Posted on 18 June 2013
The clinical advantage of a product used to promote bone growth has been questioned by research from the Centre for Reviews and Dissemination (CRD) at the University of York.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is an orthobiologic agent used to promote bone growth in spinal surgery.
In 2011, after questions were raised about the product’s safety and efficacy in the USA, Yale University brokered an unprecedented agreement with the manufacturer, Medtronic, to release all its patient-level clinical research data for unrestricted independent scrutiny. Yale then appointed two teams, CRD and the Evidence-based Practice Center at Oregon Health & Science University, to separately assess and reanalyse the company’s data.
Researchers at York conducted a full systematic review of benefits and harms. They re-analysed individual participant data from all Medtronic-sponsored randomised controlled trials (RCTs) comparing rhBMP-2 with usual practice of iliac crest bone graft (ICBG), and from one other RCT. They additionally reviewed adverse event data from 35 published observational studies.
Published in Annals of Internal Medicine, the research found that, compared with ICBG, rhBMP-2 increases the chance of successfully fusing the vertebrae, but that this does not translate into a clinically meaningful reduction in pain or improvements in function or quality of life. The small benefits in these outcomes, which are seen from six months, up to at least two years after operation, also come at the expense of more pain immediately after surgery and the possibility of an increased, albeit small, absolute risk of cancer.
CRD Director, Professor Lesley Stewart who led the York team said “This has been a ground breaking project. As well as addressing an important clinical question, the project has set a new standard in transparency and release of trial data for independent scrutiny − a development that is in the public interest and an issue that is currently being examined by the UK Parliamentary Select Committee on clinical trials. It was also reassuring to find that working completely independently the two teams reached the same broad conclusions.”
Professor Stewart added “Clinicians should discuss these findings with their patients so that they can make informed choices about the type of surgery they would prefer.”
The CRD team's investigation of reporting of adverse events in the Medtronic sponsored trials will shortly be published in the BMJ.