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# Many Drug Trial Amendments Avoidable: Study
- URL: https://www.fdaweb.com/many-drug-trial-amendments-avoidable-study/
- Published: 2016-01-14T12:00:00.000Z
- Updated: 2026-09-15T02:27:43.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5134432

> An analysis by the Tufts Center for the Study of Drug Development says that nearly half of drug trial substantial amendments are avoidable. Such amendments reduce the number of patients, and at a high cost and with longer study times, the analysis says in the latest [*Impact Report*](http://csdd.tufts.edu/uploads/Summary-JanFebIR2016%5F.pdf?ref=fdaweb.com).  
>  
> “The incidence and frequency of substantial amendments remain high and their impact on study cycle times and budget are *\[sic\]* substantial,” the report says. “Drug sponsors are responding through piloted and broad use of feasibility review committees, common protocol templates, and investigative site and patient feedback panels.”  
>  
> The researchers found that nearly 60% of protocols have at least one substantial global amendment, with Phase 2 protocols having the highest incidence of substantial amendments (77%).  
>  
> The 45% share of substantial protocol amendments deemed avoidable has increased since a similar 2010 Tufts analysis, which put the share at 33%. Among 10 primary reasons for amending protocols, the study says, a high percentage of amendments associated with recruitment/retention difficulties and study procedure feasibility were deemed avoidable. Only one in five substantial amendments is requested by a regulatory agency, and 86% of those requests were considered unavoidable.  
>  
> Researchers say that substantial protocol amendments trigger many changes, with 38% of changes related to safety assessment activities and 21% related to efficacy assessment activities. Some 35% of changes result from typographical corrections.  
>  
> Protocols containing at least one substantial amendment tend to be larger in scope (more patients, sites, and countries) than those without. When implemented, substantial amendments significantly reduce the actual number of patients screened and enrolled relative to the original plan, compared to those protocols without a substantial amendment.  
>  
> Adjusting for phase and therapeutic area differences, the report says, protocols with at least one substantial amendment have significantly longer cycle times, compared to those protocols without an amendment. On average, protocols with at least one substantial amendment had study conduct durations three months longer than those without an amendment.  
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> The total median direct cost to implement a substantial amendment was $141,000 for Phase 2 and $535,000 for Phase 3\. Highest median costs are associated with change orders to existing vendor contracts and additional fees to ethical review committees. The researchers found that incremental fees to investigative sites and the cost of additional drug supply were minimal.