Five Pivotal Moments That Make or Break Your Clinical Trial

Every drug developer faces at least one pivotal moment during a study — a tipping point that can make or break study success. Learn how to transform these pivotal moments from obstacles to advantages.

Clinical trials bridge the gap between idea and reality. Over the course of a few years, they verify whether an investigational product is safe and effective enough to reach the market. Along the way, though, anything can happen.

Every drug developer faces at least one pivotal moment during a study — a tipping point that can make or break study success. This moment may come earlier — such as a setback in patient recruitment, retention or global site selection — or later, due to unreliable forecasts or delays in data access.

How drug developers handle these opportunities dictates whether their study moves forward, needs a rescue or falters altogether. But pharmaceutical companies can often sail smoothly and navigate pivotal moments by partnering with a contract research organization (CRO) that does more than act as a vendor.

The right CRO will be an extension of the team, providing expertise and efficiencies earned by standing on the shoulders of previous successes. The right CRO will offer stability, agility and ingenuity.

With innovation and experience at hand, biotech and pharmaceutical companies can transform their pivotal moments from obstacles to advantages.

Here are five pivotal moments that can make or break a clinical trial, plus tips and solutions to ensure progress.

1. Patient recruitment and retention strategies

A successful clinical trial starts with the patients involved. Research shows that more than one out of three people in the United States would participate in a clinical trial if their doctor recommended it. Approximately 86% of people believe the option to participate in clinical trials should be discussed as a standard of care for those newly diagnosed with a disease.

Investigators are at the root of patient awareness of clinical trial opportunities. In this sense, sponsors will gain an enrollment advantage by partnering with a CRO that has an experienced network of investigators who can actively recruit from within their own networks.

Our Accelerated Enrollment Solutions (AES) business is a good example. AES has a database of more than 100 million households and uses advanced data modeling to identify patients most likely to enroll. The organization also offers a network of more than 700 investigators who can take an active role in their studies, from finding new efficiencies to local site recruitment, even globally.

With the growing focus on patient diversity in clinical trials, a strong recruitment partner will also focus on engaging patients most likely to enroll within racial and ethnic groups matching the target disease population. And, they’ll recognize that methods to reducing patient burden are a success factor in clinical trial recruitment and enrollment.

What does better patient recruitment and retention look like in action? In a recent rescue study for a biotech organization, experts at the PPD™ clinical research business of Thermo Fisher Scientific leveraged their deep investigator network to reach target enrollment. The breast cancer study had struggled from a high screen-failure rate due to the strict inclusion/exclusion (I/E) criteria. To advance recruitment and better engage investigators, we became the voice of the client with sites and converted nearly all ambivalent sites to actively enrolling sites.

By leveraging new screening technologies and taking a more active role in site engagement and patient enrollment, we were able to more than double the number of actively recruiting sites. In doing so, our clinical research team enabled the sponsor to hit the original last-patient-in (LPI) milestone 1.5 months early.

Tip: Pharmaceutical companies should routinely assess their CRO’s methods to retain study participants. The best forecasts and study designs will not be valid if 30 percent of the study population drops out — and research shows that’s often the case. While side effects, the risk of getting a placebo and time constraints can all be the basis for patients vacating a study, there are factors that sites can influence with a steady CRO partner on hand. Convenient site locations and compassionate site visits positively affect patient retention. A CRO with a focused and strategic approach to patient recruitment will save drug developers time, resources and hassle.

2. Proper balance between in-house and outsourced expertise

As the number of registered studies increases annually, the outsourcing of clinical trials and marketed products continues to gain momentum. Strategically selecting the right outsourcing models can bend the cost and time curve of drug development by maximizing quality, operational success and financial efficiencies. But sponsors face the common challenges of identifying, allocating and coordinating the number of in-house and outsourced resources needed to achieve their goals.

A strong functional service provider (FSP) creates flexibility in clinical trial outsourcing solutions and will easily customize engagements to sponsors’ requirements. In addition, as clients contend with an increasingly competitive talent market for roles, it’s important to work with a partner that has a history of demonstrated success and offers a best-in-class talent pool.

As an example, customers utilizing PPD™ Functional Service Partnership (FSP) solutions benefit from more than 25 years of FSP experience. Beyond that, they gain access to professionals backed by the full force of our global training, professional development and infrastructure. Proven and reliable outsourced expertise are critical to support key functions that drug developers can’t afford to leave to chance.

Tip: When considering an FSP engagement, ask how FSP talent differs from full-service engagements. When it comes to outsourcing clinical trial solutions, it’s not just about the resourcing model — the quality of the skillset is also a make-or-break element. We source talent for both full-service outsourcing and FSP engagements from a single talent pool, thereby ensuring all team members receive the same high quality of training and knowledge-sharing.

On top of that, PPD FSP solutions feature an innovative implementation lead role that is dedicated to the smooth onboarding of an FSP model. The implementation lead leverages deep knowledge, experience and cross-functional relationships to drive seamless onboarding and set up the partnership for success. Customers also have an assigned operations delivery lead to serve as a single point of contact that provides oversight and aligns with the sponsor on timelines, strategies and project delivery.

3. Robust methodology for clinical trial forecasts

Clinical trials and delays are not strangers, with research showing that 80 percent of clinical trials are often delayed at least one month. Most pharmaceutical companies rely on spreadsheet-based models to predict trial costs, which may not be able to capture and predict myriad variables in the same way as an intelligent forecasting solution.

The critical success factors with any model are the amount of information available about the trial and the high amount of accuracy required. Trial forecasts made 12 months before the trial start date are fine if a sufficient error bar can be tolerated, but most trials need stronger precision.

To this end, drug developers should partner with a full-service CRO that uses machine learning and AI technology to:

• Create forecasts based on specific cost drivers in a protocol
• Produce optimized site selection and recruitment that takes a multitude of variables into account

Thermo Fisher Scientific and Medidata Acorn AI recently launched PPD TrueCast, a powerful forecasting solution that offers biotech and pharmaceutical companies actionable insights to optimize site selection, trial enrollment and study cycle times. This technology combines vast patient recruitment and site performance data with predictive models and advanced analytics, putting big data into practice for the benefit of trial planning and execution.

More accurate forecasting capability can translate to real savings in both time and resources for drug developers. TrueCast reduced the average Phase III study enrollment period by an average of 1.5 months in retrospective trial simulations when site recommendation models were utilized to select a portion of the country and site footprint.

Tip: Every biotech and pharmaceutical company should ask its CRO how they build their forecasts. There are too many variables riding on these forecasts to leave them to estimates or spreadsheet modeling.

All drug developers should push for access to AI-based forecasting technology that delivers deep site-performance data in real time from an extensive global footprint of trial sites. Doing so provides several benefits, including:

• Simplified scenario planning and optimized country and site selection, which derive from the ability to forecast cycle times and enrollment performance
• The capability to automatically track study performance and predict enrollment risk during a study’s enrollment period
• Access to real-time site performance metrics to identify high-performing sites, which enables more informed decision-making — a critical factor if mitigation is needed

4. Real-world evidence driving patient centricity efforts

Real-world evidence (RWE) has robust applications throughout the clinical trial design process, as well as during post-approval research and safety studies. Forward-thinking CROs and providers of evidence-based solutions are working with sponsors to integrate the power of RWE throughout their clinical trials to enhance patient centricity. Our survey of pharmaceuticals research and development trends found that drug developers rank real-world data and real-world evidence as the top opportunity area in clinical research.

Patients are the ultimate stakeholder in the use of medical interventions, and both regulators and payers are increasing the emphasis on patient engagement. Elucidating the patient experience at various stages in a product’s life cycle can inform a patient-focused drug development strategy.

Companies benefit from partnering with experts in patient-centered research who can help them:

• Incorporate patient preferences into clinical trial designs and benefit-risk assessments
• Engage patients to better understand the patient experience related to unmet needs, burden of illness and impacts of a disease
• Include patient perspectives in identifying meaningful endpoints in trial designs
• Design and implement clinical outcome assessments and patient-reported outcomes to provide insights into treatment benefit and safety
• Build an effective and diverse recruitment strategy by leveraging data and technology to understand the profile and demographics of the target population, remove barriers and improve access

Without a strong patient-centric strategy for clinical trial design, sponsors risk delays in approval and access by not generating the right evidence for the right audiences to support their product’s value.

Tip: Improve enrollment by leveraging technology to reliably build your study design around patient preferences. While clinical trial solutions designed with patients in mind have a higher likelihood of patient participation, the need to quickly progress studies prevents the conducting of timely patient preference studies. Sponsors should consider use of a web-based tool like StudyGage that enables them to leverage data collected from thousands of patients to rapidly compare trial designs, simulate the impacts of those designs on participation, and choose a study design optimized for their needs.

With access to a predictive tool for trial design, sponsors can create more optimized clinical trial solutions by proactively considering the effect of elements such as:

• Innovative digitization and virtualization approaches
• Strategies for achieving diverse, representative samples
• Alternative data collection methods
• Study procedures
• Participant compensation
• The likelihood of being on a placebo

5. Rescue studies

The pivotal moments covered so far can certainly make or break a trial. But what about studies that have already gone off track?

The right CRO provider can revive a study that appears to be at a dead end. An experienced eye is crucial, especially if it is not immediately evident where the study failed. Most biotech and pharmaceutical companies can relate to one example: the COVID-19 pandemic. During the initial lockdowns, upwards of 400 clinical trials were put on hold, but some studies were able to continue thanks to the work of agile CRO partners.

When contracted for a rescue study in Italy during the pandemic, Thermo Fisher’s PPD clinical research business decentralized a dermatology trial in days. We had proactively developed technology to collect endpoints in a manner that would protect participant safety. When the study sponsor contacted us to rescue the study, the CRO already had the applications, devices and training that study needed and rolled out the decentralized clinical trial solutions practically on demand. As a result, the study was able to complete patient assessments without any delay.

Clinical trial solutions: Navigating pivotal moments

There will always be pivotal moments that put studies at risk. The question for biotech and pharmaceutical organizations is whether they have the right partner with them when the road gets bumpy. That choice could mean the difference between gliding down the Autobahn — or languishing on the Oregon Trail.

For more than 35 years, the PPD clinical research business of Thermo Fisher Scientific has been the partner that innovators lean on. Through your pivotal moments, we are here, guiding the transformation of clinical research and advancement of your life-changing therapies.