Counterfeit Medicines in Socioeconomic Perspective

Counterfeit medicines potentially reach 70% of the global drug markets, and the largest proportion is found in developing countries. Increasing public awareness of counterfeit medicines will automatically affect the demand for counterfeit medical products that will finally reduce counterfeit medicine activities. However, raising awareness of the dangers of counterfeit medicines is a challenging task because public health professionals need to consider diversity of social, economic and educational factors. This study examined peer-reviewed journal articles, media reports, official government and non-government reports. As many as 179 papers (1990 to 2014) were retrieved to identify the relationship between Human Development Index (HDI) of the USA, Japan, Brazil, Iran, Vietnam, Indonesia, Pakistan and Nigeria, and the type of counterfeit medicines. An electronic search was conducted using the following databases, such as Medline, Scopus, CINAHL, Embase, Google Scholar. Counterfeit disease curing medicines are found in high varieties most likely in countries with low HDI. At the same time, medicines for lifestyle are not solely found in countries with high HDI, but also exist in low to medium HDI.


Introduction
Counterfeit medicine is on the rise globally and an emerging issue in both developing and developed countries. However, the true extent of the problem is not really known because no global study has been conducted. 1 The World Health Organization (WHO) estimates that 6% of worldwide pharmaceutical sales are counterfeit and that up to 70% of all medicines sold in several developing countries are counterfeit. 1 The government authorities and medicine manufacturers have made extensive attempts to fight drug counterfeiting, but old and new counterfeiters have used several methods to escape detection. 2 Many types of medicines have been counterfeited, including antibiotics, hormones, analgesics, steroids, antihistamines, vitamins, malaria medicines, flu medicines, and HIV/AIDS medicines. 3,4 However, the exact amount of counterfeit medicine is unknown, and little reliable data are available for both developed and developing countries. In some developing countries, the problem of data gathering is made more difficult due to a lack of agreement on the definition of counterfeit medicine and these countries are often reluctant to make information on counterfeit medicine public. 3,5 Countries with low socioeconomic factor are more vulnerable to widespread counterfeit medicines due to the high price of the medications. 6 People in developing countries must choose between low price counterfeit medicines or not buying any medicine. Drugs that are frequently counterfeited in developing countries are medicines that are used to treat life-threatening diseases, such as malaria, tuberculosis, HIV/AIDS, and other serious infectious conditions. 7 In contrary, counterfeit lifestyle medicines are most likely to be found in developed countries. 8,9 In developed countries, counterfeiters aim for high demand or costly products, such as medicines used to treat erectile dysfunction, hypercholesterolemia, hypertension and cancer. 10,11 Thus, it is unclear whether counterfeit medicine is prevalent in the countries that have a low per capita income and low education level, or if counterfeit medicines are increasing in developed countries because counterfeiters target high demand and resale value.
To address the counterfeit medicine problem, WHO has developed a definition that a counterfeit medicine is a medicine which is fraudulently and deliberately mislabeled with respect to identity and/or source. Counterfeiting can apply to both branded and generic products, and counterfeit products may include products with the correct ingredients or with the wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging. 1,12 Every medicine counterfeiting activity has significant repercussions for society, potentially threatening public health because con-sumption of counterfeit medicines may lead to death or ineffective treatment.
According to Spink,13 and Moyer, 14 from Michigan State University, there are seven types of fraud and counterfeiting incidents and their potential harm to public health. The first type is adulteration, in which the counterfeiter adds more ingredients with the intention of forging components of the products. The result is a product that is impure, that has lost the active ingredient, or that is given at an improper dose. The second type is tampering, in which the counterfeiter obtains the original product and packaging, but with the intent to fraudulently use them. For example, the counterfeiter may change the expiration date or product labelling. This may lead to the death of the consumer. The third type is overrun, in which the counterfeiter outside of the quantity makes legitimate medicines in a production agreement. These activities are dangerous because the product will be distributed outside the regulated or controlled supply chain. The fourth type is theft, in which the counterfeiter steals legitimate products and sells them as legitimate products. Similar to overrun, legitimate products will be distributed outside the regulated or controlled supply chain. The fifth type is diversion, which is also known as a parallel trade, the grey market or product arbitrage. This type of fraud may result in a lack of legitimate products in the market, causing a delay in a patient getting the medicine. Another type is simulation, in which the counterfeiter copies the legitimate product but does not use the same ingredients. This will affect patient safety, as the resulting medicine is fake or of a lower quality. The last type is counterfeiting, where the counterfeiter copies exactly the same drug as the legitimate product with the intention to mislead the patient. The product and packaging of the legal medicines are fully replicated, which causes the patient to consume a product that is evidently impure.
Combating counterfeiting/fraud activities requires a strong commitment from the governments and authorities around the world. 15 Knowledge of the reasons why counterfeiters falsify medicines is also very important. The medicine product supply chain is controlled by the government under the law; however, people can help to decrease the demand for counterfeit medicines by purchasing medicines from authorised pharmacies. 16 Economic factors are one of main reasons for counterfeiting medicines. However, other motivations also exist, such as part of terrorist activities or for other criminal motives. 15,17 Socioeconomic factors contribute to counterfeiting activities in many countries. A prior study has investigated aspects of the relationship between socioeconomic variables and counterfeit medicine. 18 However, indicators of socioeconomic status, such as education, income, and culture are independent variables.
For example, people that have the same level of formal education could have different perspectives on health due to different cultural backgrounds. 19,20 These perspectives at times lead to incorrect conclusions about the relationship between socioeconomic indicators and health outcomes or health perspectives in general. The aim of this study was to determine whether or not the type of medicines (medicine for lifestyle or disease treatment) related to the socioeconomic factors based on the human development index (HDI) in eight selected countries of the world.

Identification of Studies
This search strategy and term were utilised a systematic review style an approach which is considered a legitimate study methodology. 21 To identify and highlight the primary study studies and to determine the relationship between HDI and type of medicines being counterfeited in Eight selected countries, four major electronic databases such as Medline, Scopus, CINAHL, EMBASE, Google Scholars were used. The keywords included 'counterfeiting', 'counterfeit medicines', 'substandard drugs', 'fake drugs', 'world counterfeiting', and 'counterfeit medicines' as well as 'counterfeit drugs/medicines/medicines' in eight selected countries that are the USA, Japan, Brazil, Iran, Indonesia, Vietnam, Nigeria and Pakistan. Extracted data about counterfeit medicines were analyzed using a table that categorized counterfeit medicines based on their labelling package type medicines. The medicines were then grouped into two broad classes, namely lifestyle drugs and disease curing medicine classes.

Inclusion Criteria
Records that reported on the prevalence and potential public health and socioeconomic concern of counterfeit medicines in developed and developing countries were selected using preferred reporting items for systematic reviews and Meta-Analysis (PRISMA) guideline procedure ( Figure 1). The title and abstracts of the identified articles were checked against predetermined criteria for eligibility of the study that deal with various aspects of counterfeit medicines for lifestyle and disease treatment and relevant to the study objectives. The most informative version of the study was included in multiple publication that presented identical data. A study published in Indonesian language was then translated, and relevant papers were included. The full text of all selected studies was obtained and assessed. Of 179 potential articles identified by these criteria, 58 studies were included for eligibility. Lastly, remaining ten records was included in the narrative synthesis. The selected countries were selected based on the HDI with very high HDI in USA and Japan, high HDI in Brazil and Iran, medium HDI in Indonesia and Vietnam, and low HDI in Nigeria and

Exclusion Criteria
At first, a total of 179 articles were identified through searching various database (153 articles) and other sources (26 articles). However, 53 articles were rejected because of repetition and resultant 126 articles were chosen. In the screening phase, 68 studies were excluded as they reported in language other than English and Indonesian, and did not report outcomes of interest. Subsequently, in the eligibility phase, 48 articles were eliminated as they were not included into cases in eight selected countries (USA, Japan, Brazil, Iran, Indonesia, Vietnam, Pakistan, Nigeria).

Results
A review of the 153 published and 26 additional records between 1990 to 2014 was conducted on the type of counterfeit medicines in relation with socioeconomic factors based on eight selected HDI countries. The review of the literature included peer-reviewed journal articles, media reports, government and non-government reports.  (6), antiobesity (2), anticancer (59), antipsychotic drugs (6), anti-depressant (4), Dementia drugs (6), anti-depressant (4), anti-hypertensives (14), lipid lowering drugs (22), external preparations (21), atopic dermatitis drugs (2) There were 58 relevant peer-reviewed journal articles identified, and six were based on five selected countries setting (Table 1). Additionally, there were four reports from government and media about counterfeit medicine cases from three different selected countries (Table 2 and Table 3). The general outlook comparison between counterfeit lifestyle medicines for and disease treatment in selected countries based on HDI year 1990 to 2014 is presented in Figure 2. From the graph, the number of counterfeit lifestyle medicine is very high with 16 types in the very high HDI countries followed by high and medium HDI with nine types of counterfeit lifestyle, then low HDI countries with medicines for five counterfeit lifestyle medicines for.
On the other hand, the number of counterfeit medicines for disease treatment in low HDI had the highest types as many as fourteen, followed by medium HDI with twelve types, then high HDI with nine types, and the last was very high HDI with five types of counterfeit medicines for treatment.

Discussion
Measuring socioeconomic status in practice is not simple. SES has many indicators that describe the individual's access to social and economic resources. Among the most common, used indicators are education, occupation, income, wealth, and years of school completed. 36 The HDI was utilized in this study as it is the most common value in representing the SES level in general. The Human Development Index (HDI) reflects the positive association between income on one side and health and education on the other. Thus, it offers a powerful alternative to income as a summary measure of human well-being.
The food and drug administration (FDA) announced the trafficking of fraudulent, counterfeit, and substan-dard medicines, supplements, and medical devices from several countries to the USA, including high demand lifestyle medicines such as Botox and expensive medicines such as cancer medicines. 37 The FDA proactively responds to trafficking of counterfeit medicines. Public awareness has increased sharply, however, counterfeit medicines persist. If counterfeit medicines can enter the legal supply chain in the USA, the counterfeit medicine can most likely enter the markets of other countries. 37 The cases of counterfeit medicines in selected countries with very HDI selected countries are higher than others, more likely because of efficient counterfeiting cases report file and well-organized anti-counterfeiting agency. 15 In countries with very high HDI, despite a well-protected supply chain, medicine quality control and good social and physical security, counterfeit medicines still can be found. People living in developed countries such as Japan are exposed to fake medicines via illegal websites in which unauthorized websites are difficult to monitor and can easily escape the notice of authorities. Japan is a country with a $96.5 billion expenditure in medicine, almost twice as much as Latin American medicine sales. 38 in 2010, there were 490 cases of counterfeit medicine in Japan, increasing approximately 7.3% from 2011. Lifestyle medicines (Viagra and Cialis) were the major medicine counterfeiting products.
This study found that most counterfeited medicines in very high HDI were lifestyle medicines for. In developed countries, counterfeiter generally targets high-volume, high-cost drugs. This mean that the medicines potentially targeted were lifestyle medicines. However, the data in Table 2 also suggest that list has been expanded to nearly every kind of medicines, particularly those in high demand like antiviral, anticancer medicines, etc. 39 In 2012, the Brazilian authorities established 13-digit  [29][30][31][32][33] Counterfeit medicines found in Pakistan from 2002 to 2008; Fake herbal medicines, WHO, several media report and press release: the Dengue fever medicines, antibiotic, anti-tuberculosis medicines, anti-malarial news.com, samaa.tv, tribune.com, the nation.com, medicines, heart medicines, cancer medicines.
safemedicines.org, radionz. Vietnam 34 Anti-malarial, antibiotic, anti-tuberculosis, antiretroviral medicines The State of Medicine Quality in the Mekong sub-region Indonesia 35 Total cases of counterfeit medicines from 2001 to 2008 in Indonesia were 162 cases. National Agency Drug and Food Control (BPOM) Most counterfeit medicines were Antibiotic. Total cases found: Antibiotic (39), antiviral drugs (7), drugs for improvement sexual performance (9), contraceptive (3), anti-obesity (2), anti-depressant (8), antihypertensive (5), lipid lowering drugs (4), atopic dermatitis drugs (2), anti-diabetic drugs (13), vaccine (3), anti-allergy (14), drugs for improvement sexual performance (9), antifungal (11), others (7). unique drug identifiers for securing the medicine products. Lifestyle medicines for are aimed at indications where treatment is largely a matter of patient choice and not a medical requirement. Patients consider embarrass-ing products such as erectile dysfunction, obesity, and those products are usually expensive as an apparent economic incentive to counterfeiter. 40 Unofficial and official reports about counterfeit -   35 NADFC established many ways to combat counterfeiters, including encouraging the medicine industry to collaborate with the government to eradicate counterfeit medicines, participating in Operation Storm, and raising public awareness of the dangers of counterfeit medicines.
In low socioeconomic countries, it is often hard to prove a causative link between counterfeit medicines and illness or death because limited clinical autopsies and toxicology report that explained the cause of death. 42 There is one market where price is more important than quality. The poorest consumers in Africa are forced to choose between low-quality medicines that are inexpensive or not purchasing the medicines at all. The ultimate solution to this dilemma is for the government to ensure that medicines for disease treatment are affordable for all. 7 The main factors underlying the problem of counterfeit medicines in developing countries are the weak drug regulatory control, enforcement, scarcity and/or erratic supply of basic medicine, uncontrolled distribution chains, large price differentials between genuine and counterfeit medicines, lack of effective Intellectual Property Right (IPR) protection, lack of regard for quality assurance and corruption of the health care system. 43 Trends in counterfeit medicine vary depending on many factors, such as the strength of the rule of law and rural versus urban settings. These factors vary even within countries. Health professionals play a major role in helping medicines that reach patients without endangering patients' health. 44 In Nigeria, by 2001, more than 40% of medicines in circulation were fake. 45,46 Most counterfeit medicine supplies (75%) were imported from China and India. 4,47 People living in Nigeria are thus impacted by the dangerous effects of the counterfeit medicine. In 2008, 64% of anti-malarial medicines were either counterfeit or sub-standard. 18 It is noted that low dose artesunate does not kill malaria parasite but anchorages the emerge of artesunate-resistant strains.
Several counterfeit medicines seized in Nigeria are heart medicines, cancer medicines, antibiotic, analgesic and anti-malarial. These products include medicines for lifestyleas well as for disease treatment.
Similar to Nigeria, imports of counterfeit medicines in Pakistan have also increased in recent years, along with the increase of Pakistan's local production and supply of medicines. Meanwhile, the WHO estimated that as many as 40 to 50% of needed medicines are substandard or counterfeit medicine. 33 Counterfeit medicines are rampant in both rural and urban areas. Counterfeit versions of life-saving prescription medicines for cancer and serious cardiovascular diseases were being sold to costumers in Pakistan, meanwhile counterfeit antibiotic, analgesic and antipyretic also well-noted. 43,44 In accordance with the law of supply and demand, as the price of medicines rises, poor people will search for medicines at low prices, and this leads to the vulnerability of the people who are forced to choose to buy substandard or counterfeit medicines from the illegal market. Some illegal medicines in Iran are imported from India and China. Most counterfeit medicines products seized are supplements, hormone medicines, and analgesic and antihistamine medicines. 24,48 Conclusion This review of articles shows that counterfeit medicines are available in USA, Japan, Iran, Brazil, Indonesia, Vietnam, Pakistan and Nigeria. Counterfeit medicines can enter strong drug regulatory authorities such as in USA and Japan as people living in these countries are most likely exposed to counterfeit medicines via the internet.
In very high and high development indexed countries, expensive medicines for lifestyle (e.g. sildenafil, Cialis) as well as expensive high demand medicines are counterfeited. Meanwhile, in countries with medium and low development index countries, medicines to treat life-threatening diseases such as malaria, tuberculosis and other serious conditions are counterfeited. Counterfeit medicines pos a serious threat to the public health as medicine are purposively to reduce mortality and morbidity, counterfeit medicines are extremely harmful to health and safety of patients. Furthermore, combating the counterfeit medicines problem is important to ensure patients not to lose faith in the benefits of medicines.

Recommendation
Counterfeit medicines pose an increase threat to people as well as to individuals; direct harm to policy making and social prosperity budget. People worldwide should understand about the harm of counterfeit medicines and stop purchasing counterfeit medicines. The only way to combat this lucrative fraudulent criminal is by decreasing their sales.
Improving quality of medicines, increase the availability of inexpensive essential medicines, as well as strengthening medicine regulatory authority is a very important task for developing world to combat the counterfeiter.
At the national level, sustained political and economic supports from the government to coordinate police, scientist, medicine industries as well as enforcement the laws and regulations on counterfeit medicines is crucial to combat counterfeit medicines. Meanwhile, at the international level, drug registration should be strengthened to ensure that all imported as well as local medicines industries produce high quality medicines before placing them to the market. To tackle the counterfeiter, there is also a need for continuous cooperation between the government of developed and developing countries and WHO.
Due to the expansion of the counterfeit medicines through the internet, cooperation amongst policy makers, brand owners, entrepreneurs, marketers, and other stakeholders is a key to controlling the availability and supply of the counterfeit medicines from the internet.