Ma Jia,Li Xiaoqi,Raela·Abduhilil,Sun Lihua

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

Abstract Objective To analyze relevant policies and measures on the management of orphan drug reimbursement in foreign countries to provide a reference for future reimbursement management in China.Methods According to the percentage of health care expenditure in GDP,the completeness of rare disease policies,and the total population,Russia,Australia,and India were selected as the reference.Based on the existing literature,the main content and characteristics of the reimbursement of rare disease drugs were analyzed.Results and Conclusion Russia manages rare diseases in the form of lists.Special rare diseases are reimbursed by federal or regional finances,and ordinary rare diseases are reimbursed by statutory medical insurance funds.Orphan drugs in Australia are included in the pharmaceutical benefits scheme (PBS) and the lifesaving drugs program (LSDP),LSDP provides fully reimbursed drugs for eligible rare disease patients.India’s proposal takes health system sustainability into consideration.China should carry out epidemiological research to legally determine the rare diseases,establish reasonable reimbursement standards,and improve the multi-level reimbursement system.

Keywords:orphan drugs;reimbursement management;enlightenment

In May 2018,the National Health Commission and other five departments jointly announced the “First List of Rare Diseases” (hereinafter refer to as list),which defined rare diseases in the form of a disease list.It provided a direction for the development of policies related to rare diseases in the future.The list contains 121 kinds of rare diseases.Although some drugs for rare diseases have been included in the scope of medical insurance reimbursement,China currently does not have a mature drug reimbursement system for rare diseases.This article aims to analyze the main content and characteristics of rare disease reimbursement system in other foreign countries to get reference and enlightenment for the management of rare disease reimbursement in China.

1 Overview of rare diseases and orphan drugs

A rare disease is a sickness with a very low prevalence.There are more than 7 000 rare diseases in the world,accounting for about 10% of human diseases.Orphan drugs refer to drugs used to treat rare diseases[1].There is no unified and generally accepted definition,but some countries and regions have given official definitions of rare diseases based on the number of patients or prevalence[2].The details are presented in Table 1.

Table 1 Definition of rare diseases in some foreign countries or regions

Table 2 LSDP-funded indications,drug name,trade name

Currently,there is no official definition for rare diseases in the mainland of China.In 2010,some experts suggested that either the morbidity less than 1/500 000 or the neonatal morbidity less than 1/10 000 should be taken as a definition of rare disease.China published the first “List of Rare Diseases” on May 22,2018,which stipulated the scope of rare diseases.However,it still did not propose a specific and clear definition for rare diseases and orphan drugs.

2 Reimbursement management of orphan drugs abroad

It is a universal method to define the rare disease and orphan drug in the form of law and regulation based on factors such as prevalence,number of patients,and severity.India does not have a formal definition.However,it emphasizes the importance and necessity of rare disease definition according to its own condition in the “National Rare Disease Policy Proposal (2020)”[3].Due to the differences of economic level,total population,and medical insurance system,some countries adopt different methods for the management of reimbursements for rare diseases.

China is similar to Russia,and both of them manage the rare disease in the form of lists.Besides,the percentage of health care expenditure in GDP is also close to China.Australia has a more sophisticated rare disease policy that provides lots of useful experience for us.the population of India is second to China,and it is an important factor when it takes reimbursement into consideration.Based on this,this article chooses Russia,Australia,and India as the research objects to analyze their reimbursement systems in detail to gain some inspiration.

2.1 Russia

The current medical system in Russia includes federal level and regional level.The federal budget covers most of the health care plans,and the regional budget is a supplement to the federal one to provide additional funds for regional medical needs.Each region can formulate its own particular health care plan according to its own needs and funding.The reimbursement of medicines in Russia is included in the federal and regional health care plans[4].

Russia manages rare disease according to the list of rare diseases.Orphan drugs in this list can be reimbursed.The list is determined and published by the Ministry of Health based on statistical data.There are three categories of rare diseases[2].The first category is rare diseases that are extremely expensive to treat,which will be reimbursed by the federal finance.The second category is rare diseases that are severely life-threatening and expensive to treat,and the local finance is responsible for reimbursement.The third category is common rare diseases,which are reimbursed by medical insurance.

The first category initially included 7 rare diseases,covering hemophilia,cystic fibrosis,pituitary dwarfism,Gaucher disease,malignancies of the hematopoietic system and lymphoid tissues,multiple sclerosis,and organ or tissue transplantation.Two adjustments were made in 2019 which added another 7 rare diseases.They are systemic juvenile idiopathic arthritis,mucopolysaccharidosis (type I,II,VI),hemolytic-uremic syndrome,aplastic anemia (cause unknown),and hereditary factor deficiency (II,VII,X)[5].At present,there are a total of 14 rare diseases in the first category,and the federal budget bears the higher per capita treatment costs.After adjustment,the second category still has 17 rare diseases.

Experts believe that due to economic difficulties in many regions,the stability of providing orphan drugs to patients is not as stable as at the federal level.Therefore,it is logical to gradually bring orphan drugs that are reimbursed by regions to the federal pool,and drug price has also dropped due to the federal management[5].

2.2 Australia

Australia established the health insurance system through the “National Medical Insurance Law” in 1984.Its drug reimbursements are mainly included in the pharmaceutical benefits scheme (PBS) and the lifesaving drugs program (LSDP).

The pharmaceutical companies apply to the Pharmaceutical Benefits Advisory Committee(PBAC) to enter the PBS.if they are approved,the Pharmaceutical Benefits Pricing Authority (PBPA)negotiates the price with these pharmaceutical companies.But the Minister of Health makes a final decision on whether their products are included in PBS[6].Most of the prescription drugs are included in PBS,but there are still some drugs paid by patients.In order to reduce the burden of severely rare disease patients,the government has formulated the PBS safety net to provide preferential for those patients.The PBS safety net stipulates that the annual threshold for preferential cardholders is $316.8,and for ordinary patients is $1486.8[7].Before reaching the threshold,the maximum cost for each kind of drug for preferential cardholders is $6.6,while it is $41 for ordinary patients.After reaching the threshold,the preferential cardholders can get their drugs for free,and the maximum cost for ordinary patients is $ 6.6.

Pharmaceutical companies can submit applications for PBS and LSDP simultaneously after obtaining marketing qualifications.If PBAC does not agree to include it in PBS but accepts that the drug has certain clinical efficacy,it can be included in LSDP[8].Through LSDP,the Australian government provides fully reimbursable drugs for eligible patients with rare diseases and life-threatening diseases.Currently,LSDP includes 16 drugs for the treatment of 10 rare diseases[9].

Continued Table 2

2.3 India

There is no clear and detailed reimbursement management of orphan drugs in India.In 2017,the Ministry of Health and Family Welfare of India released the first version of the “National Policy on Rare Diseases”,which was updated in early 2020.In 2017,the proposal promised to provide an initial fund of 1 billion rupees for the treatment of patients with rare genetic diseases,but in 2020,the new proposal withdrew this decision.As an alternative,it proposed to establish a platform for financing to pay for the treatment of patients with rare diseases and provide financial support of up to 1.5 million rupees for patients who need one-time treatment.At the same time,the proposal also pointed out that it was very important to determine the definition of rare diseases in line with the actual situation in India.India needs to take short-term and long-term measures to comprehensively deal with rare diseases,and stressed that due to the high cost of treatment for rare diseases,a balance should be kept between access to treatment and the sustainability of the health system.

The reimbursement of orphan drugs in the proposal includes five aspects[3]:(1) Establishing a fund for the treatment of rare diseases.(2)Establishing a rare disease management organization,which is responsible for the formulation of technical standards and the issuance and management of funds.(3) Controlling the drug price of rare diseases to ensure the affordability and sustainability of the health system.(4) Encouraging the public sector and enterprise sector to provide financial support and exploring other options for providing sustainable funds.(5) Defining the coverage of reimbursement for rare diseases.

3 Enlightenment

3.1 Carrying out epidemiological research and identifying rare diseases in the form of legislation

Definition of rare diseases is one of the important prerequisites for reimbursement of rare diseases,and it is adopted by most countries to identify them through legislation.At present,China lacks the legislative definition and epidemic data of rare diseases,which leads to the short of the most basic reference standards in the research and development,marketing and reimbursement of orphan drugs.A rare disease is a relative concept.Due to the large population base in China,some rare diseases have become normal in China,and the definitions and standards of rare diseases in other countries cannot be directly quoted.We should encourage the epidemiological study of rare diseases in China to obtain data such as the prevalence rate and the number of patients.Then,they can be discussed according to the actual situation in China.Finally,the definitions of rare diseases and their medication in the form of legislation can be made.

3.2 Establishing reasonable reimbursement standards

Different from common drugs,the unique characteristics of orphan drugs are the small number of patients,small target market and high R&D cost.Therefore,their prices are higher than common drugs.For rare diseases,once they are included in medical insurance for reimbursement,it will have opportunity costs.The policymakers will face two choices.On the one hand,they can solve more people’s health problems by allocating relatively few resources.On the other hand,more resources are needed to solve the health problems of relatively few people[3].However,patients with rare diseases also have the right to life and health,which leads to the problem of fairness and rationality.Therefore,the drugs used for rare diseases cannot be fully reimbursed.What diseases,what drugs can be reimbursed,and the reimbursement standards should be carefully discussed.

According to the experience of Russia and Australia,the rare diseases can be divided into ordinary rare diseases and special rare diseases according to the number of patients,severity,disease burden,intervention effect,and quality of life.The rare diseases should be managed by classification,and their reimbursement standards should be different,too.

3.3 Improving the multi-level reimbursement system

As to the scarcity of resources,we must consider the balance between access to the treatment opportunities and the sustainability of the health system when formulating the reimbursement system for rare diseases.Incorporating orphan drugs into medical insurance reimbursement is one of the methods to reduce patients’ burden,but the only problem of this method is the concern about the affordability and sustainability of medical insurance funds.At present,there is no current deficit in China as a whole,but in fact,there are huge regional differences.In 2018,employees’ medical insurance in 106 co-ordination areas and residents’ medical insurance in 183 co-ordination areas failed to meet their current income[10].If more expensive orphan drugs are included in medical insurance,it will undoubtedly have a huge impact on China’s medical insurance fund.

For the affordability and sustainability of medical insurance funds,we can draw lessons from the experience of reimbursement of rare diseases in Russia,Australia,and India.China should improve the multi-level reimbursement system.In addition to reimbursement through medical insurance,finance,civil affairs,commercial insurance,corporate charity and social forces can be included for the payment of rare diseases.Reimbursement of expenses for rare diseases through multi-level mode can not only reduce the consumption of medical insurance fund,but also play a strategic purchasing role of medical insurance fund.