Investigation and Analysis of Medication Disposal in Hospitals and Community Pharmacies in Taiwan

: Taiwan o ﬀ ers a ﬀ ordable access to health care through the National Health Insurance (NHI) Program, but this increases the risk of waste of medications and pollution caused by improper disposal. This research aimed to: (1) understand methods of disposal of unused medications, and public awareness of related issues, (2) understand the sources and types of unused medications and reasons for their disposal, and (3) propose improvements to current disposal practices. Data on practices and perspectives on the disposal of medications were collected from members of the public using a questionnaire, and subjected to chi-square analysis of demographic variables. The survey found that many respondents disposed of medications inappropriately, but most believed the government should establish a return system. The majority of discarded medications came from hospitals, and were most frequently discarded because patients had forgotten to take them. Based on these ﬁndings, the study proposes that receiving stations be established across Taiwan for the safe and environmentally friendly disposal of unused medications, along with a system of monthly checks and compensation for pharmacists’ costs. The study also suggests that pharmacists strengthen medication guidance, spend more time on medication counseling, better understand the reasons for medication waste, and o ﬀ er health education and advice to physicians and the public.


Introduction
Since the introduction of the National Health Insurance (NHI) Program in 1995, Taiwan has implemented nationwide health insurance, covering 99.5% of the population. Through its achievement of low-cost medical care, easy accessibility to medical treatment, and high rates of satisfaction, Taiwan's NHI Program has enjoyed widespread international prestige. However, Taiwan's health care system today is encountering mounting pressure to implement reforms as a result of Taiwan's rapidly aging population, general economic stagnation, and the heavy cost of the system. Therefore, the government has actively promoted a second-generation of health care reforms in recent years, making efforts to improve the financial quality of payers and hospitals, and thus giving full play to the role of the NHI Program [1,2].
Although the NHI Program in Taiwan protects and safeguards the health of the entire population, this protection and convenience has also led to the widespread wastage of health insurance resources. Taiwan's current "Fee-for-service" health insurance system aligns insurance payments for medical service suppliers with the costs of the services they provide [3]. According to the latest statistics from the Department of Statistics on the Ministry of Health and Welfare, Taiwan's medical expenditure has grown annually, reaching nearly NT$160 billion (USD 5.3 billion) in 2017.
However, many of the medications prescribed under this system go to waste, due to patient misuse. According to a study conducted by one medical center in 2014, about NT$2.16 million (US$72,000) worth of medications were discarded each year [4]. Statistics published by the Executive Office of the Executive Yuan show there are more than 19,000 medical institutions in Taiwan, so it is not unreasonable to estimate that the total sum being wasted each year may be as high as NT$1 billion [4]. Similar situations have frequently been reported in other countries, such as Saudi Arabia, where the cost of medication wastage has been estimated at US$10 per person per household, or an annual cost nationally of US$150 million [5]. In another study, a total of 98 kg of discarded medications were collected from a hospital during a four-week period [6].
In response to this large amount of medication wastage, the Taiwan Pharmacist Association produced recommendations entitled "Six Steps for Disposal of Unused Household Medicines", which suggested that while medications whose ingredients contain cytotoxicity or environmental hormones, such as cancer drugs, hormones, and antibiotics, should be handed over to neighboring community pharmacies or hospitals for collection, general medicines could be directly disposed of with household garbage for incineration. However, this method of disposal is not without problems. As of 2010, there were 24 incineration plants in Taiwan [7], but many counties and cities still lack such facilities, including Nantou County, Hualien County, Taitung County, and the offshore islands. In addition, recent studies have pointed out that a considerable number of residents throw unused medicines into toilets or water channels [8,9]. There is still insufficient information available on the suitability and correctness of methods of disposal of unused medicines by residents from their homes, and whether the disposed medications have been sent to incinerators or landfills, along with associated environmental issues.
The pollution of rivers and land caused by the improper disposal of unused medicines has become an important issue, both in Taiwan and abroad [10,11]. Studies of the Han river in South Korea, Ozark streams in the USA, the rivers Po and Arno in Italy, the Sindian, Dahan, and Gaoping rivers in Taiwan, the Seine river in France, and the Hoje river in Sweden have all identified the presence of antibiotics [12]. In 2015, medications such as Codeine and Ampicillin were detected in the coastal waters of southwestern Taiwan, raising concerns of dangers to aquatic organisms [13]. Similarly, three multi-drug resistant strains were detected in the rivers of Taichung City, indicating that these waters had been heavily contaminated by antibiotics [14]. Other studies have mapped the occurrence and distribution of pharmaceuticals with high detection frequencies in surface water, groundwater and rivers in Taiwan [15,16]. If pharmaceutical contamination of river systems around the world remains on this upward trend, severe health problems may be passed on to humans through the food chain. In short, excessive medication waste has added to the financial burden of the government's healthcare policies, and at the same time caused environmental pollution through improper disposal.
Kusturica et al. [17] analyzed and compared the relationship between disposal of unused medicines and environmental awareness in countries across the globe from 2005 to 2015 using peer-reviewed literature, finding that there was no set of norms for the disposal of discarded medicines. This research also found that such medications were frequently disposed of by being flushed down the toilet or poured into waterways, raising serious environmental concerns. Therefore, more receiving stations for unused medicines should be established across Taiwan, return mechanisms and regulations should be formulated, and the independent disposal of unused medicines by the public should be avoided. Aware of these environmental issues, a number of countries have developed waste drug recycling mechanisms. For example, community pharmacies in the United States, Sweden, France, Italy, and Malaysia are responsible for the collection of discarded drugs [18][19][20][21], and pharmacists also provide information about safe disposal of medications. In 2010, the U.S. Drug Enforcement Administration (DEA) even initiated a National Prescription Drug Take-Back Day, in response to growing public concern over improper disposal of unused, unwanted, or expired (UUE) medications [18].
The prevalence of polypharmacy and major polypharmacy (defined as prescription of ≥5 and ≥10 medications respectively) among elderly and disabled Taiwanese has been reported as 81% and 38%, respectively [22]. Around 80% of disabled and elderly patients take at least five kinds of medications on a daily basis, and it is extremely difficult for them to do so correctly and completely. As for the general public, there is little information available about the reasons for the excessive waste of medications, such as whether it is caused by excessive prescription at the treatment end, or failure by patients to comply with directions for use.
Traditionally, the quantity of unused medicines is calculated in terms of the number of days since the issuing of the prescription. However, this method fails to evaluate the patients' actual medication use and compliance with directions. Only when pharmacists visit patients in their homes can an accurate picture of the types and quantities of unused medicines be obtained, along with reasons for their not being taken. Therefore, data on unused medications discovered by pharmacists through their patient care services have been added to patient self-report data in the present study.
Based on the research motivation outlined above, this study aimed to: 1. Understand the methods by which members of the public in Taiwan dispose of unused medications, along with their awareness of related issues.

2.
Understand the sources and types of medications that are wasted, and reasons they are discarded.

3.
Propose suggestions to improve the current mechanisms and regulations relating to disposal of unused medications in Taiwan.

Materials and Methods
To achieve the objectives of this research, a questionnaire was designed, based on issues identified in the literature of domestic and overseas scholars [9,23]. After confirming the content of the first draft of the questionnaire, content validity analysis was performed by five experts, including pharmacists, physicians and academics, who reviewed the questions and offered suggestions on the appropriateness of the content and the clarity of the wording. The content validity index (CVI) of the questionnaire was assessed at 0.914. After the expert validity was established, the suggestions of the experts were adopted to revise the questionnaire, and a final version agreed upon for implementation. The content consists of three parts: the first part recorded basic demographic variables, with a total of six items, including gender, place of residence, age, education level, and occupation of participants, together with the location in which the survey was conducted. The second part surveyed the methods participants used to dispose of medications, and their awareness of related issues. The third part sought data on the type and quantity of medicines that were discarded and the reasons they were not used.
Participants for the study were selected by convenience sampling, and completed the questionnaire by hand. A pharmacist integrated the list of medications into the third part of the questionnaire, assisting in the identification of medications, filling in the drug health insurance code, and completing a record of the questionnaire's completion. The questionnaire was distributed to people who were returning unused medications to hospitals or community pharmacies, or who were discovered to have unused medicines by pharmacists on home visits, and were completed anonymously. The data were then keyed into Excel and analyzed using SPSS, version 25. Data from the three parts of the survey were summarized using descriptive statistics, and a chi-square test conducted to analyze whether there were differences in the awareness of drug disposal issues related to different demographic variables.
Pharmacists assisted with the disposal of any waste medications held by participants in the survey, following official procedures for collection and disposal of medications as outlined in the "Six Steps for Disposal of Household Medication Waste" issued by the Taiwan Pharmacist Association. This research was conducted after obtaining consent from Jianan Psychiatric Center Institutional Review Board (Planned S/N: 19-014), and the questionnaire was distributed from 1 December 2018 to 20 October 2019.

Demographic Data
During the research period, a total of 371 valid questionnaires and 480 prescribed medications were collected. Among the participants, 250 were returning medications to community pharmacies, 117 were doing the same at hospitals, and four were identified through home visits by pharmacists. Table 1 shows that females accounted for 53.1% of the participant with the highest number belonging to the 31-40 age group. The most common levels of education among participants at the three medicine-receiving stations were college/junior college degree, and the most common category of occupation was medical care.

Methods of Disposal of Unused Medicines and Awareness of Related Issues
The questionnaire responses revealed that the most common source of information that unused medicines should be returned to hospitals or community pharmacies was pharmacists (51.7%), followed by friends and family members (38.5%). The proportion of participants who chose to return unused medicines to hospitals or clinics was 38.3%, while 42.0% returned them to community pharmacies. For those who disposed of medications at home, 66% put them directly into trash cans, while 12.1% deposited them in toilets of waterways. A further 5.4% gave unused medications to family members or friends.
Over 95% of the participants believed that the government should establish reasonable mechanisms for disposal of unused medicines, to avoid members of the public disposing of them inappropriately. As for the environmental impacts of different methods of disposal, 82% of the participants believed that taking them to hospitals or community pharmacies was best for the environment. While 50.9% believed that the cost of disposal of unused medicines should be borne by the government, 27.2% expressed a willingness to pay for the cost of disposal themselves. Around 48% of the public felt that waste medications should be recycled once every month.

Types and Sources of Unused Medications
The highest source of unused medicines was hospitals (67.4%), and the divisions which prescribed the most unused medicines were cardiology, family medicine and general medicine, in this order. Table 2 shows the types of medicines collected, classified according to their anatomical therapeutic chemical (ATC) code [24]. This system has fourteen main anatomical/pharmacological groups or 1st levels. Categorized by level, the medicines mostly frequently collected were those used for the alimentary tract and metabolism, the cardiovascular system, and the nervous system, in that order.  Table 3 shows the total value of unused medicines returned was around US$19,276, with antineoplastic agents-Vinorelbine the highest at US$12,656, followed by psycholeptics-Olanzapine and drugs used in diabetes-Insulin glargine, worth US$1128.80 and US$ 585.90 respectively. The drug with the highest unit price was Vinorelbine at US$79.10. The medications returned in the highest quantity were antithrombotic agents, with Aspirin the highest at 1806, followed by calcium channel blockers-Amlodipine and drugs used in diabetes-Repaglinide, of which 1222 and 1000 were returned respectively.
Because different medications have different dosages, drugs with similar components collected in this study have been calculated according to defined daily dose (DDD) [25]. DDD is defined as the assumed average maintenance dose per day for a drug used for its main indication in adults. The dosages of each medication were added together and divided by DDD to obtain the result. Table 4 shows that according to DDD ranking, the highest ranked category of drug collects was antithrombotic agents-Aspirin, at 1806. This was followed by calcium channel blockers-Amlodipine and beta blocking agents-Carvedilol, at 1222 and 476.67, respectively. Concerns/misconceptions about side effects 44 (9.2) 5 Personal feeling of no effect 35 (7.3) 6 Personal feeling of no illness 33 (6.9) 7 Symptoms are relieved but the physician still prescribes the medicine 28 (5.8) 8 Occurrence of side effects 28 (5.8) 9 Medication damage, deterioration, or expiration 25 (5.2) 10 Change of prescription by physician 24 (5.0) Table 4 shows the most frequently cited reason for medicines being unused was failure of patients to follow directions for use, such as regularly forgetting to take the medication, independent adjustment of dosage without instruction from physicians, and personal concerns or misconceptions about side effects. A secondary cause of unused medicines was unnecessary prescription by healthcare providers, as in cases when drugs were provided for symptoms that no longer existed or required medication.

Discussion
According to the data obtained from the 371 questionnaires, 12.1% of the public pour unused medicines into flush toilets or waterways. As the "Six Steps for Disposal of Unused Household Medicines" was issued six years ago, this raises the question of whether there are difficulties in executing these procedures, or whether there has been insufficient promotion of the steps and their importance. In addition, this study found that 66% of the respondents still dispose of unused drugs with household garbage. This raises environmental issues, as the public are unlikely to be able to differentiate between medicines with cytotoxicity or environmental hormones and general medications, meaning that the former are most probably being released into the environment. In addition, there are no garbage disposal furnaces set up in many regions of Taiwan, including Nantou County, Hualien County, Taitung County and the off-shore islands. Even in areas with furnaces, not all garbage is sent for high-temperature incineration, with much still being buried in landfill. This is likely to cause land damage and water pollution.
On the other hand, the participants in this study correctly perceived that disposal of unused drugs at hospitals or clinics had the least harmful impact on the environment. The chi square test carried out on the data indicated that there was no significant difference in responses that could be attributed to age group (p = 0.177), level of education (p = 0.642) or occupation (p = 0.198). Although up to 82 percent of the participants had correct perceptions about safe drug disposal, there was an obvious gap between perception and practice. In addition, more than 95% of the respondents agreed that they should avoid dealing with unused drugs themselves, and that a reasonable mechanism was needed for dealing with drug disposal. From this it can be seen that the current "Six Steps for Disposal of Unused Household Medicines" does not match the public's expectations in terms of minimizing the environmental impact of drug disposal.
With regard to establishing reasonable mechanisms for the disposal of unused medicines, it was notable that although 50.9% of the respondents believed the government should bear the cost, there were also 27.5% who expressed a willingness to pay for this disposal themselves. Among this group, three demographic factors were found to be significant, namelybeing aged under 40 (p = 0.0000), having a junior college or university level of education or above (p = 0.0000), and working in the field of medical care (p = 0.0000). These figures highlight a gradually growing consciousness among the public of environmental concerns, and a perception that the disposal of waste medications is not just the government's responsibility, but one in which all people must play their part. Apart from discussing whose responsibility it is to provide locations for recycling unused medications and pay for the expenses, it is even more important to look at the frequency with which this should take place. Under the present system, there are no regulations governing how often waste medications should be dealt with. This study found that 58% of respondents believed that a specific recycling day should be specified at least once a month, and accompanied by a suitable amount of publicity about the policy, so that citizens are clear about set times at which unused medicines can be disposed of, and develop the habit of regularly taking them to medical institutions to be dealt with by pharmacists.
Under present guidelines, the government is expected to take responsibility for the collection of unused medicines that contain cytotoxicity or environmental hormones, such as cancer drugs, hormones and antibiotics at hospitals or community pharmacies. Among the 480 prescriptions studied in this research, medicines in the categories of antineoplastic and immunomodulating agents, genito urinary system and sex hormones, antiinfectives for systemic use and hormonal preparations constituted only 7.1% of the total. There are several possible reasons why so few of these medications were collected. First, the public are relatively prudent in using such types of medicines, and are thus less likely to accumulate unused portions. Second, it is possible that the public have implemented the advocated policy and taken the medicines to hospitals or pharmacy for collection but may not have been recorded on the questionnaires. Finally, the public may have disposed of unused portions of these medicines by themselves, due to an inability to differentiate between medicines that they can personally discard and those that they cannot. The fact remains that if members of the public incorrectly dispose of unused medicines due to lack of awareness of the consequences, significant damage will be caused to the environment.
Pharmaceuticals are designed to target specific metabolic and molecular pathways in humans and animals, but they often have important side effects too. When introduced into the environment they may affect the same pathways in animals having identical or similar target organs, tissues, cells, or biomolecules [10]. The implications on the broader environment of inadvertent, unconscious ingestion of chemicals with known biological effects are not yet known, but may include chronic or acute toxicity of plant and animal species, the rise of antibiotic-resistant "superbacteria", and human or livestock tolerance to medications [16]. Therefore, once these medications go into the food chain, humans are likely to be confronted with more health problems.
In addition, the results of this study show that the generation of unused medicines is related to both the ways patients use medications and the ways physicians prescribe them. Of the 480 prescriptions of unused medicines found in this study, 40.5% were the result of patients forgetting to take them, and 17.5% were caused by patients adjusting dosages by themselves without the permission of their physicians. This shows that there is considerable room for improvement of public awareness of issues related to correct use of medications. Existing domestic research suggests that pharmacists on average have only 3 min to give patients instructions for the use of medicines when dispensing prescriptions. In order to better understand whether patients are taking medicines correctly at home and sufficiently understand the medicines they are using, pharmacists should spend more time providing counseling on the appropriate use of medications [26].
Although the majority of unused medications are generated through inappropriate patient behavior, there are also problems with the issuing of prescriptions by physicians. Medications that were unused due to symptom relief accounted for 21.7% of the total. This may have been due to physicians prescribing drugs for relief of mild symptoms for too many days. However, it is also possible that patients themselves felt that their symptoms had disappeared and decided themselves to stop taking the medication earlier than instructed. Similarly, 5.8% of medications were unused because patients reported that physicians continued to prescribe them even after their symptoms had been relieved. This is a clear case of physicians contributing to waste of medicines by prescribing them unnecessarily. Some respondents indicated on the questionnaire that although they had told pharmacists that their symptoms had been eased, physicians still issued the prescription to be taken "in case of need", or offered refillable prescriptions for patients with chronic illnesses for drugs that didn't need to be taken daily. When encountering such behavior from physicians, the public tend to accept it, since the prescriptions do not entail additional medical expenses, and unused medications can be returned to pharmacies for collection.
Local government authorities have recently been setting up more receiving stations for unused medicines and providing professional support for disposal, but staff at these stations may not understand the correct disposal methods, or implement legal provisions related to environmental protection. In addition, there are currently no mechanisms for uncovering unethical practices such as clandestine recycling and utilization of discarded medications. Therefore, there is an urgent need for the government to develop a set of norms and standards. It is recommended that waste medicine receiving stations be set up in all hospitals (clinics) and community pharmacies, and regulations for monthly disposal be drafted, in order to prevent people from disposing of medications themselves at home. In addition, reasonable remuneration should be provided to pharmacists who assist in the collection of these medications. In this way, citizens across Taiwan will be able to put the principles of correct disposal of unused medicines into practice.

Conclusions
The results of this research suggest that the majority of the public have an understanding of correct methods of disposal of medications, but frequently do not put them into practice. They also believe that current government systems of disposal are in need of improvement. The generation of pharmaceutical waste can be partially attributed to failure of patients to use medications appropriately, but there are also problems with prescription of unnecessary medications. This is an issue that requires further empirical investigation.
Based on the above findings, this paper proposes the following suggestions. First, receiving stations for unused medicines should be set up across Taiwan (including the offshore islands), along with the formulation of sound mechanisms and regulations for the processes of disposal. These could include the establishment of a requirement for unused medicines to be disposed of monthly and the establishment of a system of supervision by qualified pharmaceutical personnel, who should receive reasonable compensation for their services. In addition, community and campus education should be strengthened to discourage people from disposing of unused medicines themselves. Second, patients should be provided with more comprehensive guidance from pharmacists on correct use and disposal of medications. Pharmacists should spend more time providing medication counseling services to both patients and physicians, and strive to better understand the reasons for medicines being unused. These measures promise to reduce the generation of unused medicines and lessen their harm to the environment.
While this study has produced some thought-provoking findings, there are some limitations that must be acknowledged, as follows. First, the respondents to the questionnaire were not necessarily the person taking the drugs. Some may have been family members or friends returning the drugs on behalf of the patient. As a result, the majority of the patients in the sample were not elderly or lower-educated, as had been expected. Second, the study did not exclude elderly or illiterate people, some of whom may not have fully understood the topics in the questionnaire. Third, although the importance of the questionnaire and the confidentiality of the data were emphasized to participants (and pharmacists assisted them to complete the forms), the degree of seriousness with which the questions were taken and the accuracy of the responses cannot be guaranteed, and may have been affected by personal factors related to the respondent. Fourth, because this research set out to explore the types and causes of discarded drugs, only people who had actually disposed of drugs were included in the questionnaire, so the responses are not representative of the entire spectrum of the population in terms of their ways of dealing with unused drugs and awareness of related issues.