By Maxine Bookbinder
October 11, 2013 | Failure is a known risk during any clinical trial, particularly since later stage failures can cost tens of millions of dollars in addition to valuable resources that could be redirected for other product development. The Tufts Center for the Study of Drug Development (CSDD) researched reasons for failure in an effort to help drug developers quantify the reasons.
“It is in the interest of drug developers have new products fail earlier, rather than later, in development, as earlier terminations avoid the costs of larger, more complex studies,” says Joseph DiMasi, director of economic development analysis at the Tufts CSDD.
The research, part of a larger project started in 2012, analyzed trials worldwide of drugs entering clinical development from 2000 – 2009. The core issue, says DiMasi, is that, because testing is “extraordinarily expensive,” firms want to understand why and when failures occur to plan better and make better decisions. Highlights of the analysis are in the September/October 2013 Tufts CSDD Impact Report. The study was based on a database of investigational drugs from the top 50 firms in pharmaceutical sales, confidential surveys, company pipeline reports, FDA and other government documents and web pages, internet searches, and medical literature and examined the development histories of 812 compounds.
Firms need to “fail the failures faster” in order to reduce costs and protect trial participants from unanticipated adverse drug effects. Improving the decision process, says DiMasi, will “ultimately reduce costs.”
Some failures occur due to poor clinical trial design. Improving the Phase I stage to yield better predictions could help determine sooner, rather than later, if a certain drug is financially viable.
Economic and commercial factors play a significant role in determining whether a drug is further developed. “Companies always are looking at safety and efficacy,” says Dimasi. But, “it’s not just safety and efficacy.” He states that companies must determine whether it is financially worthwhile to develop a particular drug. Certain compounds, although potentially life-saving, are possibly not tested because the economics do not support the development.
Clinical study failures vary widely by therapeutic class and phase of development. Primary reasons for failure were grouped into four categories: efficacy, safety, commercial (financial or strategic) and other (primarily formulation issues).
The study found that commercial reasons accounted for 40.9% of Phase I failures but only 27.3% of Phase II failures. Some of these include firms deciding that future costs will exceed future returns, which depend upon the likelihood of approval, anticipated future competition, and financial liability.
These can also include cases in which a pharmaceutical firm decides to exit a particular therapeutic area. Commercial viability can be difficult to determine, depending upon frequently-changing factors. Cardiovascular drugs experienced the highest prevalence of commercial failures (46.7%) among all classes of compounds analyzed.
Efficacy issues involved 53.9% of Phase II failures, including 54.3% of respiratory drug failures and 48.3% of drugs designated to treat central nervous system diseases. These included the inability to meet targeted endpoints and to demonstrate that the drug was indeed efficacious.
Efficacy issues also accounted for 52.3% of Phase III failures. Safety issues accounted for 29.5% of Phase III failures.
DiMasi notes that increased use of biomarkers might help companies determine if a compound will achieve its targets by providing better outcome clarity and efficiency.