Patient enrollment continues to be a limiting factor for trial durations

To prepare for our recent webinar “Trends in Clinical Trial Planning,” we dug into proprietary data from The Centre for Medicines Research (CMR) International, a wholly owned subsidiary of Clarivate working with leading global pharmaceutical companies to provide insights into industry trends — to strengthen R&D planning and effectiveness.

 

The length of clinical trials continues to be an industry focus. Shortening the duration means faster time to market, reducing costs and delivering treatment options to the patients that need them. As the industry continues its effort to reduce the length of clinical trials, evaluating the trends over time allows us to monitor the effectiveness of strategies and adapt as needed.

 

30 companies participated in the 2019 CMR International program, providing data on 8,000+ compounds, 35,000+ studies, 100,000+ countries and 640,000+ site-level records.

 

Development time

The data show that overall development time (time taken from compound code assigned to first world launch) has been decreasing over the last decade. In fact, development time in 2019 was the shortest it’s been since 2013. However, as seen in Figure 1, improvements have essentially plateaued over the past seven years. A closer look at the individual phases revealed that total study durations in 2019 for Phases 1 and 2, when compared with 2013, have decreased by 21% and 2%, respectively; however, the duration for Phase 3 trials has increased by 8%.

 


Source: The Centre for Medicines Research
*The development time data point for 2019 includes data from 2018 and 2019 only

 

Because Phase 3 studies usually have the primary objective of demonstrating or confirming therapeutic benefit as well as safety in the intended indication and recipient population, the required sample sizes are larger than those for Phases 1 and 2. Therefore, the effect of patient enrollment on trial durations warrants a closer look.

 

Enrollment as a limiting factor

In fact, participant enrollment is the longest clinical study interval (Figure 2), particularly for Phase 3 trials, and continues to be a limiting factor for trial durations. As such, it represents an area ripe for improvement.

 


Source: The Centre for Medicines Research

 

Across all trial phases, 53% of trial protocols need to be amended after initiation, with the majority of amendments falling during the enrollment interval (Figure 3). Therefore, improving patient identification and stratification strategies during the study design phase could improve enrollment, reduce the need for amendments and shorten trial timelines.

 


Source: The Centre for Medicines Research

 

Master protocols and biomarker-led stratification

Using genomics to define and select eligibility criteria is a common feature of biomarker-guided clinical trials, including basket and umbrella trials. These designs fall under the master protocol framework and follow the tenets of precision medicine by identifying those most likely to respond to a given therapy based on individual variability in genes, environment and lifestyle.

Using biomarkers to stratify patients can ensure that there is a good patient-therapy match, reduce attrition rates and increase the chances of trial success to almost twice that as trials without biomarker-led stratification (10.3% vs 5.5%).1

 

The use of biomarkers to select participants increases the rate of trial success from 5.5% to 10.3%

 

 

Study location and experienced sites

Another strategy is to identify countries with a large population of patients with the disease of interest, although this needs to be balanced against the complexity and timelines associated with regulatory review and approval.

Sites play a key role in identifying, recruiting and enrolling patients in clinical trials. Therefore, choosing sites with experience recruiting the chosen patient segment ensures a level of efficiency as well as access to the right patient population. Data such as that available in Cortellis provide specific site information such as their experience enrolling specific patient segments, even down to the genetic variant level, facilitating the choice of the right sites.

 

Leverage data for greater insights and faster time to market

Tapping into aggregated data sources such as those available via The Centre for Medicines Research allows us to benchmark R&D and clinical programs, set internal KPIs and make more strategic trial planning decisions. As the industry aims to reduce the length of clinical trials and speed time to market, continuing to evaluate the trends will allow us to monitor the effectiveness of new strategies and strategically address the biggest industry challenges.

Plan for the future and benchmark against the industry with The Centre for Medicines Research, an objective source of industry metrics and trends analysis built over 20 years of rigorous development.

 

References

  1. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019;20(2): 273–286. https://doi.org/10.1093/biostatistics/kxx069

 

 

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