Jia Hanxue,Zhang Fang

(School of Business Administration,Shenyang Pharmaceutical University,Shenyang 110016,China)

Abstract Objective To sort out the dimension and indicators of comprehensive value assessment of anti-tumor drugs abroad,and provide a reference for constructing a similar system in China.Methods The keywords such as antitumor drugs,value,assessment,method,and framework were used to search CNKI,WanFang database,VIP database,Embase,PubMed and Web of Science.Results and Conclusion According to the research on the value framework of anti-tumor drugs,6 first-level dimensions and 8 second-level indicators with common characteristics were summarized.In view of China’s national conditions,this study summarizes the available value judgment dimensions of anti-tumor drugs at home and abroad,so as to learn from international experience and their mature methodologies,and provide ideas for constructing a multi-dimensional value system of anti-tumor drugs in China.

Keywords:value;anti-tumor drug;multi-criteria decision analysis;evidence-based decision making;dimension;index

1 Background

With the rapid development of economy,accelerated population aging and changes in people’s lifestyles,cancer has become a major chronic disease that greatly influences the quality of human life and health.In 2017,there were 24.5 million new cancer cases and 9.6 million deaths from cancer worldwide[1].According to data from the National Cancer Center of China,the number of new cases of malignant cancer in 2017 was 3.8 million,and the number of cancer deaths was 2.6 million[2].Data from the National Bureau of Statistics show that malignant tumors have become one of the main causes of death in China.Nowadays,the price of anti-tumor drugs is still rising.Therefore,the National Health Commission and other departments have issued multiple documents to continuously improve the dynamic adjustment mechanism of the list of insured drugs so that eligible anti-tumor drugs can be included into the list of insured drugs according to the procedure to reduce patients medication burden.However,in recent years,new anti-tumor drugs have been introduced into the clinic,and the high cost of anti-tumor drugs makes the allocation of health resources face huge challenges.Therefore,when making medical decisions,the health administrative department needs to clarify the value dimensions and standards of resource allocation,which can finally realize the purpose of assisting decision-making.

In recent years,the concept of “value” has been frequently mentioned and explored to be applied to the governance of the medical and health system.The value assessment system can help stakeholders to weigh treatment options through value-based decisions.In drug price negotiation,the values considered by medical insurance payers,health commissions,pharmaceutical companies,health economics experts,medical institutions,and cancer patients are different.So we should learn from the value-based pricing mechanism in developed countries such as quality adjustment life years,costeffectiveness and other indicators.Meanwhile,it is necessary to comprehensively consider the clinical value of the drug,payer value,innovation value,and patient value to clarify different value dimensions,indicator and weights[3].In this way,a multidimensional judgment system for the comprehensive value of anti-tumor drugs can be established.

As an emerging field of drug policy research,the construction of drug value framework has received widespread attention.Standardized,scientific,and transparent drug value assessment can provide effective support for the approval of new drugs,the formulation of clinical drug guidelines,drug pricing,medical insurance compensation,and even patients’choice of medication[4].At present,the evaluation of multi-dimensional value judgments has played an important role in the medical and health decisionmaking in various countries or regions.For example,the United States,the United Kingdom,Australia,Canada,Portugal and other countries have developed anti-tumor drug value framework to evaluate new drugs for cancers.The value of drugs helps patients choose value-based therapeutic drugs.Based on the research of related literature,this article analyzes the dimensions and indicators of the existing anti-tumor drug evaluation system abroad in order to provide a reference for establishing a similar system of antitumor drugs in line with China’s national conditions.

2 Materials and methods

2.1 Literature search strategy

A literature review is carried out to comprehensively sort out the current domestic and foreign value judgment dimensions and indicators.After searching some major domestic and foreign literature databases,the current value judgment dimensions in various countries and regions are obtained.CNKI,WanFang database,VIP,Embase,PubMed,and Web of Science are searched by using the key words such as anti-tumor drugs,value,assessment,method,framework,etc.The retrieval time is from January 1,2010 to September 1,2020.

At the same time,the corresponding antitumor drug value frameworks developed by various countries and regions based on their own health decision-making needs are searched.They include the followings such as the European Society for Medical Oncology (ESMO),the Institute for Clinical and Economic Review (ICER) and the American Society of Clinical Oncology (ASCO),the National Comprehensive Cancer Network (NCCN) and Memorial Sloan-Kettering Cancer Center (MSKCC).

2.2 Inclusion and exclusion criteria

Inclusion criteria:research on the value evaluation tools,standards or methods of anti-tumor drugs in various countries and regions.The language is limited to Chinese and English.In the case of value evaluation tools on the same subject repeatedly published by the same institution,only the latest version will be retained.

Exclusion criteria:value evaluation research only for a specific tumor or a certain class of drugs.reviews,conference articles,advertisements,or news about the value evaluation tools of anti-tumor drugs.Besides,research that cannot obtain the full text will be excluded.

3 Results

3.1 Summary results

A total of 1 643 related documents were retrieved,and the literature was screened according to the inclusion and exclusion criteria.Finally,9 anti-tumor drug value frameworks were obtained,including 5 in the United States,1 in South Korea,1 in Europe,1 in Canada,and 1 in Portugal respectively.The flow chart of literature search results is shown in Fig.1.The value framework of anti-tumor drugs used by various countries and institutions is shown in Table 1.

Fig.1 Articles selection process

Table 1 Summary of frameworks for evaluating the anti-tumor drugs by countries and institutions

Continued Table 1

The DrugAbacus interactive calculator is an antitumor drug value framework developed by MSKCC.Users can set the values according to the individual’s understanding of the importance of each factor,and the program will give a recommendation accordingly[5].The price of drugs can be used to judge whether the price of anti-tumor drugs is reasonable.The framework mainly includes efficacy,toxicity,novelty,development costs,rarity,population burden,unmet need,and disease prognosis[6].

The value framework issued by the ASCO has become a tool for doctors to guide patients on medication at the clinical level,which can promote joint decision-making between doctors and patients.The key parameters of this value framework are the clinical benefit,toxicity and cost.The framework takes into account the opinions of representatives of four major stakeholders,including oncologists,patients,payers,and pharmaceutical manufacturers.The health and individual needs of the patient are paramount,and the intent of ASCO in developing the framework is to encourage patient-centered care[7].

The ICER’s value framework uses statistical methods to quantify the cost and clinical benefits of medical interventions,so as to evaluate the treatment plans or drugs.ICER traditionally uses cost-effectiveness analysis.The collected indicators not only include the impact on the health care sector,focusing on health outcomes and medical costs,but also the impact on the non-health care sector,such as the time cost of patients and the time cost of unpaid family caregivers,and transportation costs.Besides,there is the impact on society,such as the impact on production,consumption and other aspects[8].The main indicators are clinical effect,cost-effectiveness,and budget impact.

The ESMO-magnitude of clinical benefit scale(ESMO-MCBS) issued by the European Society of Medical Oncology is used to evaluate the treatment plan from progression-free survival (PFS),quality of life (QOL),overall survival (OS),toxicity,and overall response rate (ORR)[9].

The Portuguese Institute of Oncology (IPO)proposed a method called cancer value label(CAVALA).This framework is a holistic and flexible concept of value,which mainly includes expected results and costs.But the biggest advantage of CAVALA is that it allows other variables to be added later according to actual needs,such as overall survival,progression-free survival,and treatment duration[10].

Most Canadian provinces and territories rely on the pan-Canadian oncology drug review (pCODR)issued by the pan-Canadian Oncology Drug Review Expert Review Committee (pCODRERC),which provides advice on public reimbursement of cancer drugs.The review process of pCODR considers the four dimensions of value clinical benefit,economic evaluation,patient-based value and adoption feasibility.But they do not define the weight of a single decision criterion or the acceptable threshold of any standard[11].

DA Ezeife,et al.established a multi-stakeholder group based on the method of multi-criteria decision analysis,which determined and weighted the key criteria for setting up the drug assessment framework(DAF).The final DAF includes 10 criteria:overall survival,progression-free survival,response rate,quality of life,toxicity,unmet needs,equity,feasibility,disease severity,and caregiver well-being.The top 5 clinical benefit criteria account for about 64% of the total weight.DAF scores range from 0 to 300,reflecting both the expected impact of the drugs and the quality of supporting evidence[12].

In order to not only perform cost-benefit analysis,South Korea uses the multi-criteria decision analysis (MCDA) method,reflecting the social value of compensation decisions.Besides,this method can show the social preference of the public and health care professionals to fight cancer social preferences for reimbursement standard of anti-tumor drugs.Eight criteria are finally determined:disease severity,disease population size,pediatrics targets,unmet needs,innovation,clinical benefits,cost-effectiveness,and budget impacts[13].

3.2 Value dimension and index screening

Based on the 9 value frameworks from the results of the literature review,14 common value dimensions are sorted out:effectiveness,economy,safety,unmet needs,quality of life,remission rate,disease severity,cost-effectiveness,innovation,feasibility,budget impact,cost/expense,overall life,and progressfree life.Among them,effectiveness (frequency of 9),economy (frequency of 5),and safety (frequency of 5) appear more than or equal to 5 times in 9 value frameworks.Meanwhile,fairness,affordability,patient value,social value,and risk ratio appear less than twice.We only take common dimensions and indicators into account.Fig.2 shows the frequency statistics of each value dimension.

Fig.2 Statistics on the frequency of appearance of each value dimension

3.3 Value dimensions and indicators collation

Through literature review,the dimensions and indicators that need to be considered in the comprehensive evaluation of anti-tumor drugs are preliminarily determined.They are effectiveness,safety,affordability,cost-effectiveness,innovation,and budget impact,etc.Based on literature review,we further sort out the logical framework of antitumor drug value judgment standards,and then construct a multi-dimensional value judgment and index system of anti-tumor drugs.This includes 6 dimensions and 8 indicators,a total of 14 evaluations index.The indicators are further refined on the basis of dimensions.For example,the dimension of“effectiveness” can be further refined into secondary indicators such as overall survival and progress-free survival.The definitions of the primary dimensions and secondary indicators are shown in Table 2 and Table 3.

Table 2 Dimensions and interpretation

Table 3 Indicators and interpretation

4 Discussion

At present,there is no standardized comprehensive value judgment framework for anti-tumor drug in China.Therefore,this article summarizes the available value judgment dimensions for anti-tumor drugs abroad to draw on their experience and mature methodologies.Then we can build a multi-dimensional value judgment system for anti-tumor drugs in line with China’s national conditions.Besides,it also provides valuable reference for clinicians,patients,medical insurance payers and other stakeholders.This can realize value-based decision-making to provide the public with the most cost-effective medical and health services[23].

Literature studies display that the dimensions and indicators of current domestic and foreign value judgments are different,but effectiveness,safety,and economy are the gold standards for evaluating anti-tumor drugs.Therefore,a comprehensive value judgment system of anti-tumor drugs should be set up in China.According to the “Guidelines for the Comprehensive Clinical Evaluation of Anti-Tumor Drugs” issued by the Department of Pharmaceutical Administration of the National Health and Construction Commission in November 2019,the innovation of drugs should be emphasized,and the importance of innovation is further proved by foreign research.Chinese anti-tumor drug comprehensive evaluation system should aim at maintaining people’s health,and further improving the collaborative and efficient innovation system.There are few studies for evaluation of drugs in China that use disease severity and feasibility as research indicators.However,in view of the high incidence and mortality of cancer,the severity of disease should be scored for specific cancers in the research.For instance,the drugs for lung cancer,colorectal cancer,breast cancer and other cancers with high morbidity and mortality should have first priority.The “feasibility” dimension is similar to the accessibility dimension in domestic research,and it can be specifically extended to availability,affordability and timeliness of medication[24].The overall survival,progress-free survival,remission rate or objective remission rate,and quality of life in the secondary indicators can be used as specific indicators in the primary dimension of effectiveness.Indicators such as cost/expense,cost-effect,and budget impact analysis can be used as specific indicators in the first dimension of economy.Addressing unmet needs can be used as specific indicators in the first dimension of innovation.Based on the above research,the following suggestions are made for the establishment of a comprehensive evaluation system for anti-tumor drugs in China.

First,the research on the comprehensive value dimensions and indicators of anti-tumor drugs should be combined with the relevant guidance documents issued by the State Council and the National Health Commission,the characteristics of anti-tumor drugs,and the demand for anti-tumor drugs.It should not be limited to foreign research and ignore our national conditions.For example,the study finds that there is no guideline recommendation dimension in the foreign cancer value framework.However,the National Health Commission issued the “Administrative Measures for the Clinical Application of Anti-Tumor Drugs”in July 2020,which emphasized that the selection of anti-tumor drugs in medical institutions should be based on clinical needs.In addition,priority should be given to the drugs included in national essential medicines catalog,the national basic list of insured drugs,and national centralized negotiation or bidding procurement,as well as the diagnosis and treatment specifications,clinical diagnosis and treatment guidelines,and clinical pathway recommendations announced by the National Health Commission.The“Methods” also pointed out that the use of anti-tumor drugs in various institution and clinical departments should be analyzed to evaluate the suitability of these drugs,and correct the unreasonable use of drugs.Therefore,the suitability dimension should be included in the comprehensive evaluation system of anti-tumor drugs.The foreign anti-tumor drug value framework has only one dimension of accessibility.But in November 2013,the International Union for Cancer Control revised the “World Declaration Against Cancer”,of which 6 out of 9 targets included accessibility and effectiveness in cancer treatment[25].China’s government has also implemented a series of measures for anti-tumor drugs,such as the cancellation of drug markups,centralized drug purchases,and drug price negotiations,which improve anti-tumor drug supply guarantee policies.Besides,a series of work measures were formulated to ensure drug availability.Therefore,dimension of accessibility should occupy an important position in the comprehensive evaluation system for future anti-tumor drugs.

Second,the dimensions and indicators in the value framework of anti-tumor drugs established in China should not only be applicable to decision makers,but also to clinicians,patients,pharmaceutical companies,health economics experts and other stakeholders.Health decision-making based on comprehensive value not only depends on clinical effect or economic evaluation,but also requires multiple considerations such as ethics,safety,and cost.Multi-criteria decision analysis provides a solution to this problem.Multi-criteria decision-making refers to the decision-making that is selected in a set of limited(infinite) schemes that conflict with each other and cannot be shared.Multi-criteria decision-making in the health field can help decision makers choose the best from the complex value combinations,so it can be used to evaluate the decision priority of complex health policy decisions (including reimbursement decisions)[26].

Third,the value dimensions and indicators of anti-tumor drugs are not static,and need to be continuously updated according to clinical needs.The Healthy China 2030 planning outline puts forward comprehensively promoting the transformation from the center of disease treatment to the center of health.To implement this policy,it is necessary to change the way of focusing on drug efficacy to a multi-dimensional and multi-stakeholder approach,including the pharmacoeconomic value,social value,and quality of life to promote more comprehensive services.With the continuous development of antitumor technology in the future and the increasingly standardized management of anti-tumor drugs in China,new dimensions and indicators may appear in the future.

Establishing an anti-tumor drug evaluation system based on comprehensive value can assess the value and cost of anti-tumor drugs in a comprehensive way,rather than just the price of drugs.This can encourage the sustainable innovation of pharmaceutical enterprises to benefit more cancer patients.