Cost-Effectiveness Analysis of Dehydrated Human Amnion/Chorion Membrane for Treating Venous Leg Ulcers Yields a Lower Per-Patient Cost Advances

Approximately 10.5 million Medicare beneficiaries had chronic or hard-to-heal wounds in 2019, with cost projections for all wounds ranging between $22.5 to $67.0 billion USD.¹ Although innovative methods of wound care management improve outcomes,^2,3 they can be costly.⁴ Cost-effective wound care strategies are essential to ease the economic impact of hard-to-heal wounds on the Medicare program.

Dehydrated human amnion/chorion membrane (DHACM) allografts are human placental-derived tissue that act as a barrier and protects the wound bed to aid in the development of granulation tissue in acute and chronic wounds. With more than 100 advanced therapies (ATs), defined as high-cost cellular, acellular, and matrix-like products (CAMPs), on the market,⁵ DHACM (EPIFIX, MIMEDX Group, Inc.) is the most widely applied AT for Medicare patients with venous leg ulcers (VLUs).⁶

In a recently published retrospective study by Tettelbach et al,⁷ researchers investigated the cost-effectiveness of advanced therapy with DHACM in Medicare patients with a VLU. This economic evaluation used a Markov model of 4 clinical health states (chronic or recurrent VLU, post-VLU/healed, complex/infected VLU, and death) in patients treated with either DHACM or no advanced therapy (NAT). DHACM was assumed to follow parameters for use (FPFU): initiation of DHACM within 30 to 45 days of the first clinic visit or submitted claim; afterward, DHACM reapplication every 7 to 14 days.^3,6,8 NAT referred to treatment without high- or low-cost CAMPs.

The model took a Medicare perspective and simulated real-world disease progression over 3 years. Researchers used claims for 530,220 Medicare patients who developed a VLU between 2015 and 2019 to model the cohort. Patient data included comorbidities, treatments, outcomes, and hospital use. The model calculated direct medical costs, quality-adjusted life years (QALYs), and net monetary benefit at a willingness-to-pay threshold of $100,000/QALY. Costs were adjusted to reflect 2023 USD values. Researchers used univariate and probabilistic sensitivity analyses to test the uncertainty of results.

When compared with the chronic health state, the results showed the frequency of the top comorbidities was higher in the complex VLU state. Pain was more than 3-fold higher (9.5%,  31.9%), and the overall Charlson Comorbidity Index (CCI) score (a prediction of 10-year mortality based on a patient’s comorbidities) was 29% higher among patients in the NAT group and 68% higher among patients in the DHACM group. Hospital resource usage, too, increased 6-10-fold in the complex, compared with chronic, VLU state. DHACM was associated with greater reductions in hospital use than NAT.

Among 30,547 episodes involving a CAMP, a mean 4.98±5.16 applications occurred per completed claim. Chronic VLUs, which accounted for 23,486 of the episodes, had a slightly lower mean (4.47±4.44). Among the 7061 patients with a complex VLU, the mean rose to 6.65±6.8 applications. On average, complex VLUs required a statistically significant 2.2 more applications than chronic VLUs.

The cost-effectiveness analysis found DHACM FPFU was dominant over NAT over a 3-year time horizon. Compared with NAT, DHACM provided an additional 0.010 QALYs and saved $170 USD per patient. “The dominant result suggests that DHACM FPFU would be cost-effective compared to NAT in treating chronic VLUs at any willingness-to-pay threshold over a 3-year time horizon,” the authors wrote.⁷ At a $100,000 USD/QALY willingness-to-pay threshold, the net monetary benefit was $1178 USD.

As time progressed, so did the DHACM treatment advantage. DHACM was cost-effective compared to NAT at a 1-year time horizon. At the 2- and 3-year horizons, DHACM emerged dominant.

The univariate sensitivity analysis identified only 4 scenarios in which DHACM would not be cost-effective compared with NAT at a $100,000 USD/QALY willingness-to-pay threshold over a 3-year time horizon. VLU recurrence rates for DHACM and NAT, the utility score for a chronic skin ulcer, and the NAT complication rate were the most sensitive parameters.

Probabilistic sensitivity analysis estimated DHACM had a 48.26% likelihood of being dominant and a 63.01% likelihood of cost-effectiveness at a $100,000 USD/QALY willingness-to-pay threshold compared with NAT over the 3-year time horizon. At any willingness-to-pay threshold, DHACM had a more than 50% likelihood of cost-effectiveness.

Assuming 2510 patients in a hypothetical million-member plan had a chronic VLU, and 28.6% were treated with DHACM FPFU, the estimated annual budget impact of DHACM would be less than a 1-cent increase ($0.008) in per-member-per-month spending.

In the study discussion,⁷ researchers reiterated DHACM’s dominance over NAT over a 3-year time horizon. From the Medicare perspective, the upfront cost of DHACM was offset by significant reductions in hospital use, infections, and improved QALYs. The probabilistic sensitivity analysis demonstrated the robustness of the results.

Although patients with a complex VLU treated with NAT had lower CCI scores, their outcomes were poorer than those treated with DHACM. The study also identified a considerable variance in the number of CAMP applications per episode, which researchers characterized as another “take-home message” of the study.⁷ This variance was likely influenced by patient comorbidities, wound features, and socioeconomic factors.

Study limitations included its retrospective design, which demands caution in assigning causality. Furthermore, the economic model developed for the study failed to control for sociodemographic variables in the patient population, which could affect access to specialty care and the predictability of outcomes.

Overall, the study declared DHACM a cost-effective alternative to NAT for Medicare patients with a complex VLU.

“Medicare should update its reimbursement strategies to incentivize the deployment of advanced therapy in timely and routine applications, thus allowing providers to follow evidence-based best practices related to CAMP use more readily,” the authors concluded. “Most patients will see benefits, but patients with a VLU at risk for complications should be eligible early in the treatment process.”⁷

References

1. Carter MJ, DaVanzo J, Haught R, et al. Chronic wound prevalence and the associated cost of treatment in Medicare beneficiaries: changes between 2014 and 2019. J Med Econ. 2023; 26(1):894–901. doi:10.1080/13696998.2023.2232256

2. Tettelbach WH, Cazzell SM, Hubbs B, et al. The influence of adequate debridement and placental-derived allografts on diabetic foot ulcers. J Wound Care. 2022;31(9):16-26. doi:10.12968/jowc.2022.31.Sup9.S16

3. Armstrong DG, Tettelbach WH, Chang TJ, et al. Observed impact of skin substitutes in lower extremity diabetic ulcers: lessons from the Medicare database (2015–2018). J Wound Care. 2021;30:S5-S16. doi:10.12968/jowc.2021.30.Sup7.S5

4. Maxwell A. Some skin substitute manufacturers did not comply with new ASP reporting requirements. 2023. Accessed February 13, 2024. http://tinyurl.com/3nnx636p

5. Center for Medicare and Medicaid Studies. CMS Manual System Pub 100-04 Medicare Claims Processing. 2021. Accessed February 13, 2024. http://tinyurl.com/3wmkuutz

6. Tettelbach W, Driver V, Oropallo A, et al. Treatment patterns and outcomes of Medicare enrolees who developed venous leg ulcers. J Wound Care. 2023;32(11):704-718. doi:10.12968/jowc.2023.32.11.704

7. Tettelbach WH, Driver V, Oropallo A, et al. Dehydrated human amnion/chorion membrane to treat venous leg ulcers: a cost-effectiveness analysis. Wounds. 2024;33(3):S24-S38. doi:10.12968/jowc.2024.33.Sup3.S24

8. Tettelbach WH, Armstrong DG, Chang TJ et al. Cost-effectiveness of dehydrated human amnion/chorion membrane allografts in lower extremity diabetic ulcer treatment. J Wound Care. 2022;31(Suppl 2):S10-S31. doi:10.12968/JOWC.2022.31.SUP2.S10