Budget impact analysis of demineralized bone matrix in combination with autograft in lumbar spinal fusion procedures for the treatment of lumbar degenerative disc disease in Spain

Abstract

Objective: To estimate the budget impact (BI) of introducing local autograft (LA) combined with demineralized bone matrix (LA + DBM) in lumbar spinal fusion (LSF) procedures to treat lumbar degenerative disc disease (LDDD) in Spain.

Methods: A decision tree model was developed to evaluate the 4-year BI associated with introducing LA + DBM putty to replace currently available grafting methods, including iliac crest bone graft (ICBG), LA alone, and LA combined with beta-tricalcium phosphate (LA + ceramics), with 30%, 40%, and 30% market shares, respectively. The analysis was conducted for a hypothetical cohort of 100 patients with LDDD receiving LSF, assuming LA + DBM would replace 100% of the standard of care mix. The fusion rates extracted from the literature were validated by an expert panel. Costs (€2017) were obtained from different Spanish sources. Budget impact and incremental cost per successful fusion were calculated from the perspective of the Spanish National Health System (NHS).

Results: Over 4 years, replacing currently available options with LA + DBM for 100 patients resulted in an additional cost of €12,330 (€123/patient), and an additional 14 successful fusions, implying a cost of €881 per additional successful fusion. When costs of productivity loss were included, the introduction of LA + DBM resulted in cost savings of €70,294 (€703/patient).

Limitations: The lack of high-quality, homogeneous, head-to-head research studying the efficacy of grafting procedures available to patients undergoing LSF, in addition to a lack of long-term follow-up in existing studies. Therefore, the number of fusions occurring within the model’s time horizon may be underestimated.

Conclusions: Acquisition costs of DBM were partially offset by costs of failed fusions, adverse events and reoperation when switching 100 hypothetical LDDD patients undergoing LSF procedures from standard of care grafting methods to LA + DBM from the perspective of the Spanish NHS. DBM cost was entirely offset when costs of lost productivity were considered.

Keywords:

• Budget impact
• health economics
• cost
• demineralized bone matrix
• lumbar degenerative disc disease
• lumbar spinal fusion
• Spain

JEL CLASSIFICATION CODES:

• D61
• I11
• H72

Introduction

Low back pain (LBP) is the most common cause for disability in individuals aged 45 years or younger, resulting in discomfort and socioeconomic loss¹. In Spain, the prevalence of LBP has been estimated to be 14.8% in adults aged 20 years and older (17.8% in women and 11.3% in men)².

The etiology of 5–15% of LBP can be attributed to causes such as osteoporotic fracture, neoplasm, or infection, while the remaining percentage is non-specific^3–6. Disc degeneration, similar to that involved in lumbar degenerative disc disease (LDDD), “involves structural disruption and cell mediated changes” in the disc’s composition⁷. The prevalence of chronic lumbar pain in adults in Spain has been estimated to be 14.1%⁸; in 37.9%⁹ of the cases this pain is caused by degenerative disc disease, leading to a 5.3% LDDD prevalence among adults in Spain. Approximately 21.4%⁹ of these patients do not experience any clinically relevant improvement after conventional medical treatment. Based on the estimations of the Spanish adult population (38,448,240 adults)¹⁰, 439,692 patients with LDDD do not experience improvement with conventional medical treatment.

The goals of treating LDDD are to eliminate pain, correct height loss, and maintain or restore stability and mobility. Patients may be treated non-invasively^11,12, but, when spinal fusion surgery is required, the goal is to prevent motion at the painful vertebra(e) segment in patients with spine conditions¹³. This helps to prevent the damaged vertebrae from irritating or compressing nerves, muscles, and ligaments, thereby reducing the symptoms of pain. Various procedures exist to achieve lumbar spinal fusion (LSF)¹⁴, also known as arthrodesis, where an iliac crest bone graft (ICBG) may be used as a graft material. The iliac crest bone graft is often considered the gold standard grafting material for spinal fusion procedures, partially due to the osteoconductive bone available at the iliac crest, in combination with favorable fusion rates^15–17. Despite its benefits, the iliac crest operative site has been associated with donor-site morbidity¹⁸, increased medical resource use relative to other procedures¹⁹, and is limited in terms of the amount of available graft. Local autograft (LA) alone, from the primary surgery site, is limited to an even larger extent, in terms of the amount of bone that can be harvested relative to ICBG.

Due to the shortcomings associated with local and iliac crest autograft, innovative graft substitutes and extenders have been developed and adopted by practitioners. Ceramic-based grafts such as beta tri-calcium phosphate (beta-TCP) provide a synthetic osteoconductive alternative to bone graft. A second type of graft extender is demineralized bone matrix (DBM), a demineralized allograft which exposes concentrated organic bone morphogenetic proteins, resulting in a collagen bone matrix with osteoconductive and osteoinductive properties²⁰. Due to the lack of osteogenic properties, DBM is typically used as a bone graft extender together with LA, instead of as a replacement. Studies have shown that this approach has similar arthrodesis rates compared to supplementation with ICBG^21–23.

In Spain, clinicians regularly use LA, ICBG, DBM, and beta-TCP as graft or graft extension in the treatment of LDDD. While the efficacy of these bone grafts has been studied, it is currently unclear how they compare in terms of costs in Spain. In addition, in a structured literature search of economic evaluations conducted (see Supplementary material) only four economic evaluations were identified between the years 2012 and 2016^24–27. None of them were conducted from the Spanish perspective, which indicates the potential need for generating more evidence to ensure efficient budget planning at hospital and government level. The objective of this study is to evaluate the budget impact of replacing currently available standard of care procedures with LA + DBM from the perspective of the Spanish National Health Service (NHS) over a 4-year budget horizon.

Materials and methods

Patient population

A hypothetical cohort of 100 Spanish patients with LDDD undergoing single-level or multi-level LSF, who were eligible for treatment with LA + DBM, was included in the study (see Table 1).

Table 1. Summary of model inputs.

Epidemiology	Value	Note
Population size	100	Hypothetical cohort used in previous research^24
Efficacy	Fusion rate
LA + DBM	78.95%^17^,^22^,^30	Assumed to be equal to ICBG based on a lack of statistical significance between ICBG and LA + DBM found by Sassard et al.^22
LA alone	60.26%^17
LA + ceramics	57.10%^31
ICBG	78.95%^17^,^30
Procedure costs	Cost (€2017)
Lumbar spinal fusion base cost using LA	12,515^37	Used as the cost of LA only procedure
Additional cost of DBM	1,500	5cc of Grafton putty. Total cost €14,015
Additional cost of ceramics	550	10cc of beta-TCP. Total cost of €13,065
Additional cost of ICBG	1,854^38	Requires secondary surgery site and graft harvesting. Total cost €14,370
Adverse events^a	Rate; cost (€2017)
Severe pain	7.75%^18; 1,872^37
Iliac crest fracture	0.20%^18; 0	For the relevant proportion of patients, the cost of iliac crest fracture was assumed to be included through the treatment of severe pain
Vascular injury	0.06%^18; 4,984^39
Infection	1.41%^18; 4,846^37
Large hematomas	1.49%^18; 4,648^39
Prolonged wound injury	6.83%^18; 3,472^39
Nerve injury	0.99%^18; 4,380^39
Failed fusion and reoperation^b	Input value
Follow-up care	2,063^19 (€2017)	Difference between costs incurred “after successful index surgery” from the costs incurred “after unsuccessful index surgery but before pseudarthrosis repair”
Reoperation rate 1 year after index procedure	4.6%^40
Reoperation rate 2 years after index procedure	4.6%^40
Reoperation rate 3 years after index procedure	3.4%^40
Reoperation rate 4 year after index procedure	2.2%^40
Work loss^c	Input value
% patients of working age	50%	Assumption based on clinical expert opinion. Work loss costs are only applied to patients who are of working age
Cost of 1 day lost productivity	86.8^41 (€2017)
Work loss for patients with successful fusions^d	105 days	Assumption based on clinical expert opinions
Work loss for patients with unsuccessful fusions^d	228 days	Assumption based on clinical expert opinions

^aOnly applicable for ICBG procedures at the iliac crest surgery site.

^bReoperation costs are assumed to be the same as the index procedure.

^cOnly included in scenario analysis.

^dThe work loss reflects productivity loss per surgery and it is applied both at the initial surgery and at the reoperation due to failure to first surgery. The number of days for successful treatments is applied for reoperations.

Abbreviations. DBM, Demineralized bone matrix; ICBG, Iliac crest bone graft; LA, Local autograft; LSF, Lumbar spinal fusion; TCP, tri-calcium phosphate.

Interventions

As the purpose of the analysis is to estimate the economic impact of introducing DBM (specifically Grafton DBM putty) to the Spanish NHS budget for the population noted above, all patients included in the model must be eligible for treatment with DBM. Therefore, the model includes grafting with LA alone, ICBG, LA + ceramics, and LA + DBM, as these are the most used in Spain.

Alternatives such as human bone morphogenic protein-2 are also available but do not currently comprise a meaningful market share for the patients eligible in this study. In the present study, it was assumed that beta-TCP is representative of ceramic graft substitutes in general.

Modeling method

A decision tree model was designed to estimate clinical pathways experienced by patients treated with LA alone, LA + ceramics, ICBG, and LA + DBM. The decision tree structure was based on a review of previously published budget impact assessments in LSF^24,28. Two scenarios were estimated, one where LA + DBM is available for LSF procedures and one where it is not (standard of care scenario). The distribution of grafting methods in the standard of care scenario was estimated to be 40%, 30%, and 30% for LA alone, LA + ceramic, and ICBG, respectively, based on Spanish clinical expert input (see Supplementary material for additional information). In the LA + DBM scenario, it was assumed that each of the standard of care treatments were replaced by LA + DBM so that 100% of patients were treated with LA + DBM.

According to the treatment distributions above, patients were allocated to the respective treatment arm, where costs for the base LSF procedure as well as graft extender (LA + ceramics and LA + DBM) or harvesting (ICBG) were applied. All interventions took place during the first year, at which time fusion success rates were applied. Those with unsuccessful fusions were assigned a cost of follow-up, and some of those would also go on to receive a reoperation. Although all patients were at risk of adverse events during operation, only adverse events at the iliac crest surgery site for the ICBG procedure were explicitly modeled, since all model arms have the same primary surgery site at the lumbar spine. It was assumed there was no difference in adverse events at the primary lumbar spine surgical site between treatments.

The budget impact model took the perspective of the Spanish NHS over a time horizon of 4 years. This time horizon was chosen on the criteria that it should be long enough to include the most important differences in costs due to failed fusions, but also short enough to be relevant to the Spanish NHS budget horizon. The budget impact of switching from standard of care procedures (scenario where LA + DBM is not available) to LA + DBM was calculated for 100 hypothetical eligible patients in Spain. A diagram of the decision tree model is presented in Figure 1, where the black square is a decision node, green circles are probability nodes, and blue triangles are outcomes.

Figure 1. Economic model diagram. Abbreviations. DBM, Demineralized bone matrix; ICBG, Iliac crest bone graft; LA, Local autograft; LDDD, Lumbar degenerative disc disease; TCP, tri-calcium phosphate.

Model input parameters and data sources

Inputs in the analysis were categorized as population size, efficacy parameters, and costs. Table 1 summarizes each input parameter alongside the data source. Costs were expressed in €2017 and inflated as necessary using the Spanish consumer price index²⁹.

Fusion rates were defined as the proportion of patients achieving fusion after the LSF procedure, calculated as the number of successful fusions divided by the total number of fusions. For LA, LA + DBM, and ICBG, the criteria for successful fusion were based on the evaluation of radiographs from three studies comparing LA with or without a DBM to ICBG^17,22,30. Calculation details can be found in the Supplementary material. Published material adequately reporting a LA + ceramics fusion rate was sparse, but Kong et al.’s³¹ findings were used instead of alternative sources^32–34, as they had the largest sample size, analysis of statistical significance, and a control arm. The fusion rates used for the current analysis are summarized in Table 1.

Structured interviews with Spanish clinical experts were used for estimations of data not available in the literature, as well as for validation of data available in the literature (see Supplementary material for additional information). Specifically, fusion rates of the different grafting methods were validated by two physicians independently; hence, the fusion rates used in this model are considered to represent the reality of the clinical practice in Spain.

Sensitivity analyses

Economic modeling unavoidably includes uncertainty in the model structure and inputs. To quantify the impact of parameter uncertainty on the results, scenario analyses and probabilistic sensitivity analyses (PSA) were conducted.

A deterministic analysis was conducted by exploring various scenarios where structural parameters or combinations of input parameters were changed to reflect clinically or economically interesting scenarios (see Supplementary material). Scenarios of particular interest were the addition of indirect costs of lost productivity and alternative time horizons.

The PSA propagates sampling uncertainty through the model for all inputs simultaneously by drawing a random value from each parameter’s theoretical distribution, and re-calculates the model results. This procedure was iterated 10,000 times and summarized in a comparative cost plot. Fusion rates were modeled with beta distribution, costs with a gamma distribution, adverse event proportions with a beta distribution, and productivity loss with a normal distribution.

Results

In the base-case analysis, the LA + DBM scenario resulted in an additional cost of €12,330 for 100 patients over 4 years (€123 per patient). In total, there were 79 successful fusions in the LA + DBM arm, compared to 65 successful fusions in the standard of care scenario (difference of 14), implying an incremental cost of €881 per successful fusion. Annualized disaggregated costs are presented in Table 2.

Table 2. Budget impact, aggregate (per patient), €2017.

	2017	2018	2019	2020	Cumulative 2017–2020
Cost of surgical procedure
Standard of care scenario	1,323,652 (13,237)	0 (0)	0 (0)	0 (0)	1,323,652 (13,237)
LA + DBM scenario	1,401,520 (14,015)	0 (0)	0 (0)	0 (0)	1,401,520 (14,015)
Incremental	77,868 (779)	0 (0)	0 (0)	0 (0)	77,868 (779)
Cost of failed fusions
Standard of care scenario	72,357 (724)	0 (0)	0 (0)	0 (0)	72,357 (724)
LA + DBM scenario	43,417 (434)	0 (0)	0 (0)	0 (0)	43,417 (434)
Incremental	−28,940 (−289)	0 (0)	0 (0)	0 (0)	−28,940 (−289)
Adverse event cost
Standard of care scenario	16,985 (170)	0 (0)	0 (0)	0 (0)	16,985 (170)
LA + DBM scenario	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Incremental	−16,985 (−170)	0 (0)	0 (0)	0 (0)	−16,985 (−170)
Reoperation cost
Standard of care scenario	0 (0)	20,969 (210)	20,008 (200)	14,173 (142)	55,150 (552)
LA + DBM scenario	0 (0)	13,512 (135)	12,893 (129)	9,133 (91)	35,538 (355)
Incremental	0 (0)	−7,457 (−75)	−7,115 (−71)	−5,040 (−50)	−19,613 (−196)
Total
Standard of care scenario	1,412,995 (14,130)	20,969 (210)	20,008 (200)	14,173 (142)	1,468,145 (14,681)
LA + DBM scenario	1,444,937 (14,449)	13,512 (135)	12,893 (129)	9,133 (91)	1,480,475 (14,805)
Incremental	31,943 (319)	−7,457 (−75)	−7,115 (−71)	−5,040 (−50)	12,330* (123)

*Note: Numbers are subject to rounding error.

Abbreviations. DBM, Demineralized bone matrix; LA, Local autograft.

In the scenario analysis including costs of productivity loss calculated by the human capital method³⁵, the LA + DBM scenario resulted in cost savings of €70,294. With an increasing time horizon, the budget impact decreases: a 3-year horizon results in a budget impact of €17,370, while a 5-year horizon results in a budget impact of €9,180.

In the comparative cost plot derived from the PSA (Figure 2), the 45° line signifies where the two competing scenarios have the same cost. Below the line, the standard of care scenario is cost saving, and above the line the LA + DBM scenario is cost saving. The LA + DBM scenario was cost saving in 47.2% of the PSA iterations, implying that there is a non-negligible probability that the LA + DBM scenario may be cost saving.

Figure 2. Probabilistic sensitivity analysis cost plane.

Discussion

The analysis in the present study shows that the acquisition costs of DBM were partially offset by costs of failed fusions, adverse events, and reoperation when switching 100 hypothetical LDDD patients undergoing LSF procedures from standard of care grafting methods to LA + DBM from the perspective of the Spanish NHS. The costs were entirely offset when considering costs of productivity loss. From the Spanish NHS perspective, the acquisition cost of DBM drives the higher cost of the LA + DBM scenario in the first year. Costs related to failed fusions and reoperations are higher in the standard of care scenario, due to the lower average rate of successful fusions for LA alone and LA + ceramics.

Previous research found that replacing ICBG with LA + DBM in the UK for 100 patients resulted in cost savings of £44,467 over 2 years²⁴. The results of the model in the present study are similar when comparing against ICBG only, indicating cross-population validity. Differences between the UK and present study arise largely due to the inclusion of LA alone and LA + ceramics in the standard of care scenario, with different cost and efficacy profiles from ICBG. The present study also supports previous findings that indirect costs comprise a large portion of total costs³⁶.

This study was limited by a lack of high quality, homogeneous, head-to-head research into the efficacy of grafting procedures available to patients undergoing LSF. The present study selected the most appropriate evidence from the published literature (see Supplementary material for details), but future research may use more sophisticated evidence synthesis methods, such as a formal meta-analysis, to collect efficacy evidence from multiple sources. Each study used to derive efficacy inputs to the model assessed patient follow-up at 2 years, except for the LA + ceramics study, which followed patients for 1 year. This seems to imply that the LA + ceramics fusion rate was underestimated relative to the other treatments, but the LA alone comparator arm fusion rate was 73%³¹ compared to the LA rate in the LA + DBM study (60%¹⁷). The resulting ambiguity of these opposing effects highlights the benefits of meta-analysis.

Patient follow-up in efficacy studies is related to another limitation, in that all studies reporting fusion rates lack long-term patient follow-up. The actual number of fusions that would occur over the model’s 4-year time horizon was underestimated as the trial data followed patients for 1 (LA + ceramics) or 2 years (LA alone, ICBG, LA + DBM).

Due to the complicated nature of the efficacy parameters in the model, the PSA is likely to be an important feature of the analysis as it quantifies the sampling uncertainty of the input parameters. In fact, the PSA highlighted the importance of exploring model sensitivity, as the deterministic results show cost savings for the standard of care scenario, but 47.2% of iterations resulted in cost savings for the LA + DBM scenario. Scenario analyses reveal that, while direct payer-related costs may increase somewhat when adding DBM to the treatment mix, a more accurate description of the total costs of LDDD treated by LSF procedures includes work loss where adding DBM to the treatment mix results in costs savings. Scenario analyses also show that the budget impact decreases with longer time horizons, and that a 5-year horizon is associated a budget impact of €9,180 (€92/patient).

The budget impact model is well suited to synthesizing costs from a variety of clinical and economic sources. The budget impact analysis focuses on costs, and future research should look at complementary cost-effective analyses. As stated above, meta-analyses should be conducted to provide robust estimates of efficacy for each treatment. Further, the budget impact of introducing LA + DBM in other geographies or procedures, such as long bone operations, is likely to be of interest to payers.

Conclusions

Replacing standard of care grafting methods with LA + DBM for Spanish patients undergoing LSF procedures to treat LDDD resulted in an additional cost to the Spanish NHS over 4 years, and an increase in the number of successful fusions. The cost of DBM acquisition was partially offset by higher successful fusion rate and lower adverse event and reoperation rates, and was entirely offset when costs of lost productivity were considered.

Transparency

Declaration of funding

The study was funded by Medtronic International Trading SARL.

Declaration of financial/other relationships

At the time of writing, KG and MP served as paid consultants to Medtronic as employees of PAREXEL International. KG is currently an employee of Quantify Research. MA and CP are employees of, and have received sponsorship from, Medtronic. MA owned stock in Medtronic. XM and CH received research grants from Medtronic. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Previous presentations

Preliminary findings of this research were presented at the 2017 European ISPOR conference in Glasgow.

Acknowledgments

No assistance in the preparation of this article is to be declared.