Budgets are being squeezed, economic disruption is on the horizon and the clinical development industry is bracing itself for a new set of global challenges. These shifting headwinds are a continuation of the major disruption the sector has dealt with in recent years. From the global pandemic to the war in Ukraine, clinical development has been operating against an increasingly complicated backdrop. However, with every challenge comes opportunity. Biopharmaceutical companies, sponsors and CROs can apply learnings from data gathered over the past five years, and use it to redefine development to become more resilient to future challenges.

The COVID-19 pandemic took the industry and the world by surprise. The emergency measures implemented in response to global lockdowns have left a lasting mark on clinical development, but not all were negative. The sudden shift to online and remote operations accelerated digitisation. Clinical development personnel explored new methods of conducting studies enabled by digital technologies – such as decentralised clinical trials, remote patient monitoring and virtual trials. However, the overall impact on operations was huge, particularly in the initial months. A Phesi analysis at the time (published May 2020) found that of 300,000 global clinical trial sites, there had been a 38% increase in suspensions from the beginning of the year.

While the scale of disruption caused by a global event like the pandemic might have been expected, local events have also been shown to have far-reaching consequences. The industry remains exposed to disruption by regional events and natural disasters, such as the recent devastating earthquakes in Turkey and Syria.

One recent event that has caused exceptional challenges to clinical development is Russia’s invasion of Ukraine. Ukraine and Russia were home to 4.4% of the world’s 65,593 investigator sites at the time of the invasion, most of which were suspended in March 2022 when war broke out. In the months since, clinical development investigators in Ukraine have shown true resilience, with almost half of investigator sites continuing to recruit. However, the conflict, combined with the pandemic, did damage that will impact the industry for years to come. Phesi analysis found that studies in disease indications including schizophrenia, ulcerative colitis and Crohn’s disease have been disproportionately affected.

The impact of such events makes the importance of building a more agile and resilient clinical development industry even more clear. This is a global industry, with sites and investigators in trials spread across the world. A major event in one area will inevitably have a knock-on effect elsewhere. It is imperative that sponsors take a smarter, more dynamic approach to planning trials to protect against both regional and global disruption. Sponsors that are able to accurately forecast trial enrolment and trial supplies can optimise country and site selection and apply resources more appropriately.

Phesi’s global analysis of all clinical trials conducted in 2022 assessed 80,917 records to explore trends in clinical development. The review showed that oncology receives the highest investment – with three of the top five most-studied disease areas in oncology indications. Breast cancer was the most-studied disease for the second year running, followed by COVID-19, prostate cancer, solid tumours and stroke (see figure 1).

However, despite continued investment in oncology, the data revealed a widespread scale-back of all activity. For example, the number of recruiting sites for breast cancer fell by 12.5%, with 113 fewer recruiting trials in 2022 compared with 2021.

In addition to a reduction in early-stage clinical development activity, 2022 saw a significant increase in terminations at phase 2, with the attrition rate increasing by 42% when compared with the five-year average (see figure 2). With 28% of trials cancelled during phase 2 in 2022, there will be an inevitable reduction of new therapies reaching the market.

In addition to the decline in development activity, there is a continuation of the challenge of clinical trial recruitment, which has long plagued the industry. Poor patient recruitment increases cycle times, causing delays and in some cases, suspensions, and greatly increases the financial burden. For example, a new Phesi analysis of all US cancer trials found that 2,298 of 11,826 sites enrolled only a single patient over the past three years. Single patient sites have an average cost-per-patient of $130,000, almost ten times that of the average well-performing site. These findings correlate with research conducted by the Tufts CSDD, showing that 11% of sites fail to enrol a single patient and 37% under-enrol.

Not only are sites with low numbers of patients financially inefficient, they also bring data quality for some trials into question. Data generated by sites with one or very few patients are far less reliable, especially in cancer trials, where there are typically a set of subjective disease measures included. Data outliers are less easily identified when there is no available comparison. This increases the risk of measurement deviation – an issue that is likely to create delays during the approval stage.

Another challenge that continues to pose a problem is diversity. Almost half of US cancer clinical trials have no Hispanic or Latin American representation, and 42% do not include a single black patient.

This is despite the FDA’s draft guidance on improving enrolment of underrepresented racial and ethnic populations in clinical trials. Published in April, the guidance encourages trial sponsors to define enrolment goals for underrepresented groups as early as possible in clinical development, highlighting cancer as a priority area for improvement. As the FDA continues to make diversity a priority, not representing the full patient population in the clinical development process will lead to delays in drug approvals.

Taken together, these analyses show that a new approach to clinical development is needed. To future-proof against upcoming challenges, the industry must learn from the recent disruption and adopt a data-driven and patient-centric approach to trial design and execution.

‘To future-proof against upcoming challenges, the industry must learn from the recent disruption and adopt a data-driven and patient-centric approach to trial design and execution’

Leveraging accurate historical trial data, patient records and data on investigator site performance, combined with AI-driven predictive analytics, significantly improves protocol design and investigator site selection for smarter and more representative trials.

With access to dynamically updated data and reviewing design and operational feasibility in real time, sponsors can run accurate ‘what if...?’ scenarios to overcome the challenges encountered by the industry daily. A data-driven approach to design moves sponsors away from ‘gut feelings’, avoids amendments and challenges preconceptions about recruitment trends.

Through applying accurate, performance-based analytics of country and site performance, poorly performing sites and countries can be eliminated early on, removing bumps in the road further down the line.

To be truly patient-centric, sponsors must also consider the burden of participation on patients. By minimising patient requirements as much as possible, the development process can be further streamlined and the need for unnecessary protocol procedures and unethical placebo and control arms reduced. For many conditions, sufficient data exists to allow the use of digital patient profiles, digital twins and digital trial arms.  These are created by collating real-world patient data generated by similar or identical trials. Sponsors can use these methods to accurately model safety and efficacy outcomes – reducing the overall number of patients needed and accelerating studies. Digital arms can even replace ‘wet’ trials in some instances where the data exists, which offers huge financial and time savings.

Major disruption can drive innovation. With further challenges on the horizon, now is the time to take advantage of the vast quantities of data available and combine these with modern predictive analytics technologies to design and execute better trials. A data-led, patient-centric approach is the future of clinical development. Looking at the successes – and mistakes – of the industry will drive progress and build a resilient industry that is better able to cope with global challenges supporting the focus on finding breakthrough cures and treatments. The data to design better trials exists. By harnessing it, clinical programmes and individual trials will become more efficient and life-changing therapies will reach patients as soon as possible.

Gen Li is President and Founder of Phesi