One key issue facing pharmaceutical clinical development organizations has been increasing clinical trial cycle times. Despite substantial effort and attention from the industry on this issue, overall development timelines continue to increase, at both the programme and study levels. Indeed, cycle time continues to be a major area for improvement for drug development, given the current time to market — reported as 13.8 years to go from target identification to first approval in a major market (Pharmaceutical Benchmarking Forum 2016 R&D Performance: Success Rates & Cycle Time, KMR Group, June 2016). Companies that can master the operational challenges and restraints in study design can not only reap rewards of shorter cycle times but can also see first-mover advantages, revenue benefits, longer market protection and improved productivity through reduced expenditure on conducting clinical trials.
In this article, selected results from the Clinical Trial Cycle Time Study, an annual benchmarking initiative conducted by KMR Group, are presented. The study is based on proprietary data, which are collected directly from companies and carefully scrutinized. More than 17,000 interventional studies from 25 sponsors and contract research organizations (including 15 of the top 20 pharmaceutical companies by revenue) that were conducted in 2005–2015 were included in the assessment.
For trials that were completed in the most recent data window (2013–2015), analysis of the total trial duration — the time between protocol approval and the final clinical trial report — shows that the median cycle time for phase II and phase III studies was about 40 months (Fig. 1). Phase I studies involving patients took 32 months, whereas the cycle time for phase I studies involving healthy volunteers has remained stable over time, at about 15 months.
One key trend is that total median cycle time of phase II and phase III trials has increased in the past decade. Phase II has shown the most significant increases, with trials taking 7 months longer than they did in 2006–2008. Although there has been a small improvement in phase III cycle times in recent years, these still remain 6 months longer than for trials conducted in 2006–2008. The increase in phase II trial cycle time has been so substantial that there is now no statistically significant difference between phase II and III cycle time, even though phase III studies continue to enrol more than three times as many subjects as phase II studies.
There are multiple reasons for the increase in cycle times for the later phases. Companies seem to be shifting trial design strategies and have been steadily increasing the complexity and scale of phase II studies. Phase II studies have increased in size, from a median 88 subjects randomized in 2005–2007 to 108 subjects in 2013–2015. Phase III, on the other hand, shows an opposing trend, with the median number of subjects randomized decreasing over time (408 subjects in 2005–2007 compared with 347 in 2013–2015).Another interesting change in trial design across both phases is in treatment duration. The treatment period has increased, but the largest changes have been in phase II, for which treatment cycle times were 23% longer in 2013–2015 compared with the most recent non-overlapping period (2010–2012).
Other factors have also been important in driving the increases in cycle times. A statistical assessment (that is, single regressions and analyses of variance) of drivers responsible for increases or decreases in cycle times was carried out, and one notable finding was that trials of large molecules (such as monoclonal antibodies) were more time consuming than trials for traditional small-molecule drugs. Even when taking into account study size and disease complexity, this difference continued to be significant, partially explaining cycle time increases, as the industry has shifted to pursuing large molecules in the past decade. Using outsourcing and conducting trials in emerging markets were also associated with significant increases in the cycle time of phase III trials.
Understanding and evaluating cycle time performance through peer assessments and benchmarking is a key step in understanding a company's cycle time position. Once the results are distilled, companies can take steps to evaluate their trial designs and correct inefficient operational processes, resulting in advantages that go beyond shorter cycle times.
The authors of this article are employees of KMR Group, a leading management consultancy that focuses on benchmarking, analytics and performance management for biopharmaceutical companies.
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Martin, L., Hutchens, M. & Hawkins, C. Clinical trial cycle times continue to increase despite industry efforts. Nat Rev Drug Discov 16, 157 (2017). https://doi.org/10.1038/nrd.2017.21
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