Background

The MMRC is a non-profit, disease-focused consortium dedicated to accelerating the development of novel compounds and combination treatments for multiple myeloma through a unique industry/institutional partnership.  Founded in 2004, the MMRC currently includes 16 N. American centers with expertise in multiple myeloma and a primary focus on rapid initiation and completion of Phase 1 and 2 clinical trials.  Eight of the 16 member institutions are National Cancer Institute (NCI)-designated cancer centers.  A number of critical business processes have been implemented within the MMRC to improve trial performance, from funding of dedicated project managers at member institutions to incorporation of a clinical trial management system and the development of standard contracts acceptable to all member institutions.  Trials conducted within the Consortium are carefully monitored and tracked for operational performance using industry-standard metrics.

Methods

36 of 46 Phase 1 and 2 trials performed by the MMRC between 2006 and 2012 that contained sufficient information on one or more of the following metrics were analyzed: time to negotiate a clinical trial agreement (CTA), time to activation, and successful study accrual and completion.  MMRC site-based project managers entered all metrics via remote EDC.  Time to complete the CTA was defined as the time to a final contract and budget (in the case of NCI trials, time to negotiate a letter of intent was used).  Time to activation was defined as the time from receipt of a final protocol at a participating center to the site initiation visit.  Accrual success rate was defined as the percentage of studies that met accrual goals at the time of study completion.  Performance of MMRC trials was compared to benchmarks published in the peer-reviewed literature (Dilts DM, et al.  J Clin Oncol2006; Durivage HJ, et al. ASCO 2010) and by the NCI (Doroshow et al. Operational Efficiency Working Group 2009).

Results

Of the 46 (30 company-sponsored and 16 investigator-initiated) ongoing or completed Phase 1 and 2 trials conducted within the MMRC in the 2006-2012 period, required information on time to complete the CTA, start-up time and successful study accrual was available for 22, 36 and 35 trials, respectively.  Results of the analysis can be found in the table below.

Metric  MMRC(1)  Dilts(2)  Durivage(3)  Doroshow(4)*  
Mean Time to CTAC (CTA Completion-Days) 74  100  NR  111  
Mean Time to TA (Trial Activation- Days)  147  189  NR  303  
Accrual Success  (N (%) of Studies)  33/35 (94%)  NR  112/170 (66%)  NR  
Metric  MMRC(1)  Dilts(2)  Durivage(3)  Doroshow(4)*  
Mean Time to CTAC (CTA Completion-Days) 74  100  NR  111  
Mean Time to TA (Trial Activation- Days)  147  189  NR  303  
Accrual Success  (N (%) of Studies)  33/35 (94%)  NR  112/170 (66%)  NR  

(1) Includes up to 36 Phase 1 and Phase 2 studies conducted by 16 institutions (2006-2012)

(2) Includes 218 studies conducted at Vanderbilt-Ingram Cancer Center and affiliated sites (January 2001-June 2005)

(3) Includes 170 Phase 2 investigator-initiated trials conducted by 8 centers (2005-2009)

(4) Includes 137 NCI early development Phase 2 N01 and Cooperative Group Trials (2006-2008)

NR=not reported

*Numbers reported in Doroshow et al. are medians

View Large

Completing the CTA took 25% to 33% less time for MMRC trials compared to benchmark studies.  Activating MMRC trials also took less time compared to other trials: 52% less time compared to NCI Phase 2 trials (Doroshaw et al.) and 22% less time compared to other benchmark studies.  When comparing the start-up times for the MMRC to the NCI data, it is interesting to note that half of the MMRC member institutions are NCI-designated cancer centers.  Almost all (94%) of the MMRC trials met accrual goals at the time of study completion as compared to 66% of comparable studies.

Conclusion

Trials conducted under the MMRC exceeded published benchmarks across some of the most critical and time-consuming stages of study conduct where performance metrics were evaluated.  In addition to the stringent business processes that have been implemented, the Consortium serves as a deep, domain knowledge resource for myeloma research and may provide a further advantage for expeditious and effective conduct of clinical trials.  Despite these impressive results, there are opportunities for improvement such as compressing the time from study concept to final protocol. The MMRC continually optimizes the development process to expedite the advancement of promising therapies for patients living with multiple myeloma and strives to serve as a model for other diseases.

Disclosures:

Harrison:MMRC: Employment. Anderson:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Raje:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Richardson:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Chari:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Jagannath:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Berdeja:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Fay:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Hofmeister:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Jakubowiak:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Zimmerman:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Krishnan:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Kumar:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Lonial:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Martin:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Wolf:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Orloff:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Reece:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Trudel:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Roy:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Siegel:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Stewart:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Talpaz:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Vij:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Zonder:MMRC: Research investigators participating in the consortium receive funding for a project manager Other. Goldberg:MMRC: Employment. Levy:MMRC: Employment. Dietz:MMRC: Employment. Capone:MMRC: Employment. Auclair:MMRC: Employment. Young:MMRC: Employment. Giusti:MMRC: Employment.

Topics:
multiple myeloma, computed tomographic angiography, cancer care facilities, american society of clinical oncology, clinical trials cooperative groups

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2013 by The American Society of Hematology
2013
Sign in via your Institution