Participants
The data-selection flow-chart for this study is presented in Figure 1. Application of the exclusion criteria to the study date ranges resulted in a PHD extract with data for 178,204 unique patients from 1,085 hospitals and institutions. Within this extract, there were 23,020 patients with ICD-10 codes related to lumbar fusion surgeries during the initial procedure study period, of whom 6,848 patients were excluded because they did not receive V-CBA or rhBMP-2, received both V-CBA and rhBMP-2, or the graft used could not be definitively determined. This process resulted in a final dataset for analysis with 16,172 patients from 172 hospitals and institutions, of whom 6,588 patients received V-CBA and 9,584 patients received rhBMP-2 during the initial procedure. All-cause inpatient readmissions during the 12-month follow-up period were identified for 1,482 patients in the V-CBA group and 2,021 patients in the rhBMP-2 group, which were then used to identify potentially relevant follow-up re-admissions.
Initial Patient, Procedure, and Hospital Characteristics
The distributions and statistical comparisons of initial patient, procedure, and hospital characteristics are presented in Table 1. The mean patient age (SD) in each group was V-CBA=60.86 (13.13) and rhBMP-2=60.74 (13.46) years and the majority of patients in each group were female (V-CBA=55.45%; rhBMP-2=55.32%), white (V-CBA=84.79%; rhBMP-2=87.80%), and non-Hispanic (V-CBA=84.82%; rhBMP-2=90.90%). The mean CCI (SD) at the initial procedure was higher in the V-CBA group (0.92 [1.39]) than in the rhBMP-2 group (0.78 [1.20]). This difference resulted from significantly higher incidences in the V-CBA group for certain individual comorbidities, including (with P-values from Fisher’s exact test) any malignancy (0.0001), cerebrovascular disease (0.0141), chronic obstructive pulmonary disorder (0.0086), diabetes with (0.0025) and without complications (0.0003), hemi- or paraplegia (<0.0001), metastatic solid tumor (<0.0001), myocardial infarction (0.0002), peptic ulcer disease (0.0233), and peripheral vascular disease (0.0184).
The most prevalent health insurance status in each group was Medicare (V-CBA=49.73%; rhBMP-2=48.72%), and the majority of initial visit admission types, initial admission sources, and initial discharge statuses were elective (V-CBA=91.61%; rhBMP-2=91.21%), transfer from non-healthcare facility (V-CBA=53.55%; rhBMP-2=72.40%), and home/homecare/self-care (V-CBA=61.57%; rhBMP-2=58.67%), respectively. In the V-CBA group, 62.46% of the procedures included cage insertion (compared with 59.13% in the rhBMP-2 group) and 13.74% of the procedures involved treatment of multiple levels (compared with 11.26% in the rhBMP-2 group).
For hospital size, the most prevalent in the V-CBA group was 500+ beds (47.92%), compared with 1 to 299 beds in the rhBMP-2 group (42.38%). For both groups, the majority of hospitals were teaching hospitals (V-CBA=69.52%; rhBMP-2=53.08%) serving urban populations (V-CBA=91.45%; rhBMP-2=99.94%), and the most prevalent US region represented in both groups was the South (V-CBA=55.98%; rhBMP-2=44.18%).
Statistical comparisons identified the following confounding initial patient, procedure, and hospital characteristics, which were treated as covariates in the multivariate regression models for the primary cost and resource utilization analyses: race, ethnicity, Charlson comorbidity index, health insurance status, initial admission type, initial admission source, initial discharge status, cage insertion, multiple levels treated, hospital size, hospital teaching status, hospital population served, and hospital region.
Hospitalization Charges and Resource Utilization
The unadjusted mean hospitalization charges (SD) for the initial procedure were $118,917 ($77,459) for the V-CBA group and $143,678 ($102,312) for the rhBMP-2 group (P<0.0001; Wilcoxon rank-sum test). Unadjusted hospitalization charges (SD) for the 12-month follow-up period were $108,763 ($120,353) for the V-CBA group and $120,449 ($131,041) for the rhBMP-2 group (P=0.0477; Wilcoxon rank-sum test).
The adjusted mean initial procedure and follow-up hospital charges (95% CIs) are presented in Figure 2. After adjusting for confounding factors, the mean initial procedure and follow-up hospital charges (95% CIs) remained significantly lower in the V-CBA group ($109,061 [$106,969–111,153] and $108,315 [$101,316–115,314], respectively) versus the rhBMP-2 group ($160,191 [$157,085–163,296] and $130,406 [$122,998–137,813], respectively). Given that this disparity may be skewed by the potential for higher cost variability between the groups during multiple-level treatments, an ad hoc analysis was performed on data only from patients who received single-level treatment (V-CBA=86.26% and rhBMP-2=88.74%). In theory, charges for the single-level procedures would be more standardized and could potentially provide for a better-aligned reference comparison. After adjusting for recalculated confounding factors for the ad hoc analysis (see Single-level Only Cohort data, Table 1), mean initial procedure hospitalization charges (95% CIs) for single-level treatments only remained significantly lower for the V-CBA group ($103,064 [$100,983–105,146]) versus the rhBMP-2 group ($149,620 [$146,469–152,772]; Figure 3).
The mean initial procedure and follow-up LOS are presented in Table 2. The unadjusted LOS (SD) for initial procedure hospitalizations were 3.91 (4.48) days for the V-CBA group (range: 0–95 days) and 3.67 (3.30) days for the rhBMP-2 group (range: 0–81 days; not significant [ns]). Unadjusted cumulative LOS (SD) for the 12-month follow-up period were 7.97 (12.38) days for the V-CBA group (range: 0–282 days) and 7.10 (8.52) days for the rhBMP-2 group (range: 0–92 days; ns).
After adjusting for confounding factors, the mean initial procedure LOS (95% CIs) were significantly lower in the V-CBA group (3.77 days [3.66–3.89 days]) versus the rhBMP-2 group (3.88 days [3.77–3.99 days]), but significantly higher for the cumulative follow-up hospitalizations in the 12-month period (7.87 days [7.21–8.53 days] versus 7.46 days [7.04–7.89 days], respectively). The notably wider variability in unadjusted follow-up LOS range for the V-CBA group (0–282 days) compared with the rhBMP-2 group (0−92 days) may have influenced the adjusted follow-up LOS results in spite of being treated as a covariate.
Table 2. Mean Hospital Lengths of Stay (Full Cohort)
No. Days
|
Initial Procedure
|
|
Follow-up ^
|
Group
|
P-value
|
|
Group
|
|
V-CBA
(n = 6,588)
|
rhBMP-2
(n = 9,584)
|
|
V-CBA
(n = 1,482)
|
rhBMP-2
(n = 2,021)
|
P-value
|
Unadjusted †
|
3.91
|
3.67
|
0.0948
|
|
7.97
|
7.10
|
0.0694
|
(SD)
|
(4.48)
|
(3.30)
|
|
|
(12.38)
|
(8.52)
|
|
Adjusted ‡
|
3.77
|
3.88
|
<0.0001*
|
|
7.87
|
7.46
|
<0.0001*
|
(95% CI)
|
(3.66, 3.89)
|
(3.77, 3.99)
|
|
|
(7.21, 8.53)
|
(7.04, 7.89)
|
|
^ Did not include patients who may have received follow-up treatment outside of the Premier Healthcare System.
† Wilcoxon rank-sum test.
‡ Multivariate regression models were adjusted with the following confounds as covariates: race, ethnicity, Charlson comorbidity index, health insurance status, initial admission type, initial admission source, initial discharge status, cage insertion, multiple levels treated, hospital size, hospital teaching status, hospital population served, and hospital region.
* Statistically significant.
Potentially Relevant Follow-up Re-admissions
The distributions and statistical comparisons of potentially relevant 12-month follow-up re-admissions are presented in Table 3. The 12-month incidence of cardiac complications was significantly higher in the V-CBA group (0.71%) versus the rhBMP-2 group (0.23%; P<0.0001), as was the incidence of pneumonia (1.21% versus 0.76%, respectively; P=0.0038). However, these differences were consistent with those for individual comorbidities in the V-CBA group at the initial procedure (Table 1), which could not be controlled in this analysis. The incidences of all other re‑admissions, including subsequent lumbar fusion procedures, deep vein thrombosis, hematoma, nervous system complications, pulmonary embolism, sepsis, surgical-site infection, and urinary tract infections were generally similar between the groups.
As with the cost analyses, the inclusion of multiple-level treatments could potentially skew the incidence of follow-up re-admissions between the groups. Therefore, a second ad hoc analysis was conducted on follow-up re-admissions among the single-level treatments only in an effort to standardize these comparisons. The incidence of cardiac complications remained significantly higher in the V-CBA group versus the rhBMP-2 group (0.44% vs 0.15%, respectively; P = 0.0125), which remained consistent with individual comorbidities in the V-CBA group for patients receiving single-level treatments only (Table 1). However, the incidence of subsequent lumbar fusion procedures was significantly lower among patients receiving V-CBA in this better-aligned comparison (3.66% versus 4.56% in the rhBMP-2 group;
Table 3. Incidence of Potentially Relevant 12-Month Follow-up Re-admissions
|
Full Cohort †
|
|
Single-level Only Cohort ‡
|
Re-admissions, n (%)[1]
|
Group
|
P-value
|
|
Group
|
P-value
|
V-CBA
(n = 6,588)
|
rhBMP-2
(n = 9,584)
|
|
V-CBA
(n = 5,683)
|
rhBMP-2
(n = 8,505)
|
Patients with all-cause 12-month follow-up re-admissions[2]
|
1482 (22.5)
|
2021 (21.08)
|
–
|
|
971 (17.1)
|
1198 (14.1)
|
–
|
Re-admitted patients with potentially-relevant procedures/diagnoses[3]
|
|
|
|
|
|
|
|
-Subsequent lumbar fusion procedures
|
623 (9.46)
|
831 (8.67)
|
0.0879
|
|
208 (3.66)
|
388 (4.56)
|
<0.0001*
|
-Cardiac complications
|
47 (0.71)
|
22 (0.23)
|
<0.0001^
|
|
25 (0.44)
|
13 (0.15)
|
0.0125^
|
-Deep vein thrombosis
|
6 (0.09)
|
3 (0.03)
|
0.1725
|
|
4 (0.07)
|
3 (0.04)
|
0.7073
|
-Hematoma
|
22 (0.33)
|
30 (0.31)
|
0.8878
|
|
13 (0.23)
|
20 (0.23)
|
0.5990
|
-Nervous system complications
|
17 (0.26)
|
14 (0.15)
|
0.1422
|
|
13 (0.23)
|
9 (0.11)
|
0.1990
|
-Pneumonia
|
80 (1.21)
|
73 (0.76)
|
0.0038^
|
|
50 (0.88)
|
46 (0.54)
|
0.1432
|
-Pulmonary embolism
|
28 (0.43)
|
37 (0.39)
|
0.706
|
|
19 (0.33)
|
22 (0.26)
|
0.8748
|
-Sepsis
|
2 (0.03)
|
5 (0.05)
|
0.7081
|
|
0 (0)
|
1 (0.01)
|
1.0000
|
-Surgical-site infection
|
15 (0.23)
|
20 (0.21)
|
0.8634
|
|
8 (0.14)
|
9 (0.11)
|
1.0000
|
-Urinary tract infections
|
144 (2.19)
|
171 (1.78)
|
0.0727
|
|
81 (1.42)
|
93 (1.09)
|
0.6341
|
† Planned analyses were conducted on the Full Cohort.
‡ Ad hoc analyses were conducted on the Single-level Only Cohort, which only included patients who received treatment at a single level of the spine.
* Statistically significant, Fisher’s exact test.
^ Statistically significant, Fisher’s exact test. Notably, differences observed in follow-up diagnoses between groups corresponded with significant comparisons in related initial Charlson comorbidities within each cohort (Table 1).
- All percentages were based on the total number of patients within each cohort who received V-CBA or rhBMP-2 during the initial procedure.
- Patients with more than one re-admission were counted only once. Did not include patients who may have received follow-up treatment outside of the Premier Healthcare System.
- Except subsequent lumbar fusion procedures, repeats of the same diagnosis were counted only once. Did not include patients who may have received follow-up treatment outside of the Premier Healthcare System.
P<0.0001). The incidences of all other readmissions, including deep vein thrombosis, hematoma, nervous system complications, pneumonia, pulmonary embolism, sepsis, surgical-site infection, and urinary tract infections were generally similar between the single-level treatment groups.