Quality of reporting of serious adverse drug events to an institutional review board: a case study with the novel cancer agent, imatinib mesylate.
OBJECTIVE
Serious adverse drug event (sADE) reporting to Institutional Review Boards (IRB) is essential to ensure pharmaceutical safety. However, the quality of these reports has not been studied. Safety reports are especially important for cancer drugs that receive accelerated Food and Drug Administration approval, like imatinib, as preapproval experience with these drugs is limited. We evaluated the quality, accuracy, and completeness of sADE reports submitted to an IRB.


METHODS
sADE reports submitted to an IRB from 14 clinical trials with imatinib were reviewed. Structured case report forms, containing detailed clinical data fields and a validated causality assessment instrument, were developed. Two forms were generated for each ADE, the first populated with data abstracted from the IRB reports, and the second populated with data from the corresponding clinical record. Completeness and causality assessments were evaluated for each of the two sources, and then compared. Accuracy (concordance between sources) was also assessed.


RESULTS
Of 115 sADEs reported for 177 cancer patients to the IRB, overall completeness of adverse event descriptions was 2.4-fold greater for structured case report forms populated with information from the clinical record versus the corresponding forms from IRB reports (95.0% versus 40.3%, P < 0.05). Information supporting causality assessments was recorded 3.5-fold more often in primary data sources versus IRB adverse event descriptions (93% versus 26%, P < 0.05). Some key clinical information was discrepant between the two sources.


CONCLUSIONS
The use of structured syndrome-specific case report forms could enhance the quality of reporting to IRBs, thereby improving the safety of pharmaceuticals administered to cancer patients.
Dorr
David A
DA
Oregon Health and Science University, Portland, Oregon, USA.
Burdon
Rachel
R
West
Dennis P
DP
Lagman
Jennifer
J
Georgopoulos
Christina
C
Belknap
Steven M
SM
McKoy
June M
JM
Djulbegovic
Benjamin
B
Edwards
Beatrice J
BJ
Weitzman
Sigmund A
SA
Boyle
Simone
S
Tallman
Martin S
MS
Talpaz
Moshe
M
Sartor
Oliver
O
Bennett
Charles L
CL
D016907:Adverse Drug Reaction Reporting Systems / Q000458:organization & administration / Q000592:standards* / Q000706:statistics & numerical data*; D000970:Antineoplastic Agents / Q000009:adverse effects; D001549:Benzamides; D002986:Clinical Trials as Topic; D017723:Drug Utilization Review / Q000458:organization & administration / Q000592:standards / Q000706:statistics & numerical data; D050723:Fractures, Bone / Q000139:chemically induced; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D000068877:Imatinib Mesylate; D007239:Infections / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy; D010879:Piperazines / Q000009:adverse effects; D011358:Product Surveillance, Postmarketing / Q000592:standards / Q000706:statistics & numerical data; D011367:Professional Staff Committees; D011654:Pulmonary Edema / Q000139:chemically induced; D011743:Pyrimidines / Q000009:adverse effects; D013997:Time Factors
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate