Assessment of knowledge, attitude, and practice of disposing and storing unused and expired medicines among the communities of Kathmandu, Nepal.

BACKGROUND: Unused medicines can be stored by many people at their places of residence and houses for later use. This study evaluated knowledge, and attitudes regarding unused and expired medicines and explored medicine storage and disposal practices among selected households in the Kathmandu valley, Nepal.
METHOD: A cross-sectional study with a two-stage cluster survey design was done using a semi-structured questionnaire from April to October 2021. The sample size (total number of households) after adjusting for design effect and non-response rate was 210 and the study population was the household heads. Simple random sampling was done to select clusters during the first stage and systematic random sampling to select households during the second stage. Descriptive statistics and t-test/one-way ANOVA were used to compare the respondents' average knowledge scores. Practice variables were presented using frequency distribution.
RESULTS: Around half the respondents were from the Kathmandu district, nearly 20% were from Bhaktapur and 30% were from Lalitpur. Nearly two-thirds were male and about 25% had a bachelor's degree. Nearly 90% of respondents agreed that storage of excess medicines at home may promote self-medication. Similarly, 97.6% of respondents agreed there is a lack of adequate information on the safe disposal of unused medicines. The majority [125 (59.5%)] of participants always checked the expiry date of medicines. The safe methods of medicine disposal were not known by 137 (65.2%) participants. Throwing in a dustbin was the preferred method of expired medicine disposal.
CONCLUSION: The level of knowledge and practice of disposing of unused and expired medicines requires improvement. Educational interventions may help improve awareness further. Creating a chart summarizing disposal procedures of common medicines is important. Similar studies in other regions are required.

Introduction

Many medicines have an expiry date and should not be used by patients after that date. Unused and leftover medicines can be stored by many people in their places of residence and houses for later use. Similarly, the medicines remaining after the patient’s recovery or after the occurrence of any adverse drug reactions can also be stored. All of these can contribute to the wastage of medicines [1,2].

Medicines are very important for enhancing the quality of life and managing disease conditions [3]. Proper and safe disposal of medicines is important as inappropriate and unsafe disposal can have harmful effects with traces of disposed medicines persisting in the environment and the water systems [4]. Safety precautions should be taken with the leftover medicines to avoid accidental and hazardous effects, especially among children, the elderly, and pregnant women. Misuse and abuse can also occur because of the leftover medicines in the households [5].

Safe disposal of medicines is an important issue. There is a lack of knowledge about safe and proper medicine disposal practices among consumers [6,7]. The common method used to dispose of medicines are throwing in the garbage, flushing down the toilets, and sharing with relatives and friends [8-10]. Programs for safe medicine disposal exist in developed countries but are lacking in developing countries like Nepal. Pharmacists are also unaware of the safe medicine disposal in developing countries [10]. The systems for medicine take-back are well established in developed countries like Canada, Australia, the United States, and Sweden [11,12]. Guidelines have been framed by the World Health Organization (WHO) for waste management in the pharmaceutical sector and burning the waste in the open-air is not recommended due to its possible toxicity to the environment [13].

In Nepal, there is evidence of poor awareness among the pharmacists working in community pharmacies about the safe disposal of medicines [14]. The provision of color coding and segregation of waste is missing in the pharmacies. Improper medicine disposal practices were seen in Pokhara, Nepal [13]. Proper storage of medicines is very important to maintain their therapeutic efficacy and prevent degradation. Improper disposal of medicines can lead to the presence of different types of medicines like hormones, tranquilizers, antiepileptics, antidepressants, and drugs against cancer in the water systems. Different types of toxic substances can be released along with gases that can affect human health [3,15-18].

Studies exploring the knowledge about the safe storage and disposal of medicine have not been carried out in Nepal. Hence, this study was conducted in the Kathmandu valley. The valley is divided into the three districts of Kathmandu, Lalitpur, and Bhaktapur. The findings of this study can be important to policymakers, health professionals, pharmaceutical companies, and the community in general.

The study evaluated knowledge, and attitude regarding unused and expired medicines and explored medicine storage and disposal practices among selected households in the Kathmandu valley, Nepal.

Methodology

Study area and period

The study was conducted in the Kathmandu Valley from April to October 2021. Kathmandu is the capital and the most populous city of Nepal. Healthcare is most developed in Kathmandu, and the valley is home to some of the best hospitals and clinics in the country. The area of Kathmandu valley is 665 square kilometers with a population of 1.442 million. The number of health facilities in the district is 2320 which is a high proportion of the total number in Nepal (6934) [19,20].

Study design

This was a cross-sectional study with a two-stage cluster survey design.

The quantitative study was conducted using a semi-structured questionnaire. The variables of age, gender, literacy, occupation, work experience, educational status, monthly income, number of household members, religion, and district of residence were recorded.

Sampling

There are 21 municipalities in the Kathmandu valley (18 urban municipalities and 3 rural municipalities). One ward (cluster) of each of these municipalities was randomly selected. This was followed by selecting 10 households randomly from each of the 21 selected clusters to obtain a total sample size of 210, similar to the one used during the WHO Expanded Program on Immunization (EPI) survey [21].

Simple Random sampling was used to select the clusters during the first stage and systematic random sampling to select households during the second stage.

There were 40 households selected from Bhaktapur district as it has 4 municipalities only. Kathmandu has 11 and Lalitpur has 6 municipalities so there were 110 samples from Kathmandu and 60 samples from the Lalitpur districts of the Kathmandu valley.

The study population was the household heads (HHH). If the HHH was not available at the time of the visit and two subsequent attempts, then the interview was conducted with the person who was acting as HHH in that household. The research assistant hired and trained for this study identified the ward office and handed over the ethical approval letter from the Nepal Health Research Council. After obtaining administrative approval, he selected 10 households using systematic random sampling and the sampling frame provided by the ward office. He then collected data from these 10 households.

Sample size calculation

There was one published study from Pokhara (Western Nepal) showing that 50% of the respondents were practicing proper drug disposal [10]. We took this as the reference to calculate the sample size for this study. As a similar study was not done earlier in the Kathmandu valley, we decided to use a margin of error of 10% giving a proper practice range of 40–60% with a 95% confidence interval for the sample size. We used www.openepi.com to calculate the sample size of 97 using these parameters. This sample size was multiplied by a design effect of 2 to adjust the variance introduced due to clusters (random wards) giving a sample size of 193, which was further adjusted with a 5% non-response rate giving the final minimum sample size of 203. As we planned to select an equal number of households from each randomly selected ward from each of the 21 municipalities of the Kathmandu Valley, we decided to randomly select 10 households from each municipality giving the final sample size of 210 for this study. The ward was selected using the “randbetween” function using the number of wards in each municipality as the frame whereas households were selected randomly from the sampling frame of the selected clusters using a systematic random sampling method. This was a two-stage cluster sampling with random sampling at both stages.

Data collection tool

A semi-structured questionnaire was designed by the researchers based on the literature and referring to the medicine disposal guidelines from the WHO and other international and national agencies [10,17,18]. The questionnaire had three sections. Section I obtained demographic details regarding age, gender, literacy, educational status, occupation, monthly income, work experience, family size, and district of residence. Section II contained questions regarding knowledge and attitude toward medicine storage and disposal. The knowledge questions were structured as multiple-choice questions (MCQs) whereas attitude questions measured agreement with the statement using a 4-point Likert scale. For the knowledge MCQs, right answers were scored as ‘1’ and wrong answers as ‘0’. A similar type of scoring has been used in other studies [10,17]. Section III contained questions about the disposal practice of unused and expired pharmaceuticals among the households. Some questions were open-ended to allow respondents to explain the barriers and facilitators of good practices.

The questionnaire was translated into the Nepali language for obtaining valid responses from the participants who cannot understand English. A bi-lingual expert performed a forward translation, and another bi-lingual expert independently performed the backward translation. The original and backward translated questionnaires were discussed by the study team multiple times and corresponding changes were done to the Nepali language questionnaire. The questionnaire was completed during a face-to-face interview by a trained data collector. The Nepali version of the questionnaire was pretested by administering it to 10 households among a non-selected cluster of the Kathmandu district by the research team members and queries raised by the respondents were noted. Necessary changes were made to the questionnaire to establish the face validity.

The finalized Nepali questionnaire was sent to five content experts for content validation. As per their reports, some of the questions were modified and corrected by the study team. A pilot test was done among 20 households, and the Cronbach’s alpha obtained was 0.863 for Knowledge and 0.866 for Attitude. Since the practice was measured using a mixed type of questions, internal consistency was not computed for this section.

Knowledge score was calculated by adding the correct (coded as 1) and incorrect (coded as 0) responses to 10 knowledge questions (Q1-Q10) with a possible score between 0 and 10 (maximum score of 10).

This scale was summarized using a histogram and descriptive statistics.

The histogram was found to be “tentatively” bell-shaped, so parametric tests (t-test and one-way ANOVA) were used to compare the knowledge score among different subgroups. T-test was used to compare knowledge scores among subgroups with two categories and one-way ANOVA and used to compare knowledge among subgroups with more than two categories.

The overall mean knowledge score was calculated using simple random.

PSS file by one of the team members. Once all the data were entered, it was checked with the original and any inconsistencies found were corrected as per the unique ID and the corresponding questionnaire by the study team. The final data was saved securely in the principal investigator’s personal laptop. A working copy with the de-identified file was used for the data analysis.

Descriptive statistics were used to present the data and t-test/one-way ANOVA tests to compare the average knowledge scores among respondents. Practice variables were presented using frequency distribution among the study population. Analysis of knowledge and attitude scores by municipalities and analysis of practice questions by districts are provided in the appendix. A p-value of less than 0.05 was considered statistically significant.

Ethical considerations

Ethical approval was obtained from the Ethical Review Board of Nepal Health Research Council, dated 24th March 2021 with a reference number 124/2021P.

Results

Table 1 shows the background characteristics of the respondents. Around half, 110 (52.4%) of the respondents were from Kathmandu district whereas 40 (19%) respondents were from Bhaktapur, and 60 (28.6%) respondents were from Lalitpur districts.

Table 1

Demographic characteristics of the study participants.

Variables	Number (Percentage)
District
Kathmandu	110 (52.4)
Bhaktapur	40 (19.0)
Lalitpur	60 (28.6)
Age (Median = 30 years)
<30 years	100 (47.6)
>= 30 years	110 (52.4)
Gender
Male	131 (62.4)
Female	79 (37.6)
Literacy status
Literate	195 (92.9)
Illiterate	15 (7.1)
Education level
No formal education and primary level	24 (11.4)
Secondary level	85 (40.5)
University level	101 (48.1)
Occupation
No work	22 (10.5)
Daily wage	108 (51.4)
Service	26 (12.4)
Retired	29 (13.8)
Housewife	16 (7.6)
Others	9 (4.3)
Average monthly income (NPR)
No income	32 (15.7)
Less than 10000	28 (8.8)
10000–20000	60 (29.4)
20000–40000	72(35.3)
40000–60000	22 (10.8)
Number of family members (Median = 5)
<5	85 (40.5)
>= 5	125 (59.5)

Note: The working experience variable is not described as 78% of cases had missing information.

Demographic characteristics of the participants

Knowledge response of the participants

Table 2 shows the responses to the ten knowledge questions. The complete questionnaire is shown in the Appendix. Nearly all the respondents (97.1%) had correct knowledge of the responsibility of the healthcare professional to improve knowledge of proper disposal of “unused medicine” at the household level. Around 97% of the respondents identified correct responses for inappropriate disposal of medicines in an unauthorized manner causing various harmful effects.

Table 2

Correct and incorrect responses for knowledge statements.

Question	Correct responseN (%)	Incorrect responseN (%)
Q1. ‘Expiry date of medicine’ means:	22 (10.5)	188 (89.5)
Q2. The term ‘Medicine disposal system’ refers to:	35 (16.7)	175 (83.3)
Q3. The term ‘Medicine take back system’ for the expired medicines is:	56 (26.7)	154 (73.3)
Q4. Inappropriate disposal of medicines in an unauthorized manner can cause all except:	203 (96.7)	7 (3.3)
Q5. The best method for preventing the hazardous effect of unused medicines can be:	155 (73.8)	55 (26.2)
Q6. The best strategy for preventing the hazardous effect of expired medicines can be:	116 (55.2)	94 (44.8)
Q7. Healthcare professionals will be responsible for improving the knowledge among households about the proper disposal of ‘Unused medicines’?	204 (97.1)	6 (2.9)
Q8. The responsible person (s) for improving the knowledge among households about the proper disposal of ‘Expired medicines’ is (are) healthcare professionals.	54 (25.7)	156 (74.3)
Q9. Most medicines should be stored in:	58 (27.6)	152 (72.4)
Q10. Storing excess medicines at home may promote self-medication:	191 (91.9)	19 (9)

The knowledge scores were significantly different only among respondents with different educational levels (p-value < 0.05). So, a pairwise comparison was done for this variable using Tukey’s HSD post hoc test, and a statistically significant difference was observed between respondents with Secondary and University levels of education only (Table 3).

Table 3

Comparison of knowledge scores among different subgroups of respondents.

Variable	Mean ± SD	p-value
District		0.473a
Kathmandu	6.57 ± 1.20
Lalitpur	6.78 ± 1.21
Bhaktapur	6.75 ± 1.03
Age		0.875b
< 30 years	6.68 ± 1.13
>= 30 years	6.65 ± 1.22
Gender		0.986b
Male	6.66 ± 1.20
Female	6.67 ± 1.13
Literacy status		0.254
Literate	6.69 ± 1.16
Illiterate	6.33 ± 1.29
Education level		0.015 a
None and Primary	5.54 ± 1.31
Secondary	5.51 ± 1.51
University	5.97 ± 1.06
Occupation		0.311
No work	6.68 ± 1.39
Daily wage	6.76 ± 1.20
Service	6.62 ± 1.10
Retired	6.38 ± 1.02
Housewife	6.31 ± 1.01
Other	7.22 ± 1.09
Monthly income		0.429a
No income	6.81 ± 1.26
< 10,000	6.17 ± 1.20
10,000–20,000	6.65 ± 1.21
20,000–40,000	6.69 ± 1.16
40,000–60,000	6.73 ± 0.99
Number of family members		0.498
< 5	6.60 ± 1.20
>= 5	6.71 ± 1.20

Note:

a = One-way ANOVA,

b = Independent samples student’s t-test.

Analysis of attitude of the participants

Table 4 shows that nearly 70% of the respondents “strongly agreed” and the remaining 29.5% “agreed” that outreach and awareness programs on the disposal of unused and expired medicines should be initiated.

Table 4

Distribution and summary statistics for the attitude questions.

Statement	Strongly Agreen (%)	Agreen (%)	Disagreen (%)	Strongly Disagreen (%)	Mean Score ± SD (Range: 1–4)
Q11: Unused medicines should not be thrown into dustbins	68 (32.4)	62 (29.5)	61 (29.0)	19 (9.0)	2.35 ± 1.21
Q12: Burning of expired medicines can release toxic substances which can be inhaled by the people	145 (69.0)	58 (27.6)	1 (0.5)	6 (2.9)	1.38±0.65
Q13: Unsafe practices of medicines disposal can pollute the environment	140 (66.7)	65 (31.0)	3 (1.4)	2 (1.1)	1.37±0.57
Q14: There should be a public awareness program about the harmful effects of improper medicine disposal practices	143 (68.1)	60 (28.6)	2 (1)	5 (2.4)	1.38±0.64
Q15: Community pharmacists have an important role in mitigating the problem of improper medicine disposal practices	105 (50.0)	91 (43.3)	2 (1)	12 (5.7)	1.65±0.78
Q16: Unused and expired medicines present potential risks at home	134 (63.8)	72 (34.3)	2 (1)	2 (1)	1.39±0.57
Q17: There is a lack of adequate information on the safe disposal of unused medicines	147 (70.0)	58 (27.6)	1 (0.5)	4 (1.9)	1.35±0.57
Q18: Children are more vulnerable to the risks associated with unused and expired household medicines	142 (67.6)	65 (31)	1 (0.5)	2 (1)	1.35±0.55
Q19: Doctors and health professionals should provide advice on the safe disposal of unused and expired household medicines	136 (64.8)	71 (33.8)	3 (1.4)	0 (0)	1.39±0.57
Q20: Drug take-back programs for unused and expired medicines should be mandatory	136 (64.8)	65 (31)	2 (1)	7 (3.3)	1.43±0.69
Q21: Outreach and awareness programs about how to dispose of unused and expired medicines should be initiated	146 (69.6)	62 (29.5)	1 (0.5)	1 (0.5)	1.32±0.51

Similarly, 70% of the respondents “strongly agreed” and the remaining 27.6% “agreed” that there is a lack of adequate information on the safe disposal of unused medicines. Likewise, nearly 65% of the respondents “strongly agreed” and another 34% “agreed” that doctors and health professionals should advise on the safe disposal of unused and expired household medicines.

An attitude score was computed by adding the responses to questions 11 to 21 and it was summarized using a histogram and descriptive statistics. The mean attitude score was 16.3 with a standard deviation of 4.497. This means 95% of the responses were between 16.30 ± 24.50 i.e., 7.30 and 25.30. As the minimum and maximum possible values of the attitude scale were 11 and 44 for these 11 questions measuring attitude, the scale mean was towards the minimum value suggesting a positive attitude towards the medicine storage and disposal mechanisms covered by these 11 questions. The histogram of the attitude scale was not bell-shaped, so the median test was used to compare attitude scores (dependent variable) with other (independent) variables (Table 5).

Table 5

Comparison of attitude scores among different subgroups of respondents.

Variable	Median± IQR	p-value
District		0.026 c
Kathmandu	14.00 ± 5.25
Lalitpur	17.00 ± 8.00
Bhaktapur	14.00 ± 6.75
Age		0.797
< 30 years	14.50 ± 7.00
>= 30 years	14.00 ± 8.00
Gender		0.544
Male	14.00 ± 6.00
Female	15.00 ± 9.00
Literacy status		0.515
Literate	14.00 ± 7.00
Illiterate	17.00 ± 11.00
Education level		0.194
None and Primary	14.5±10
Secondary	14 ±7
University	15 ±8
Occupation		0.194
No work	15.00 ± 9.00
Daily wage	14.00 ± 9.00
Service	14.00 ± 6.00
Retired	16.00 ± 7.00
Housewife	14.00 ± 2.00
Other	16.00 ± 8.00
Monthly income		0.087
No income	15.00 ± 8.00
< 10,000	16.50 ± 9.00
10,000–20,000	15.00 ± 9.00
20,000–40,000	14.00 ± 6.00
40,000–60,000	14.00 ± 2.00
Number of family members		0.733
< 5	15.00 ± 7.00
>= 5	14.00 ± 8.00

Note:

“c” represents the independent sample median test.

The median attitude score was significantly different according to the district of residence. So, a pairwise comparison was done, and it revealed a statistically different attitude score between Kathmandu (14) and Lalitpur (17) districts only. Kathmandu and Bhaktapur had a low median attitude scale (positive attitude) than the Lalitpur district.

Analysis of the practice of the participants

As the practice questions were mixed in nature (rating scale, multiple choices, true/false etc.), the practice score was not generated, and the results were presented descriptively using frequency distribution. Results for practice showed that 125 (59.5%) participants always checked the expiry date of medicines. For the statement regarding what do you do with any quantity of purchased medicine remaining unused at your home/hostel, many, 75 (35.7%), participants responded throwing it away in household garbage. Similarly, for taking medications as per a Doctor’s/ Pharmacist’s advice, about 120 (57.1%) participants responded that they always follow the advice. Practicing self-medication for minor illnesses like fever and headache was done sometimes by 80 (38.1%) respondents. The results regarding the readability of the expiry dates in the medicine dosage forms were responded to as always by 126 (60.0%) respondents.

The safe methods of medicine disposal were not known by 137 (65.2%) participants. Most respondents, 121 (57.6%) always used all prescribed medications as recommended. Eighty eight (41.9%) participants said that they rarely store unused medications. For liquid medicines, 144 (68.6%) participants never emptied the liquid in the toilet and recycled the glass bottle. Similarly, advising family members on proper medicine disposal was rarely carried out by 71 (33.8%) participants. of those responding 156 (74.3%) thought that the hazardous effect of unused and expired medicines can be minimized or controlled by providing proper guidance to the consumers. Excess quantity supplied was quoted as a reason for leftover or unused medicines at home by 69 (32.9%) respondents. Other reasons mentioned were storing the medicines for future use, sharing the medicines with their friends and relatives, and addressing the need for medicines in emergencies.

Throwing in a dustbin was the preferred method of expired medicine disposal by 135 (64.3%) respondents. Other comments were to burn the remaining medicines for their disposal. The best location to educate the community about the appropriate disposal of unused medicine was identified as the pharmacy while dispensing by 89 (42.4%) respondents. Other methods mentioned were the use of social media, the internet, and mass media to educate people about safe disposal practices.

Unused medicines were kept at home for future use by 141 (37.1%) respondents. The fact that safe disposal of medicines is necessary to prevent adverse reactions was mentioned by 96 (45.7%) participants. Other comments were to prevent environmental pollution and protect people from possible toxic effects of medicines.

Discussion

Medicine disposal is an important issue for the safety of our environment and human health. Medicines eventually reach the consumers and the patients. Not all medicines that reach consumers are consumed and some are leftover and stored in the houses of the consumers. WHO reports that more than half of the medicines are not properly prescribed and dispensed. This can lead to unwanted and unnecessary storage of medicines at houses [22]. In a developing country like Nepal, out-of-pocket expenditure is commonly incurred for buying medicines and managing health conditions. WHO estimates this expenditure as 70% of out of pocket expenditure [23].

In this study, knowledge scores were less among the participants from Kathmandu district, age more than 30 years, males, illiterates, participants having none or primary level of education, housewives, people having a monthly income less than 10000 NPR (80.65 USD) and with less than 5 family members. Similarly, the attitude scores were lower for participants from Kathmandu and Bhaktapur districts, those aged more than 30 years, males, illiterate, with secondary educational level, daily wage earners, service, and housewife groups, having monthly income between NPR 20000–40000 and 40000–60000 (162–323 and 323–484 USD) and participants with more than 5 family members. These groups of people should be prioritized for interventions for safe medicine disposal practices.

Knowledge

There are few studies about the roles of pharmacists in educating patients about safe medicine disposal but, their knowledge about safe disposal practices may not be good enough to provide consistent information to the patients [24]. The safe methods of medicine disposal were not known by 137 (65.2%) participants. Similarly, the medicine disposal system was also incorrectly answered by 83.3% of people. ‘Medicine take back system’ for the expired medicines was also incorrectly responded to by 73.3% of people. Another study mentioned that only 13.3% of respondents were aware of the proper medicine disposal methods and only 1% of participants knew about returning the medicines to the pharmacies for the medicine take-back systems [25]. A study revealed that about half (50.1%) of the participants had a good knowledge concerning the disposal of unused and expired medicines [26].

Attitude

Our results showed that about 70% of the respondents “strongly agreed” and the remaining “agreed” that outreach and awareness programs on the disposal of unused and expired medicines should be initiated. This is very similar to another study, where almost 70.8% of participants knew about the waste related to medicines and 59.2% checked the expiry dates of the medicines. This study also showed that 53,5% of the respondents strongly agreed that unused medicine can be a great risk at home [27].

The United States Food and Drug Administration (FDA) has recommended take back systems such as returning medicines to the pharmacies for safe disposal, as proper methods to be used by households [28]. Compared to the current study the situation was different in countries like Malaysia, where nearly all participants (93%) knew about the drug take-back systems [29]. The evidence also shows that participants from India knew better about the system for returning expired medicines to the pharmacies [25].

Likewise, nearly 65% of the respondents “strongly agreed” that doctors and health professionals should provide advice on the safe disposal of unused and expired household medicines. The best location to educate the community about the appropriate disposal of unused medicine was identified as at the pharmacy while dispensing. The largest proportion of participants, 120(31.3%), also preferred religious places to educate the public about proper medicine disposal methods, followed by community meeting places 100(26%). However, different preferences were shown in Malaysia where 60.7% of the respondents mentioned that the best way to educate the public about the disposal of unused medication was through school, university, and public campaigns [30].

Practice

A meta-analysis showed that the prevalence of storing medicines in houses was 77% [31]. In our study also only 88 (41.9%) participants said that they rarely store unused medications while 91.9% believed that storing excess medicines at home may promote self-medication. In Nepal like in many other developing countries, many medicines including prescription-only medicines can be purchased over the counter. While responsible self-medication can reduce the pressure on health systems inappropriate self-medication can lead to various adverse effects including the development of antimicrobial resistance [32,33]. The unsafe medicine disposal practices can also promote intoxication among the wildlife and can promote antimicrobial resistance [34]. A study from Nepal has mentioned that storage of unused and expired medicines at home can increase the risk of accidental or intentional ingestion of these substances and may create emergencies [35]. Another study from India has shown that about 87% of the community participants stored unused medicines at home [36]. This was more than in our study where only 41.9% of respondents stored unused medicines and in another study from Ethiopia, where 52.4% of participants stored medicines in their homes [37].

Results for practice showed that 125 (59.5%) participants always checked the expiry date of medicines. Good readability of the expiry dates in the medicines were responded to as always by 126 (60.0%) respondents. This finding was like a study from India, where two-thirds of the respondents always checked the expiry dates of the medicines [30]. The participants believed that the medicine becomes toxic if used after its expiry dates [30]. Majority of participants believed that the expired medicine must be returned to the manufacturers in another study done among dental residents [25].

The labelling of medicines is very important and should mention the expiry date in an easily visible manner. This becomes more important among the elderly and those with poor literacy [34]. Sharing the knowledge about the proper disposal of medicines is an urgent and important issue and the participants suggested that the dispensing pharmacist should explain the expiry dates of all the medicines with a special emphasis on the near-to-expiry ones.

For the statement on what do you do with any quantity of purchased medicine remaining unused at your home/hostel, many 75 (35.7%), participants response was throwing it away in the household garbage. This finding is like a study done in India, where more than 75% of respondents discarded expired medicines in the garbage which eventually reached the landfill sites [36]. Another study from India revealed that dental students also stored expired medicines and the preferred way to dispose of medicine was via normal household garbage [30]. Sasus et al found that half of the population surveyed had unused, leftover, or expired medicines at home, and over 75% of the population disposed of them through the normal waste bins, which ended in the landfills or dumpsites [38].

Medicines returned to pharmacies are not refunded in Nepal as most medicines are imported from the neighboring country, India, and are discarded under the supervision of the importers [39]. Improper practices for medicine disposal are seen among the people from the Nepali community and the researchers recommend that the government initiate medicine take-back systems.

Limitations

No physical checking of medicine storage was carried out, and the analyses and interpretation were purely based on the responses of the household heads. The reasons for storing the medicines in the houses of the participants were not studied.

Conclusion and recommendation

Educational level was the factor affecting knowledge whereas district of residence was the factor affecting attitude in this study. People knew about the expiry of medicines and methods to safely dispose of expired medicines. However, they practiced self-medication and stored medications at home and the safe methods of medicine disposal were not known by more than half of the participants. Most participants disposed of the unused and expired medicines in household garbage and the sink. This may cause harmful effects on the environment and can also have a harmful impact on the health of the public. This study also showed that there is a good level of knowledge and practice in disposing unused medicines among the public of Kathmandu Valley, Nepal. Educational interventions may help improve awareness of proper methods of medicine disposal. Developing and promoting a chart summarizing disposal procedures of common medicines can strengthen knowledge.

The medicine takeback system can be initially implemented in community pharmacies located in major cities and information about the system be widely disseminated. Similar studies in other regions are required.

19 Apr 2022

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Academic Editor at PLoS One”

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors assessed the knowledge, attitude and practice regarding the storage and disposal of unused and expired medicines in households of the Kathmandu valley in Nepal. I have below provide my comments and suggestions.

General

�  The methodology seems to be a bit unclear e.g. the sampling, of the sampling sufficient and if it is representative of the households in the Kathmandu valley. Please clarify.

�  Please critically revise the text across the manuscript for proper flow of ideas especially, the Introduction and Discussion sections.

Abstract

�  Objective: ‘to know’, please consider revising it to an action verb.

�  Please indicate the sample size in the abstract

�  The results subsection contains a lot of information on background variables. The authors could consider focusing on the main findings.

Introduction

�  The terms drug and medicine have been used in interchangeably throughout the manuscript. Please consider using the term medicine in the manuscript consistently.

�  In the introduction section, many of the paragraphs lack coherence with disjointed sentences. Please consider revising the introduction section with clear flow of in each of the paragraphs.

�  Page 7, line 108-110, please revise or possibly take it out as it seems to be a repetition.

Methodology

Please consider subdividing the methodology section into subsections:

�  Study area and period

�  Study design

�  Sampling

Here please clearly present the sample size determination aspect and the sampling technique aspects separately.

Sample size determination:

Please clarify how the sample size 210 was demined/calculated? Considering a multistage sampling was employed have the authors taken design effect in the sample size calculation? Please explain.

Sampling technique:

In regard to the sampling technique, in selecting the 10 households from each cluster please clarify what criterion was used to select a specific household (as the term quota sampling indicates nonprobability sampling).

�  Data collection and management

Please provide the questionnaire used in the study

�  Data entry analysis and management

�  Ethical considerations

Results

�  Please revise the sentence ‘Table 1 shows that around half of the respondents were from Kathmandu district whereas nearly 205 of respondents were from Bhaktapur and 30% respondents were from Lalitpur.’

�  How representative is the sample in the present study to the population of Kathmandu valley?

�  Although about half of the participants were described to have a university degree or higher the occupational categories represent mainly manual labor? Could the authors please explain this mismatch?

�  The authors could consider providing a more detailed age categorization.

�  The questions employed to assess the knowledge of participants (as presented in Table 2) are not clear (e.g. Q1 ‘Expiry date’: what aspect of this concept was measured?) what aspects were measured. Please consider making them clear.

�  Page 13, ‘Similarly, nearly 9 out of 10 respondents mentioned that the storage of excess medicines at home may promote self-medication.’ Can the authors clarify the perspective used in asking this question? Self-medication could involve prescription-only or OTC medicines. What view point was used in asking this question?

�  Page 13, lines 193 to 199 seems to belong in the Methodology section. Please consider moving it.

�  Page 13-14, lines 200-205, please explain how the different mean values were calculated, in the Methodology section.

�  In the ANOVA test for the mean knowledge score across educational levels please consider collapsing some of the groups to get sufficient numbers per cell. E.g. 1: primary or no formal education, 2: secondary education and 3: university education

�  Please explain the superscript in Table 5 (District, 0.026c).

�  What is the-value cut-off used to determine statistical significance. Please indicate (as in the Monthly income 0.087 in Table 5 seems to be considered significant)?

�  Page 21, line 238-241: was the interpretation based on a post hoc test? Please clarify

Discussion

�  Please provide a short summary of the main findings of the study in the first paragraph.

�  The discussion seems to focus on the practice aspect and the organization seems to lack flow. I think the authors could consider revising it in a way that discussion of the main findings on knowledge and attitude presented discussed in comparison with findings from other studies comes before the part about the practice aspect. The adjustment of the flow and presentation of the idea accordingly will be helpful to readers to follow the story message of the study findings in the context if previous studies.

�  Page 23, lines 84 to 89, the text provided seems to be out of place please consider moving this to the introduction or revise it in a way that it fits in to the idea of the discussion in a better way.

Reviewer #2: The research did not consider the design effect for sample size determination and the sampling technique was needing a probability method to include households in the study. The discussion should focus on the findings and discuss in comparison to other literatures.

Reviewer #3: Line 112 - "Cross-Sectional" is repeated twice. Kindly revise

Results: Information detailed in Table 1 are repeated extensively in-text. No need for the repetition

Table 1: Table to be formatted according to the journal's specification

Lines 188-192: Repetition of information detailed in Table 2. Kindly revise

Table 4: Not sure if the mean is the appropriate measure of central tendency here. The median has been postulated especially when using a Likert scale. The authors may want to explain their choice of mean. Also the authors to check that Table is formatted according to journal's specification

Lines 217-225: There is no need to repeat the information in the table in-text. One may highlight one or two important ones and then refer to the table.

Line 226: Same comment about the use of mean/median

Line 232: The more reason why should not be considered here at all

Table 5: please indicate the meaning of "c" in 0.026c as a footnote

Line 253: "Maximum respondents" - Authors may consider using "majority of the respondents"

Lines 280-289: The segment is not too relevant to the findings of the study. The authors may want to delete.

Line 293: Full stop(.) after "self-medication"

Lines 301-304: Using medical and nursing students for comparison here may not be too appropriate because of their knowledge base about medicines versus the general public

Lines 335-337: This statement can be re-phrased for better clarity

Lines 367-368: This part of the conclusion does not reflect results of the study - Please see Line 252 -"The safe methods of medicine disposal were not known by many, 137 (65.2%) participants". The authors to kindly revise this section of the manuscript.

Line 440 (reference no 20: "Organization WH"- To be corrected -World Health Organization

**********

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Prof Joseph O. Fadare

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Submitted filename: Comments to disposal.docx

Click here for additional data file.

24 May 2022

Revision letter

Lalitpur, Nepal

Date: 23rd May 2022

To

The Editor-in-Chief

PLOS ONE

Sub: Submission of the revised version of the manuscript for consideration of publication

Dear Editor-in-Chief,

We are resubmitting the manuscript “Assessment of knowledge, attitude, and practice of disposing and storing of unused and expired medicines among the communities of Nepal.” after revising it and making necessary corrections for consideration of publication in your esteemed journal. We are grateful to the reviewers for their constructive comments.

The amended Role of Funder statement in the cover letter is: "The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript."

The response to specific comments is as follows:

General comments

�  The write of the manuscript has grammatical, spelling and punctuation errors to be corrected.

Response: Thank you. We have corrected it as suggested.

Specific comments

1. Title need to be modified as ‘Assessment of knowledge, attitude and practice of disposing and storing of unused and expired medicines among the communities of Nepal’.

Response: Thank you. We have corrected it as suggested.

2. Method

• Clustering is applied for multistage sampling techniques of large population. Why multi-staging was applied for your research? How many households are in each cluster?

Response: Kathmandu valley has a large population and there are 21 municipalities. We needed to represent households of these 21 municipalities and thus we used the multi-staged cluster sampling approach. We selected 10 households from each cluster to fulfill the sample size obtained for the two-stage cluster survey. The 21 clusters were selected using simple random sampling methods from all the clusters (wards) listed in each of the municipalities. There were minimum number of 1800 households in Mahankal Gaupalika of Lalitpur district and maximum number of 82336 households in the Kathmandu Metropolitan City of Kathmandu districts as per 2011 census. The number of households in each cluster were as low as 200 and as high as 2576.

• The quota sampling technique is not appropriate for selecting the households as there will be different size households in each cluster. It would have been good to use probability method of selecting the households in each cluster as the method of sampling and then sample size could be increased to increase representativeness of the data.

Response: We calculated the sample size for the study and based on it we needed around 210 households. Thus, we decided to select 10 households randomly from each of the randomly selected clusters. We agree that a proportional allocation would have been better, but it would not give a representative sample size for municipalities with small number of households for this study. We could have increased the sample size using a different margin of error but the budget from the funding agency was not sufficient to include a greater number of respondents.

• The sample size determination would have been considering the design effect of multistage design to increase sample size. Why you did not consider it? Why did you determine to take 10 households from each cluster? It would have been good to include more households in the study.

Response: We have used the design effect of 2 in the sample size calculation and we also added a 5% non-response error thereafter. Details are provided below as minimum sample size without these adjustments was 97 only.

• Make it clear whether the pilot study was conducted on the households under the cluster of interest.

Response: Yes, we conducted the pilot test on the households under the cluster of interest in Lalitpur district.

• It would have been great to collect practice data, at least better to be supported, by observation method of data collection in each household.

Response: We used the questionnaire to obtain the “self-declared” data on practice; our study design was not based on observation. This is a very good suggestion, and we will use it if we do a similar study with a larger sample size in the future.

3. Results

• The description of Table 1 is not in agreement with the one presented in the table (205 versus 19% of respondents in Bhaktapur cluster)

Response: The total is 205 and 40 households were from Bhaktapur district as it has 4 municipalities only. Kathmandu has 11 and Lalitpur has 6 municipalities so there are 110 samples from Kathmandu and 60 samples from the Lalitpur districts of Kathmandu valley. This has been mentioned in the methods on page 11 line 205.

• After finishing the description of the findings, you have to put the referring table in the bracket as (Table …)

Response: Thank you. We have corrected it as suggested. Page 14, line 217.

• The overall description of the findings of practice of disposing and storing medicines has redundancy. So, put it in summarized form

Response: This has been edited as per the suggestion.

4. Discussion

• The introduction part of the discussion is not related to your findings rather focus on health insurance and about WHO guidelines. Therefore, please edit and discuss based on the findings you got in a clear and brief manner by comparing your findings with other similar literatures with justification.

Response: This has been edited and the details of the health insurance and WHO guidelines has been deleted. Findings have been discussed with other similar literature with justification.

• Based on the statistical analysis of knowledge and attitude, which group of people will be the target group for intervention strategies and discuss them very well.

Response: Knowledge scores were less for the participants from Kathmandu, age more than 30 years, males, illiterates, participants having none or primary level study, housewives, people having less than 10000 NPR (80.65 USD) and having less than 5 family members. Similarly, the attitude scores showed less scores for participants from Kathmandu and Bhaktapur, having age of more than 30 years, males, literates, with primary educational level, belonging to daily wage, service, and housewife groups, having monthly income NPR 20000-40000 and 40000-60000 (162-323 and 323-484 USD) and participants with more than 5 family members. This has been added in discussion section. Page number 24, Line number 320-328.

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

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https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

Response: We have formatted the manuscript as per the guidelines of the journal.

2. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

Response: The grant number is 2554, 24th March 2021, Funding Agency is the Nepal Health Research Council.

3. Thank you for stating the following financial disclosure:

“The study received funding of Nepalese rupees 125000 from the Nepal Health Research Council”

Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.""

If this statement is not correct you must amend it as needed.

Response: The amended Role of Funder statement in the cover letter is: "The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript."

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

Response: Thank you.

4. Thank you for stating the following in the Competing Interests section:

“PRS I have read the journal's policy and the author of this manuscript PRS has the following competing interests

Academic Editor at PLoS One”

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: ""This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Response: Updated Competing Interests statement in our cover letter mentions "This does not alter our adherence to PLOS ONE policies on sharing data and materials.”

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

Response: Thank you

________________________________________

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

Response: Thank you

________________________________________

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

Response: Thank you

________________________________________

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Response: We have copyedited the manuscript to improve the standard of written English.

________________________________________

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors assessed the knowledge, attitude and practice regarding the storage and disposal of unused and expired medicines in households of the Kathmandu valley in Nepal. I have below provide my comments and suggestions.

General

�  The methodology seems to be a bit unclear e.g. the sampling, of the sampling sufficient and if it is representative of the households in the Kathmandu valley. Please clarify.

Response: - We have used a sampling method that is representative of the households of the Kathmandu valley. The sample size is small due to the selection of one ward (or cluster) of the 21 municipalities to conduct the study within the budget provided.

�  Please critically revise the text across the manuscript for proper flow of ideas especially, the Introduction and Discussion sections.

Response: This has been carried out.

Abstract

�  Objective: ‘to know’, please consider revising it to an action verb.

Response: – We agree and are sorry for not catching this earlier. We have made the change requested. Page 3, line number 39.

�  Please indicate the sample size in the abstract

Response: Thank you. We have added the sample size in the abstract. Page 3, line number 43.

�  The results subsection contains a lot of information on background variables. The authors could consider focusing on the main findings.

Response: Thank you. We have focused on the main findings as suggested. Page 3, line number 49-56.

Introduction

�  The terms drug and medicine have been used in interchangeably throughout the manuscript. Please consider using the term medicine in the manuscript consistently.

Response: We have changed the term “drug” to “medicine” throughout the manuscript as suggested.

�  In the introduction section, many of the paragraphs lack coherence with disjointed sentences. Please consider revising the introduction section with clear flow of in each of the paragraphs.

Response: The Introduction section has been edited and the required corrections carried out.

�  Page 7, line 108-110, please revise or possibly take it out as it seems to be a repetition.

Response: We have taken out these sentences.

Methodology

Please consider subdividing the methodology section into subsections:

�  Study area and period

Response: We have added the study area and period as suggested. Page 6, line number 105-106.

�  Study design

Response: Has been added separately as suggested. Page 7, line number 107.

�  Sampling

Here please clearly present the sample size determination aspect and the sampling technique aspects separately.

Response: This has been presented separately as suggested. Page 7, line number 113-129.

Sample size determination:

Please clarify how the sample size 210 was demined/calculated? Considering a multistage sampling was employed have the authors taken design effect in the sample size calculation? Please explain.

Response: There was one published study from Pokhara (Western Nepal) showing 50% of the respondents doing the proper practice of drug disposal and we have provided the reference in the revised manuscript. We took this as the reference to calculate the sample size for this study. As such a study was not done earlier in Kathmandu valley, we decided to use a margin of error of 10% giving a proper practice range of 40-60% with a 95% confidence interval for the sample size. We used www.openepi.com to get the sample size of 97 using these parameters. This sample size was multiplied by a design effect of 2 to adjust the variance introduced due to clusters (random wards) giving a sample size of 193, which was further adjusted with a 5% non-response rate giving the final minimum sample size of 203. As we planned to select an equal number of households from the one randomly selected ward of each of the 21 municipalities of the Kathmandu Valley, we decided to randomly select 10 households each from each municipality giving the final sample size of 210 for this study. The ward was selected using the “randbetween” function in using the number of wards in each municipality as the frame whereas households were selected using systematic random sampling in the sampling frame obtained from the selected ward (cluster) office. This was a two-stage cluster sampling with random sampling in both stages.

Sampling technique:

In regard to the sampling technique, in selecting the 10 households from each cluster please clarify what criterion was used to select a specific household (as the term quota sampling indicates nonprobability sampling).

Response: The research assistant hired and trained for this study identified the ward office and handed over the ethical approval letter from the Nepal Health Research Council there. Once he got the administrative approval, he randomly selected the 10 households using the sampling frame provided by the ward office. He then proceeded with the data collection from these 10 households. We decided to select 10 households from each of 21 municipalities so fulfill the minimum sample size for the two-stage cluster survey design used in this study.

�  Data entry analysis and management

Response: The collected questionnaires were first assigned with the unique id, and it was checked manually by the study team. Once the study team was satisfied with the filled questionnaire, then it was entered directly into the pre-finalized SPSS file by one of the study members. Once all the data were entered, it was checked with frequencies and any inconsistencies found were corrected as per the unique id and the corresponding questionnaire by the study team. The final data was saved securely on the principal investigator’s personal laptop. A working copy with the de-identified file was used for the data analysis.

Please provide the questionnaire used in the study

Response: This has been added as a supplementary file.

�  Data entry analysis and management

Response: Has been mentioned as suggested.

�  Ethical considerations

Response: has been added as suggested.

Results

�  Please revise the sentence ‘Table 1 shows that around half of the respondents were from Kathmandu district whereas nearly 205 of respondents were from Bhaktapur and 30% respondents were from Lalitpur.’

Response: This has been done. Table 1 shows that around half, 110 (52.4%) of the respondents were from Kathmandu district whereas 40 (19.5%) of respondents were from Bhaktapur and 60 (28.6%) respondents were from Lalitpur.

Page 11, line number 203-205.

�  How representative is the sample in the present study to the population of Kathmandu valley?

Response: We have used a two-stage cluster sampling and the study population represents all the households of the Kathmandu valley.

�  Although about half of the participants were described to have a university degree or higher the occupational categories represent mainly manual labor? Could the authors please explain this mismatch?

Response: This may reflect the current economic situation in Nepal. Many persons with a degree and other educational qualifications may not be obtaining a job commensurate with their qualifications and may be involved in other occupational categories including manual labor. This was not an objective of our study, so we did not investigate it further.

�  The authors could consider providing a more detailed age categorization.

Response: The age, a continuous variable, was categorized into two categories using median as the cut-off value. We used the median to divide the whole data into two parts as the median is not prone to the presence of outliers and extreme values.

�  The questions employed to assess the knowledge of participants (as presented in Table 2) are not clear (e.g. Q1 ‘Expiry date’: what aspect of this concept was measured?) what aspects were measured. Please consider making them clear.

Response: We have provided the complete statements in table 2.

�  Page 13, ‘Similarly, nearly 9 out of 10 respondents mentioned that the storage of excess medicines at home may promote self-medication.’ Can the authors clarify the perspective used in asking this question? Self-medication could involve prescription-only or OTC medicines. What viewpoint was used in asking this question?

Response: In Nepal like in many other developing countries many medicines including prescription-only medicines can be purchased over the counter. While responsible self-medication can reduce the pressure on health systems inappropriate self-medication can lead to various adverse effects including the development of antimicrobial resistance. Page 23, line number 293-297.

�  Page 13, lines 193 to 199 seems to belong in the Methodology section. Please consider moving it.

Response: Yes, this sentence has been moved to methodology as suggested. Page 10, line number 174-176.

�  Page 13-14, lines 200-205, please explain how the different mean values were calculated, in the Methodology section.

Response: It has been added in the methodology section.

The first mean and 95% confidence errors were computed using a simple random sampling approach while the second mean and its 95% confidence error were computed using a complex/cluster sampling analysis plan in IBM SPSS software as we have used a two-stage cluster survey design in this study.

�  In the ANOVA test for the mean knowledge score across educational levels please consider collapsing some of the groups to get sufficient numbers per cell. E.g. 1: primary or no formal education, 2: secondary education and 3: university education

Response: We agree and have presented the modified analysis accordingly.

Descriptives

Knowledge scale

N Mean Std. Deviation Std. Error 95% Confidence Interval for Mean Minimum Maximum

Lower Bound Upper Bound

1 24 5.54 1.318 .269 4.99 6.10 2 7

2 85 5.51 1.151 .125 5.26 5.75 3 8

3 101 5.97 1.063 .106 5.76 6.18 3 8

Total 210 5.73 1.147 .079 5.58 5.89 2 8

ANOVA

Knowledge scale

Sum of Squares df Mean Square F Sig.

Between Groups 10.950 2 5.475 4.291 .015

Within Groups 264.116 207 1.276

Total 275.067 209

The p-value is still significant!

�  Please explain the superscript in Table 5 (District, 0.026c).

Response:

- The title of this table is not correct. It has been corrected as “Comparison of attitude score among different subgroups of respondents”

- The “c” represents the independent sample median test, and it is added to the bottom of table 5.

-

�  What is the-value cut-off used to determine statistical significance. Please indicate (as in the Monthly income 0.087 in Table 5 seems to be considered significant)?

Response: The cut-off used to determine the statistical significance was 0.05. The p-value of 0.087 of the monthly income in Table 5 was not statistically significant. We have made changes and not bolded or highlighted it now.

�  Page 21, line 238-241: was the interpretation based on a post hoc test? Please clarify

Discussion

Response- Yes, it was based on the post-hoc test given by the IBM SPSS software.

�  Please provide a short summary of the main findings of the study in the first paragraph.

Response-Thank you. We have provided it now in the first paragraph of the main finding.

�  The discussion seems to focus on the practice aspect and the organization seems to lack flow. I think the authors could consider revising it in a way that discussion of the main findings on knowledge and attitude presented discussed in comparison with findings from other studies comes before the part about the practice aspect. The adjustment of the flow and presentation of the idea accordingly will be helpful to readers to follow the story message of the study findings in the context if previous studies.

This has been done.

�  Page 23, lines 84 to 89, the text provided seems to be out of place please consider moving this to the introduction or revise it in a way that it fits in to the idea of the discussion in a better way.

Response: We have deleted these sentences as suggested by the second reviewer.

Reviewer #2:

The research did not consider the design effect for sample size determination and the sampling technique was needing a probability method to include households in the study.

The discussion should focus on the findings and discuss in comparison to other literatures.

Response: Thank you. We have used a design effect of 2 while calculating the sample size and used 5% non-response rate as the sample size was 97 without these adjustments. We selected one ward (cluster) randomly from each of 21 municipalities using “randbetwen” function of excel. The research assistant compiled the sampling frame (households) in the selected clusters and selected 10 households using systematic random sampling in the sampling frame provided by the ward office after getting approval from the administrators. This was a two-stage cluster sampling design.

We have now focused on the key finding and compared and contrasted these with the literature.

Reviewer #3: Line 112 - "Cross-Sectional" is repeated twice. Kindly revise

Response: Thank you. We have done the correction now.

Results: Information detailed in Table 1 are repeated extensively in-text. No need for the repetition

The repetition has been reduced.

Table 1: Table to be formatted according to the journal's specification

Response: Thank you. We have revised it now.

Lines 188-192: Repetition of information detailed in Table 2. Kindly revise

Response: Thank you. We have revised it now.

Table 4: Not sure if the mean is the appropriate measure of central tendency here. The median has been postulated especially when using a Likert scale. The authors may want to explain their choice of mean. Also the authors to check that Table is formatted according to journal's specification

Response: The mean and standard deviation presented here are the “weighted average” based on frequencies and the forced Likert scale as weights. This is a proxy of the “consensus index” and is used here to show the direction of the attitude. We have used the median and IQR while comparing the attitude scale with background variables in Table 5.

Thank you. We have formatted the table according to the journal’s specification.

Lines 217-225: There is no need to repeat the information in the table in-text. One may highlight one or two important ones and then refer to the table.

Response: Thank you. We have made the suggested changes.

Line 226: Same comment about the use of mean/median

Response: When a scale is formed using a Likert item, it will have different levels of measurement i.e. interval from ordinal. Thus, we have summarized the attitude scale using mean and standard deviation. We have not used regular arithmetic mean and standard deviation to summarize the individual item, however, as they cannot be done as per their measurement scale.

Line 232: The more reason why should not be considered here at all

Response: We have treated the attitude scale as the interval scale variable and hence it was assessed with a histogram to check whether the parametric or non-parametric tests were appropriate for the summated attitude scale variable.

Table 5: please indicate the meaning of "c" in 0.026c as a footnote

Response: The “c” means independent sample median test.

Line 253: "Maximum respondents" - Authors may consider using "majority of the respondents"

Response: Thank you. We have changed as per the suggestion now.

Lines 280-289: The segment is not too relevant to the findings of the study. The authors may want to delete.

Response: Thank you. We have deleted it from the text.

Line 293: Full stop(.) after "self-medication"

Response: Thank you. We have added the full stop now.

Lines 301-304: Using medical and nursing students for comparison here may not be too appropriate because of their knowledge base about medicines versus the general public

Response: Thank you. We have modified the text as per the suggestion. More studies on medicine disposal among the general public has been added as suggested. Page 23, line number 301 to 306.

1. Nepal S, Giri A, Bhandari R. Poor and Unsatisfactory Disposal of Expired and Unused Pharmaceuticals: A Global Issue. Curr Drug Saf. 2020;15(3):167-172.

2. Manocha S, Suranagi UD, Sah RK. Current Disposal Practices of Unused and Expired Medicines Among General Public in Delhi and National Capital Region, India. Curr Drug Saf. 2020;15(1):13-19.

3. Kahsay H, Ahmedin M, Kebede B, Gebrezihar K, Araya H, Tesfay D. Assessment of Knowledge, Attitude, and Disposal Practice of Unused and Expired Pharmaceuticals in Community of Adigrat City, Northern Ethiopia. J Environ Public Health. 2020;2020:6725423.

Lines 335-337: This statement can be re-phrased for better clarity

Response: Thank you. We have re-phrased the statement now.

Lines 367-368: This part of the conclusion does not reflect results of the study - Please see Line 252 -"The safe methods of medicine disposal were not known by many, 137 (65.2%) participants". The authors to kindly revise this section of the manuscript.

Response: Thank you. We have revised this section of the manuscript.

Line 440 (reference no 20: "Organization WH"- To be corrected -World Health Organization

Response: Thank you. We have corrected reference number 20 as suggested.

________________________________________

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Prof Joseph O. Fadare

New references have been added and several references have been renumbered. The changes suggested by the reviewers have been accepted and carried out in the manuscript using red font. All cited references are accurate. The revisions have been approved by all the authors.

Hoping for a favorable consideration

Thanking you

Yours Sincerely,

Nisha Jha and coauthors

Professor, Department of Pharmacology

KIST Medical College

Imadol, Lalitpur, Nepal

E-mail: nishajha32@gmail.com

Phone: 00977-01-5201680

Fax: 00977-01-5201496

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

14 Jun 2022

21 Jul 2022

Revision letter

Lalitpur, Nepal

Date: 22nd July 2022

To

The Editor-in-Chief

PLOS ONE

Sub: Submission of the revised version of the manuscript for consideration of publication

Dear Editor-in-Chief,

We are resubmitting the manuscript “Assessment of knowledge, attitude, and practice of disposing and storing unused and expired medicines among the communities of Nepal.” after revising it and making necessary corrections for consideration for publication in your esteemed journal. We are grateful to the reviewers for their constructive comments.

The response to specific comments is as follows:

Abstract

Comment 1- In page 55 of the manuscript file, on page 3 line 39 to 41, ‘The study explored the status of medicine disposal and storage practices and evaluated knowledge, attitude, and practice of medicine storage and disposal techniques among households of the three districts of the Kathmandu valley, Nepal.’ Please revise the sentence, as it stands it seems a bit confusing and contains repetitions.

Response: This has been corrected as:

The study evaluated knowledge, and attitude regarding unused and expired medicines and explored medicine storage and disposal practices among selected households in the Kathmandu valley, Nepal.

Comment 2- In page 55 of the manuscript file, on page 3, the sentences in Results subsection ‘The safe methods of medicine disposal were not known by 137 (65.2%) participants. Throwing in a dustbin was the preferred method of expired medicine disposal.’ Seem to be contradictory to the conclusion subsection ‘There is good level of knowledge and practice 58 of disposing the unused medicines among the public of Kathmandu Valley’ please explain why or correct the conclusion

Response: The statement has been corrected in the conclusion part as stated below.

The level of knowledge and practice of disposing of unused and expired medicines requires improvement.

Introduction

Comment 3 - At the end of the introduction section the objective stated ‘This study evaluates medicine disposal and storage practices and knowledge, attitude, and practice of medicine storage and disposal techniques among households residing in the three districts of the Kathmandu valley.’ Please make the objective presented at the end of the introduction section the same as the one in the abstract (of course after revising the sentence to be concise and clear)

Response: This has been changed as suggested.

The study evaluated knowledge, and attitude regarding unused and expired medicines and explored medicine storage and disposal practices among selected households in the Kathmandu valley, Nepal.

Methodology

Comment 4- ‘study area and period’: in this subsection the authors could consider providing a short introduction to Kathmandu to readers (as the readership of the journal is international) who may not be familiar with the area. For example, the authors could describe the general socio-demographic and health information of the area.

Response: A description of Kathmandu has been added as suggested at the beginning of the Methodology section.

Comment 5 - Was there a cut-off score to identify a respondent considered knowledgeable on medicine storage and disposal?

Response: We did not use any cut-off score to classify the knowledge score.

Comment 6- Have the authors considered conducting a regression analysis (for the knowledge and attitude scores) to assess the factors associated to them in a manner that will take account of potential confounders? This is crucial in determining which factors are really responsible for/predict knowledge or attitude after controlling for other potential confounders.

Response: Thank you. Since the knowledge score was only significantly different according to one of the socio-economic variables on the t-test/1-way ANOVA and other variables had a p-value > 0.25, it did not make sense to proceed with the multivariate analysis to find an independent effect controlling for confounders using regression analysis. Attitude score was found to be skewed and so an independent samples median test was used to compare it across socio-demographic variables, linear regression was not applicable for this data and thus it was not considered for the multivariate analysis.

Results

Comment 7- Please use subheadings to identify sections such as ‘Demographic characteristics’, ‘Knowledge’, ‘Attitude’ and ‘Practice’. This would help o low o ideas and for ease of following by readers.

Response: This has been added as suggested.

Discussion

Comment 8- I believe the discussion section still requires more work in terms of structure and flow of ideas. I find it difficult to follow the thread of thought in this section. In my opinion, starting by providing a summary of the main findings in the first paragraph and in the following paragraphs expounding on these findings by comparing with other studies and discussing implications might improve this section. In terms of order the themes and findings within knowledge, attitude and practice components could be presented in the sequential paragraphs.

Response: This has been corrected as suggested.

Conclusion

Comment 9- I notice a similar issue in the Conclusion where practice issues are presented before addressing knowledge.

Response: This has been addressed as suggested.

Comment 10- Please address this and be consistent in terms of ideas (i.e. I believe the findings should inform the discussion and conclusions).

Response: Thank you. This has been corrected as suggested.

Reviewer #3: Most of the suggested revisions were not carried out by the authors.

Examples:

Comment 11- Lines 301 -304 : Using medical and nursing students for comparison here may not be too appropriate because of their knowledge base about medicines versus the general public

Response: Thank you for the comment. The newly added references are for comparing the results with the general public and not with the nursing and medical students.

Comment 12- Lines 335-337: This statement can be re-phrased for better clarity

Response: This has been rephrased as: Another study mentioned that only 13.3% of respondents were aware of the proper medicine disposal methods and only 1% of participants knew about returning the medicines to the pharmacies for the medicine take-back systems.25

Comment 13- Lines 217-223: There is no need to repeat the information in the table in-text. One may highlight one or two important ones and then refer to the table.

Response: The corrected part is written as: The knowledge scores were significantly different only among respondents with different educational levels (p-value < 0.05). So, a pairwise comparison was done for this variable using Tukey’s HSD post-hoc test, and a statistically significant difference was observed between respondents with Secondary and University levels only (Table 3).

Comment 14- The tables to conform to the journal's specifications

Response: The tables are as per the guidelines of the journal.

Comment 15- Overall, the standard of English language needs to be improved upon

Response: The manuscript has been copyedited for language issues.

________________________________________

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #3: Yes: Prof. Joseph O. Fadare

Hoping for a favorable consideration

Thanking you

Yours Sincerely,

Nisha Jha and coauthors

Professor, Department of Pharmacology

KIST Medical College

Imadol, Lalitpur, Nepal

E-mail: nishajha32@gmail.com

Phone: 00977-01-5201680

Fax: 00977-01-5201496

Submitted filename: Response to Reviewers 22nd July.docx

Click here for additional data file.

25 Jul 2022

Assessment of knowledge, attitude, and practice of disposing and storing unused and expired medicines among the communities of Kathmandu, Nepal.

PONE-D-21-38637R2

Dear Dr. Jha,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

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Academic Editor

PLOS ONE

27 Jul 2022

PONE-D-21-38637R2

Assessment of knowledge, attitude, and practice of disposing and storing unused and expired medicines among the communities of Kathmandu, Nepal.

Dear Dr. Jha:

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