By Maxine Bookbinder

September 24, 2015 | Despite a trend toward shorter clinical trial cycle times, recent data analysis asserts that Phase II/III cycles have actually increased.

KMR Group, a benchmarking and data analysis company focusing on biopharmaceuticals, assessed cycle times for more than 6000 Phase II and III trials individually since 2005 from 27 companies using proprietary industry data. After comparing company cycle times, it found an increase of 16.4% in Phase II and 55.4% in Phase III.  KMR defines total cycle time as the interval from Protocol Approval to Clinical Trial Report, and the group reports cycle time both with and without treatment times.

The research environment is evolving as regulators and payers require tighter oversight of safety, efficacy, and cost effectiveness. Subsequently, companies increase patient sample sizes, extend treatment times, and monitor adverse effects more closely.  This changing climate is forcing pharma to re-examine trial designs to maintain costs and cycle times.

Study start-up, from getting started in a country to site initiation, is greatly responsible for increased cycle times, says KMR President and Founder Linda Martin. “When country start-up is efficient, and takes into account the country-specific recruitment rates, the result is that the entire trial timeline is reduced, while at the same time optimizing resources, a powerful combination.  When companies realize they can’t deliver the number of patients, they then have to set up rescue sites. That lengthens time.” 

In addition, pre-launch research should reveal whether a test site can provide the required number of patients needed, how many sites are needed and, in a global test, which countries are easiest to work with, says Martin. Identifying rate limiting factors, such as a company’s process limits, bottlenecks, and country-specific performance and idiosyncrasies are key.   “China, for example, is a challenging and complex country to work with; however, its large population can make it an attractive test country. The trade-off in startup delays relative to recruitment opportunities, as well as the infrastructure cost to get into the country, and what many companies cite as ‘high patient costs’ may give companies pause.”    

Emerging markets also have trade-offs, says Martin.  Residents may be eager to participate in clinical tests for the first time, resulting in quicker enrollments. However, these countries take longer to set up in. The data quality and integrity must also be verified. “Ideally, this confluence of factors and their impact are verbalized at the start; it is what KMR Group deems ‘risk management’ and epitomizes its philosophy when it comes to its tools and data.” 

Another challenge to reducing cycle time is the increased use of CROs to offset financial constraints.  Martin notes that CROs have had “a positive impact” on clinical trials and offer more flexible resources. However, they also, “introduce a new element into the process and add complexity. These relationships need to be nurtured and managed effectively to get the best outcome.” KMR did not analyze CRO performance as part of this assessment.

The development of personalized medicine and rare disease exploration can impact cycle trends, as well. Ironically, although they involve fewer patients, they can have longer cycle times due to the difficulty of fulfilling enrollment. “It will take energy to find the right patients for studies,” notes Martin.  Potential patients must submit to diagnostics to determine if they have a specific biomarker, an extra step in an already complex process.

Before initiating tests, companies should strategize, review performance data, and “be more systematic, conservative and realistic,” says Martin. “Everyone is optimistic at the beginning. But how many sites are really needed? Can certain sites actually provide needed patient numbers?”  Martin suggests that companies talk to people already at that site, whether domestic or international, to determine if it can accommodate the protocol design, to review previous studies conducted there, and to use those figures as a contrast to what is being proposed. (KMR provides this data to its subscribers.)  

Electronic Data Capture (EDC) allows for real-time information and updates, minimizing time and energy, thus reducing cycle time. Most companies have already transitioned to EDC in a majority of trials.   

Another element that can reduce cycle time is how multi-test sites are completed.  A company that begins multiple simultaneous tests, whether nationally or globally, will likely complete its study before a company conducting sequential tests. 

Martin says that companies have succeeded in reducing costs and increasing efficiency. “But navigating the dynamic between major and emerging markets, site performance, and size of study is a complex endeavor. Companies that do this will achieve improvements. Those that don’t will fall behind.”