Article type
Year
Abstract
Background: There is increasing concern about selective nonreporting of outcome data, particularly from industry funded clinical trials. Controversy around the use of recombinant human bonemorphogenetic protein-2 (rhBMP-2) for spinal fusion has stemmed from this issue.
Objectives: To investigate whether published results of industry-funded trials of rhBMP-2 in spinal fusion accurately reflect the underlying trial data.
Methods: We compared three different data sources: (1) publicly available journal publications and conference abstracts; (2) confidential individual participant data (IPD); (3) confidential clinical study reports (CSRs). The manufacturer of rhBMP-2 products (Medtronic Inc.) provided complete IPD and CSRs for all their trials of rhMBP-2 in spinal fusion. We identified publications and conference abstracts through comprehensive literature searches. Across the three data sources we compared meta-analyses of effectiveness outcomes and the number and type of reported adverse events.
Results: Eleven of 17 manufacturer-funded studies were published; between 56 and 88% of collected effectiveness outcomes were reported in these publications. Despite some missing data from publications, meta-analyses of primary pain outcomes were almost identical across the three data sources. Only 23% of the total adverse events collected in published RCTs were reported in the published literature. RCTs evaluating the licensed preparation of rhBMP-2 (INFUSE®) reported just 11% of their collected adverse events. Several journal articles reported only ‘serious’, ‘related’, or ‘unanticipated’ adverse events, without defining these terms. Confidential CSRs presented considerably more adverse event data than did publications.
Conclusions: The published literature only partially represents the total data known to have been collected on the effects of rhBMP-2. While this did not substantially influence meta-analyses of primary effectiveness outcomes, reporting of adverse event datawas inadequate and inconsistent. In the absence of IPD, access to full CSRs can produce more accurate, reliable and robust findings with less time and effort than relying on incomplete published data.
Objectives: To investigate whether published results of industry-funded trials of rhBMP-2 in spinal fusion accurately reflect the underlying trial data.
Methods: We compared three different data sources: (1) publicly available journal publications and conference abstracts; (2) confidential individual participant data (IPD); (3) confidential clinical study reports (CSRs). The manufacturer of rhBMP-2 products (Medtronic Inc.) provided complete IPD and CSRs for all their trials of rhMBP-2 in spinal fusion. We identified publications and conference abstracts through comprehensive literature searches. Across the three data sources we compared meta-analyses of effectiveness outcomes and the number and type of reported adverse events.
Results: Eleven of 17 manufacturer-funded studies were published; between 56 and 88% of collected effectiveness outcomes were reported in these publications. Despite some missing data from publications, meta-analyses of primary pain outcomes were almost identical across the three data sources. Only 23% of the total adverse events collected in published RCTs were reported in the published literature. RCTs evaluating the licensed preparation of rhBMP-2 (INFUSE®) reported just 11% of their collected adverse events. Several journal articles reported only ‘serious’, ‘related’, or ‘unanticipated’ adverse events, without defining these terms. Confidential CSRs presented considerably more adverse event data than did publications.
Conclusions: The published literature only partially represents the total data known to have been collected on the effects of rhBMP-2. While this did not substantially influence meta-analyses of primary effectiveness outcomes, reporting of adverse event datawas inadequate and inconsistent. In the absence of IPD, access to full CSRs can produce more accurate, reliable and robust findings with less time and effort than relying on incomplete published data.