seasoned executives to young and creative technologists – I’ve been energized by the lessons that I learn from each. The different perspectives that they have and the different approaches to staff engagement, communication, and problem solving have shaped me as a leader today.

It is important to note that active listening, and honest reflection are the most powerful tools that you can develop and use to grow and improve yourself. The most successful and fastest growing staff that I have seen are masters at these skills; I call them sponges. These people are driven but modest, curious and not defensive. They spend their time and energy seeking to understand what they could have done better or how others see things differently. 

I spend at least an hour at the end of each day reflecting on what I think I did well and what I think I could have done better. I’m not afraid to ask for feedback and not afraid to be told that I could have done something better or different.

IRT is the heart and brain of the clinical trial

Over the course of my career, I have noticed a paradigm shift in how clinical trials are conducted. Some of the therapy areas we work in are incredibly complex – especially in personalized medicines and phase IB/II combination trials. Today, clients rely on IRT vendors to design tailored solutions for these trials to progress compounds faster. For perspective, when I first started in this industry, IRT was mainly used for randomizing patients and managing clinical supplies. In contrast, the studies today rely on IRT to be the “brain” of a clinical trial, making complex decisions about the patient journey, such as dose calculation, based on data feeds coming and going from a variety of tangential clinical data sources.

I have heard of several cases where patient safety was impacted as a result of data integration discrepancies. The IRT vendor is virtually the only unblinded party in the clinical trial orchestra, and is often relied on to report potential safety issues with blinded laboratory results. The randomization and adaptive nature of trials, as well as the cost of biologics and challenges of securing comparators, has made the assurance of adequate supply for patients extremely challenging. For example, we can decide which patients will participate in studies based on lab or other data we import into our systems, with all the dosing decisions automated and controlled through the IRT. The IRT also calculates exclusion and inclusion criteria based on bioimaging data or different results from the study coordinator, as well as making sure the investigator and the nurse are blinded to what the patient is receiving. The complexities around dose adjustment are immense and involve risk, but it’s rewarding to see our customers looking to us less as suppliers and more as partners who can help navigate some of the complexities in trials. Using a good IRT from a good vendor, coupled with process integration with a solid CMO, can ensure the right drug at the right time to the right patient, while saving millions in distribution costs and reducing instances of supply overages.

The IRT has become the heart and brain of the clinical trial, much like the concertmaster, or first violin that sets the cadence of the orchestra; they are a small piece of the entire orchestra, but their leadership and execution is critical to a successful performance.

Perfecting a solo performance… but in the wrong key

I’ve witnessed another big shift in the industry during my career: the days of blockbuster drugs are coming to an end. The focus is now on more targeted therapies with smaller patient populations that require less lofty sales goals to recoup R&D expenditure. This shift in strategy, along with the fact that trial design has become more complex (and by extension, more expensive), coupled with cost pressures on national healthcare systems around the world, has increased price sensitivity and skepticism of the value assigned to recently-approved therapies by their creators.

By extension, this market dynamic has permeated the R&D realm through the same hyper-focus on cost containment. An unfortunate side effect of this squeeze is that it may prevent specialized vendors and suppliers from investing in innovative solutions and process enhancements that can contribute greater efficiency in overall clinical trial conduct. When I first started, I would joke with colleagues that an adaptive trial design was a great idea, but would take nearly a decade for the industry to embrace. Now, a large percentage of studies are fully adaptive. The pace of change in the biopharmaceutical industry and the willingness to try things differently has improved in recent years, and serves as the foundation for effective innovation with returns that can be realized in the shorter term. When things change, there’s always a risk that the pendulum can shift too far in one direction. And as the industry begins to focus more on cost containment, it needs to be done in a more precise manner; balancing the pillars of both financial responsibility and innovation equally, while keeping the greater goal in mind. A soloist can sing every note with precision and conviction, but if done in the wrong key will ultimately detract, not add to the overall performance.

Don’t underestimate the lasting impact of exceptional leadership

When I started at Almac Group, I was employee number 41 in the Technologies Business Unit. Now we’re over 600 strong, and part of the almost 5,000 employees who make up the Almac family across seventeen different global facilities. I’m extremely proud to work for the company. Almac’s founder, Sir Allen McClay, was an inspiration to me and a constant force of positive momentum. He was dedicated to focusing on his people – his colleagues, his family – and was driven by an internal resolve to transform human health for the better. He instilled a tremendous passion in everyone at Almac, an organization now governed by the McClay Foundation, a private trust of his namesake that takes a long term view of sustainable business growth. I’ve stayed with Almac for 18 years because of the culture and the inspirational people.