Development of clinical trials in a cooperative group setting: the eastern cooperative oncology group

Abstract

Purpose: We examine the processes and document the calendar time required to activate phase II and III clinical trials by an oncology group: the Eastern Cooperative Oncology Group (ECOG).

Methods: Setup steps were documented by (a) interviewing ECOG headquarters and statistical center staff, and committee chairs, (b) reviewing standard operating procedure manuals, and (c) inspecting study records, documents, and e-mails to identify additional steps. Calendar time was collected for each major process for each study in this set.

Results: Twenty-eight phase III studies were activated by ECOG during the January 2000 to July 2006 study period. We examined a sample from 16 of those studies in detail. More than 481 distinct processes were required for study activation: 420 working steps, 61 major decision points, 26 processing loops, and 13 stopping points. Median calendar days to activate a trial in the phase III subset was 783 days (range, 285-1,542 days) from executive approval and 808 days (range, 435-1,604 days) from initial conception of the study. Data were collected for all phase II and phase III trials activated and completed during this time period (n = 52) for which development time represented 43.9% and 54.1% of the total trial time, respectively.

Conclusion: The steps required to develop and activate a clinical trial may require as much or more time than the actual completion of a trial. The data shows that to improve the activation process, research should to be directed toward streamlining both internal and external groups and processes.

Figure 1

Level 0 process flow map for activating a phase III study at Eastern Cooperative Oncology Group (ECOG). Days are the median calendar days from receipt to acceptance by the process. Notes: Concept Development refers to the time the concept was developed by the PI when data was available (n=5). Brown boxes represent joint efforts between ECOG and external governmental agencies. Grant development is necessary only if additional funding was requested from a pharmaceutical firm; Regulatory Affairs Development is necessary only if the source of the IND is not held by the NCI or if commercial agents are only used for the study. While initial FDA review is within 30 – 45 days, studies required multiple loops to attain final FDA approval. Abbreviations: CTEP, National Cancer Institute Cancer Therapy Evaluation Program; CIRB, National Cancer Institute Centralized Institutional Review Board; CDE, National Cancer Institute Common Data Elements; FDA, US Food and Drug Administration.

Figure 2

Median Number of Development and Study Open Days for Phase II and III ECOG Clinical Trials opened for accrual and closed from 1/2000 to 7/2006

Figure 3

Median days for development for therapeutic studies activated from 1/2000 to 7/2006. Figure 3a are Phase II studies (n=71) and Figure 3b are Phase III studies (n=28).

Figure 3

Median days for development for therapeutic studies activated from 1/2000 to 7/2006. Figure 3a are Phase II studies (n=71) and Figure 3b are Phase III studies (n=28).