Medicine Storage, Wastage and Associated Determinants Among Urban Households: A Systematic Review of Household Surveys

Background: Irrational household storage of medicines is a world-wide problem resulting medicine wastage and associated harms, which imposes an additional burden on the health care system. The study has performed a systematic review of household surveys to provide strong evidences and policy implications through a comprehensive and comparative understanding of available global literatures. The review also maps existing literature on the burden, outcomes and affecting socio-economic factors of medicine storage and wastage. Methods: Five electronic databases were searched (from inception to 2019) for surveys that reviewed in-home medicine storage modality, size, cost and main determinants. The methodological quality of included studies was appraised through an adapted checklist developed by past studies. Results: From the initial 2604 records we identi ﬁ ed, 22 studies met our inclusion criteria. In 16 studies, medicine storage rates were reported for more than 70%. The maximum rate of potential (not in use medicines) and real (expired or without expiration date medicine) wastage were about 70 and 40 percent, respectively. The most common classes of medicines found in households belonged to the nervous system (18%) and anti-infective for systemic use (15%). Income, education, age, presence of chronic illness, female gender and insurance coverage were among the factors in�uencing medicine storage. The most commonly used method of disposal was throwing them in the garbage. Conclusions: Factors beyond medical needs determined medicine storage in the studied contexts which urges effective strategies in the supply and demand side of the medicine consumption chain. The �rst necessary step to mitigate home storage is adequate legislation and strict enforcement of regulations on dispensing, prescription and marketing of medicines. Patient pressure on excessive prescription, irrational storage and use of medicines deserve e�cient community centered programs for increasing awareness of these issues. Hazardous consequences of inappropriate disposal should be mitigated by different take back programs, particularly in low and middle income countries.


Background
Home storage of medicines is a worldwide health problem that can occur because of improper utilization of medicines and/or nonadherence with drug therapy [1][2][3][4][5].During past years, medicine utilization pattern has changed, leading to greater purchasing volumes and, excessive accumulation at home [6].According to the World Health Organization (WHO) more than 50% of medicines are prescribed and dispensed inappropriately, which cause unnecessary storage.[7] Medicines availability at home provokes irrational use of medicines and associated risks such as adverse drug events, accidental intoxication, disease concealment, drugdrug reaction, antibiotic resistance and nally economic loss [8][9][10][11][12].Seventy-ve percent of unintentional poisonings in the United States have occurred due to improper storage of drugs at home [13].Storage medicine in unsuitable places also triggers medicine wastage which imposes an economic burden on households, the health sector and the society [14][15][16].According to Siler et al.,40% of prescription drugs in the United States never actually used instead are either expired or thrown away [17].
By review of medicine chain, it can be clari ed that the problem starts with over prescription by health professionals [18][19][20], continues through improper decisions such as over-purchasing [6], non-adherence with medicine [19,21,22] and drug saving for future usage [3,23,24] and lasts with medicine wastage and its negative consequences [14,[25][26][27][28]. several systematic reviews have been conducted for assessment of different aspects of the medicine supply and consumption chain, for example, self-medication practice [29][30][31][32][33][34][35][36], medicine wastage [37,38] and disposal of unused medication [39,40].All of them attempted to determine the burden of the problem to households and society in terms of health-related risks and environmental or scal measures.Only one systematic review has investigated medicine home storage as a prior stage for wastage, selfmedication and associated risks.[41].Hussein et al (2016) have systematically reviewed related literature to study trends and practices in medicine storage; the last date of the study search was 2016.The authors included nine eligible studies then descriptively presented the storage and disposal pattern, types of stored medicine by drug name and associated risks of inappropriate storage and disposal of medicines.Finally, researchers qualitatively listed affecting factors without supporting the effect size and signi cance measures [41].Considering the importance of socio-economic determinants of medicine storage and wastage, we conducted the current systematic review to map existing evidence on the size and modality of stored medicine both individually and according to the Anatomical Therapeutic Chemical (ATC) classi cation [42].Such evidence could inform future researches on this eld.Together with, we fully scrutinized the household surveys who estimated socio-economic determinants of storage and wastage of medications through econometric models all around the world.The results of this part of the study can provide comprehensive evidence for planning and management strategies to mitigate the problem.

Method literature search procedure
This review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [43], and applying the PRISMA checklist (Additional le 1).PubMed, EMBASE, OVID, SCOPUS, ProQuest, and Google scholar were sought from inception to February 2016.All of the keywords were in English and the search strategy was restricted to English language publications.The terms used in this review were informed using a recent systematic review [37] and expanded based on co-author agreement (Additional le 2).The electronic search was complemented by hand-searching of related articles and the reference lists of nal studies.The research update was conducted using the same strategy in February 2019.Editorials, commentaries and opinion pieces were all excluded.To nd full-texts or inaccessible English versions, email contact was made by the authors.Due to the heterogeneity of papers, a meta-analysis was not performed and the results of studies are presented descriptively.

Requirements for inclusion
Screening of studies was conducted by two reviewers (AM&AJ), who reviewed studies independently.Initially, the titles and abstracts of studies were screened.Full texts were investigated for eligibility related reports.Disagreements were resolved by helping a third reviewer (MN).All population based household surveys which met following criteria were included in this systematic review: 1) study explicitly identi ed medicine storage and its determinant factors among households or individuals, 2) study reported quantitative survey data about this review's main questions, and 3) study published in or translated into English.Where papers included both urban and rural households, results were extracted for urban households.Studies reporting solely medicine wastage in terms of the proportion of households than medicine were excluded.Studies focusing solely on a speci c medicine or population subgroup were excluded.Finally, several studies were excluded because they were not a household survey and the source of data collection was pharmacies of occasional charity campaigns.

Extraction of items
Two reviewers (AM&AJ) extracted the following data from studies: the country where the study was conducted, year of publication, description of households included, sampling techniques, sample size, data for storage rate and place, medicine type, amount, category, method of disposal and numerical data for key determinants of medicine storage and wastage.The extracted data for inhome medicines were classi ed according to the rst level of the ATC classi cation.For studies not reporting their results in terms of ATC classi cation, the researchers classi ed both individual medicine or any reported category, based on the Guidelines for ATC Classi cation and Daily Dose De ned (DDD) assignment (2018) [42].The real wastage (expired or without expiration date) as well as the potential wastage (not in used medicine) was measured separately.

Outcomes
To answer the study question, following outcomes were selected: medicine storage rate (as a percentage of households), medicine per household, real medicine wastage, potential medicine wastage, category of medicines, category of wastage medicine, the frequency of individual medicine, factors associated with storage and wastage medicine, cost of wastage medicines, dosage forms of medicine, storage place and disposal method were reviewed.

Quality assessment
The methodological quality of eligible studies was assessed using an adapted version of the quality assessment checklist which had been developed and used by West et al [37].The researchers rated each question by giving the following answers Yes, No, Partial, Not applicable, or Unclear.

Literature search and eligible studies
Figure 1 provides information on the number of identi ed articles.From a total of 2604 initially identi ed citations, 578 were duplicates and 1991 did not meet the inclusion criteria.Finally, 35 full texts were fully scrutinized, of which 13 were excluded because of the lack of relevance, and 22 were recognized as eligible for nal review.A study was excluded because it was conducted in a rural area [44].Although two articles papers studied both urban and rural population, we were not able to separate results for urban subjects [1,45].Study by Wongpoowarak et al., reported only medicine wastage without providing data for storage modalities and its determinants [46].Three studies were excluded because they had reported medicine storage in terms of the household than medicine [28,47,48].Two studies were non-English [49,50], 2 studies addressed a speci c medicine [51,52] and 2 studies were focused on a particular population subgroup [53,54].

Characteristics of studies
All the studies were cross-sectional and used a questionnaire for gathering the relevant data from the study subjects.Two studies investigated both urban and rural household to assess medicine wastage but only urban household data was extracted [26,55].A total of 12750 households were included across the 22 studies from 2002 to 2019.The majority of studies were published from 2010 onwards (n = 18, 82%).The sample sizes varied within the studies included in this review.The lowest sample size was 102 households, whilst the highest sample size was 2600 (Table 1).The majority of studies were from the Asia and Africa although there was a wide range of geographical locations including Nigeria: 2, Jordan: 1, Saudi Arabia and Persian Gulf Countries: 1, Tanzania: 1, Iraq: 1, India: 4, Sudan: 1, Palestine: 1, Thailand: 1, Iran: 1, Serbia: 3, Uganda: 1, Pakistan: 1, Indonesia: 1 and Ethiopia:1.

Methodological quality
The quality assessment is summarized in Fig. 2. No articles were excluded based on quality appraisal.All the studies were population-based and they covered a total of 12750 households.Most studies presented an appropriate sampling method as probability sampling was used much more often (72.7%,n = 16) than nonprobability sampling (27.2%, n = 6).Most studies had good congruity between the research methodology and their research question, data collection, data analysis and interpretation of results so most studies were of good quality.The objectives were clearly stated and, in most studies, the results were well reported (86.3%, n = 19).Rate of wastage was explicitly reported in only three studies.However, for the rest, data were extracted according to the method which was introduced by Zargarzadeh et al [56].None of the studies found a con ict of interest and in less than half of them, ethical approval was reported.

Cost
The monetary value of wasted medicines was reported by 6 studies highlighting that between 10% and 50% of medicines belong to the wasted medicines.The study by Abou-Auda reported the value of wasted medicine for Saudi Arabia and the other Persian Gulf countries separately [21].However, this represents only a fraction of the wasted medicines at home, and the actual value of the wasted medicines is certainly greater than this (Table 4).

Conditions of storage
According to a guideline from WHO [69], the appropriate storage condition is keeping the medicines in out of reach places for children, for example, a cabinet or refrigerator which can protect them from being affected by environmental factors such as heat, humidity, light, and dust.Storage conditions of medicines were addressed in seven studies involving 3148 households [3, 22, 59-61, 64, 65].Results showed that a considerable amount of household medicines did not have appropriate storage conditions.Regarding the results of the studies, only about 40-60% of the medicines were in appropriate condition [3,22,59, 61, 65] (Fig. 4).The disposal method of medicine Of the 22 studies, six [15,55,57,[65][66][67] addressed the disposal practice among households.The most commonly used method of medicine disposal was throwing them in the garbage.According to the results of studies in Serbia [55,66,67], Nigeria [57], India [65], and Brazil [15], more than 80% of the households disposed of their medicines in the garbage.While medicine take-back program has globally known as a gold standard practice and has been conducted by many developed countries [70][71][72][73][74] but according to our results, the rate of households who adhering the take-back programs was reported from 0 [57,65] to 8% [15] (Fig. 5).

Discussion
This systematic review aimed to map the main ndings of published surveys on medicine storage and key determinants among households.The majority of the articles are from Asia and Africa, three from Europe and one from South America, indicating medical storage and related wastage of resources are problems in Asia and Africa.The paucity of published papers in Europe and Oceania should not be attached to the ignorance of the problem in that region; however, this might be because of their drug take-back policies in the form of social campaigns or routine back to pharmacy strategies [73,[75][76][77].The present systematic review not only maps global evidence on the modality and causality of household medicine storage but also remarkably addresses possible solutions for dealing with the problem in different contexts.
Given that our systematic review only examined household surveys that quantitatively represent the problem from the consumer's perspective, the results should be treated with caution.Therefore, a deeper exploration of medicine storage reasons and consequences through qualitative study designs and from other stakeholder's perspectives (healthcare providers and decisionmakers) could be supplementary for our results.
A total of 12750 households were included from 22 household surveys.In 16 studies (72.7%), more than 70% of households had medicine which half of them reported over 90% storage frequency.This high rate of storage raises the incidence of medicines wastage and its potential associated risks.Although in several countries medicine storage can be explained by disease pattern and health problems, for example, a high proportion (Gastrointestinal tract) GIT medicines in Jordan [61], malaria and anti-infective medicines in Tanzania [64], Iran [56], Ethiopia [60], Uganda [19] and Nigeria [24] and heart and diabetes medicines in Palestine [22], India [65] and Mexico [78], however in most of the countries the storage and consequently wastage are due to inappropriate prescription practice and inadequate patient adherence [3,14,19,21,22,60,66,79].
Patient attitudes and social values are important contributing factors that stimulate medicine storage and wastage in different forms.According to the studies from Saudi Arabia, Kuwait, UAE, Qatar, Oman and India, patients gratify drug prescription as an outcome of their visit to public health facilities [21,65].The role of patient attitudes has been con rmed by Hu J et al., and Norris P et al., implying that immigrants from developing countries like China, India, Korea, Egypt and other Asian and African countries have different perceptions towards accessing and use of medicines which triggers irrational use of medicines [80,81].
This review found evidence con rming that expired medicines were being used by households in low-and middle-income countries [24,66].Dayum et al., has reported that more than 97% of Nigerian households used expired medicine or kept them for future use [24].The same evidence either has been reported from high-income countries.[28,82] In Australia, households stated that they used expired medicines either one year or longer, after expiration [82].
Based on the literature, to some extent medicine wastage is inevitable because of several reasons such as patient death, treatment failure, medicine change and side effects [37].Then, to tackle medicine storage and wastage, smaller packages and shorter duration of prescriptions were endorsed as effective approaches by studies from both developed and developing countries [3,56,60,62,64,77,83,84].
Paracetamol (Acetaminophen) belonging to group N was the most stored medicine among participated households.Although the nding is not surprising because paracetamol is the rst-line treatment for pain and fever management [2,22,57,61], however the availability, affordability, convenience, product marketing and misconception about its safety compared to NSAIDs (Non-steroidal anti-in ammatory drugs) has made the paracetamol family be the rst choice of self-medication among people [2,22,57,61,62].Despite a limited number of studies reported that keeping a limited stock of these medicines might be cost-saving due to lower physician visit [3,26,62,63], but a much larger number of studies warned about the rising rate of self-medication, medicine wastage and its undesirable consequences [26,[85][86][87].The second most widely stored medicines were group J (15%).Antibiotics are the most known medicines in this group.Despite most health systems, antibiotics were licensed as prescription-only drugs, but they are easily purchased without a prescription [3,19,21,26,56,62].The discrepancy between the legislation and daily practice, high expectation about antibiotics effectiveness, low awareness regard to antibiotic resistance and adverse events, high cost of physician consultation have cited as reasons for antibiotics storage [88][89][90][91][92].The same evidence has been presented by Sawair et al., implying that patients visited the second physician because they did not receive antibiotics from the rst physician [93].
According to results reported by included studies, categories N (18%), J (15%), and A (14%), are the most stored medicines at home.This systematic review recognized a consistency between storage and wastage of these categories con rming the idea that medicine storage could potentially yield wastage. Inversely the category C, despite getting forth order among stored medicines, was not found among the rst ranks of potential and real wasted drugs.Such discrepancies have been attributed to the prescription and dispensing policies by several studies as well as patient's better compliance with treatment by others [2,3,56,60,65].
One of the main objectives of our systematic review was to study predicting factors of home storage of medicines, which can provide valuable evidence for designing and administering e cient health policies for mitigating the problem.Because of existing heterogeneity among the included studies, it was not possible to conduct a quantitative analysis of reported results.Thus the quantitative results of studies have narratively been synthesized.The results of the included studies showed that family size, number of employed members, level of education, health insurance coverage, being a woman, higher age group, economic state, presence of chronic illness, were associated with an increased number of home storage.
The positive association between home storage and wastage of medicine and household's purchasing power (higher income or lower prices) has also been con rmed by studies from high-income countries indicating that the problem is worldwide and factors beyond real health needs determine medicine demand and utilization [28,76,94,95].
According to the ndings of this study [22,56], insurance was recognized as a positive motive for more storage as well as more wastage, suggesting that, although having medical insurance could nancially protect household members against catastrophic health expenditures, but the lack of strict control on prescription, selling and demand of medicine could encounter entire health system to the rising cost of unnecessary storage and wastage of medicines.The presence or absence of medical insurance has been introduced as a stronger factor even than family income as a determinant of medicines stored at home [22,56].
The impact of education on drug storage is interestingly different from that on wastage.Most of the literature reported a positive association between the level of education of the household's head and the amount of medicine storage [3,22,56,[59][60][61].However, the number of medicine wastage was reported higher for illiterate or less educated counterparts [2,3,24,59].It is obvious that education level prevents drug wastage through better compliance with the treatment or better storage practice [3,19,22,26,59, 61] but according to the studies, educated people also tend to purchase more medicines from retail pharmacies, store medicines for future use and are more prone to self-medication [3,19,22,26,59,61].there are signi cant differences between men and women in terms of medicine storage modality, amount and wastage.Notwithstanding the higher rate of in-home storage among women [19,58], the lower wastage rate was linked to households whose stored medicines were organized by female subjects [15].Other studies have con rmed high storage rates among women [15,95,96] with some reasons such as; gender-related physiopathology, lifestyle, contact to the health system and other biological differences such as pregnancy [96,97].However other variations such as; women's tendency to excessive purchase and self-medication, lacks medical reasoning and can potentially be the focal point for improvement [98].A study by Becker showed that wasted medicine was more frequently used by men than women [83].
To the best of our ndings, there was a considerable variation in medicine storage place among studied countries, since the storage location was reportedly associated with decreased adherence, unfavorable clinical outcomes and potentially hazardous consequences [99][100][101].WHO guideline [69] seems to be a good solution for this problem in which the appropriate place is keeping medicine in enclosed, at a cool or dry place, at an inaccessible place for children.
Medicine package either can in uence storage and wastage.According to the literature, there was a positive association between oversized drugs and home storage especially for acute conditions such as pain or nausea and vomiting.Ekedahl et al., proposed a feasible way to decrease the volume of unused medicines in which a small "starter pack" is prescribed whenever a new treatment is initiated.If the consumption stopped, only small volumes would be stocked or discarded [23].A recent study by Bach et al., has reported 27 to 30% wastage in 3.5 mg vials of bortezomib compared to 1.5 mg vials [84].
The majority of the studies (72.7%) highlighted that most countries, did not have any guidelines for disposal of medicines, not only imposes a nancial burden on society but also creates environmental hazards through the accumulation of chemical ingredients in land lls and freshwater resources.High-income countries have conducted several schemes for disposal of household's unused medicines which could be adopted as a practical solution for low and middle-income countries.For example, the National Return and Disposal of Unwanted Medicines (Nat RUM) scheme in Australia which provides a route to return leftover medicines to community pharmacies [73].Studies in Sweden and Australia suggested a unitary medicine take-over system or educational campaigns at the national level instead of state-run programs [71,73].In Nebraska, especial boxes placed in pharmacies that allow consumers to return their medicines to the pharmacy [102].Arkaravichien et al [103]., and Yang et al [104]., proposed that the national health system can provide nancial incentives for pharmacies and households who participate in take-back schemes.

Strengths
This systematic review focused on the most important part of the consumption chain which is before medicine wastage and its related harms to the environment.Furthermore, most of the home storage was reviewed and reported which we believe our study results can provide evidence for decision-making at individual and community levels.
Limitation of the study Since all of the included studies have on quantitative household's medicine storage, then the household's preferences or their experiences as one of key in uential factors in triggering inappropriate storage or wastage have not addressed decently.The existing heterogeneity in design and results of included studies hampered pooled estimation and drawing consensus on main related concerns.

Conclusion
This systematic review gathered evidence from different geographical and demographical settings implies that in-home medicine storage is a worldwide problem that could lead to irrational use, wastage of medicine and hazardous outcomes associated with.
Factors beyond medical needs determine medicines storage in studied contexts which urges effective strategies in the supply and demand side of the medicine consumption chain.The rst necessary step to mitigate home storage is adequate legislation and strict enforcement of regulations on dispensing, prescription and marketing of medicines.Also, proper educational interventions targeting both health professionals and community members could be helpful in this regard.Patients pressure on excessive prescription, irrational storage and use of medicines and inappropriate disposal practices deserve e cient community centered programs for increasing awareness of these issues.The current data suggests that in low-and middle-income countries health systems should necessarily pay more attention to setting medicine return back programs to prevent environmental hazardous impacts of improper disposal of wasted medications.

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Table 2
The effect of Patient-related factors on medicine storage.

Table 2
The effect of Patient-related factors on medicine storage.