The primary objective of this study was to compare data from a large nationwide US healthcare system related to initial procedure and 12-month follow-up hospitalization charges and resource utilization for lumbar fusion surgeries using rhBMP-2 versus VCBA. The secondary objective was to assess the incidence of potentiallyrelevant readmissions during the follow-up period, including any subsequent lumbar fusion procedures. This was the first known study to compare these two grafts, and the use of a nationwide healthcare database enabled access to a large, geographically-diverse patient population through high-quality economic and clinical data that are more representative of real-world evidence than those from a single hospital or institution.
The present data showed that hospitalization charges were significantly lower when VCBA was used in US lumbar fusion surgeries versus rhBMP-2, with $51,130 less in adjusted mean initial procedure charges, and $22,091 less in adjusted mean followup hospitalization charges (Fig. 2). Although the use of rhBMP-2 is almost universally reported to increase hospitalization costs [6, 12, 13, 25–27], the question remains as to why such large disparities should exist, as they cannot be explained by direct product costs alone. A definitive answer to this question is beyond the scope of this study and its data; however, an exploration of potential causes is warranted, albeit speculative. Some factors, (eg, comorbidities, health insurance status, hospital region, and others), can be effectively eliminated because the statistical analyses used in this study adjusted for these confounding initial characteristics. As such, the disparity is likely explained by a cluster of smaller contributing factors, one of which is direct product cost. Other potential contributors include non-cost-effective use of rhBMP-2 by defaulting to largerthanneeded kits at procedure outset, and expense of adjunct products and procedures sometimes used with rhBMP-2, such as demineralized bone matrix or platelet-rich plasma (PRP). Unlike rhBMP2, which is provided as an osteoinductive growth factor along with a collagen sponge, VCBA is similar to autograft in that it is osteoconductive, osteoinductive, and osteogenic, making the use of adjuncts unnecessary. However, since adjunct usage was not consistently captured in the present dataset, it could not be specifically evaluated.
Additional costs could also be attributed to operating room time required for preparation of rhBMP-2 (≥ 15 minutes) versus VCBA (< 5 minutes), as well as that required for preparation of rhBMP-2 adjuncts (eg, spinning/prep of PRP). Supporting this possibility, a study by Hall and colleagues of multi-level instrumented posterolateral fusion (IPLF) surgeries using VCBA reported a mean operative time of 211.1 (± 87.3) minutes with an average of 4.1 levels treated . Yet, Glassman and colleagues reported a mean operative time of 248 (± 58.5) minutes with IPLF surgeries using rhBMP-2 (average 1.96 levels treated) and 270 (± 33.6) minutes in those using ICBG (average 1.98 levels treated) . As noted by Hall, the use of V-CBA thus corresponded with an average of 37- and 59-minute faster surgeries than with rhBMP-2 and ICBG, respectively , in spite of the more-than-double average number of levels treated. Such disparities in operative time could potentially contribute to exponential differences in cost beyond those associated with direct costs and may partially explain the present results.
Another closely-related potential contributor to the observed disparities in hospital charges may be procedure complexity, as surgeons may tend to default to rhBMP-2 in more complex cases. To this end, the present data could only differentiate between single- and multiple-level surgeries, and multiplelevel surgeries have substantially wider variation in costs, particularly when three or more levels of treatment are involved. Thus, it was hypothesized that such surgeries may have had undue influence on these data, in spite of the categories being treated as covariates in the main analysis. In an effort to isolate their potential influence, an ad hoc cost analysis was conducted as a reference comparison using only charge data from single-level fusion procedures, which involved 86.26% (n = 5,683) and 88.74% (n = 8,505) of V-CBA and rhBMP-2 patients, respectively (Fig. 3). In theory, single-level cases should be more standardized, yet even under these more-aligned conditions, the adjusted mean initial procedure hospitalization charges remained significantly lower in the V-CBA group, with $46,556 less charges than in the rhBMP-2 cases. These results suggest that procedure complexity, while still a likely contributor, does not contribute substantially to the cost disparity.
The difference in initial procedure charges may also be partially influenced by the statistically significant increase of 0.11 days in adjusted mean initial procedure LOS found in the rhBMP-2 group (Table 2). However, the potential influence of this factor on charges was not reflected in the cumulative follow-up LOS, for which a significant mean increase of 0.41 days was observed in the VCBA group, in spite of the $22,091 cost differential during this period. Notably, the unadjusted LOS range in the V-CBA group exhibited significantly wider variation (0–282 days) than in the rhBMP-2 group (0 − 92 days), which likely contributed to these results and may be related to the significantly higher initial CCI for this group. However, given such small disparities at both time points, it is difficult to attribute any further clinical or practical significance to these results.
Regarding 12-month follow-up re-admissions, it is important to consider that these data may underestimate their incidence, as our analysis was restricted to hospitalizations within the Premier Healthcare System. However, it is reasonable to expect that that the proportion of patients seeking treatment outside of the Premier Healthcare System was evenly distributed between the groups. It is also important to note that, unlike with the primary cost and LOS analyses, it was not possible to remove the influence of the confounding variables from these data due to their binary nature. Thus, their interpretation requires consideration of the confounding variables and, in particular, the individual Charlson comorbidities.
Accordingly, although the majority of potentially relevant 12-month re-admissions were similar between the groups, significantly higher rates of cardiac complications and pneumonia were observed in the V-CBA group versus the rhBMP-2 group (Table 3). However, these differences corresponded to the significantly higher prevalence of related pre-existing diagnoses in the V-CBA group (Table 1), including cerebrovascular disease, chronic obstructive pulmonary disorder, diabetes with chronic complications, myocardial infarction, and peripheral vascular disease. This trend remained in the ad hoc analysis of single-level treatment only, with only the cardiac complications remaining significant (Table 3). Therefore, the differences in 12month follow-up re-admissions between VCBA and rhBMP-2 are expected and align with corresponding differences in initial comorbidities.
The presence of malignancy and metastatic solid tumor in both groups during the initial procedure is worth noting, as these comorbidities are contraindicated with rhBMP-2 . VCBA can be used in patients with cancer, although it is not recommended when the patient is considered immunocompromised, such as may occur when actively receiving treatment (eg, chemotherapy or radiation). However, in the present data, it was not possible to determine if such treatments were received concomitantly. Further, a follow-up analysis revealed that the presence of these comorbidities did not appear to substantially alter rates of readmission for either of the V-CBA or rhBMP-2 groups, as only one such patient was re-admitted (from the rhBMP-2 group for urinary tract infection; data not shown).
There were no significant differences in rates of subsequent lumbar fusions procedures between the V-CBA and rhBMP-2 groups for the full cohort. However, these rates were significantly lower in the V-CBA group among patients receiving single-level treatments only (Table 3), in spite of the fact that the VCBA group had statistically higher rates of initial comorbidities with the potential to negatively impact clinical outcomes. The low rate of subsequent lumbar fusion with rhBMP-2 is a frequentlycited benefit over ICBG and a principal justification of its cost [11, 13, 27]. As such, the performance of VCBA in this study is notable, especially in light of the substantially lower average initial hospitalization charges observed for V-CBA patients, and in spite of the higher level of initial comorbidities in this group.
Large database studies have inherent limitations. For instance, the data from the PHD reflect the dollar amount that was billed for patient services, which may not reflect the final charges to the patient or third-party claims paid to the hospital or provider. Those final charges would only be available to the hospitals and are beyond the scope of this study, but may provide additional insight into the costs associated with a given treatment. Further, although this study provides access to high-quality economic and clinical data, some potentially-relevant patient and procedure details were unavailable, such as extended medical histories, other diagnostic details, surgical approaches used, surgeon seniority/specialty, or fusion outcomes. This granularity may have helped differentiate patient characteristics or other factors that could have an impact on clinical outcomes or help explain disparities in cost. As well, some patients may have received follow up treatment outside of the Premier Healthcare System, and therefore their outcomes and readmissions data would have been unavailable. Additionally, the grafting material used during the initial procedure was collected by the PHD as a subjective text string and, in some cases, the data entered was not sufficient to definitively determine the material used. Thus, some patients with data relevant to V-CBA or rhBMP-2 in this study may have been inadvertently excluded. Finally, the present data represented economic and clinical information from US hospitals only, and thus did not permit characterization for other regions.