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Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.

Publication ,  Journal Article
Schroen, AT; Petroni, GR; Wang, H; Gray, R; Wang, XF; Cronin, W; Sargent, DJ; Benedetti, J; Wickerham, DL; Djulbegovic, B; Slingluff, CL
Published in: Clin Trials
August 2010

BACKGROUND: A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. PURPOSE: We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. METHODS: A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. RESULTS: Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (<35% actual/predicted accrual rate) were consistently closed due to insufficient accrual. LIMITATIONS: This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. CONCLUSION: Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining accrual benchmarks for early trial termination or redesign is feasible, but better accrual prediction methods are critically needed. Future studies should focus on identifying trial factors that allow more accurate accrual predictions and strategies that can salvage open trials experiencing slow accrual.

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Published In

Clin Trials

DOI

EISSN

1740-7753

Publication Date

August 2010

Volume

7

Issue

4

Start / End Page

312 / 321

Location

England

Related Subject Headings

  • Statistics & Probability
  • Research Design
  • Pilot Projects
  • Patient Selection
  • Neoplasms
  • Humans
  • Clinical Trials, Phase III as Topic
  • Benchmarking
  • 5203 Clinical and health psychology
  • 4905 Statistics
 

Citation

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ICMJE
MLA
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Schroen, A. T., Petroni, G. R., Wang, H., Gray, R., Wang, X. F., Cronin, W., … Slingluff, C. L. (2010). Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials. Clin Trials, 7(4), 312–321. https://doi.org/10.1177/1740774510374973
Schroen, Anneke T., Gina R. Petroni, Hongkun Wang, Robert Gray, Xiaofei F. Wang, Walter Cronin, Daniel J. Sargent, et al. “Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.Clin Trials 7, no. 4 (August 2010): 312–21. https://doi.org/10.1177/1740774510374973.
Schroen AT, Petroni GR, Wang H, Gray R, Wang XF, Cronin W, et al. Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials. Clin Trials. 2010 Aug;7(4):312–21.
Schroen, Anneke T., et al. “Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials.Clin Trials, vol. 7, no. 4, Aug. 2010, pp. 312–21. Pubmed, doi:10.1177/1740774510374973.
Schroen AT, Petroni GR, Wang H, Gray R, Wang XF, Cronin W, Sargent DJ, Benedetti J, Wickerham DL, Djulbegovic B, Slingluff CL. Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials. Clin Trials. 2010 Aug;7(4):312–321.
Journal cover image

Published In

Clin Trials

DOI

EISSN

1740-7753

Publication Date

August 2010

Volume

7

Issue

4

Start / End Page

312 / 321

Location

England

Related Subject Headings

  • Statistics & Probability
  • Research Design
  • Pilot Projects
  • Patient Selection
  • Neoplasms
  • Humans
  • Clinical Trials, Phase III as Topic
  • Benchmarking
  • 5203 Clinical and health psychology
  • 4905 Statistics