PMA Fusion Bone graft 70x more economical than autograft

A robust cost-utility analysis of bone grafting, recently published in Clinical Economics and Outcomes Researchfound that a particular biologic for spinal fusion, when faced with the cost of local (free) 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-enriched bone graft i-factor versus the 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 spinal fusion biologics through the rigorous premarket approval process – one is a BMP-2 recombinant bone graft and the other is a peptide-based bone marrow manufactured by Westminster, Colorado-based Cerapedics, Inc.

The first bone graft with the P-15 peptide was originally formulated and marketed in 1999 for dental applications by Ceramed, the predecessor company to Cerapedics. It was later reformulated as i-FACTOR Bone Graft Putty and began the arduous PMA (pre-market approval) regulatory and clinical study process for use as a spinal fusion biologic in the ACDF at a single level. It took Cerapedics nearly 15 years to obtain the rare premarket approval (only two ever granted by the FDA) for i-FACTOR in spinal fusion.

Cerapedics describes i-FACTOR as a peptide-enhanced bone graft that “attracts, attaches and activates” osteogenic cells to build bone where it is placed and nowhere else.

Significant cost-benefit difference for i-FACTOR

The cost of a device or treatment often carries an outsized weight when it comes to coverage decisions. Insurers require unambiguous data indicating that a treatment or solution provides enough benefit to justify its cost.

An insurer’s willingness to pay (WTP) is based on factors such as the cost of the treatment, 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. Additionally, QALYs are measured over time. One QALY is equivalent to one year of perfect health or two or more years of less than perfect health.

How, concretely, can this translate into a clear and unambiguous measure of profitability? For the i-FACTOR economic study, the research team used, in part, the well-researched and validated Abbreviated 36-Item Survey (SF-36) and then transformed it into a weighted utility to calculate a quality of life. measurement for patients.

According to lead author Jared Ament, MD, the objective of the economic study was to compare the i-FACTOR cost-benefit ratio of Cerapedics to local autograft in patients undergoing anterior cervical discectomy and fusion surgery ( ACDF).

The model used data from the Investigational Device Exemption (IDE) study approved by the FDA and published in 2016. The study randomly assigned patients to receive an autograft (n=154) or i-FACTOR (n=165) and showed i-FACTOR to be significantly non-inferior to autograft in terms of fusion rate, significant improvements in neck disability index (NDI), high neurological success rate or adverse event rates individually. More importantly, i-FACTOR demonstrated a statistically higher overall clinical success rate 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 the following year, reaching a rate of 97.3% (compared to 94.4% for autograft) . Again, overall success remained statistically superior in the i-FACTOR cohort.

Modeling of 5,000 iterations / 52 input parameters

The research team used patient outcome data from the IDE study to generate a Markov model with nodes representing transitions between health states and associated costs and utility scores. The model took into account health status, direct medical costs, and indirect costs, such as labor productivity, and assumed a cost of $750 for i-FACTOR versus autograft (free). Overall, the model was used to run a Monte Carlo simulation of 5,000 iterations to calculate the break-even results.

The research team used a one-way sensitivity analysis to analyze 52 input parameters to determine which parameters had the most influence on the conclusions. They then conducted a probabilistic sensitivity analysis (PSA) on the 52 input parameters more 350 health state transition probabilities.

Conclusion: The probabilistic sensitivity analysis of the study demonstrated that i-FACTOR was profitable in more than 2/3 of the 5000 iterations.

The Markov model describes the health and work status of the patient at each follow-up period. Each node represents the transition to health states associated with different costs and utility scores. / Source: Authors of the study

i-FACTOR QALY vs Autograft QALY

Finally, the study team calculated the incremental cost-effectiveness ratio (ICER) for i-FACTOR and compared it to autograft. (To calculate the 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.

Moreover, at each additional instant, and for societal costs at all instants, i-FACTOR is economically dominant (ICER

About the Author

The study was led by Dr. Jared Ament, MD, MPH, Director of Outcomes Research and Co-Director of Spinal Neurosurgery within the Neurosurgery and Spine Group and President and Founder of Neuronomics, a think tank that performs economic analyzes of health care, such as the one described in the current study

Dr. Ament received his MD from the Medical School for International Health (a collaborative program between Ben-Gurion University in Israel and Columbia University in New York) and his Masters in Public Health from the University from Harvard.

Dr. Ament is a fellow-educated neurosurgeon and president and founder of Neuronomics, a think tank that performs economic analyzes of health care, such as the one described in this study.

Dr. Ament summarized his study of i-FACTOR for OTW: “In a robust cost-utility analysis, i-FACTOR reduced costs in the first year compared to the control group (autograft) in the IDE ACDF [investigational device exemption] test population. Incremental cost-effectiveness was found to be very cost-effective even at 90 days ($13,333 per QALY [quality-adjusted life-year]). At 1 year and beyond, these values ​​have become negative, suggesting a “dominant” economic strategy.

“The results are considered conservative because in a real-world setting, many surgeons use other, more expensive grafts in addition to autograft,” Dr. Ament added.

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.

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