Drug Safety Data and HEOR Driving Clinical Trial Costs and Time
The healthcare marketplace has seen seismic shifts over the past five years. Austerity measures have strained the reimbursement climate in many EU countries and driven government payers to scrutinize every new drug as never before. Healthcare reform in the United States has the potential to add coverage for 30 million uninsured Americans. As a result, pharmaceutical companies are working even harder to gain favorable formulary placement with private payers.
While there are regional differences in the global healthcare market, one thing is universal: regulators and payers want more data. And with the stakes raised, the value of that data has never been higher. Regulatory approval is no longer the finish line for a new drug. Clinical development teams must arm their commercial organizations and market access teams with the most useful data possible. That means building rigorous safety, efficacy and even health economic endpoints into early-stage trial protocols.
Rising clinical trial budgets are not solely the byproduct of elevated healthcare costs. Many market forces are working to change the way trials are designed and executed. Chief among these clinical cost drivers is the demand for more data to satisfy regulators and payers alike. The growing hunger for clinical data has manifested itself in two key areas: drug safety data and health economic and outcomes research (HEOR). This demand for more and different forms of data has become a requirement of regulators and payers worldwide.
The definition of the perfect drug is changing, and that definition is no longer being shaped by drug-makers alone. Institutions that govern market access are gaining more power and influence over drug approval and reimbursement status. Producing the most efficacious drug would be great, but if the benefit-risk profile or the health economic prospects of the drug are weak, then it might not be good enough.
As expected, generating more clinical data per trial comes with a high price tag. Clinical executives surveyed for a recent Cutting Edge Information study report an average Phase IIIa trial topping $30 million in trial operations cost, according to Figure 1. Patient enrollment targets are a real cost driver for a trial’s total cost and the main reason that the average Phase III trial costs six times more than the average Phase II trial. But trial managers are also lifting patient enrollment for another reason: to comply with more rigorous data requirements.
Figure 1: Average Total Cost of Clinical Trials by Phase for all Therapeutic Areas
In theory, adding more patients to the protocol is an easy way to gain more definitive answers. Clinical teams use Phase IIIb to continue searching for clinical significance. It is not uncommon for Phase IIIb trials to attempt to recruit more patients than Phase IIIa . Data from this benchmarking study indicate that the average Phase IIIb trial enrolled 868 patients versus the average Phase IIIa trial at 795 patients — almost four times the patient recruitment totals of the average Phase II trial (238 patients).
The quest for more patients is most often accompanied by trial delays. Analyzing clinical managers planned trial duration versus actual trial duration shows that the average mid- to late-stage trial runs over by approximately 25%. Clinical managers surveyed repeatedly reported that the longest delays occur during the patient recruitment stage — specifically the period from 50% enrollment to last patient in (LPI).
Trial delays, no matter the cause, are very costly. The drive for more patient data may lead to unintended consequences. Even when patient recruitment gets off to a strong start, high enrollment targets make finding the final 50% of patients more challenging.