Although it is widely acknowledged that protocol design plays a crucial role in the success of clinical research studies, how protocols have changed over time and the impact of these changes on clinical trial performance have never been quantified. To measure protocol design trends, the Tufts Center for the Study of Drug Development analyzed data on 10,038 unique phase 1-4 protocols conducted between 1999 and 2005. Tufts Center for the Study of Drug Development analyzed study conduct performance data on 57 individual phase 2 and 3 protocols administered at US-based investigative sites. The results of this study indicate that the number of unique procedures and the frequency of procedures per protocol have increased at the annual rate of 6.5% and 8.7%, respectively, during the time period measured. Investigative site work burden to administer each protocol increased at an even faster rate of 10.5% between 1999 and 2005. Additionally, during this time period, study conduct performance--that is, cycle time and patient recruitment and retention rates--worsened; and the number of protocol amendments, observed serious adverse events, and length of case report forms increased substantially. Implications of these results for simplifying protocol designs and minimizing negative effects on study conduct performance are discussed.
The Tufts Center for the Study of Drug Devdopment analyzed 8,3 I 7 clinical trial protocols to benchmark protocd complexity by phase and therapeutic area and to characterize trends in clinical trid complQxify and the Men ' placed on study staff to execute p t o c d procedures between 2000 and 2007. 'Wide vmiability in protocd complexity and w d burden was observed across therapeutic meas, within and between clinical research phases. Phase I protocds are the most compZex and the most demanding to execute. The mean number of t e tal procedures per protocd in phase 4 studits and the wolf burden associated with phase 1 p m t d grcrv the fastest between the periods 2000-2003 and2004-2007. Thecomplexi@ and w d burden of phase 3 protocols also grcw rapidly thing &is period. Protocols in anti-infee, immunomodulation, CNS, and oncdogy are consistently the most complex and Mensome to execute. Reasons for the wide vuriability m pdmd complexity and w d burdm by phase and therapeutic area are disd . This study provides insight into areas where pdocol design improvements should be targeted.
The Tufts Center for the Study of Drug Development and Medidata Solutions Inc analyzed data from 9737 protocols and 130,601 investigative site contracts associated with these protocols to derive updated benchmarks characterizing protocol complexity. The results of the study indicate that protocol design complexity continues to grow rapidly. Nearly all phase I, II, and III complexity measures associated with protocol execution increased significantly (eg, P < .0001) from 2001-2005 to 2011-2015. These measures include the number of unique and total procedures performed per patient over the course of a study, the site work effort to administer protocol procedures, the number of study volunteer visits, and the total number of procedures performed per study volunteer visit. The total cost per planned study volunteer per visit also increased significantly (eg, P < .0001) as did the total cost per study volunteer across all planned study visits. Phase I protocols remain the most complex and the most demanding to execute. Phase III protocols have seen the most substantial growth in protocol complexity. Phase IV protocols saw only modest increases in executional complexity during the 10-year time horizon. The implications of the study findings are discussed.
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