Moving Forward From rhBMP-2

Abstract

A few years ago, a storm of controversy not only called into question the safety of recombinant bone morphogenetic protein-2 (rhBMP-2) [1], but also introduced an approach that addressed a fundamental weakness in the foundations of evidence-based medicine. Nearly half of all clinical trials are never published [2–4]; those that are often exclude important data and may face long delays to publication [5–6], and individual patient level data has rarely been available for re-analysis [7–8]. Moreover, financial conflicts of interest have been associated with actions that have had the potential to bias the conduct and dissemination of clinical research. All of these foundational weaknesses were at issue when a series of publications in the Spine Journal [1] suggested that the investigators behind the key publications supporting rhBMP-2 had significant financial conflicts of interest and that the published reports of these industry-sponsored studies may have incompletely reported important adverse events. In response to these concerns, Medtronic (Minneapolis, Minnesota) provided the Yale University Open Data Access (YODA) Project with the opportunity to apply its model [9–10] of data transparency and data stewardship to clarify the effectiveness and safety of rhBMP-2. This model entailed the oversight of two independent systematic reviews based on individual patient level data from all clinical trials conducted by Medtronic and the subsequent availability to scientists of the individual patient-level data from the trials. As part of this initiative, Medtronic fully granted jurisdiction over the data to the YODA Project and funded the effort. This project was conceived as a new type of industry-academic partnership to address the problem of unpublished and selectively published clinical evidence, with the hope of advancing open science, developing norms for good stewardship of clinical trial data, and serving patients and society, all while respecting legitimate industry concerns about the use of previously proprietary clinical trial data.