Health Technology Assessment of A New Generation of Domestic Cryosurgical System

CAO Xiao-Meng1, GAO Song2, ZHU Xu2, WANG Mei2, ZHANG Hong-Zhi2, CHENG Xue-Hui1*

【Abstract】Objective We aimed to evaluate the technology of the new generation of domestic co-ablation system and provide evidence-based evidence for the fine configuration of this kind of equipment. Methods Mini-Health Technology Assessment (HTA) template was used to evaluate the configuration of a new generation of domestic co-ablation system by literature research and expert consultation from technical, patient, hospital and economic level. Results The technology of co-ablation is innovative; It is safe in the treatment of lung and pancreatic cancer without serious complications. Co-ablation is noninferior to argon-helium cryoablation in terms of efficacy and safety for the treatment of non-small cell lung cancer. Compared with argon-helium cryoablation, the patients with pancreatic head cancer who received co-ablation has a better survival rate. According to the forecast of 250 cases per year, the payback period of investment is 2.2 years. The average length of hospital stay and total cost of co-ablation are lower than traditional surgery and three-dimensional appropriate radiotherapy. Conclusion The evaluation results show that the introduction of this technology can realize the upgrading of tumor ablation technology, help to reduce the average length of hospital stay and relieve the economic pressure of patients, and the equipment investment returns are considerable, which has configuration value.

【Key words】Medical equipment; A new generation of domestic co-ablation system; Health technology assessment; Mini-HTA; Evidence-based configuration

[CLC No.] R730.4; R730.8 [Document code] A

Seen from the traditional treatment methods, tumor can be treated by surgery, radiotherapy and chemotherapy. In order to minimize the patient’s trauma, minimally invasive treatment has been becoming more and more important. Ablation therapy is the main method of local minimally invasive interventional therapy for tumor at present. Guided by image device, it uses one or more pieces of puncture needle(s) to insert into the tumor and inject chemical substances or heat or chill to kill the tumor cells, thus causing tumor tissue necrosis and absorption, and achieving the effect of reducing or eliminating tumor. Co-ablation technology is a new original ablation technology of China integrating cryoablation and thermal ablation. It leads the formation of ice crystal inside and outside the cells via cryoablation, and causes mechanical damage and dehydration due to osmotic pressure difference, which leads to necrocytosis and cell apoptosis of sublethal zone. Meanwhile, it reduces bleeding by the hemostatic effect of thermal ablation and integrates different ablation technologies to make good for deficiency, which can more thoroughly kill the tumor, features good safety and efficacy, and possesses broad prospect in treating solid tumor[1].

DOI: 10.12010/j.issn.1673-5846.2022.08.008

Author affiliation: 1. Cancer Hospital of Peking University and Medical Engineering Department of Beijing Institute of cancer prevention and treatment, Key Laboratory of malignant tumor pathogenesis and transformation research, Ministry of education, Beijing 100142, China;

2. Department of interventional therapy, Cancer Hospital of Peking University and Beijing Institute of cancer prevention and treatment, Key Laboratory of malignant tumor pathogenesis and transformation research, Ministry of education, Beijing 100142, China

*Corresponding author: Cheng Xuehui, E-mail: 13811037425@163.com

Health technology assessment (HTA) refers to systematic evaluation on the properties, efficacy, safety and economy of health technology through evidence of evidence-based medicine, to provide scientific basis for decision makers to make decisions. For hospitals requiring rapid decision-making but with limited resources, it is rather difficult to carry out comprehensive HTA, not in compliance with actual demands. Mini-HTA emerged at the right moment. HTA based on the actual demands of hospital features high evaluation efficiency and less resource consumption, which provides reference basis for decision makers to select medicine and introduce medical technical device. In this study, Mini-HTA is adopted to comprehensively evaluate the co-ablation system, to provide evidence support for introduction of the medical device by hospitals.

1. Data and methods

1.1 General data

The data are from literature retrieval and expert and department consultation. Literature retrieval mainly refers to retrieval by subject term and keyword with such keywords as “hypothermal ablation therapy”, “cryoablation therapy”, “Combo knife” and “co-ablation system” in PubMed, Emabse, Cochrane Library, Chinese Journal Full-text Database, Wanfang Data Knowledge Service Platform, as well as official website and relevant database of HTA organization both in and abroad. The search time is from the establishment of the database to August 30, 2021. The language is limited to Chinese and English.

1.2 Methods

Mini-HTA is implemented by the evaluation list composed of a series of standard entries. The most representative is the Mini-HTA evaluation list developed by Danish Centre For Health Technology Assessment (DACEHTA)[2]. The contents of evaluation on new technology mainly include 5 levels: basic information, technology, patients, hospital and economy, covering 26 questions in total[3]. The technology level includes the range of application, difference from traditional technologies, influences on patients (including safety and efficacy), whether recommended by the country or organization, etc.; patient level includes the influences of psychological, physiological and social activities; hospital level includes the consideration of software and hardware conditions, influence on the existing diagnosis and treatment items, whether there are successful cases, etc.; economic level includes hospital operation expenses and income, patients expenses increase or decrease, etc. During evaluation, the items in the list can be deleted as appropriate based on hospital conditions, decision-making standard and evaluation scheduling.

The Mini-HTA approach adopted in this study takes the Mini-HTA evaluation list developed by DACEHTA as the reference, and integrates the evidences of the influences of co-ablation system on safety, efficacy, economy and society and ethics based on the actual demand of the hospital, to perform comprehensive systematic evaluation.

2. Evaluation results

2.1. Technical features

2.1.1 Innovation  

Co-ablation system is more destructive to tumor. Previous trials showed that, heating after cryoablation can lead to changes in chemical composition of cells, alternate cooling and heating leads to rise in phase-transition temperature and reduces the heat capacity, hence more easily destructing the cells[4].

Co-ablation needle has three layers of inner cavity (Figure 1). The innermost layer is the inflow channel of liquid nitrogen and absolute ethyl alcohol, the intermediate layer is the outflow layer of waste liquid and waste gas, and the outermost layer is the vacuum heat insulating layer, which can effectively prevent the frostbite and burns of puncture route.

Figure 1 Structure of Co-ablation Needle Body

Meanwhile, liquid nitrogen and other easily acquired consumables are adopted for the device to replace the previously imported devices that rely on nonrenewable gases such as argon and helium, which remarkably lowers the operative treatment cost and possesses good popularization and application prospect.

2.1.2 Indications   

Cryoablation can treat lung cancer[5], pancreatic cancer[6], prostatic cancer[7], bone and soft-tissue sarcoma[8] and cancer pain[9] of different stages, which can effectively control the progress of early tumor, and treat early liver cancer to the effect similar to that of surgical excision[10]. Cryoablation therapy can improve the treatment effect of advanced non-small cell lung cancer, improve the immunologic function of patients and prolong the survival time, hence improving the quality of life[11]. After extensive investigation, co-ablation system has been applied in the treatment of multiple tumor types in other hospitals, including pancreatic, lung, breast and maxillofacial tumors.

2.1.3 Safety   

In a prospective, non-inferiority, multi-center and randomized controlled trial[5], the efficacy and safety of treating patients suffering from stage III-IV non-small cell lung cancer (NSCLC) in China by co-ablation system and argon-helium cryoablation system were compared, and the safety results showed that the occurrence rate of complications (pneumothorax, pleural effusion, hemoptysis, pericardial effusion, and local bleeding of puncture site) of co-ablation group and argon-helium cryoablation group was 29.26% (12/41) and 30% (12/40) respectively, without obvious difference. All adverse events of the two groups are slight and can be self-cured, with no special treatment required.

In a clinical research[12], the safety of treating patients with unresectable pancreatic cancer in China by cryoablation system and co-ablation system was compared. The results showed that, there was no significant difference in the incidence of postoperative pancreatic fistula and delayed gastric emptying between the two groups, and the co-ablation system group was not subject to postoperative hemorrhage or pulmonary infection.

2.1.4 Efficacy   

Yang et al.[5] reported the results of the study on the efficacy of co-ablation system compared with argon-helium cryoablation system. Totally 81 patients with non-small cell lung cancer were included into the study, among which 41 cases of the trial group were treated by co-ablation system, and 40 cases of control group were treated by argon-helium cryoablation system. The main endpoint criteria are the ice crystal coverage and disease control rate one month after the operation. The results showed that, the ice crystal coverage of co-ablation system and argon-helium cryoablation system was (99.24±2.18)% and (98.66±3.79)% respectively, and the disease control rate one month after the operation was 97.6% and 95% respectively, reaching the non-inferiority criteria.

Qian Zhuyin et al.[12] reported the results of the efficacy of treating unresectable pancreatic cancer by co-ablation system compared with argon-helium cryoablation system. There were 35 cases in co-ablation system group and 101 cases in argon-helium cryoablation system group. The study results showed that, the survival rate of patients with pancreatic head carcinoma in co-ablation system group was obviously higher than those of argon-helium cryoablation system group within one year after the operation.

It is clearly recommended in the Diagnostic and Treatment Standards for Renal Cell Carcinoma (2018)[13] that co-ablation can be used to treat renal carcinoma. In 2019, National Health Commission of the People's Republic of China vigorously promoted the minimally invasive cryoablation technique for tumor, and included the cryoablation of liver tumor, lung tumor and breast tumor into the List of Core Technologies of National Cancer Regional Medical Center[14]. Besides, the Expert Consensus on the Operation Specification of Treating Malignant Lung Tumors by Percutaneous Hot and Cold Multimodal Ablation[15] and the Expert Consensus on the Operation Specification of Treating Malignant Liver Tumors by Hot and Cold Multimodal Ablation[16] were issued in 2020 and 2021 respectively, recommending the treatment of lung cancer and liver cancer patients by hot and cold multimodal ablation. The expert consensus was issued by the Specialized Committee for Interventional Oncology of China Anti-cancer Association, Chinese College of Interventional Physicians of Chinese Medical Doctor Association, and Expert Committee on Interventional radiation Therapy of the Chinese Society of Clinical Oncology jointly with the experts from Interventional science group of the Radiology Association of Chinese Medical Association. It refers to the consensus on the operation specification of treating liver cancer and lung cancer by hot and cold multimodal ablation, which embodies the approval of experts from tumor intervention field on the technical safety and efficacy of hot and cold multimodal ablation technology.

2.1.5 Cost effectiveness

2.1.5.1 Hospital level   

The medical device recommended by Beijing Hospitals Authority is adopted to perform economic benefit analysis on the co-ablation system via benefit analysis evaluation form. Cost accounting covers the expenses of device procurement, manpower, repair and maintenance, materials (hygienic material, office supplies, etc.), water and electricity and installation site reconstruction.

Upon investigation, the market price of co-ablation system is about RMB 5 million, with no need of site reconstruction and extra device allocation by hospital. Accounting is performed on income according to the charging standards for combined liquid nitrogen solid tumor ablation released by Beijing Municipal Medical Insurance Bureau: RMB 8,000 for each lesion and no more than 60% additional cost for lesion ≥ 3 cm. By investigating the duration of single treatment with the device, the consumption of materials for each operation (mainly absolute ethyl alcohol, liquid nitrogen and hygiene materials for operation), unit price of materials, device power and other data, the cost to use the device, manpower, materials, water and electricity is accounted, to obtain per capita cost of about RMB 4,200. According to the predicted annual average department workload of 250 cases and accounting of per capita charge of RMB 12,000 and cost of RMB 4,200, the predicted payback period of the device is 2.2 years, and a net income of RMB 1.95 million can be increased for hospital, showing good economic benefits. See Table 1.

2.1.5.2 Patient level   

From the patient's perspective, evaluate the economy of co-ablation system compared with other treatment methods. Taking lung cancer as an example, in terms of hospital stay, the average hospital stay is 4.75 d for co-ablation, 5.7 d for thoracotomy and 7.1 d for thoracoscopic lobectomy in traditional surgical treatment of lung cancer [17]. The standard hospital stay of radiotherapy for lung cancer is longer, about 54 d[18]. In terms of average total hospitalization expenses, the average total hospitalization expenses of co-ablation treatment are RMB 37,000, while those of traditional surgical treatment are RMB 46,000 for thoracotomy and RMB 47,000 for thoracoscopic lobectomy [17]. The cost of three-dimensional appropriate radiotherapy for lung cancer is RMB 40,000-70,000 [18]. To sum up, in the treatment of lung cancer, compared with traditional surgery and three-dimensional appropriate radiotherapy, the average hospital stay is shorter and total hospitalization expenses are lower for patients treated by co-ablation, hence more economical.

Table 1 Cost Accounting and Recovery Analysis

2.2 Society and ethics

2.2.1 Hospital level   

Based on the actual situation of our hospital, this paper investigates the influence of introducing co-ablation system, and explores its feasibility and suitability, including personnel qualifications, training needs, hardware settings and so on.

In 2017, the National Health and Wellness Committee issued the Management Standard for Tumor Ablation Therapy Technology (2017) [19], based on which professional training was carried out in our hospital. The department has professionals with the qualification to perform co-ablation, who can understand the characteristics of ablation technology itself, accurately control the indications and contraindications, and have rich practical experience in perioperative patient management.

In addition, the co-ablation system needs to be guided by computerized tomography (CT) or ultrasonic diagnostic instrument. Angio-CT system has been introduced into our hospital, and its excellent digital subtraction function and 64-row spiral CT can meet the requirements of co-ablation.

There are other ablation technologies in the hospital, including microwave, radio frequency, argon-helium cryoablation and other interventional therapy technologies. Although the indications of the interventional therapy technologies overlap, there are certain differences in clinical use due to different technical characteristics. The introduction of co-ablation can supplement the existing technologies, and different types of patients can choose appropriate treatment technologies according to their illness conditions to further improve the quality of medical services.

2.2.2 Patient level   

The influences of co-ablation on patients' ethical psychology and quality of life are analyzed from the patient's level. Co-ablation is carried out according to ethical principles in line with national laws and regulations following the principles of "full notification, full understanding and independent choice"; it makes clear the indications of treatment, meets the needs of patients, and treats suitable people; clarifies the contraindications, and excludes the inapplicable and high-risk population, which significantly reduces the treatment risk [15-16].

Under the guidance of imaging device, percutaneous puncture to the target lesion is done by co-ablation with the wound of only about 2 mm, and treatment can be realized under local anesthesia, avoiding the risk caused by general anesthesia. The patient has no pain during the treatment, thus improving the keenly feel of some patients with cancer pain before operation [20], and proved to have good tolerance during the treatment. In addition, this technology has low requirements for patients, patients with poor cardiopulmonary function and elderly patients can tolerate the operation, which has little psychological impact on patients. Therefore, it can avoid the strong physiological and psychological stress caused by surgery and help to achieve the treatment objective and postoperative rehabilitation. In addition, the co-ablation has no obvious effect on patients' quality of life and labor ability, and the study showed that the quality of life and pain score of patients have no obvious change before and after cryoablation treatment [5]. After cryoablation, patients recover quickly, the average hospital stay is short, and the influence on daily life is tiny [5].

3. Summary and discussion

3.1 Summary

In this study, the Mini-HTA method was used to comprehensively evaluate the technical characteristics, safety, efficacy, economy and social impact of the co-ablation system in the treatment of malignant tumors.

In terms of technical characteristics, the co-ablation system adopts the internationally original cold and hot multimodal tumor ablation technology, which is more destructive to tumors and can be applied to many tumor species, including pancreatic, lung, breast and maxillofacial tumors. In terms of safety, a multicenter randomized controlled trial (RCT) showed that there was no serious adverse event in the treatment of patients with non-small cell lung cancer by co-ablation system, and there was no significant difference in the incidence of adverse reactions compared with argon-helium cryoablation system. A clinical study explored the safety of co-ablation system in the treatment of unresectable pancreatic cancer in China. The results showed that the incidence and severity of postoperative complications in the co-ablation system group were lower than those in the cryoablation system group. In terms of efficacy, a RCT showed that compared to the argon helium cryoablation system, the co-ablation system had non-inferiority in the treatment of non-small cell lung cancer patients. Another clinical study showed that the survival rate of patients with pancreatic head cancer treated by co-ablation system was significantly higher than that of argon-helium cryoablation system within one year after operation. It is clearly recommended in the Diagnostic and Treatment Standards for Renal Cell Carcinoma (2018) that co-ablation system can be used to treat renal cell carcinoma. In terms of economy, from the hospital level, the predicted payback period of investment for the co-ablation system is 2.2 years, and it can bring a net income of RMB 1.95 million to the hospital every year afterwards, which has good economic benefits; from the perspective of patients, compared with other surgical operations, radiotherapy and other treatment methods, the system has shorter hospital stay, lower hospitalization expenses and better economy. In terms of social impact, from the hospital level, the department has professionals qualified to perform co-ablation, and the hospital has introduced the Angio-CT system, which can meet the requirements of co-ablation; at the patient level, patients with poor cardiopulmonary function and elderly patients can tolerate the operation, and this technology has no obvious effect on patients' mental health, quality of life and labor ability.

Generally speaking, the co-ablation system is innovative, safe, effective in clinic, short in payback period of device investment, and has considerable economic benefits, which can shorten the hospital stay of patients and ease the economic burden. Therefore, the co-ablation system has configuration value.

3.2 Discussion

Under the general situation of "Healthy China 2030" national strategy and deepening the reform of medical and health system and public hospitals, it is of great significance to rationally allocate health resources and improve the utilization efficiency of limited health resources. Mini-HTA, as a decision-making management mode of hospital health technology configuration, the scientific and reasonable HTA methods are organically combined with objective evidence-based data, which shows obvious value in the application of new technologies and the elimination of backward technologies, the control of medical expense growth, the improvement of technical effects and the promotion of patient safety. Co-ablation system belongs to international innovative medical devices, and there is no evaluation of this medical device in China at present. In this study, the characteristics, safety, efficacy, economy and social impact of Mini-HTA method were comprehensively evaluated, which provided evidence for the configuration of co-ablation system, improved the evaluation mechanism of medical device configuration, and enriched the practical application of Mini-HTA theory in hospitals.

However, there are some limitations in this study: 1) qualitative description of the existing literature can not quantitatively analyze and evaluate the heterogeneity among the included studies, so some research results may be biased; 2) the co-ablation technology is an internationally original new treatment technology, and it was approved to debut China in 2017. At present, there are few documents and clinical trials related to safety, efficacy and economy, and some evaluation materials come from internal resources of the hospital, so the evidence is not sufficient. With the deepening of research and the increasing and perfection of clinical guidelines and evidence-based configuration, evaluators need to update the evaluation results in time to ensure the accurate decision-making and rational use of medical institutions.

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(Received on: January 24, 2022)