A robust, cost-utility analysis of bone graft, which was recently published in ClinicoEconomics and Outcomes Research, found that one particular spine fusion biologic, when put up against the cost of (free) local autograft in cervical fusion procedures (considered the gold standard) would be justified even if the price was increased 70 times.
The economic analysis is titled: “Cost-Effectiveness of Peptide Enhanced Bone Graft i-Factor versus Use of Local Autologous Bone in Anterior Cervical Discectomy and Fusion Surgery.”
Only Two FDA Approved Spine Fusion Biologics in the United States.
The U.S. Food and Drug Administration (FDA) has approved two spine fusion biologic products via the rigorous Pre-Market Approval process—one is a recombinant BMP-2 bone graft and the other is a peptide-based bone graft manufactured by Westminster, Colorado-based Cerapedics, Inc.
The first bone graft with the P-15 peptide was originally formulated and commercialized in 1999 for dental applications by Ceramed, the predecessor company to Cerapedics. Later it was reformulated as i-FACTOR Bone Graft Putty and began the arduous PMA (premarket approval) regulatory and clinical study process for use as a spine fusion biologic in single-level ACDF. It took Cerapedics almost 15 years to achieve the rare (only two ever granted by the FDA) premarket approval for i-FACTOR in spinal fusion.
Cerapedics describes i-FACTOR as a peptide enhanced bone graft that will “Attract, Attach, and Activate” osteogenic cells to build bone where placed and nowhere else.
Significant Cost Benefit Differential for i-FACTOR
The cost of a device or treatment often has an outsized weighting when it comes to coverage decisions. Insurers require unambiguous data that a treatment or solution provides enough benefit to justify its cost.
An insurer’s willingness-to-pay (WTP) is based on factors such treatment cost, the quality-adjusted life years (QALYs) provided by the treatment, and the value assigned to each QALY.
A typical value assigned to a QALY is $100,000. Also, QALYs are measured over time. One QALY equates to one year of perfect health or two or more years of less than perfect health.
How, in a practical way, can this be translated into a clear, unambiguous cost effectiveness measure? For the i-FACTOR economic study, the research team used, in part, the well-studied and validated 36-item short-form survey (SF-36) and then transformed it into a weighted utility to calculate a quality-of-life measure for patients.
According to senior author Jared Ament, M.D., the goal of the economic study was to compare Cerapedics’ i-FACTOR cost-benefit to local autograft in patients undergoing anterior cervical discectomy and fusion (ACDF) surgery.
The model used data from the 319-patient FDA approved investigational device exemption (IDE) study published in 2016. The study randomly assigned patients to receive autograft (n=154) or i-FACTOR (n=165) and showed that i-FACTOR was significantly non-inferior to autograft in terms of fusion rate, significant improvements in neck disability index (NDI), high neurological success rate, or rate of adverse events individually. More importantly, i-FACTOR demonstrated a statistically higher rate of overall clinical success than the autograft control at 12 months.
These patients were also included in a 24-month follow-up study published in 2018 which found that more patients had fused in the following year, reaching a rate of 97.3% (versus 94.4% for autograft). Again, overall success remained statistically superior in the i-FACTOR cohort.
5,000 Iterations Modeling / 52 Input Parameters
The research team used the IDE study patient outcome data to generate a Markov model with nodes representing transitions between health states and associated costs and utility scores. The model accounted for health state, direct medical costs and indirect costs, such as work productivity, and assumed a cost of $750 for i-FACTOR over (free) autograft. Overall, the model was used to run a 5,000-iteration Monte Carlo simulation to calculate the cost-effectiveness outcomes.
The research team used one-way sensitivity analysis to analyze 52 input parameters to determine which parameters exerted the most influence on conclusions. They then conducted a probabilistic sensitivity analysis (PSA) on all 52 input parameters plus 350 health state transition probabilities.
Conclusion: the study’s probabilistic sensitivity analysis demonstrated that i-FACTOR was cost-effective in greater than 2/3 of the 5,000 iterations.
Markov model depicts patient’s health and work status at each follow-up period. Each node represents transition to health states associated with different costs and utility scores. / Source: Study authors
i-FACTOR QALY vs Autograft QALY
Finally, the study team calculated the incremental cost-effectiveness ratio (ICER) for i-FACTOR and compared that to autograft. (In order to calculate incremental cost-effectiveness ratio; divide the cost difference by the QALY difference of the two interventions). The data showed that at 90 days, the incremental cost-effectiveness ratio for i-FACTOR was $13,333/QALY, well below the $100,000/QALY WTP threshold.
Further, at every additional time point, and for societal costs at all time points, the i-FACTOR is economically dominant (ICER <$0/QALY) due to greater QALY benefits and i-FACTOR’s lower initial cost.
About the Author
Leading the study was Dr. Jared Ament, M.D., M.P.H., director of outcomes research and co-director of Spine Neurosurgery at the Neurosurgery & Spine Group and president and founder of Neuronomics, a think-tank that conducts healthcare economic analyses, such as the one described in the current study
Dr. Ament earned his M.D. from the Medical School for International Health (A collaborative program between Ben-Gurion University in Israel and Columbia University, New York) and his Master of Public Health at Harvard University.
Dr. Ament is a fellowship-trained neurosurgeon and president and founder of Neuronomics, a think-tank that conducts healthcare economic analyses, such as the one described in the current study.
Dr. Ament summarized his study of i-FACTOR for OTW: “In a robust cost-utility analysis, i-FACTOR reduced costs within the first year compared to the control group (autograft) in the ACDF IDE [investigational device exemption] trial population. The incremental cost-effectiveness ratio proved highly cost-effective even at 90 days ($13,333 per QALY [quality-adjusted life-year]). At 1 year and beyond, these values became negative, suggesting a ‘dominant’ economic strategy.”
“The results are felt to be conservative since, in a real-world setting, many surgeons are using other more costly grafts in addition to autograft,” added Dr. Ament.
Other members of the research team were Bart Thaci, University of California, Davis, Sacramento, CA: Randy Yee, Neuronomics LLC, Los Angeles, CA: Kee Kim, Neurosurgery & Spine Group, Los Angeles, CA: Amir Vokshoor, Institute of Neuro Innovation, Santa Monica, CA: J Patrick Johnson, Cedars Sinai Medical Center, Los Angeles, CA.
