Cause Analysis and Preventive Measures of Drug Shortage

Zhou Ziyang,Ma Jia,Liu Fuyao,Liu Yuhan,Sun Lihua

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

Abstract Objective To study the current situation and the root cause of drug shortage in China,and put forward countermeasures and suggestions accordingly for relevant national policy decisions.Methods Based on literature research,questionnaire survey and expert consultation,the causes of drug shortage in China were comprehensively investigated,and fishbone diagram was used to further analyze the logical relationship among the causes.Results and Conclusion The main reasons for the shortage of drugs are the low profit of production enterprises and insufficient active pharmaceutical ingredients (APIs).The other reasons include uncertain demand,standard problem and few exclusive manufacturers.Besides,the monopoly of circulation enterprises also leads to the shortage of drugs to a certain extent.It is suggested that we should increase the punishment of monopoly,optimize the market environment,and establish a reasonable drug price mechanism.In addition,enterprises should participate in the information communication platform of medical institutions to solve the asymmetry between supply and demand.The research on clinical drugs to substitute drugs in need should be strengthened,and the reporting system of drug discontinuation should be improved.

Keywords:drug shortage;causes;preventive measure

China’s shortage of drugs refers to drugs that are clinically necessary and irreplaceable are in short supply or unstable for some time in a certain area after being approved for marketing by China’s drug regulatory authority[1].Most countries and regions in the world have experienced drug shortages frequently,which becomes a global problem[2].In recent years,the problem of drug shortages in China has become more serious.A study based on the status of drug shortages in some provinces shows[3]the average number of drug shortages was 66 in 2016,77 in 2017,and 85 in 2018.The number of drug shortages is on the rise.As a result,some patients are not able to take medicines in time,which will aggravate the patient’s condition,delaying treatment opportunities and even endangering the lives of patients.

Stable supply of medicines can ensure the safety of public health.The report of the 19th National Congress of the Communist Party clearly pointed out China should implement the healthy strategy,completely abolish the profits of medicines for medical care and improve the medicine supply guarantee system[4].The Party Central Committee and the State Council attach great importance to the problem of drug shortages.The government has promulgated some policies and measures to guarantee the supply of shortage drugs.One is to ensure the supply and the other is to stabilize prices.In terms of supply guarantee,measures such as establishing small-variety production bases,online notification after review and approval,independent filing for procurement,establishing and improving the normal reserve mechanism,suspending production reports,and other measures to improve the production and supply of drugs to meet clinical needs[5-7].In terms of price stabilization,the market price of shortage drugs and active pharmaceutical ingredients (APIs)should be standardized[8].The illegal acts such as monopoly should be punished as soon as possible,and the supervision of drug prices must be strengthened to control the malicious price increase of drugs[7].In recent years,China has continuously strengthened the supply of medicines and achieved positive results,but the problem of drug shortage still cannot be ignored.Therefore,literature research,questionnaire surveys and expert consultation methods are used in this paper to find out the current situation and reasons for drug shortages.Besides,fishbone diagram is applied to analyze the reasons,and some correspondent countermeasures and suggestions are put forward for this problem.

1 Analysis of the current situation of drug shortage in China

In 2017,nine departments including the former National Health and Family Planning Commission and the National Development and Reform Commission issued “Opinions on Reforming and Improving the Guarantee Mechanism for Supply Drugs”,which proposed that by the end of 2017,a mechanism for collecting and analyzing shortages of drugs should be established.Drug monitoring,early warning and inventory management system must be improved.Therefore,this study inquired about the relevant official websites of China’s provinces and autonomous regions from January 2018 to August 2020 and collected drug shortage lists released by 17 provinces(autonomous regions),as shown in Table 1.

Table 1 Drug shortage information

In April 2020,the National Health Commission of the People’s Republic of China and other departments jointly issued the “National Management Measures for Drug Shortage List (Trial)”.Article 6 stipulates that drugs are in short in 3 or more provinces in the same period,if the linkage mechanism such as direct connection to the Internet,independent filing,and drug reserves cannot effectively solve the shortages within a certain time,a national basic list of drug shortages will be formed.With reference to this provision,combined with the information inquired,this study takes the shortage of drugs that appear in the list announced in 3 or more provinces in the same year as the subject.After summarizing the queried information,a total of 28 drugs are sorted out in the drug shortage list published by 3 or more provinces,as shown in Table 2.

Table 2 List of shortages of drugs

2 Reasons and countermeasures of drug shortages based on domestic and foreign literature

2.1 Literature search

The keywords of “drugs” and “shortage” are used to search in the CNKI,VIP and Wanfang databases.We obtain 644 articles,267 articles,and 813 articles respectively from these databases.Documents that can obtain the full text of the background,current situation,cause analysis,influencing factors,and implementation strategies of drug shortages are included.Then,the documents irrelevant to the research,duplicate documents,and documents without full-text are excluded.114 articles are obtained through preliminary screening of abstracts and titles,and 66 articles are finally included after full-text screening.

2.2 Literature review results

Because of different economic development and medical systems,reasons for drug shortages and countermeasures are different in various countries.Therefore,this research focuses on analyzing current research in China.

The shortage of drugs is caused by multiple factors.These factors are distributed in multiple links in the drug supply chain,such as production,circulation,and use.Problems or changes in any one or several links may lead to drug shortages.Through analyzing relevant domestic documents and learning from foreign documents,based on the above three main links,the reasons and countermeasures are found out.The results are shown in Table 3.

Table 3 Causes and countermeasures of drug shortage based on literature

In this study,66 articles included are used as the denominator,and the number of articles whose reasons for drug shortages are proposed as the numerator,and the proportions are calculated.Then the proportions are sorted from high to low,as shown in Fig.1.

Fig.1 Summary of the causes of drug shortages based on literature

3 Research and analysis on the causes and countermeasures of drug shortage based on questionnaire

Based on previous literature research,this study summarizes the causes of drug shortages and preventive measures.Then,a questionnaire is designed.Manufacturing enterprises,distribution companies and medical institutions are selected as the survey subjects.

3.1 Distribution and recovery of the questionnaire

The researchers asked the experts from the Provincial Health Commission to distribute the questionnaires and recover them in the medical institutions by mail.At the same time,the questionnaires for production and distribution enterprises were distributed by mail through pharmacists in the pharmacy department of tertiary hospitals.During the pre-investigation period,a total of 30 questionnaires were sent out and 9 questionnaires were returned,with a return rate of 30%.153 questionnaires were issued for formal investigation and 23 questionnaires were returned,with a return rate of 15%.One reason for the low recovery rate was that some enterprises might not exist anymore,and other enterprises might no longer produce drugs.Secondly,the questionnaire was distributed indirectly,the actual distribution rate might not be high,resulting in a poor recovery rate of the questionnaire.Therefore,this research conducted the second questionnaire survey.In the second survey,50 questionnaires were distributed through telephone interviews and face-to-face interviews,including 20 from medical institutions,9 from distribution companies,and 21 from manufacturing enterprises.The recovery rate is 100%,and the effective rate is 100%.Since there are uncontrollable factors in the first survey with low return rate of the questionnaire,the questionnaire analysis of this research adopts the results of the second survey.The specific situation is shown in Table 4.

3.2 Survey results of manufacturing enterprises

3.2.1 Causes of drug shortages

The causes of drug shortages from manufacturing enterprises are shown in Table 5.

Table 4 Questionnaire distribution and recovery

Table 5 Reasons for shortage of drugs in manufacturing enterprises

3.2.2 Preventive measures for drug shortage

Three manufacturers proposed that the state should relax restrictions on raw material approvals to encourage production.Besides,they proposed to increase drug prices appropriately to ensure reasonable profits.One manufacturer suggested that the government provide appropriate incentives to produce low-priced drugs.

3.3 Survey results of circulation enterprises

3.3.1 Causes of drug shortages

The causes of drug shortages reported by circulation enterprises are shown in Table 6.

Table 6 Reasons for shortage of drugs in circulation enterprises

3.3.2 Preventive measures for drug shortage

Two circulation enterprises proposed to increase the number of drug manufacturers to ensure a reasonable supply of drugs.One circulation company proposed to increase the penalties for manufacturers that abandon the bid after winning the bid.Another circulation company suggested that the government should increase the review of the monopoly of the circulation company.Once discovered,they should be severely punished.Besides,the market should be cleaned up to ensure reasonable profits for the enterprise.

3.4 Survey results of medical institutions

3.4.1 Causes of drug shortages

The reasons for shortage of drugs in medical institutions are shown in Table 7.

Table 7 Reasons for shortage of drugs in medical institutions

3.4.2 Preventive measures for drug shortage

To prevent drug shortages,four medical institutions proposed that the price of bidding drugs should be dynamically adjusted.Three medical institutions proposed designated production and centralized procurement of shortage drugs.Two medical institutions proposed to increase drug prices appropriately.Two medical institutions proposed to establish early warning mechanism for drug shortage.One medical institution recommended designated manufacturers to produce emergency drugs to ensure clinical application.One medical institution recommended that distribution companies strengthen their inventory and transportation management.

3.5 Analysis of the main reasons for drug shortage based on questionnaire survey

In this study,the number of questionnaires from enterprises/medical institutions with drug shortages in each link was used as the denominator,and the number of questionnaires selected for the reasons for drug shortages as the numerator,the ratio was calculated,and the ratios were sorted from high to low,as shown in Fig.2.

Fig.2 Summary of the causes of drug shortages based on questionnaire surveys

4 Reasons and countermeasures for shortage of drugs based on expert consultation

Interviewees should be engaged in medical work for a long time with rich experience in drug management.Therefore,scholars from colleges and universities in pharmaceutical management and health economics,and experts from hospitals and government with rich experience in drug management are selected to discuss the causes and countermeasures of drug shortages.Through expert consultation,in addition to the drug shortages caused by the production and circulation in the literature,we get the following reasons for drug shortages and countermeasures.

(1) Affected by the drug bidding and procurement policy,the winning price of the drug has cut the profit of the producer,and the enterprise is unwilling to produce drugs at a low profit.

(2) Environmental protection has strict requirements for pharmaceutical production.Enterprises cannot meet these requirements in a short period of time.Faced with rising environmental protection costs,they cannot produce these drugs.

(3) The varieties of drugs in shortage are dynamic,and shortages in different time and regions will be different.The dynamic characteristics of the drug insufficient supply in a short period are more common clinically.

Experts point out that the main reasons for the shortage of drugs are the low bid prices caused by drug procurement policy and environmental protection issues.

5 Analysis of the main reasons for the shortage of drugs and their relationships

5.1 Causes of drug shortages

The above studies have found that the main causes of drug shortages lie in manufacturing enterprises.Based on unwilling to produce,unable to produce,and other reasons,this study uses fishbone diagram to further analyze the reasons for drug shortages in manufacturing enterprises,as shown in Fig.3.

Fig.3 Fishbone diagram of the causes of drug shortages in manufacturers

5.2 Analysis of the causes of drug shortage based on fishbone diagram

Since the causes of drug shortages from expert consultation cannot be quantified,this study comprehensively integrates the causes of drug shortages in literature research and questionnaire surveys,as shown in Fig.4.

Fig.4 Causes of drug shortages based on literature and questionnaires

At the same time,considering the causes of the shortage of drugs given by experts and combining with the fishbone diagram,we make a structural analysis of the reasons,and the details are as follows.

(1) The low bid price caused by the procurement policy is the main reason mentioned in all three research,which is in accordance with the shortage of drugs caused by the low profit and unwillingness to produce in the fishbone diagram.(2) The API is the second reason that has been mentioned in the above three research.Enterprises are unable to produce drugs due to monopoly of APIs or shortage of APIs,leading to drug shortages.(3) Exclusive production or fewer manufacturers is the third reason for drug shortages.It is mentioned in questionnaire surveys and expert consultations,which leads to drug shortages.(4) Unstable demand is another reason for drug shortage mentioned in literature research and questionnaire survey.Corresponding to the uncertain demand and low demand in the fishbone diagram,the latter belongs to the profit category in the fishbone diagram.(5) Rising production costs are the fifth reason for drug shortages.It has been mentioned in literature studies and questionnaire surveys.(6) Environmental protection is one of the reasons for the shortage of drugs mentioned in the experts’ consultation.Corresponding to the increase in environmental protection costs and environmental protection standards in the fishbone diagram,the former is the low profit that makes enterprise unwilling to produce.But the latter is the standard problem that prevents enterprises from producing.(7)Other reasons mentioned in the literature research,such as low prices,enterprises unwilling to produce,and imperfect procurement policies,all belong to the profit category in the fishbone diagram.The improved production qualifications and standards belong to the standard category in the fishbone diagram.The high cost of distribution channels,supply sources,and distribution are the reasons for the shortage of drugs in circulation enterprises,so they are not reflected in the fishbone diagram.(8) The other reasons selected in the questionnaire survey correspond to the major profit categories in the fishbone diagram.The monopoly and low distribution profits of other circulation enterprises are the reasons for the shortage of drugs in the circulation enterprises,which are not reflected in the fishbone diagram.

To sum up,the main reasons for the shortage of drugs are low profits of manufacturers and the monopoly of APIs.The second is the exclusive production or few manufacturers,uncertain demand,and standard issues.The monopoly and low profits of circulation enterprises have also led to a shortage of drugs to a certain extent.

6 Preventive countermeasures for drug shortage

In the literature,other researchers have put forward some countermeasures to prevent drug shortages,such as establishing an early warning mechanism,improving drug supply systems,optimizing procurement policies and market environments.Therefore,combining the actual situation,this study analyzes the previous articles based on the primary and secondary causes of drug shortages to put forward the following countermeasures.

6.1 Promoting the construction of medical price and credit evaluation system for procurement,and curbing monopoly from the source

The low profits of enterprises are mostly due to the excessively high prices of raw materials and the monopoly of raw materials.At the end of 2017,the National Development and Reform Commission formulated the “Price Guidelines for Drug Shortages and API Operators”,which clarified the manifestations of various price monopoly in the field of shortage drugs and APIs,illegal identification,and exemption conditions for price monopoly agreements,etc.However,it has not risen to the legal level yet.The problem of drug shortages should be curbed from the source,and price monitoring should be organized to provide timely warning of abnormal changes in the price and supply of raw materials.Once monopoly of APIs occurs,severe penalties will be imposed.The “Guiding Opinions of the National Medical Security Administration on Establishing a Pharmaceutical Price and Procurement Credit Evaluation System” issued by the National Healthcare Security Administration in August 2020 clarified the price of drugs and dishonesty in procurement and its correspondent penalty.It is recommended that this credit evaluation system be promoted as soon as possible to prevent enterprises from malicious bidding.At the same time,the anti-monopoly law enforcement of the State Administration of Market Supervision and Administration has a deterrent effect on pharmaceutical enterprises that bid maliciously.

6.2 Find out the number of the manufacturing enterprises

The actual number of the enterprises that have obtained the production approval for drugs in short should be found out.Besides,their production capacity must be determined.If there are many manufacturers of the drug,it means that the review and approval is not the root cause.The causes may lie in other links.On the contrary,it is necessary to give priority to the review and approval of the drug,and increase the number of manufacturers to guarantee the supply.

6.3 Enterprises should understand market needs by participating in the instruction of information communication platform

To strengthen the connection between supply and demand and reduce the shortage caused by poor information,enterprises should participate in establishing information communication platform of medical and health institutions.The government can determine the purchase volume through reasonable calculations.Then it offers the company a determined market demand scale to enhance the company’s production power.Meanwhile,the government can sign procurement contracts with several enterprises to ensure sufficient drugs supply with good quantities and reasonable prices.

6.4 Strengthen the research on the clinical substitutability of drugs and improve the drug discontinuation report system

If there is a substitute for the same kind of drugs in the clinic,it can solve the insufficient or unstable supply of the drugs.However,this is not a shortage problem.Although the National Health Commission has issued the “Technical Guidelines for the Classification of Drug Shortages in Medical Institutions and Alternative Uses”,there are still different perceptions related to the clinical substitutability of drugs.It is recommended to use scientific and reasonable alternative drugs based on the actual situation.The list of alternative drug references can be offered by the government to reduce the shortage of drugs.At the same time,for drugs not on the list of drug shortages,there is currently no requirement to report the discontinuation of production.These drugs may not be in shortage at that time,but if an emergency occurs,for instance,some or all of the manufacturers stop production for some reason,it will lead to insufficient supply of drugs.Therefore,China should improve the drug discontinuation report system,and all drugs must be reported in advance before the planned discontinuation to avoid the occurrence of drug shortages.

6.5 Adopt multiple strategies to solve environmental problems

Penalties should be imposed on enterprises that do not meet environmental protection standards.Besides,relevant manufacturing enterprises must attach importance to environmental protection standards.The enterprise may appoint other production enterprises to produce drugs in short during the period of suspension due to their non-compliance with environmental protection standards.Meanwhile,emergency drugs should be given policy support.