Is too much irrelevant data slogging the pace to registration?
Conclusions of a Pharm Exec May 15 Roundtable on finding ways to build efficiencies into an increasingly costly and complex clinical trials process have been bolstered by new research from the Tufts Center for the Study of Drug Development. Based on extensive survey data drawn from a working group of 15 major drug makers, Tufts’ latest work provides fresh answers to a basic strategic question: given the growing awareness of how complex most trial protocols have become, what exactly is contributing to the run up in costs – and where and how can the biggest savings be made, without impairing the integrity of the process for regulators and patients?
The Tufts research renders a startling conclusion. Trial sponsors, in attempting to anticipate or meet the high expectations of all stakeholders in the process, are accumulating vast amounts of protocol data that are either irrelevant to the results or end up not being used by regulators. Tufts researchers reviewed data compiled for 140 protocols submitted by the 15 participating companies, involving in total more than 25,000 separate procedures. All the protocols covered phase II(a) through phase III(b) for compounds completed since 2009; the largest therapeutic segment covered was oncology, with 31 protocols. The study tied each of the protocol procedures to a primary, secondary, tertiary and exploratory endpoint, using the clinical study report and analytical plan. Reviewers then determined the proportion of protocol procedures that are not associated with the primary or key secondary endpoints. Next, an economic assessment was made to quantify the cost of performing these “non-core” procedures.
“What we found was that nearly one out of four procedures can be classified as non-core, costing sponsors approximately 20 per cent of every study budget on the collection of data that was not material or may never be used,” study coordinator and Tufts senior research fellow Ken Getz told Pharm Exec. In monetary terms, that 20 per cent amounts to an average of $1.1 million for each protocol budget, a figure that does not include all the staff time spent in collecting, managing and analyzing this non-essential clinical data. Extending this finding to the total number of active protocols performed each year, as reported by the FDA, the cost to the industry overall in performing these non-core procedures amounts to a staggering $3 – $5 billion per year.
What are the most frequent procedures that can be defined as non-core? The list includes dietary evaluations/nutrition monitoring, hematology scans, TSH testing, and unmasked physician reviews including physical examinations. Again, oncology studies had the highest proportion of non-core activities among the therapeutic areas included.
The Tufts research indicates that industry is beginning to get serious about bending the cost curve for this mission critical aspect of the new drug development process, with many of the 15 sponsors noting their high level of cooperation in furnishing data that could be viewed as commercially sensitive. For its part, Tufts hopes the work will help companies boost their in-house trial management efficiencies. There is also a rich new vein of evidence from the work that can be used to launch a dialogue with regulators and other stakeholders, on two fronts: (1) improved clarity from regulators on what they really need to render the best clinical judgment around registration; and (2) cooperation within industry in finding better and potentially novel medical or clinical applications for all the data that has been collected, but sits unused.