Trial Protocols Up Costs and Inefficiencies: Study

Recent studies by the Tufts Center for the Study of Drug Development find that protocol design practices increase clinical costs and inefficiencies, place a growing burden on internal and external staff performance, and affect study volunteer recruitment and retention rates. The July/August Impact Report published by the center (purchase or subscription required) updates benchmarks on protocol design practices and looks at ways drug companies can optimize their study designs.

Researchers found that protocol procedures increased substantially for Phase 1, 2, and 3 trials in the study period from 2001 to 2015. Phase 1 and 2 trials were the most complex, having the largest number of distinct and total procedures in the most recent time studied, while Phase 3 trials saw the highest rate of increase in the mean number of distinct and total procedures performed per protocol, from 2001-2005 to 2011-2015.

The total number of endpoints rose 86% between the two periods, and procedures supporting the endpoints contributed a much higher volume of non-core data due to increases in secondary supplementary, tertiary, and exploratory endpoints, the report says. Researchers say that a 61% increase in the average number of study inclusion and exclusion criteria from 2001-2005 to 2011-2015 reflected sponsors’ growing interest in targeting more narrowly defined and stratified patient populations.

Drug makers doubled the number of countries and increased the number of investigative sites by 63% from 2001-2005 to 2011-2015, while the mean number of patients declined 18%. And while some individual procedure costs declined, the overall number of procedures per protocol grew, driving the total direct procedure costs per patient visit up 14%.

Tufts says that Phase 3 study start-up and data management cycle times have increased, tracking the protocol complexity increases. And across all phases, implementation of protocol amendments increased patient enroll timelines substantially, most notably in Phase 1 trials.

Companies reported that they expect electronic case report form data in the primary electronic data capture to decline as a share of all data collected, highlighting, the report says, the growing challenge of data coordination and integration. The most substantial increases are expected from smart phones, electronic clinical outcome assessments, electronic health and medical records, mobile health and wearable devices, and eSource data (data collected digitally without needing to transcribe them to an electronic data capture system).