1168 Journal Reports / The Spine Journal 13 (2013) 1167–1169

to these reports would support more accurate and reliable investigation,

with less time and effort than relying on incomplete published data.

PMID: 23778905 [PubMed - in process. Available at: http://www.ncbi.

nlm.nih.gov/pubmed/23778905].

Reprinted with permission from Annals of Internal Medicine. Simmonds

MC, Brown JV, Heirs MK, Higgins JP, Mannion RJ, Rodgers MA, Stewart

LA. Safety and effectiveness of recombinant human bone morphogenetic

protein-2 for spinal fusion: a meta-analysis of individual-participant data.

Ann Intern Med 2013;158(12):877-89.

http://dx.doi.org/10.1016/j.spinee.2013.07.015

Reporting of industry funded study outcome data: comparison of

confidential and published data on the safety and effectiveness of

rhBMP-2 for spinal fusion. Rodgers MA, Brown JV, Heirs MK,

Higgins JP, Mannion RJ, Simmonds MC, Stewart LA. BMJ

2013;346:f3981.

OBJECTIVE: To investigate whether published results of industry funded

trials of recombinant human bone morphogenetic protein 2 (rhBMP-2) in

spinal fusion match underlying trial data by comparing three different data

sources: individual participant data, internal industry reports, and publicly

available journal publications and conference abstracts.

DATACOLLECTION AND SYNTHESIS: The manufacturer of rhBMP-

2 products (Medtronic; Minneapolis, MN) provided complete individual

participant data and internal reports for all its studies of rhMBP-2 in spinal

fusion.We identified publications and conference abstracts through compre-

hensive literature searches. We compared outcomes provided in the in-

dividual participant data against outcomes reported in publications. For

effectiveness outcomes, we compared meta-analyses of randomised con-

trolled trials based on each of the three data sources. For adverse events,

meta-analysis of the published aggregate data was not possible and we com-

pared the number and type of adverse events reported between data sources.

RESULTS: 32 publications reported outcomes from 11 of the 17 existing

manufacturer sponsored studies. For individual randomised controlled tri-

als, 56% (9/16) to 88% (15/17) of effectiveness outcomes known to have

been collected were reported in the published literature. Meta-analyses of

effectiveness data were almost identical for pain outcomes and similar for

fusion across the three data sources. A minority of adverse event data

known to have been collected were reported in the published literature.

Several journal articles reported only ‘‘serious,’’ ‘‘related,’’ or ‘‘unantici-

pated’’ adverse events, without defining these terms. Others reported

a small proportion of the collected adverse event categories. Around

23% (533/2302) of the total adverse events collected in published rando-

mised controlled trials have been reported in the literature, with rando-

mised controlled trials evaluating the licensed preparation (Infuse)

reporting around 11% (122/1108) of collected adverse events.

CONCLUSIONS: The published literature only partially represents the

total data known to have been collected on the effects of rhBMP-2. This

did not lead to substantially different results for meta-analysis of effective-

ness outcomes. In contrast, reporting of adverse event data in trial publica-

tions was inadequate and inconsistent to the extent that any systematic

review based solely on the publicly available data would not be able to

properly evaluate the safety of rhBMP-2. Analysis of individual participant

data enabled the most complete, detailed, and in-depth analysis and was

not more resource intensive than extracting, collating, and analysing aggre-

gate data from multiple trial publications and conference abstracts. Confi-

dential internal reports presented considerably more adverse event data

than publications, and in the absence of individual participant data access

to these reports would support more accurate and reliable investigation,

with less time and effort than relying on incomplete published data.

PMID: 23788229 [PubMed - in process. Available at: http://www.ncbi.

nlm.nih.gov/pubmed/?term523788229].

Reprinted from: Rodgers MA, Brown JV, Heirs MK, Higgins JP, Mannion

RJ, Simmonds MC, Stewart LA. Reporting of industry funded study

outcome data: comparison of confidential and published data on the safety

and effectiveness of rhBMP-2 for spinal fusion. BMJ 2013 Jun

20;346:f3981. Creative Commons Attribution License.

http://dx.doi.org/10.1016/j.spinee.2013.07.016

RhBMP-2 is superior to iliac crest bone graft for long fusions to the

sacrum in adult spinal deformity: 4- to 14-year follow-up. Kim HJ,

Buchowski JM, Zebala LP, Dickson DD, Koester L, Bridwell KH.

Spine 2013;38(14):1209-15.

STUDY DESIGN: Matched cohort comparison.

OBJECTIVE: To compare the use of bone morphogenetic protein (BMP)

or iliac crest bone graft (ICBG) on the long-term outcomes in patients un-

dergoing long fusions to the sacrum for adult spinal deformity.

SUMMARY OF BACKGROUND DATA: No long-term studies beyond

a 2-year follow-up have been performed comparing the use of BMP versus

ICBG for fusion rates in long fusions to the sacrum in adult spinal

deformity.

METHODS: A total of 63 consecutive patients, from 1997-2006, com-

prised of 31 patients in the BMP group and 32 patients in the ICBG group,

operated on at a single institution with a minimum 4-year follow-up (4-14

yr) were analyzed. Inclusion criteria were ambulators who were candidates

for long fusions (thoracic as the upper level) to the sacrum. Exclusion crite-

ria were revisions, neuromuscular scoliosis, ankylosing spondylitis, and pa-

tients who had both BMP and ICBG used for fusion. Oswestry Disability

Index and 3 domains of the Scoliosis Research Society score were used to

assess outcomes.

RESULTS: The 2 groups were similar with respect to age, sex, smoking

history, comorbidities, BMI, number of fusion levels and Cobb angles. Eight

patients in the BMP group underwent a posterior only, whereas 23 under-

went combined anterior and posterior (A/P) surgery. All 32 patients in the

ICBG had A/P fusion. The average BMP level was 11.1 mg (3-36 mg).

The rate pseudarthrosis was 6.4% (2/31) in the BMP and 28.1% (9/32) in

the ICBG group (P 5 0.04) using Fisher exact test and odds ratio 5 5.67.

The fusion rates for BMP group were 93.5% and 71.9% for the ICBG group.

Oswestry Disability Indexes were similar between groups. However, the

BMP group demonstrated superior sum composite Scoliosis Research Soci-

ety scores in pain, self-image and function domains (P 5 0.02).

CONCLUSION: BMP is superior to ICBG in achieving fusion in long con-

structs in adult deformity surgery. The rate of pseudarthrosis was signifi-

cantly higher in the ICBG group than BMP group. The concentration and

dosage of recombinant human bone morphogenetic protein 2 (rhBMP-2)

used seems to have an effect on the rate of fusion and pseudarthrosis rate be-

cause no patient receiving more than 5 mg per level had apparent or detected

pseudarthroses (n 5 20/20).

Level of Evidence: 3.

PMID: 23392417 [PubMed - in process. Available at: http://www.ncbi.

nlm.nih.gov/pubmed/?term523392417].

Reprinted with permission from: Kim HJ, Buchowski JM, Zebala LP,

Dickson DD, Koester L, Bridwell KH. RhBMP-2 is superior to iliac crest

bone graft for long fusions to the sacrum in adult spinal deformity: 4- to

14-year follow-up. Spine 2013;38(14):1209-15.

http://dx.doi.org/10.1016/j.spinee.2013.07.017

Cancer after spinal fusion: the role of bone morphogenetic protein

(BMP). Lad SP, Bagley JH, Karikari IO, Babu R, Ugiliweneza B,

Kong M, Isaacs RE, Bagley CA, Gottfried ON, Patil CG, Boakye M.

Neurosurgery 2013 Jun 14 [Epub ahead of print].

BACKGROUND: Bone morphogenetic protein (BMP) is used in tens of

thousands of spinal fusions each year. A trial evaluating a high-dose