By Exploristics CEO, Aiden Flynn.
For many years, the pharmaceutical industry has faced an ongoing challenge of trying to improve the speed, efficiency and profitability of drug development despite rising R&D costs. Then in 2020, the COVID-19 pandemic hit. Not only did it present new widescale practical challenges to the industry in the delivery of ongoing clinical trials, but it also highlighted entrenched inefficiencies in the clinical trial landscape impacting studies seeking to deliver new therapies at pace to meet the global emergency (1).
Pressures encountered during the pandemic have forced a conservative industry to take stock of its development approach and examine key areas in need of change. Areas identified to date have included the need for wider collaboration, more effective data sharing, more innovative trial design and a more open-minded approach to adopting and embedding digital solutions into the R&D process (2, 3, 4). None of these insights are new. However, it has taken COVID-19 to shine a stark new light on them to create fresh momentum for change.
Questions on Quality
One important issue highlighted was the general quality of the clinical studies initiated to evaluate potential COVID-19 therapeutics. The need for fast solutions gave rise to large numbers of studies. However, this often came at the cost of quality, with studies failing due to inconclusive or ambiguous results. This was not helped by the recruitment difficulties encountered and inadequate study design meaning that studies were often too small to have sufficient statistical power to detect meaningful treatment effects (5). Trials failing due to inconclusive results is not uncommon, with or without a pandemic. However, understanding why is difficult because failed studies don’t often get published. This means there is limited systematic data on how frequently or why trials fail, even in late-stage development.
In 2011 a review of research protocols found that almost a third of the studies it examined were statistically inconclusive and found that optimism bias could be playing a significant role in their inconclusiveness (6). The study suggested that trial design was over reliant on an intuitive approach and integrating a more systematic review of existing relevant evidence would better inform design choices such as power calculations and chosen treatment effects (6). Moreover, a more recent appraisal in 2016 found quite widespread difficulties in the approaches used in clinical research (7), with the majority of new research not preceded or accompanied by systematic literature reviews to provide context and inform study design. Here it was concluded that reform was required to produce more effective, transparent patient centric clinical research at the same or even reduced cost. Given that concerns around the limitations of common development approaches have been raised well before the pandemic, why has there not been more change?
Seizing on Successes
The publication of highly successful studies, perhaps, overshadows the many that fail and go unpublished. Indeed, effective vaccines and therapeutics were successfully delivered to tackle COVID-19 via well planned and designed studies such as the RECOVERY trial. Nevertheless, the development difficulties encountered during the pandemic should reignite debate around whether current development approaches are as responsive, robust, efficient and cost-effective as they could be in meeting new healthcare challenges.
The pandemic has provided industry with a ‘Road to Damascus’ moment. A chance to reassess old research habits and embed a more targeted approach to clinical development. Acknowledging these lessons is an important step. However, practical change is now required to change course and ensure that industry is well-placed to meet 21st century healthcare needs.
- Horsley, A. R. et al., Large scale clinical trials: lessons from the COVID-19 pandemic. M.J. Open Respiratory Research 2022: 9: e001226. DOI: 10.1136/bmjrep-2022-001226
- Park, J. J. H. et al., How COVID-19 has fundamentally changed clinical research in global health. The Lancet Global Health 2021: 9, 5: 711-722. DOI: 10.1016S2214-109X (20)30542-8.
- Szepessy, E., et al., COVID-19 Kickstarts a new era of pandemic preparedness in Europe. Lancet Infectious Diseases 2022: 22,3: 315-316.
- Nurturing growth: Measuring the return of pharmaceutical innovation 2021. Deloitte
- Janiaud, P., et al., Challenges and lessons learned from COVID-19 trials: Should we be doing clinical trials differently. J. Cardiol. 2021: 2021 Sep; 37(9): 1353–1364.
- Djulbegovic, B., et al., Optimum bias leads to inconclusive results: an empirical study. Clin. Epidemiol. 2011: 64(6): 583-593.
- Ioannidis, J. P. A., Why most clinical research is not useful. 2016: PLOS Medicine 13(6): e1002049. https://doi.org/10.1371/journal.pmed.1002049
Read more on the statistical strategies for disrupted clinical trials.