Irrational use of medicine in Arab countries: findings from a systematic review of literature (2000–2019)

Abstract

Objective

This study aimed to analyse the patterns of the irrational use of medicines in Arab countries and to determine the factors contributing to these patterns.

Methods

A systematic literature review was conducted using two major databases: PubMed and Scopus. The systematic search targeted original studies conducted in Arab countries from 2000 to 2019. A conceptual framework was adopted from a previous study and was utilized to assess the irrational use of medicines and its influencing factors.

Results

A total of 136 studies from 16 Arab countries were included. Almost all were cross-sectional studies. Most focused on evaluating the irrational use of medicines rather than investigating the cause. The number of medications per encounter was 2.3 which is within the limits of developed countries (2.7). The percentage of antibiotics per 100 encounter was 50.1% and the percentage of injections prescribed per 100 encounter was 15.2%. The consumption of antibiotic and injections was much higher than that recommended by WHO. At the same time, the review identified that one fourth of all medications were unnecessarily prescribed.

Summary

The literature review revealed that the irrational use of medicine is prevalent in most Arab countries. Excessive use of antibiotics was the most commonly observed pattern. Therefore, there is a need to conduct further research to identify the factors that drive the irrational use of medicines in Arab countries and then to make recommendations to mitigate this issue.

Introduction

The irrational use of medicines is a complex and prevalent problem worldwide. The World Health Organisation (WHO) has reported that over 50% of all medicines are prescribed, distributed, or sold improperly around the world.^[1] The irrational use of medicines represents a major conundrum for healthcare systems, in both developing and developed countries.^{[2, 3]} The prevalence of irrational medicine use is evident in high-income countries (e.g. Canada, USA, Australia and Kuwait) and low-income countries.^[4] The irrational use of medicines manifests itself in various forms, including excessive use of antibiotics and suboptimal dosing, polypharmacy, overuse of injections, prescribing medicines that contravene clinical guidelines and patient self-treatment with prescription medicines.^[5]

The irrational use of medicines can lead to detrimental health outcomes including an increase in adverse drug reactions,^[6] particularly among co-morbid and geriatric patients. This can result in the emergence of antimicrobial drug resistance,^{[7, 8]} drug dependency (e.g. tranquilisers and pain killers),^[1] longer hospitalisation, reduction in the quality of drug therapy and lack of trust in healthcare policy.^[9]

Additionally, it has far-reaching implications on local economies, increasing the overall expenditure on health and wasting valuable resources,^{[1, 3, 10]} due to patient demand^[11] and consumption of scarce resources.^[7] Only a few developing countries are currently monitoring the irrational use of medicines.^[12]

Various factors drive this phenomenon, such as unregulated availability of medicines, lack of awareness, skills, or independent information, unethical promotion of medicines, high workload for healthcare providers and commercial incentives.^[11] These drivers can be mapped into various stages of the cycle of medicine use. They can generally be categorised into those stemming from prescribers, patients, health system, supply system, industry impacts, drug information or misinformation, regulations, or a combination thereof.^[1] The WHO reported that about one-third of people worldwide could not access essential medicines.^[11] Consequently, patients are more driven to obtain medicines with or without medical guidance or even resort to self-medication.^[13] Self-medication can lead to several risks, including polypharmacy, misdiagnosis, drug overdose, adverse drug interactions and prolonged duration of use.^{[14, 15]}

Many drug use indicators described by the WHO, both core and complementary, are used to describe irrational patterns of drug use and prescribing behaviour.^[16]

The current study targeted Arabic-speaking countries in the Middle East and North Africa region. Pharmaceutical practices in Arab countries are generally identical, with slight differences in policies, regulations and education.^[17] Consumers in Arab countries can access medications conveniently without a formal prescription as long as they are willing to pay.^[17]

This study systematically reviewed the literature related to the irrational use of medicines in Arab countries. The objectives were: (i) to analyse the patterns of the irrational use of medicines through predefined indicators and (ii) to identify the factors that contribute to the irrational use of medicines in Arab countries using the categorisation described by Mao et al.^[3]

Methods

Study design

This study adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines^[18] to conduct a systematic review of the literature on the irrational use of medicines in Arab countries. It was registered in the ‘International prospective register of systematic reviews (PROSPERO)’ under the number ‘CRD 42020171231’.

Scope of the study

The definition of irrational use of medicines is quite broad. Hence, the current study adopted the conceptual framework developed by Mao et al.,^[3] where WHO’s Access to Medicine Guidelines was followed^[11] to conceptualise their final framework. The guideline divided the definition into four patterns: using too many kinds of drugs, inappropriate choice of antibiotics and injections, unnecessary use of drugs and adherence to clinical guidelines (objective 1). Additionally, the framework was also utilised to synthesise the reviewed data, where nine indicators were used to assess the factors beyond these patterns (objective 2).

Inclusion and exclusion criteria

Peer-reviewed studies published in English were included, while, commentaries, editorials and letters to the editor, books and book chapters and systematic reviews (including narrative reviews and meta-analyses) were excluded.

Regarding study design: case-control study, cohort study, retrospective study, cross-sectional study, before and after comparison, pilot study and stimulated methods were included for both objectives, while qualitative studies were also accepted for objective 2. Biopharmaceutical studies, laboratory studies and studies that did not report study designs/data collection methods/sampling framework/sample size/study population were excluded. Except for qualitative studies, studies with a sample size of less than 50 people, 30 prescriptions per facility, a minimum of 2 pharmacies/health facilities or 2 or less facilities were excluded

Search strategy

Papers reporting relevant studies assessing the irrational use of medicines were retrieved by thoroughly searching PubMed/MEDLINE and Scopus databases from the years 2000 to 2019. To ensure the comprehensiveness of key search terms, a pilot search in the PubMed database was conducted, where a combination of free text and index terms was employed to maximise the retrieval of potentially relevant studies. The final search keywords were:

• (Drug OR medicine OR pharmaceutical product OR injection drug OR antibiotic),

• And (misuse OR rational OR ration OR proper OR abuse OR over),

• And (prescribe OR prescription OR use OR dispense OR self-treatment OR self-medication OR health-seeking behaviour OR self-prescript OR over the counter OR polypharmacy)

• And (Arab OR Arabic OR Middle East OR Algeria OR Bahrain OR Comoro’s OR Djibouti OR Egypt OR Iraq OR Jordan OR Kuwait OR Lebanon OR Libya OR Mauritania OR Morocco OR Oman OR Palestine OR Qatar OR Saudi Arabia OR Somalia OR Sudan OR Syria OR Tunisia OR United Arab Emirates OR Yemen),^[19]

• And (General public or community or general population).

A further manual search was conducted on the reference lists of the included articles to identify if more studies potentially meet the criteria. Moreover, the search was limited to papers published in the English language.

Study selection

The eligibility of each paper, mapped to the inclusion and exclusion criteria, was assessed independently by two reviewers: AM and KA. First, the title and the abstract were screened, followed by the full text. The reference lists were searched to retrieve related papers. Excluded articles were documented along with a justification. Finally, discussion and mutual consensus resolved any inconsistent opinions between the reviewers. Endnote X7 (Clarivate Analytics) was employed to manage the overall process.

Quality assessment

The quality of each selected paper was evaluated based on a 10-point checklist from the Critical Appraisal Skills Program (CASP).^[20] Specifically, the study used an adapted CASP checklist for qualitative and cohort studies. The ratings were obtained through the checklist where one point was given if the criteria were fulfilled for each question with a maximum score of 10. The reviewers (AM and KA) rated the literature independently, and the average score between them was calculated as the final score. Disagreements between the reviewers were resolved through a discussion until a consensus on all scores was reached.

Data extraction

Two researchers (AM and KA) independently undertook data extraction. The patterns of the irrational use of medicines, along with their critical factors, were synthesised in line with Mao et al^[3] conceptual framework, which was derived from the WHO guidelines. Any inconsistent opinions were discussed and settled via consensus by the reviewers. The identified indicators were extracted without any calculation or revision. These indicators included the number of medicines per encounter, the percentage of antibiotics prescribed per 100 encounters, the number of antibiotics per encounter and the percentage of injections prescribed per 100 encounters. The researcher employed the terms used by the studies, where polypharmacy was defined as four, five, or more medicines per prescription. Studies characterised drugs as unnecessary if there was no clinical indication for such medication, and the physicians themselves reported that they had prescribed a medication unnecessarily or for unjustified reasons.

Results

Retrieval, identification and characteristics of the studies

The initial search yielded 7720 potentially relevant articles. After applying the inclusion and exclusion criteria, 136 studies were included. Figure 1 represents a flow chart of study identification and inclusion/exclusion. Table 1 indicates the number of publications per Arab country. Sixteen countries had at least one publication that met the eligibility criteria, while six countries (i.e. Algeria, Comoro’s, Djibouti, Mauritania, Morocco and Somalia) had none. Table 2 summarises the key factors reported by the included studies. The studies were grouped by rural/urban setting, type of facility studied and population studied.

The average score for the quality assessment of literature was 8.1 out of 10. Ninety studies (66.1%) were conducted in three countries Kingdom of Saudi Arabia (KSA) (40.4%), Jordan (15.4%) and Egypt (10.3%). More than half of the publications (52.1%) were carried out in the last 5 years (2015–2019), and 29.3% of the literature was generated within the period 2010–2014, while 18.6% of the studies were conducted in the first 10 years of the study period. In addition, more than half of the included studies were carried out in urban areas (56.6%) and just over a third (36.0%) in both urban and rural areas, whereas only two publications were conducted solely in rural areas.

Most papers (93.3%) were cross-sectional studies. Population surveys were employed in 41.2% of the studies in all Arab countries, followed by prescription surveys and facility surveys, while only two qualitative studies met the criteria. The public was the key study population in most Arab countries, followed by patients from clinical settings. Primary health clinics were the most studied facilities, followed by hospitals. The exception was in Lebanon, Qatar and Palestine, where a community pharmacy location was more frequently studied. Overall, most of the literature focused on evaluating irrational drug usage rather than investigating its contributing factors.

Patterns of irrational use of medicines

Table 3 summarises the indicators related to the irrational use of medicines. Table 4 summarises the median for each of these indicators as measured in Arab countries.

Number of medicines per prescription

Data on the number of medicines per prescription were obtained from 33 studies conducted in 11 Arab countries, covering a total of 95,166 prescriptions. The results showed significant variation among Arab countries, where the number of medicines per prescription varied from 1.1 in Egypt to 2.9 in Kuwait and Yemen. The median number of medicines per prescription was 2.3. Three out of twelve studies conducted in the KSA reported more than four drugs per encounter. No significant correlation to urban/rural settings and health facilities was found. The average number of medicines per prescription decreased from 2.5 from 2010 to 2014 to 2.3 from 2015 to 2019.

Polypharmacy

The data on polypharmacy were obtained from 42,947 participants in four Arab countries. The median of 11 studies found in these countries showed a high percentage of polypharmacy (61%), ranging from 13.2% in Jordan to 76.8% in Oman. Generally, polypharmacy is considered an issue of concern in three Gulf countries: Oman (76.8%), the KSA (61%) and the United Arab Emirates (UAE) (48.3%). The percentage of polypharmacy in hospitals (68.7%) is higher than in primary healthcare (PHC) facilities (17.7%). It increased slightly from 61.0% during the period 2010–2014 to 63.3% during the period 2015–2019. No significant correlation to geography or population was found.

Percentage of antibiotics prescribed per 100 encounters

Fifty-nine studies in 15 Arab countries investigated the percentage of prescribed antibiotics per encounter for 292,127 participants. The median for all countries is 50.1% ranging from 13.1% in Oman to 82.4% in Egypt. The percentage of antibiotics prescribed per 100 encounters was the highest at 63.2% during the period 2015–2019 followed by 43.0% in 2010–2014. This percentage was higher in PHCs (56.7%) and pharmacies (57.7%) than in hospitals (43.3%). No significant correlation to urban/rural settings was found.

Number of antibiotics per encounter

Only two studies discussed the number of antibiotics per encounter. They were conducted in two different Arab countries (Oman and Sudan) with 423 total participants. The number of antibiotics per encounter ranged between 2 and 2.5 (median 2.3).

Percentage of self-medication with antibiotics

The data on self-medication with antibiotics were retrieved from 53 publications in 10 countries with a total of 49,955 participants. The median was 38%, ranging from 8.5% in Bahrain to 78% in Iraq. Minor differences were found between adults (37.5%) and children (40.2%). The percentage of self-medication with antibiotics decreased throughout the study period, starting at 40.7% in 2000–2009 and decreasing in turn to 35.8% in 2010–2014 and 34.1% in 2010–2019. Studies carried out in PHC facilities reported the highest percentage of self-medication with antibiotics (40.8%), followed by hospitals (24.4%) and pharmacies (20%).

Percentage of injections prescribed per 100 encounters

Data on the percentage of injections prescribed per 100 encounters were retrieved from 13 publications in seven countries that included a total of 43,984 participants. The percentage of injections prescribed per 100 encounters in hospitals (26.6%) is significantly higher than in pharmacies (3.1%) and PHC facilities (1.6%), with the median being15.2%. Studies carried out in both urban and rural areas have a higher percentage of injections prescribed per 100 encounters (18.1%) than those conducted in urban areas only (11.7%). This percentage was the highest (18.1%) from 2000 to 2009, dropping to 8.7% from 2010 to 2014 before increasing slightly in the final 5 years from 2015 to 2019. The UAE and Jordan reported the lowest percentage among Arab countries at 2.2% and 3.9%, respectively.

Percentage of unnecessary drugs per 100 encounters

Seven publications in six Arab countries with a total of 8034 participants illustrated the percentage of unnecessary drugs prescribed per 100 encounters. The data indicated that 25.8% of drugs were unnecessarily prescribed. No significant difference was found in regard to urban/rural settings, population studies and health facilities. Only one study reported the percentage of unnecessary drugs per 100 encounters during the period 2010–2014. The percentage showed a significant downward trend over time, from 50.4% between 2000 and 2009 to 19.2% between 2015 and 2019. PHC facilities were found to prescribe a higher percentage of unnecessary drugs per 100 encounters (41.3%) compared to hospitals (30.7%). Studies carried out in urban areas showed a lower percentage of unnecessary drugs per 100 encounters (25.8%) compared to those conducted in both urban and rural areas (41.3%).

Adherence to prescribing guidelines

The adherence to guidelines was determined by using a sample of 1160 prescriptions, as indicated in three studies conducted in three Arab countries. One study conducted in Jordan found that less than 50% of prescriptions adhered to prescription guidelines, while the two other studies found adherence to be more than 50%. In total, 55.3% of the prescriptions complied with the guidelines. However, the available data were not sufficient for rigorous analysis to draw a strong conclusion.

Factors associated with the irrational use of medicines

Despite numerous efforts to describe the patterns of irrational use of medicines, only 19 studies from six Arab countries analysed factors associated with it. Just over half, or 52.6%, of these studies were carried out in the KSA followed by three studies in Bahrain, two studies in both Jordan and Kuwait and one each in Egypt and Tunisia. However, it is worth mentioning that we have described only eight indicators because the ninth factor was not included in any of the selected articles. As shown in Table 5, the patient’s lack of knowledge was reported in five studies (four countries) while pressure from patients was mentioned in four studies (three countries) as a reason for the irrational use of medicines. All factors were studied in KSA except patient insurance status. Other factors had very limited data to assess the reasons behind the irrational use of medicines.

Discussion

This review of the literature revealed patterns of irrational use of medicines and some of its driving factors. A high percentage of polypharmacy, antibiotics prescription and antibiotic self-medication were reported. The consumption of antibiotics and injections was much higher than that recommended by WHO. At the same time, the review identified that one-fourth of all medications were unnecessarily prescribed.

To the best of our knowledge, this is the first systematic review that covered the irrational use of medicines and its leading factors within Arab countries. The study had some limitations that should be acknowledged. First, we only searched two major databases. It might have been possible to retrieve more studies if more databases had been used. Second, non-English materials and reports from government health departments could have been used to add more to the data on irrational medicines use. Third, only 16 out of 22 Arab countries were included in this review. Finally, no literature was found describing the percentage of antibiotics with the wrong course.

Prescribing of too many kinds of medicines

Our review showed that 2.3 medicines were prescribed per patient encounter. This is slightly lower than the one reported by the WHO for some areas, such as the Eastern Mediterranean (2.7), Africa (2.6) and South East Asia (2.5).^[2] However, 20% of the studies conducted in KSA reported more than four medicines per prescription.

For this indicator, a lower value signifies a more rational use of medicine.^[21] The lower number of medicine per prescription suggests that the physician has a greater sense of responsibility towards their patient’s health outcome and that the patients are more cognisant of the risks associated with the inappropriate use of medicines.^[21]

The Arab countries reported an aggregate percentage of polypharmacy of 61%, which is higher than India (13%),^[22] Japan (21.5%),^[23] and Australia (36.1%).^[24] More than half of the studies conducted in KSA reported polypharmacy, which contributed to high percentage of polypharmacy reported by Arab countries. Polypharmacy and the need for multiple medications are expected to be prominent due to the increase in elderly co-morbidities. Elderly patients receive on average 4.26 medicines per prescription, significantly higher than children for example who only receive on average 1.86 medicines per prescription. This high percentage of polypharmacy among the elderly is mainly driven by patients with a cluster of diseases,^[25] where the elderly population needs multiple medications.^[26]

Inappropriate use of antibiotics and injections

Antibiotics are important medications but are commonly overused. In developing countries, antibiotics are largely used without medical guidance due to lax regulation on the sale or distribution of prescription medicines.^[27] In Arab countries, the problem of irrational antibiotic use is entrenched. The percentage of antibiotics prescribed per 100 encounters in Arab countries was 50.1%, which is lower than in Eastern Mediterranean Regional Office (EMRO) (53.2%), but higher than in Africa (47%) and South East Asia (46.3%).^[2] The WHO reported that countries with a prevalent infectious disease could expect to prescribe antibiotics in 15–25% of patient encounters.^[17] Antibiotic consumption increases rapidly in low-and middle-income countries compared to high-income.^[28] Furthermore, the percentage of antibiotics per encounter was higher in PHCs (56.7%) and pharmacies (57.7%) than in hospitals (43.3%), which implies that antibiotics were dispensed upon patient request without prescriptions. The period from 2015 to 2019 recorded the highest percentage (63.2%) of antibiotics prescribed per encounter, indicating an increase in the use of antibiotics within Arab countries.

The utilisation of antibiotics for self-medication is a common practice among South East Asia and Arab countries,^[29] as well as in some developed countries.^[30] It is a universal problem and variations regarding such practices are obvious around the globe,^[31] where 50% of all antibiotics were purchased over-the-counter (OTC).^[32] Factors such as OTC sales of antibiotics, expensive medical consultations, weak regulations and dissatisfaction with medical practitioners^[27] may lead to self-medication in Arab countries. Different regions may report different rates of antibiotics use due to differences in the availability of antibiotics, antibiotic prescribing or dispensing, the incidence of infectious diseases and patient-related factors.^[33]

The percentage of encounters in which an injection was prescribed was 15.2% in Arab countries. This percentage is higher than in the Americas (13.2%) and Southeast Asia (9.1%), but lower than in Europe (17.2%), EMRO (20.1%) and Western Pacific (23.2%).^[2] However, it is still much higher than the WHO standard of 1%.^[34] The percentage of injections prescribed per 100 encounters during the study period may highlight fluctuation in injection and indicate a declining use in general. This might be explained by sociocultural beliefs, where patients believe that it would be better to reduce the use of injections due to various reasons such as painful administration, the probability of infection and high costs.^[21]

Unnecessary prescription

The data indicated that 25.8% of drugs were unnecessarily prescribed, which increases the cost of medications for patients and the economic burden on healthcare systems.^[35] It could indicate inadequate prescriber’s knowledge or understanding of drug use,^[36] lack of adherence to guidelines and the desire for personal freedom from rules and restrictions.^[37]

Further improvement and future research

In Arab countries, there are, however, differences in the way the irrational use of medicines is recognised and framed as a public health issue, and the literature rarely identified causes, strategies and needed interventions to minimise the irrational use of medicines. Future research to determine more precisely the causes of irrational medicines use in Arab countries and the differences between these countries and the effectiveness of implemented procedures is in dire need.

The problem of irrational use of medicines should be recognised as a public health problem and policies and regulations should be put in place according to the research data and learned from successful approaches in other countries.

Conclusion

This systematic review showed that polypharmacy and antibiotic use in primary healthcare facilities and pharmacies represent challenging patterns of medicines use in Arab countries. Although the data are somewhat limited, the irrational use of medicines results from a combination of factors related to patients and health systems. This study highlights the need for interventions at various levels: patient level, healthcare provider level and policymaker level.

Acknowledgements

I would like to thank the late Prof. M. Azmi Hassali, without whom this project would never have been possible. I hope we did you proud. Many thanks as well to Mr. Hazem Osrof and Mrs. Xenia Kafarnah for their great job in revising the final manuscript.

Author Contributions

AM, YA, SCO and KA made substantial contributions to the conception and design of the study as well as the analysis and interpretation of the data. AM and KA made substantial contributions to data collection. All authors drafted the work or revised it critically for important intellectual content. All authors reviewed, critiqued and approved the final version submitted for publication.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of Interest

The authors declare that there are no conflicts of interest.

Data Access

The authors had complete ongoing access to the study data, through Universiti Sains Malaysia (USM) library database during the PhD study period.

Data Availability

The data underlying this article are available in the article and in its online Supplementary Material.

REFERENCES