Centralized medical monitoring in phase III clinical trials: the National Surgical Adjuvant Breast and Bowel Project (NSABP) experience.
BACKGROUND
There is a need for data quality assurance procedures in phase III cancer trials. At the National Surgical Adjuvant Breast and Bowel Project (NSABP) 'real-time' systems have been developed for quality assurance and study monitoring: (1) manual review and triage of data forms by data managers at the time of submission; (2) computerized edit checking of all submitted data forms; (3) systematic review of eligibility, treatment compliance and toxicity in the first 100 patients of a new protocol; (4) prospective centralized medical review of all reported serious adverse events, treatment failures, second primary cancers and deaths; (5) quarterly review and approval of study summary data files by project statistician; and (6) on-site auditing.


OBJECTIVE
To assess the utility of an additional final comprehensive review of all patient records to confirm eligibility, disease status and vital status prior to manuscript submission.


METHODS
Four phase III NSABP studies, which had been monitored using the triage-based quality assurance program described above, were selected for analysis (n = 7972). Charts for 5965 patients were identified that had not been previously medically reviewed for protocol events of recurrence, second primary cancer or death. Submitted source documents and data forms of these 5965 NSABP patient records underwent medical review to verify patient eligibility, disease status and vital status.


RESULTS
This final comprehensive review found no additional treatment failures or deaths, identified seven additional cases of ineligibility, was time-intensive requiring enormous use of expensive resources, and was therefore judged not to add significantly to the integrity of the database.


CONCLUSIONS
Our findings are influenced by the procedures the NSABP employs for quality assurance and study monitoring for Phase III clinical trials and may have limited generalizability to other settings.


CONCLUSIONS
In the presence of multiple quality assurance and data monitoring systems, the rare discrepancies found between the data forms and source documentation does not support the routine use of a final comprehensive chart review for phase III trials at the NSABP Biostatistical Center.
Soran
A
A
NSABP Biostatistical Center, Pittsburgh, PA 15213, USA. soran@nsabp.pitt.edu
Nesbitt
L
L
Mamounas
E P
EP
Lembersky
B
B
Bryant
J
J
Anderson
S
S
Brown
A
A
Passarello
M
M
D001943:Breast Neoplasms / Q000601:surgery / Q000628:therapy*; D002985:Clinical Protocols; D026661:Clinical Trials Data Monitoring Committees / Q000592:standards*; D017326:Clinical Trials, Phase III as Topic / Q000592:standards*; D003131:Combined Modality Therapy; D019983:Guideline Adherence / Q000592:standards*; D006801:Humans; D007414:Intestinal Neoplasms / Q000601:surgery / Q000628:therapy*; D008485:Medical Audit; D011785:Quality Assurance, Health Care / Q000379:methods; D014481:United States