Cost-Effectiveness of ABM/P-15 Versus Allograft in Degenerative Spondylolisthesis Surgery

Abstract

Study Design.

Randomized controlled trial.

Objective.

The aim of this study was to investigate whether ABM/P-15 was cost-effective compared with allograft as a bone graft extender for uninstrumented posterolateral fusion for degenerative spondylolisthesis with spinal stenosis in elderly patients.

Summary of Background Data.

In an increasingly elderly population with higher expectations of good health and quality of life, the need for durable surgery with minor risks of implant-related reoperations is growing. Specifically for lumbar fusion surgery, the need for a reliable bone graft material with acceptable fusion rates and low graft-related morbidity and risk of reoperation is important.

Methods.

This cost-effectiveness analysis was based on a single-center, blinded, randomized controlled trial, where patients with symptomatic degenerative spondylolisthesis were randomly assigned 1:1 to either ABM/P-15 or Allograft as bone graft material in uninstrumented posterolateral fusion. Quality-adjusted life years (QALY) were obtained from EQ-5D-3L. Use of health services was obtained from patient charts, costed and accumulated up to 10 years after index surgery.

Results.

The study included 101 patients with no inter-group differences in preoperative characteristics. On the basis of a bootstrapped analysis, the estimated the mean QALY gain for the ABM/P-15 group was 0.42 points (95% CI [−0.17; 1.08], P=0.185) greater compared with the Allograft group. Compared with the Allograft group, patients in the ABM/P-15 group had 20% less costs due to a significantly lower reoperation rate (18% vs. 43%, P=0.024), fewer visits to the outpatient clinic, magnetic resonance images, and fewer days of hospitalization.

Conclusions.

The choice of bone graft material significantly affected cost-effectiveness of posterolateral lumbar fusion in elderly patients with degenerative spondylolisthesis at 10-year follow-up. ABM/P-15 showed dominance over Allograft with improved outcomes, lower health care costs, and lower reoperation rate.

For patients experiencing persistent symptoms from degenerative spondylolisthesis (DS), surgical intervention—typically decompression and fusion—may be recommended. The standard approach involves screw fixation, with or without interbody cages. However, performing fusion surgery in elderly patients presents challenges due to poor bone quality and an increased risk of complications.¹ These concerns have led Scandinavian spine surgeons to advocate for non-instrumented spinal fusion in patients over 65 years old.

In an elderly population with increasing expectations for good health and quality of life even into old age, the need for durable surgery with a low risk of implant-related reoperations is growing. Specifically, in lumbar fusion surgery there is a need for a reliable bone graft material with acceptable fusion rates and minimal or no graft-related morbidity or risk of reoperation.^2,3 A wide variety of approved bone graft alternatives are currently available for clinical use, one of which is an anorganic bovine-derived hydroxyapatite matrix with a synthetic 15 amino acid residue (ABM/P-15, peptide-enhanced bone graft). Earlier studies have shown superior or comparable fusion outcomes compared with autograft or allograft,^4–8 but information on long-term cost-effectiveness is lacking.

The aim of this study was to investigate whether the synthetic allograft ABM/P-15 is cost-effective over a 10-year observation period compared with allograft as a bone graft extender for uninstrumented posterolateral fusion in elderly patients with degenerative spondylolisthesis with spinal stenosis.

MATERIALS AND METHODS

Study Design

This cost-effectiveness analysis was based on data from a double-blind randomized controlled trial comparing quality-adjusted life year (QALY) outcomes and fusion rates in patients who underwent decompression and uninstrumented fusion procedures at one to two levels for lumbar degenerative spondylolisthesis (DS).

From 2012 to 2013, patients aged 60 and older who were referred to the Spine Centre at Middelfart Hospital with symptomatic degenerative spondylolisthesis were screened for inclusion. Inclusion criteria were one-level to two-level DS defined as a slip of at least 3 mm on standing x-rays, irrespective of instability on flexion-extension x-rays, and a Konno’s⁹ symptom severity score of 7. Patients with previous spine surgery, concurrent malignant disease, fracture or infection of the spine, dementia, or inability to read and write Danish were excluded. The Regional Spine Centre of Southern Denmark requires a period of 12 weeks of unsuccessful conservative treatment before referral.

The study was approved by the local Regional Committee on Health Research Ethics for Southern Denmark (S-20160107) and was registered at ClinicalTrials.gov (NCT04166981) before inclusion of patients.

Randomization

Patients were randomized 1:1 in blocks of 8 to either ABM/P-15 or Allograft bone. Sealed envelopes containing the allocation were opened in the operating theater after decompression and decortication of the transverse processes had been performed. Patients and investigators were blinded to the allocation of bone graft allocation until publication of two-year data. Both the Statistician and Health Economist were blinded to the allocation of patients at the 10-year follow-up.

Sample Size Rationale

Sample size was determined based on the two-year follow-up, with an effect size of 12 points on the Oswestry Disability Index (ODI) as the primary outcome measure. With a significance level of 0.05 and a power of 0.80, it was estimated that 46 patients would be required in each group. Accounting for possible dropout within the first two years, at least 50 patients were required in each groups.

Interventions

In both groups, patients underwent midline-sparing bilateral partial hemilaminectomy at the affected level(s). After decompression, the posterolateral gutters were prepared bilaterally by decorticating the lateral facets and the transverse process of the two adjacent vertebrae. In the ABM/P-15 group local autograft was mixed with 5ccs of ABM/P-15 per level of fusion as per instruction by the manufacturer. In the Allograft group, local autograft was mixed with 30grams of allograft per fusion level, obtained from fresh frozen femoral heads, the amount of allograft bone per fusion level was based on previous studies.^10,11 The mixed graft material was divided evenly between levels and gutters.

Postoperatively, patients were asked to wear a soft brace and were instructed by a physiotherapist to avoid lifting more than 2 kg, and avoid maximal flexion, extension and rotation for the first three months. All patients underwent surgery at a single institution by a team of nine fellowship-trained spine surgeons with at least five years of practice. Decisions to reoperate in the study period were guided by MRI findings, clinical examinations, and ultimately with shared decision-making between the patient and surgeon.

Data Collection

Effectiveness

The measure of effectiveness was cumulative 10-year quality-adjusted life years (QALY) gained. The Danish version of the EQ-5D-3L was used to obtain patient-reported outcomes preoperatively and at one-year, two-year, five-year, and ten-year follow-up. The EQ-5D-3L reports current health status in three levels of five dimensions and can be converted to an index ranging from 0 to 1, where 1 denotes perfect health, 0 denoted death, and negative values for states worse than dead. QALYs were estimated as the time-weighted EQ-5D index scores from baseline to 10-year follow-up. For patients who died during follow-up period, the latest reported health state was assumed until time of death and thereafter assigned a value of zero.

Resource Use and Costs

A micro-costing analysis of health care utilization from a societal perspective was performed for the 10-period. Where possible, the bottom-up analysis included patient-related cost drivers such as surgery time, consumables, and subsequent use of health care resources, including consultations with surgeons, readmissions, and reoperations. As most patients had retired at the time of inclusion, productivity loss due to absence from work was not considered. A detailed explanation of the construction of cost variables is available in the supplementary materials, Supplemental Digital Content 1, http://links.lww.com/BRS/D12.

Data on all cost drivers were obtained individually for each patient from time of inclusion until death or end of the 10-year study period. Data on hospital length of stay, time in operating theater, and the number of outpatient visits with surgeons, anesthetists, physiotherapists, and nurses, as well as telephone consultations with outpatient nurses were obtained from electronic patient records.

Data on number of lumbar x-rays, CT-scans, and MRI scans performed during the study period were obtained from the regional image registry.

The Finance Department at Lillebaelt Hospital was consulted to determine the unit cost of health care resources to value resources in a transparent and consistent manner. Hospital admission-related costs were based on a mixture of bottom-up and top-down calculations, including assumptions regarding time spent by nurses, doctors, and physiotherapists during these activities. All costs included salaries and department overheads.

Total health care costs were accumulated for the 10-year follow-up as the sum of each cost driver multiplied by its corresponding unit cost. Ten-year costs were estimated as net present values at 2023 price levels in Danish Kronor (DKK) and converted to Euro (€) using the exchange rate 1€=7.45 DKK.

Statistical Analysis

Baseline characteristics were compared between groups using unpaired t test for continuous data and χ² test for categorical data. Data are presented with frequencies, means, 95% CIs and p-values of differences. QALY gains for patients with missing data were imputed after adjustment for baseline difference and death. Missing data points were assumed missing at random. Resource use and cost data are reported as means and 95% CIs.

The mean incremental cost-effectiveness ratio (ICER) was estimated using seeming unrelated regression with 10-year QALY gains and 10-year accumulated costs as dependent variables and treatment group as the independent variable. The estimated parameters were interpreted as the mean incremental difference in QALYs and accumulated costs. To assess statistical uncertainty, these regressions were repeated using 1000 bootstrap replications. Statistical variation was illustrated graphically in a scatter plot.

RESULTS

A total of 101 patients were included in the randomized trial: 51 were allocated to the ABM/P-15 group and 50 to the Allograft group. All patients received the allocated treatment. Study follow-up is presented in (Fig. 1). The mean age at inclusion was 70.5 years and 76% were women. No statistically significant differences were identified between the groups at baseline (Table 1).

Figure 1.

Consort chart of patient flow and data availability.

TABLE 1.

Preoperative Patient Demographics

	ABM/P-15 (N=50)	Allograft (N=51)	P
Age, mean (95% CI)	71.0 (69.4; 72.8)	70.1 (68.1; 72.0)	0.455
Female, n (%)	36 (72)	41 (80)	0.322
BMI, kg/m2, mean (95% CI)	27.4 (26.3; 28.6)	26.4 (25.4; 27.5)	0.193
Diabetes mellitus, n (%)	7 (14)	6 (12)	0.737
Hypertension, n (%)	31 (62)	23 (45)	0.089
MMSE test, mean (95% CI)	28.6 (28.2; 29.0)	29.2 (28.9; 29.5)	0.020
Walking distance, meters, mean (95% CI)	127 (68.0; 187.3)	120 (71; 170)	0.854
Duration of leg pain, n (%)			0.681
<3 mo	2 (4)	2 (4)
3–12 mo	16 (32)	22 (43)
>12–24 mo	15 (30)	14 (27)
>24 mo	17 (34)	13 (26)
Levels decompressed, mean (95% CI)	1.5 (1.3; 1.6)	1.4 (1.3; 1.5)	0.559
Levels fused, mean (95% CI)	1.3 (1.2; 1.4)	1.2 (1.1; 1.3)	0.219

^* χ² test, MMSE screening test for dementia.

EQ-5D data were collected at all follow-up times points up to 10 years or until death. Data were available for 94% of patients at the two-year follow-up, at 87% at the five-year follow-up, and 74% at the 10-year follow-up. Both groups improved significantly from baseline to the 10-year follow-up (Table 2).

TABLE 2.

Mean scors and between group differences in EQ-5D values from baseline to 10-year follow-up

	ABM/P-15	Allograft	ΔMean	P
EQ-5D (95% CI)
Preoperative, (n=50; 51)	0.55 (0.49; 0.61)	0.54 (0.48; 0.60)	0.009 (−0.07; 0.09)	0.825
1-year (n=50; 48)	0.80 (0.76; 0.85)	0.81 (0.77; 0.86)	−0.009 (−0.08; 0.06)	0.773
2-year (n=48; 47)	0.83 (0.78; 0.88)	0.80 (0.75; 0.86)	0.029 (−0.04; 0.10)	0.425
5-year (n=45; 43)	0.82 (0.75; 0.88)	0.77 (0.71; 0.83)	0.046 (−0.04; 0.13)	0.298
10-year (n=38; 37)	0.74 (0;63; 0.84)	0.72 (0.63; 0.82)	0.010 (−0.13; 0.15)	0.890

Missing EQ-5D data were imputed, and patients who died during follow-up contributed QALY gain from inclusion until the time of death. On the basis of bootstrapped analysis, the ABM/P-15 group demonstrated a greater mean QALY gain of 0.42 points (95% CI [-0.17; 1.08], P=0.185) compared with the allograft group. Although this difference was not statistically significant, it suggests a moderate QALY gain in favor of the ABM/P-15 group.

Accumulated 10-year resource use and related costs are shown in Table 3. Variations in accumulated costs indicate that the ABM/P-15 group consistently used fewer health care resources. During the 10-year study period, 46% of patients in the ABM/P-15 group underwent MRI scanning compared with 60% in the allograft group (P=0.194). Significantly fewer reoperations were performed in the ABM/P-15 group compared with the allograft group (9 [18%] vs. 22[43%], P=0.024).

TABLE 3.

Ten-Year Accumulated Consumption of Health Care Resources and Costs

	ABM/P-15		Allograft
	Consumption	Cost (€)	Consumption	Cost (€)	Δ Cost (€)	P
Surgery-related costs
OR time	135.2 (55.4)	1133.3 (464.1)	163.7 a (72.4)	1372.2 (606.8)	−239.0	0.059
Theater time	210.6 (77.3)	1765.4 (648.3)	241.7 (103.9)	2026.0 (870.8)	−260.6	0.146
Bone graft	1.1 (0.04)	885.9 (224.1)	1.16 (0.06)	854.1 (342.2)	31.8	0.592
Implants	0.1 (0.30)	236.8 (717.9)	0.16 (0.46)	371.4 (1097.6)	−134.6	0.468
OR base cost of startup	1.18 (0.39)	1030.0 (338.8)	1.43 (0.67)	1249.4 (586.7)	−219.4	0.024
Inpatient care
Days admitted to hospital	5.46 (2.75)	3757.7 (1892.0)	6.93 (5.49)	4772.1 (3778.7)	−1014.4	0.152
Outpatient care post-surgery
Telephone consults	0.71 (1.38)	19.1 (37.0)	0.79 (1.34)	21.1 (35.7)	−2.0	0.806
Physiotherapy consults	0.2 (0.53)	34.4 (91.3)	0.33 (0.68)	55.9 (116.9)	−21.6	0.375
Surgical consults	0.86 (1.72)	206.5 (413.8)	1.26 (1.66)	302.6 (400.7)	−96.1	0.303
Anesthetic consults	0.18 (0.39)	43.7 (93.5)	0.43 (6.67)	103.9 (161.7)	−60.6	0.024
Preoperative admission interview	0.11 (0.32)	24.7 (69.8)	0.25 (0.58)	55.35 (125.8)	−30.6	0.202
Radiology
MRI-scan	0.89 (1.21)	275.7 (375.7)	1.33 (1.38)	412.6 (428.1)	−136.9	0.142
CT-scan	0.2 (0.53)	49.3 (130.9)	0.51 (2.07)	126.2 (511.1)	−76.9	0.390
Lumbar x-ray	0.63 (0.81)	42.6 (54.7)	1.28 (1.61)	86.7 (109.0)	−44.1	0.033

Mean (SD).

The cost of the individual health-related expenses are further explained in the supplementary table, Supplemental Digital Content 1, http://links.lww.com/BRS/D12.

In the ABM/P-15 group the most common reoperation was adjacent level decompression (n=5), followed by index level refusion (n=2), hematoma evacuation (n=1), and facet joint ablation (n=1). In the allograft group, the most common reoperations were adjacent level decompression (n=12), followed by index level refusion (n=7) and hematoma evacuation (n=3). Time from initial surgery to reoperation is shown in Figure 2.

Figure 2.

Kaplan-Meier plot of time to reoperations between the ABM/P-15 group and allograft group.

On the basis of the difference in health care consumption and reoperations, the difference in accumulated 10-year costs was estimated at €−2.913 (95% CI [−5.135; −969] P<0.001), indicting lower mean cost in the ABM/P-15 group.

At 10-year follow-up, ABM/P-15 demonstrated dominance over allograft with improved QALY gains and cost savings. Figure 3 illustrates the statistical uncertainty in the cost-effectiveness analysis using a scatter plot based on 1000 bootstrapped replications.

Figure 3.

Illustrates incremental cost-effectiveness ratio (ICER) after bootstrapping with 1000 replications.

DISCUSSION

This cost-effectiveness analysis of bone graft extenders for fusion in degenerative spondylolisthesis demonstrates that ABM/P-15 is economically dominant over allograft, with improved QALY gains and lower overall health care cost. Dominance implies that ABM/P-15 is cost-effective regardless of willingness-to-pay threshold.

The observed cost savings were driven primarily by reduced reoperation rates and lower perioperative resource use in the ABM/P-15 group. Although the acquisition cost of ABM/P-15 may be higher than that of allograft, the initial expense was offset by downstream savings related to hospital length of stay, postoperative complications, and revision surgery. These findings highlight the importance of adopting a comprehensive time horizon that captures not both index procedure costs and subsequent health care utilization.

From a methodological perspective, we refrained from reporting the ICER, as dominance renders ICER estimates potentially misleading. In accordance with the CHEERS II statement,¹² we presented joint incremental costs and QALY gain. In the cost-effectiveness plane, the majority of bootstrapped replications were located in the southeast quadrant (less costly, more effective). Positive net monetary benefit was observed for all positive threshold values.

Earlier studies have investigated the cost-effectiveness of ABM/P-15 versus local autologous bone in cervical discectomy and fusion surgery. Thaci et al. ¹³ constructed a Markov model and found that ABM/P-15 dominated local autologous bone graft at 90 days postoperatively. Although initial surgical costs were higher, cost savings increased through two-year follow-up. In our study, initial surgical costs were similar between groups, and cost savings were primarily driven by lower health care utilization and fewer reoperations.

Clinically, our findings align with previous evidence suggesting that ABM/P-15 facilitates reliable fusion rates and functional recovery comparable to or superior to allograft.^5–8,14 Improved fusion outcomes likely translate into fewer costly reinterventions, reinforcing the economic findings.

Previous studies of spinal fusion have shown that cost-effectiveness depends on fusion durability and subsequent reoperation rates.¹⁵ Five-year reoperation rates after surgery for degenerative spondylolisthesis have been reported at 10% to 23% for instrumented fusion, and somewhat higher for decompression alone.^16,17 These rates are comparable to our five-year reoperation rates, although considerably more reoperations were performed after five-year follow-up in our study.

Although fusion rates were higher in the ABM/P-15 group, as previously reported by Jacobsen and colleagues, we observed more reoperations in the allograft group during the five-year to ten-year follow-up. This was unexpected, as improved fusion rates might theoretically increase adjacent-segment degeneration.

This study has several limitations. The cost analysis was primarily based on bottom-up estimates; however, certain assumptions were required, particularly regarding hospital stay and outpatient visits. These assumptions introduce a risk of overestimation or underestimation of true costs. Nevertheless, all available data from the local Finance Department were incorporated to maximize accuracy. In addition, the original trial was powered to detect differences in the Oswestry Disability Index, whereas the present analysis focuses on EQ-5D as the principal outcome.

The strengths of this study include the randomized design with blinding of both the primary investigator and the statistician, which reduces the risk of bias. Long-term follow-up was acceptable, with good compliance over 10 years and standardized outcome and cost measures available for both groups. Finally, the extended 10-year horizon provides valuable insight into the treatment durability long-term economic impact.

It should be noted that the study was conducted within a publicly funded health care system. Differences in cost structures and clinical practice patterns may limit generalizability to other health care settings.

CONCLUSIONS

The choice of bone graft material significantly influenced the cost-effectiveness of uninstrumented posterolateral lumbar fusion in elderly patients with degenerative spondylolisthesis at 10-year follow-up. ABM/P-15 demonstrated economic dominance over allograft, with improved long-term outcomes, lower health care utilization, and fewer reoperations.

Key Points

• This is a 10-year cost-effectiveness study on patients with degenerative spondylolisthesis enrolled in a randomized controlled trial with decompression and fusion over one to two levels and randomized 1:1 to either ABM/P-15 or Allograft.

• 101 patients were enrolled, mean age was 70.5 years at inclusion, 76% were women. Seventy-four percent had available EQ-5D data until time of death or 10-year follow-up.

• We found significantly fewer reoperations in the ABM/P-15 group compared with the Allograft group (18% vs. 43%, P=0.024), and a net QALY gain estimated at 0.42 points in the ABM/P-15 group.

• ABM/P-15 showed dominance over Allograft with improved 10-year outcomes and lower costs, due to an overall lower health care utilization.

Supplementary Material

brs-51-677-s001.docx ^{(22KB, docx)}