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Health Policy 117 (2014) 297–310

Contents lists available at ScienceDirect

Health Policy

journa l h om epa ge: www.elsev ier .com/ locate /hea l thpol

erspectives of physicians practicing in low and middlencome countries towards generic medicines:

narrative review

ohamed Azmi Hassali a,∗, Zhi Yen Wongb, Alian A. Alrasheedya,ahad Saleema, Abdul Haniff Mohamad Yahayab, Hisham Aljadheyc

Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden,enang, MalaysiaPharmacy Department, Hospital Teluk Intan, Jalan Changkat Jong, 36000 Teluk Intan, Perak, MalaysiaCollege of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia

r t i c l e i n f o

rticle history:eceived 4 June 2013eceived in revised form 16 July 2014ccepted 24 July 2014

eywords:erspectiveeneric medicinesow and middle income countrieshysicianeview

a b s t r a c t

Objectives: This review was conducted to document published literature related tophysicians’ knowledge, attitudes, and perceptions of generic medicines in low- and middle-income countries (LMICs) and to compare the findings with high-income countries.Methods: A systematic search of articles published in peer-reviewed journals from January2001 to February 2013 was performed. The search comprised nine electronic databases.The search strategy involved using Boolean operators for combinations of the followingterms: generic medicines, generic medications, generic drugs, generic, generic substitution,generic prescribing, international non-proprietary, prescribers, doctors, general practition-ers, physicians, and specialists.Results: Sixteen articles were included in this review. The majority (n = 11) were from highincome countries and five from LMICs. The main difference between high income countriesand LMICs is that physicians from high income countries generally have positive viewswhereas those from LMICs tend to have mixed views regarding generic medicines. Fewsimilarities were identified among different country income groups namely low level ofphysicians’ knowledge of the basis of bioequivalence testing, cost of generic medicinesas an encouraging factor for generic medicine prescribing, physicians’ concerns towardssafety and quality of generic medicines and effect of pharmaceutical sales representativeon generic medicine prescribing.

Conclusion: The present literature review revealed that physicians from LMICs tend to havemixed views regarding generic medicines. This may be due to differences in the health caresystem and pharmaceutical funding system, medicine policies, the level of educationalinterventions, and drug information sources in countries of different income levels.

∗ Corresponding author. Tel.: +60 12 4421605.E-mail addresses: azmihassali@usm.my (M.A. Hassali),

ongzy88@gmail.com (Z.Y. Wong), alian-a@hotmail.comA.A. Alrasheedy), fahaduob@gmail.com (F. Saleem), dulha5@yahoo.comA.H. Mohamad Yahaya), haljadhey@ksu.edu.sa (H. Aljadhey).

http://dx.doi.org/10.1016/j.healthpol.2014.07.014168-8510/© 2014 Elsevier Ireland Ltd. All rights reserved.

© 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

The major challenge faced by many health care

providers and policy makers in the world is the everescalating health care costs [1,2]. Within this context,the cost of pharmaceuticals constitutes the second largestcost in health care provision after the staffing costs [3].

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There could be many reasons for increased pharmaceu-tical expenditure, including a rise in disease prevalence,an increase in population risk factors, changes in clinicalthresholds for treatment, and the emergence of new med-ical treatments [4,5]. The situation is worsening in low-and middle-income countries (LMICs) where the house-hold out-of-pocket payments are a higher proportion of thetotal expenditure than in high income countries [6]. In thischallenging scenario of health care provision, one of themechanisms suggested to minimize the costs of medicinesis the encouragement of greater use of generic medicines[7–10].

Generic medicine can be defined in different ways[11–13]. However, generic medicine is commonly under-stood as defined by World Health Organization (WHO) tomean “a pharmaceutical product, usually intended to beinterchangeable with an innovator product that is man-ufactured without a licence from the innovator companyand marketed after the expiry date of the patent or otherexclusive rights.” [14]. Generic medicines are required tohave the same active substance, strength, route of admin-istration, identity, quality, purity, efficacy and the sameintended use of the brand name medicines [15–18]. How-ever, the generic and brand name formulations of themedicines can have some minor differences, such as theinactive ingredients (e.g., preservatives, flavours), colour,shape, and product packaging [15,17,19]. Despite differ-ent regulatory guidance for marketing approval of genericmedicines, bioequivalence testing is a fundamental regu-latory requirement for approval of generic medicine [12].Generic products are considered to be bioequivalent only iftheir rate and extent of absorption do not show a significantdifference from the reference product [7]. Moreover, bio-equivalence can be waived only if scientifically appropriatebased relevant scientific principles and considerationsincluding the Biopharmaceutics Classification system (BCS)[20]. In BCS, medicines are categorized into four categoriesbased on solubility and intestinal permeability [21]. BCStakes into consideration dissolution, solubility and intesti-nal permeability when granting biowaivers [12]. Thus,bioavailability and bioequivalence studies can be waivedif the product is categorized under BCS Class I (i.e. high sol-ubility and high permeability) and if the immediate releaseformulation exhibits rapid in-vitro dissolution [22]. More-over, biowaivers can be granted to BCS Class III (i.e. highsolubility and low permeability) [23].

Different countries have different health policies andhealth care systems, as well as different regulations andpolicies related to generic medicine utilization [24]; hence,it is believed that physicians’ perspectives and knowledgeof generic medicine will differ accordingly. Physicians playan important role in improving the generic utilization rate.In fact, in most countries, the physician is the key per-son in the medicine use process. The physicians start theprocess by prescribing or ordering medications, and thisis normally followed by pharmacists, who will in turndispense the medications. However, in some countries,

physicians are involved in the dispensing role as well[25,26]. Hence, physicians have a great influence on select-ing either generic or original-brand medicines for patients.Previous literatures had reported that information given by

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prescribing doctors on generic medicines could influencepatients’ acceptance and use of these products [27–30]. Inaddition, physician prescribing practice using internationalnon-proprietary name (INN) is important in encouragingthe use of generic medicines among patients [31]. Forexample, patient confusion over medicine names whichwas identified as one of the main barriers to the accep-tance of generic medicines can be avoided if physiciansused an INN in prescribing [32–35]. However, prescrib-ing by INN alone does not stimulate generic medicine useunless accompanied by pharmaceutical policies to encour-age the use of generic medicine [36]. The understanding ofphysicians’ perceptions, knowledge, and attitudes towardsgeneric medicine will have an important influence onpatients’ selection of medicines. Therefore, this review wasconducted to document the published literature relatedto physicians’ knowledge, attitudes, and perceptions ofgeneric medicines in LMICs. By understanding physicians’perspectives in LMICs, researchers and health policy mak-ers can formulate more efficient interventions to increasethe rate of generic medicine prescribing in respectivecountries.

2. Methods

An extensive literature search was carried out in severalelectronic databases available at the authors’ institutionlibrary. A systematic search of articles published in peer-reviewed journals between January 2001 and February2013 was performed. The search comprised nine electronicdatabases including CINAHL Plus with Full Text, ISI Webof Knowledge, Science Direct, Springer Link, JSTOR, WileyOnline Library, ProQuest, PubMed, and Scopus. The searchstrategy involved using Boolean operators for combina-tions of the following terms: generic medicines, genericmedications, generic drugs, generic, generic substitution,generic prescribing, international non-proprietary, pre-scribers, doctors, general practitioners, physicians, andspecialists. Equivalent terms in thesauruses or MedicalSubject Heading (MeSH) browsers were used wheneverpossible.

In this review, both qualitative and quantitative stud-ies which reported physicians’ knowledge, attitudes, andperceptions towards generic medicines were included. Sys-tematic reviews, case studies, commentaries, essays, legalanalyses, consensus statements, and letters to editors wereexcluded from the review. Studies were excluded if theywere written in languages other than English. Articlesreporting clinical trials for evaluating the efficacy betweengeneric and branded products were also excluded from thisreview. Similarly, articles mentioning bio-similar productswere also excluded. Each study was reviewed by all authorswith disagreement resolved by consensus. A number ofvariables were assessed, including the study design, thecountry of origin, the objective, the number of respondents,the outcomes and limitations.

A total of 10,588 titles and abstracts were identified

from the electronic search of all nine databases. Sub-sequently, 10,554 titles and abstracts were not relatedto physicians’ perceptions, attitudes, and knowledge ofgeneric medicine. Duplicated citations were identified and

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Titles and abstra cts ide nti fied by electro nic s earch of all nine database. (n=10,588)

Full text o f articles retrieved for further ass essment (n= 3 4)

Studies related to ph ysicians’ percepti on, attitude and knowledge of generic medicine and which satisfied th e sele cti on crite ria were included in the review (n=16)

Title and abstr act s not rel ated to physicians’ perception, attitude and knowledge of generic medicine and duplic ation (n=10,554)

Articles not assessing physicians’ perception, attitude and knowledge of generic medicine but rather largely looking at the clinical effectiveness of generic medicines were excluded (n=18)

chart of

etrecfi

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Fig. 1. Quorum flow

xcluded. The full texts of 34 articles were retrieved for fur-her evaluation. Lastly, 18 out of the 34 articles that did noteally assess physicians’ perceptions, attitudes, and knowl-dge of generic medicine, but rather looked largely at thelinical effectiveness of generic medicines were excludedrom further analysis. The quorum flow chart for selectionn this review is shown in Fig. 1.

.1. Description of included studies

The studies discussed in this review article wererranged according to the country income level. Accordingo the World Bank, countries are classified to low-incomeountry, lower-middle income country, upper-middlencome country and high-income country using grossational income (GNI) per capita [37]. The GNI per capita

s calculated using the Atlas conversion factor with the aimo reduce the impact of exchange rate fluctuations in theross-country comparison of national incomes [37]. A listf countries included in this review is showed in Table 1.tudies from high income countries were included in theesults to allow comparison between findings from LMICsnd high income countries.

Thirty-four studies were identified but eighteen studiesere excluded as they did not fulfil the selection crite-

ia. Subsequently, 16 published studies were included inhe review as shown in Table 2. Of the 16, the majorityn = 11) were from high-income countries: United States of

merica (n = 2), Australia, Finland, Canada, Germany, Italy,reece, Slovenia, Saudi Arabia and a study conducted in

wo countries—Greece and Cyprus. Four were from upper-iddle income countries: Malaysia, Turkey, Jamaica, and

the review process.

Iraq. One was a lower-middle income country—Pakistan.Most of the studies were quantitative, while four studiesused qualitative methods. One study took an internationalperspective, but the focus of each of the rest was an indi-vidual country.

2.2. Methodological quality

Each study was reviewed by all authors and a consen-sus meeting was convened to ensure quality assurance. Themost prominent pitfall identified was a lack of generaliz-ability of study results to whole populations, as the studieswere restricted to certain geographical areas, governorates,or provinces [35,38,39]. There were three studies in whichlimitations were not mentioned by the authors [26,40,41].Five studies suffered from low response rate [42–46] andone study suffered from a high number of missing values insome questions although it had a good response rate [47].Two studies used convenience sampling [48,49] and onestudy might have a sampling bias [50] which could limitthe generalization of their findings. There was one studylimited by lack of distinction between primary care andsecondary care physicians [51].

3. Results

A summary of studies included in the review inves-

tigating physicians’ perception, attitude and knowledgetowards generic medicines is shown in detail in Table 2.A summary of the variables that were investigated in thestudies is presented in Table 3.

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Table 1List of countries and GNI per capita [37].

No. Country GNIa per capita (2011) Income groups

1 United States of America 50,660 High income2 Australia 50,130 High income3 Finland 47,720 High income4 Canada 46,860 High income5 Germany 44,670 High income6 Italy 36,260 High income7 Cyprus 28,840 High income8 Greece 24,940 High income9 Slovenia 23,930 High income10 Saudi Arabia 21,210 High income11 Turkey 10,510 Upper middle income12 Malaysia 8,830 Upper middle income13 Iraq 4,970 Upper middle income

14 Jamaica

15 Pakistan

a Gross National Income.

4. Discussion

In this review, physicians in LMICs tend to havemixed views of generic medicines whereas physiciansin high-income countries generally have positive views.One possible explanation for this finding could be dueto the differences in health care and pharmaceuticalfunding systems and medicine policies among countries[6,31,36,52,53]. However, the difference in study designsand cross-country differences make comparisons of resultsproblematic. Moreover, differences in the findings can beattributed to other factors such as disease prevalence, geo-graphical region and the socio-demographic structure ofthe country’s population.

Complexities in the health care and pharmaceuticalfunding systems in LMICs may account for the differ-ences in opinions towards generic medicines. Low-incomecountries have a less reliable collection of tax revenue andsubsequent low public spending on health and other socialexpenditure [6]. As a result of this, low-income countriesare heavily dependent on external resources such as privateinsurance, donor funding, patients’ out-of-pocket paymentand the provision of services based on faith-based charities[6]. However, this external dependence poses a major prob-lem in which funding in low-income countries varies fromyear to year [54]. Such variation poses major planning dif-ficulties in health care allocation [54]. In fact, most of thehealth care costs are paid out of pocket by patients in LMICs.Thus, in most of the studies reviewed, cost was reportedto be the main reason in prescribing generic medicines[35,38,45–47,51]. In contrast, high income countries havedeveloped social health protection that is based on riskpooling system [55]. In this system, funds dedicated forhealth care are collected through prepayment [55]. How-ever, low-income countries spend proportionately lesspublic funding on health, private insurance plays a minorrole and household out-of-pocket payments are a higherproportion of the total expenditure than in middle- andhigh-income countries [6]. In high-income countries, indi-

viduals pay few health care costs directly. The medicalexpenses are borne mainly by social health insurance orby the government [55]. In high-income countries, use ofgeneric medicine is one of the cost containment measure

4,800 Upper middle income1,140 Lower middle income

that commonly adopted by policy makers and insurancecompanies [7,31]. As a result of that, earlier exposureto generic medicines and experience in using genericmedicine may lead to positive views of generic medicinesamong physicians in high-income countries.

Pharmaceutical financing by health care stakeholdershas also been seen as an enabler for generic medicine usein certain countries [56]. In terms of pharmaceutical fund-ing at the population level, there are two main systems,namely the public and private systems. In fully public sys-tems, medicines are financed, procured and distributedby a centralized government unit [53,56]. In a mixed sys-tem, public funding from central budgets or social healthinsurance is used to reimburse patients or private phar-macies [53,56]. The alternative way is that medicines aresupplied through government medical stores and healthfacilities but paid for by patient fees. In fully private sys-tems, patients or private insurance systems bear the wholecost of medicines purchased from private pharmacies anddrug sellers [53,56]. Most high income countries (94%) arecovered with insurance system [52]. Medicines are coveredfor reimbursements in all the health insurance systems ofall the high-income countries [52]. However, the oppositescenario was observed in LMICs. Only 45% or 18 low-income countries have medicine benefits in their insurancesystem [52]. Consequently, patients’ out-of-pocket pay-ments for medicines are higher in low-income countries.In short, physicians in LMICs may be less sensitive towardsmedicine cost as in LMICs most of the pharmaceutical costsare paid by out-of-pocket payments [52]. Moreover, lackof policies and strategies by government or third partypayers that encourage prescribing generic medicines asa cost containment strategy hinders the wide utilizationof generic medicines in the health care system in LMICs.However, in most high income countries, there are sev-eral policies and initiatives that encourage and supportprescribing generic medicines [24,31]. These policies canbe categorized into two groups, namely supply-side anddemand-side policies [7]. Supply-side policies are related

to market entry, pricing and reimbursement issues relatedto generic medicines [7]. In contrast, demand-side poli-cies are mostly related to interventions at the prescribingand dispensing levels as well as purchasing by consumers

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Table 2A summary of studies in the review investigating physicians’ perception, attitude and knowledge towards generic medicines.

Author Study description Country Objective Outcome Limitation

Barrett(2005)[44]

Sample size: 2050Response rate: 21%(n = 425)Sampling: Non-probabilitysamplingMethods: Web surveyTarget group: PhysiciansSource of sample:American MedicalAssociation master file ofphysicians in the UnitedStatesFunding source: Notmentioned by author(s)

United Statesof America(high income)

To investigatephysicians’opinions aboutgenericmedicinessubstitutionand theirpattern ofprescribing ofgenericmedicines.

Perception of physician towards generic medicines:(1) Only 42% of physicians agreed that generic medicines must be therapeuticallyequivalent to brand innovator drugs.(2) However, 36% of the physicians in this study perceived that therapeutic failures were aserious problem with generic medicines.Physicians’ prescribing practice:Physicians supported generic substitution in most cases (78%).Factors affecting physicians’ choice of medicines:73% of physicians said they were aware of the price differences between brand innovatordrugs and generic medicines. Physicians said they felt pressured by patients, health careplans or insurance companies to prescribe generic medicines. However, they also claimedthat a patient’s needs influenced their choice to prescribe brand medicines over genericmedicines.Knowledge of BE regulatory requirement:(1) The majority of physicians (90%) stated that they were knowledgeable about genericbioequivalence.(2) Older physicians were more likely to say they knew enough about the bioequivalenceof generic medicines.

The limitations, similarto other surveys,included non-responsebias, wording ofquestions and order ofquestions, and use ofnon-random samplingtechnique. Thus, theimpact of such issuescannot be ruled outwith certainty, normeasured.

Pereiraet al.(2005)[50]

Sample size: 375Response rate: 29%(n = 110)Sampling: RandomMethods: Mail surveyTarget group: PhysiciansSource of sample: Collegeof Physicians and Surgeonsof Ontario websiteFunding source: FatherSean O’Sullivan ResearchCentre of St Joseph’sHealthcare, Hamilton,Ontario, Canada

Canada (highincome)

To surveyCanadianphysicians andpatients ontheir attitudestowardsgenericmedicines,importance ofbioequivalenceto Coumadin©

and theirperceptionsabout genericWarfarin.

Perceptions of physician towards generic medicines:Respondents held neutral view on generic Warfarin although a minority of them hadconcerns about it.Physicians’ prescribing practice:(1) 65% of the respondents generally supported generic substitution.(2) 43.6% of respondents agreed or strongly agreed that for narrow therapeutic indexdrugs, brand innovator drugs should not be substituted with generic equivalents.(3) 44.0% of respondents prefer to prescribe original warfarin for patients starting warfarintherapy.(4) 40.0% of them felt not comfortable about generic substitution of warfarin.(5) 19.4% of them reported difficulties in managing the switch.Knowledge of BE regulatory requirement:Only 14.5% of the respondents were familiar with the specific bioequivalencerequirements that are applied to generic warfarin in Canada.

Sampling bias might belimitation of the study,as those physicianswith more interest ingeneric substitution orwith some concernswere more likely tohave participated. Theopinions of allphysician specialtygroups might not berepresentedadequately.

KersnikandPeklar(2006)[40]

Sample size: 200Response rate: 58.5%(n = 117)Sampling: RandomMethods: Postal surveyTarget group: GeneralpractitionersSource of sample:National databaseFunding source: NationalHealth Insurance Instituteand research grant fromNational Research Agency(ARRS)

Slovenia (highincome)

To examinegeneralpractitioners’attitudetowardsgenericprescribing

Perception of physician towards generic medicines:88.9% of them perceived generic medicines to have the same effectiveness as originalbrand medicines.Factors affecting physicians’ choice of medicines:(1) Academic detailing affects respondents’ generic prescribing decision (60.7%)(2) They were willing to switch to cheaper generic versions (96.3%) if prices were lower by25–35% than brand innovator medicines.

Limitations were notmentioned by theauthors.

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Table 2 (Continued)

Author Study description Country Objective Outcome Limitation

Hassaliet al.(2006)[38]

Sample size: 10Response rate: NotapplicableSampling: ConveniencesamplingMethods: QualitativeinterviewTarget group: Generalpractitioners (GPs)Source of sample:Advertisement in theweekly newsletter ofDivision of GeneralPractice, Melbourne BranchFunding source: Notmentioned by author(s).

Australia (highincome)

To investigatefactorsaffecting theGPs’ genericmedicineprescribing.

Perception of physician towards generic medicines:GPs in Melbourne had mixed attitudes prescribing of generic medicines. Moreover,misconceptions about the safety and efficacy of generic medicines still persist amongsome GPs.Factors affecting physicians’ choice of medicines:(1) Cost was reported to be the main reason in prescribing generic medicines.(2) Major factors influencing the practice were identified such as the safety profile of themedicine, cost and patient compliance.Effect of pharmaceutical sales representatives on prescribing of generic medicines:Respondents agreed that drug advertising and marketing can influence their choice ofmedicine brands.Barriers to prescribing of generic medicines:There were three main reasons why GPs opposed generic medicines: patient confusionarising from substitution, concerns over bioequivalence and the risk of less money forresearch-based companies to discover new drugs.Knowledge of BE requirement:GP had poor knowledge of the bioequivalence standard.

The study was anexplorative qualitativestudy conducted withten generalpractitioners in onestate in Australia(Melbourne). Hence,generalization ofresults to other parts ofthe country might belimited.

Heikkiläet al.(2007)[48]

Sample size: 25 generalpractitioners and 24specialistsResponse rate: NotapplicableSampling: ConveniencesamplingMethods: StructuredinterviewTarget group: Generalpractitioners andspecialistsSource of sample: NorthSavo and Central FinlandFunding source: Notmentioned by author(s)

Finland (highincome)

To investigatethe opinions,attitudes andexperiencesthat physiciansand customershave of genericsubstitution.

Perception of physician towards generic medicines:Most of the physicians interviewed (n = 42, 86%) perceived that generic substitution was agood reform measure. However, more than half of the physicians thought thatinterchangeable medicines in certain medicine groups are not of the same safety andeffectiveness as the original brand medicines.Others:The topics related to generic substitution that were most discussed by patients andphysicians during consultations were the lower cost of the generic medicines followed bytheir side effects. Patients also talked about the efficacy and availability of genericmedicines during the consultations.

The participants wereconveniently selectedfrom two areas, namelyNorth Savo and CentralFinland. Hence, theresults of the studywere not generalizableto all Finnishphysicians. Moreover,the results representedthe opinions and viewsduring the first year ofmandatory genericsubstitutionimplementation.

Tsiantouet al.(2009)[47]

Sample size: 1463Response rate: 82.3%(n = 1204)Sampling: StratifiedsamplingMethod: Postal surveyTarget group: PhysiciansSource of sample: GreekMedical AssociationdirectoryFunding source: Notmentioned by author(s)

Greece (highincome)

To investigatethe prescribingpractice ofphysicians inGreece with afocus on factorsthat influencetheir decisionon genericprescribing

Perception of physician towards generic medicines:Physicians had positive views on the safety, efficacy and quality of generic medicines.Physicians’ prescribing practice:The majority of respondents (70.8%) reported that they did not prescribe genericmedicines.Factors affecting physicians’ choice of drug:(1) The appearance of side effects, patients’ insurance coverage, patient income and cost ofthe drug were identified as important factors that affected their selection of medicines.(2) Participants’ age and their opinion of generic medicines were two factors influencinggeneric medicines prescribing.Effect of pharmaceutical sales representatives on prescribing of generic medicines:(1) Companies’ sales representatives were considered as the second most importantsource of information.(2) 74.2% of them claimed that they were not affected by sales representatives.

The study wassubjected to all thelimitations that mighthappen with similarmail surveys.Moreover, while thesurvey had a good highresponse rate, but thehigh number ofmissing values in somequestions, particularlyquestions related tothe quality, efficacyand effectiveness ofgeneric medicines,might lead to bias inthe study findings.

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Theodorouet al.(2009)[51]

Sample size:Greece: 1463 Cyprus: 240Response rate:Greece: 82.3% (n = 1204)Cyprus: 80.4% (n = 193)Sampling: Proportionalstratified samplingMethods: Postal surveyTarget group: physiciansSource of sample: Notmentioned by author(s)Funding source: Notmentioned by author(s)

Greece andCyprus (highincome)

To investigateattitudes andfactors thatinfluencephysicians’prescribingdecisions andpractice inGreece andCyprus.

Perception of physician towards generic medicines:(1) The majority of doctors in both countries agreed that the effectiveness, safety andefficacy of generic medicines may not be excellent but they are acceptable.(2) Physicians believed that new drugs are not always better and their high prices are notnecessarily justified.Physicians’ prescribing practice:Cypriot physicians prescribed more generic medicines than Greek physicians.Factors affecting physicians’ choice of drug:(1) Clinical effectiveness was the most important factor to be considered in drug selectionin both countries.(2) About 60% of physician considered cost of medicines to patients important or highlyimportant when prescribing medicines.

Lack of distinctionbetween primary careand secondary carephysicians.

Alghasham(2009)[41]

Sample size: 900Response rate: 85.8%(n = 772)Sampling: StratifiedsamplingMethods:Self-administeredquestionnaireTarget group: PhysicianSource of sample:Different setting in centralSaudi ArabiaFunding source: Notmentioned by author(s)

Saudi Arabia(high income)

To examinephysicians’practices,attitudes andother factorsinfluencingprescribing ofgenericmedicines

Perception of physician towards generic medicines:(1) Even though most physicians (79%) supported generic substitution, there were certainclinical situations where they preferred to use brand name medicines.Factors affecting physicians’ choice of medicines:(1) 72% of them believed that price difference between generic and original medicineshelped them to switch to generic medicines.(2) Physicians did not report significant difference in pressure from patients in prescribinggeneric or brand medicines.Effect of pharmaceutical sales representatives on prescribing of generic medicines:(1) Physicians reported receiving visits and samples more frequently from representativesof brand name companies.(2) Physician reported that generic drug representatives were their first source ofinformation followed by pharmacists.Knowledge of generic medicines:(1) The majority (96%) of the physicians knew enough about the therapeutic value ofgeneric medicines.(2) 75% of the respondents reported that they knew the price differences.

Limitations were notmentioned by theauthor.

Fabianoet al.(2012)[42]

Sample size: 303Response rate: Notmentioned by author(s)Sampling: Not mentionedby author(s)Methods: Web-surveyTarget group: FamilyPaediatrician (FP)Source of sample: AllItalian family paediatricianFunding source: Notmentioned by author(s)

Italy (highincome)

To collectinformationregarding FP’sperception ofgenericmedicines andgenericprescribing

Perception of physician towards generic medicines:The majority of them believed that efficacy of generic medicines were sufficient (33.6%) orgood (45.2%).Physicians’ prescribing practice:13.5% of them declared that generic medicines would always be prescribed when available.Barriers to generic prescribing:Factors that hindered FP prescribing generic medicine were insufficient knowledge ofgeneric medicines (20.4%) and scepticism about the reliability of bioequivalence test andthe safety of generic medicines (54.4%).Knowledge of generic medicines:The findings of the study reported that 37.2% and 32.6% of them declared having asufficient or fairly good knowledge of generic medicines, respectively.

The major limitation ofthe study was the smallsample size.

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Table 2 (Continued)

Author Study description Country Objective Outcome Limitation

Hamannet al.(2013)[49]

Sample size: 410Response rate: Notmentioned by author(s)Sampling: ConveniencesamplingMethods: Hypotheticaldecision scenario,structured questionnaireTarget group: PsychiatristsSource of sample:Psychiatrists attendingannual meeting of theGerman Psychiatrists’Association (DGPPN)Funding source: Nofunding received

Germany (highincome)

To display thesubjectiveviews ofpsychiatriststowardsgeneric versusbrandedpsychotropicmedicines withspecial focuson whatinfluences theirchoice betweenbranded andgenericmedicines invarious clinicalsituations

Perception of physician towards generic medicines:(1) Most of the psychiatrists judged branded drugs were slightly better than generic ones’with all the potential difference the author asked.(2) The most pronounced difference between generic and branded medicines was placeboeffect.Physicians’ prescribing practice:Psychiatrists preferred to use branded drugs for their own use but for patients, theypreferred to prescribe generic medicines in the two scenarios of hypothetical depressionand schizophrenia.Factors affecting physicians’ choice of medicines:Additional predictors for choosing generic medicines were higher share of outpatients,less negative attitude toward generic medicines and higher uncertainty tolerance.

The study had somelimitations. First, ahypothetical decisionscenario was used.Second, not allpotential factorsinfluencing prescribinghabits were studied.Third, Conveniencesampling was used.Hence, generalizationfor all psychiatristsmight not be possible.

Shranket al.(2011)[43]

Sample size: 2764Response rate: 30.4%(n = 839)Sampling: Stratifiedrandom samplingMethods: Web surveyTarget group: PhysicianSource of sample:e-Rewards Physician Paneland the American MedicalAssociation (AMA)Physician Master fileFunding source: Careerdevelopment award fromNational Heart, Lung andBlood Institute(K23HL090505-01) andresearch grant from CVSCaremark

United Statesof America(high income)

To evaluatephysicians’perceptionsabout genericmedicines andpotentialbarriers togenericmedicine use.

Perception of physician towards generic medicines:(1) About 67% of the respondents somewhat or strongly agreed that generic medicines areas effective as brand innovator medicines.(2) Over 23% of the physicians surveyed expressed negative perceptions about efficacy ofgeneric medicines.(3) However, 50.6% of respondents were concerned about the quality of generic medicines.Physicians’ prescribing practice:More than a quarter preferred not to use generic medicines as the first-line medicines fortheir family members and themselves.Factors affecting physicians’ choice of medicines:The age of respondents was reported to be associated with physicians’ perception ofgeneric medicine with older physicians showing more negative perceptions towardsgeneric medicines than younger physicians.Effect of pharmaceutical sales representatives on prescribing of generic medicines:Physicians reported that pharmaceutical company representatives were the mostcommon source of information (75%) about the market entry of generic medicines.

The sample size wasdrawn from a samplingframe that had in itthose physicians whowere willing toparticipate in surveys.Thus, they might bedifferent to themajority population.Also, the response ratewas very low.Moreover, some agegroups (i.e. youngphysicians) and femalephysicians were lesslikely to participate inthe study, while thosebetween the age of 55and 64 wereoverrepresented.Furthermore, socialdesirability bias couldhave biased the results.Moreover, in this studyface validity wasperformed butconstruct validity ofthe questions was not.

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Chua et al.(2010)[39]

Sample size: 325Response rate: 26.8%(n = 87)Sampling: ConveniencesamplingMethods: Postal surveyTarget group: Generalpractitioners (GPs)Source of sample: PrivateMedical Practice ControlDepartment, MedicalPractice Division, Ministryof Health Malaysia, 2007registryFunding source: Notmentioned by author(s)

Malaysia(upper middleincome)

To evaluategeneralpractitioners’knowledge andperception ofgenericmedicines inPenang,Malaysia.

Perception of physician towards generic medicines:33% of the respondents had doubts about the efficacy of generic medicines while only10.3% thought that generic medicines produced more side effects than their counterpartoriginal brand.Physicians’ prescribing practice:85.1% of the respondents claimed that they actively prescribed generic medicines in theirpractice.Factors affecting physicians’ choice of drug:Respondents’ age and years of practising were found to be significantly associated withactive prescribing of generic medicines.Knowledge of generic medicine:(1) The majority of the GPs thought that generic medicines must be in the same dosageform (65.5%) and dose (81.6%) as the brand name medicines.(2) Only 49.4% of the respondents believed that generic medicines are bioequivalent tobrand name medicines.Knowledge of BE regulatory requirement:Only 4.6% of the respondents correctly identified the bioequivalence standard for genericproducts.

The low response rateis one of the limitationsof the study. Moreover,the study wasconducted in one state(State of Penang).Hence, thegeneralization of thefindings to all GPs inMalaysia is notpossible.

Toklu et al.(2012)[46]

Sample size: 115Response rate: 49% (n = 56)Sampling: ConveniencesamplingMethods: SurveyTarget group: PrescribersSource of sample:Haydarpasa NumuneEducation and TrainingHospital and MarmaraUniversity HospitalFunding source: Notmentioned by author(s).

Turkey (uppermiddleincome)

To investigatethe knowledgeand attitudes ofpatients,communitypharmacistsand physiciansregarding theuse of genericmedicines.

Perception of physician towards generic medicines:32% of the prescribers perceived that generic medicines did not differ from the originalbrand innovators.Factors affecting physicians’ choice of medicines:Their knowledge and attitude about generic substitution were not related to sex, age orprofessional experience. For 92% of the prescribers, cost was the most important factortaken into consideration regarding generic substitution.Knowledge of generic medicines:(1) However, 82% of the prescribers were unsure about the bioequivalence of genericmedicines.(2) Healthcare providers have insufficient knowledge about generic medicines.

The major limitation ofthe study was the lowresponse rate and thesmall sample size.

Sharradet al.(2009)[35]

Sample size: 10Response rate: NotapplicableSampling: PurposivesamplingMethods: QualitativeinterviewTarget group: PhysiciansSource of sample: Centralcity and rural regions inBasrahFunding source: Notmentioned by author(s)

Iraq (uppermiddleincome)

To explorefactorsaffectinggenericmedicineprescribing inIraq.

Physicians’ prescribing practice:Mixed reactions when physicians were asked whether they prescribed generic medicine.Factors affecting physicians’ choice of medicines:(1) The major factors affecting physicians’ choice of medicines were drug availability, costof medicine, safety and quality of the medicine, economic situation of the patient anddisease severity.(2) Low cost of the generic medicines was the most common incentive to encourageprescribing of generic medicines.Effect of pharmaceutical sales representatives on prescribing of generic medicines:All physicians agreed that advertising positively influenced their choice of genericmedicines.Pharmaceutical industry representatives were one of the main drug information sources.Barriers to generic medicine prescribing:The most common reason why physician opposed generic medicines was potential clinicalproblems. Other factors that hindered physicians from prescribing generic medicines werepatient confusion, concerns about the quality and efficacy of generic medicines, anddisease severity.Knowledge of BE regulatory requirement:Physicians had little or no knowledge about bioequivalence criteria required.

The study was anexplorative qualitativestudy conducted withten physicians in onecity in Iraq (Basrahcity). Hence,generalization ofresults to other parts ofthe country is limited.

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Table 2 (Continued)

Author Study description Country Objective Outcome Limitation

Gossell-Williams(2007)[45]

Sample size: 100Response rate: 60% (n = 60)Sampling: RandomsamplingMethods: Survey by multichannels (i.e. email, fax, byhand, phone)Target group: PhysiciansSource of sample: YellowPages of local telephonedirectory of 2005 issued byCable and WirelessFunding source: Notmentioned by author(s)

Jamaica (uppermiddleincome)

To investigateattitudes ofJamaicanphysicianstowardsgenericsubstitutionand issuesrelated to theuse of genericmedicines.

Physicians’ prescribing practice:Most of the surveyed physicians (49%) had a preference for prescribing generic medicineswhereas 29% of the physicians prescribed generic medicines and brand innovatormedicines in 50:50 ratios.Factors affecting physicians’ choice of medicines:Cost was the main factor (70%) influencing generic medicines prescribing. 33% ofrespondents reported clinical problems encountered with specific generic medicines;most of the clinical problems were associated with anti-infective agents.Knowledge of generic medicine:There were doubts about whether the generic medicines are bioequivalent andtherapeutically equivalent to the innovator medicines.

Recruitment andhaving access tocontact details ofphysicians to invitethem to participate inthe study was alimitation. The use of adirectory does notcover all physicians inthe country.

Jamshedet al.(2011)[26]

Sample size: 11Response rate: NotapplicableSampling: SnowballsamplingMethods: QualitativeinterviewTarget group: DispensingdoctorsSource of sample: Karachi,PakistanFunding source: UniversitiSains Malaysia

Pakistan (lowermiddleincome)

To exploredispensingdoctors’knowledge,perception andattitudetowardsgenericmedicines andfactorshindering andfavouringgenericmedicine use.

Mixed views and attitude of dispensing doctors towards generic medicines were reported.Thematic content analysis identified five themes: (1) knowledge of generic medicines, (2)perception regarding generic medicines, (3) attitudes towards generic medicine, (4)attitudes towards marketing strategies by industries for original brands and genericmedicines, and (5) recommendation to further enhance generic ultilization.

Limitations were notmentioned by theauthors.

M.A. Hassali et al. / Health Policy 117 (2014) 297–310 307

Table 3A summary of the variables that were investigated in the studies.

Study The variables

Perception ofphysiciantowardsgenericmedicines

Physicians’prescribingpractice

Factorsaffectingphysicians’choice ofmedicines

Effect ofpharmaceuticalsalesrepresentativeson genericmedicineprescribing

Barriers togenericmedicineprescribing

Knowledge ofbioequivalenceregulatoryrequirement

Knowledge ofgenericmedicines

Barrett (2005) [44]√a √ √ √

Pereira et al. (2005)[50]

√ √ √

Kersnik and Peklar(2006) [40]

√ √

Hassali et al. (2006)[38]

√ √ √ √ √

Heikkilä et al.(2007) [48]

√

Tsiantou et al.(2009) [47]

√ √ √ √

Theodorou et al.(2009) [51]

√ √ √

Alghasham (2009)[41]

√ √ √ √

Fabiano et al.(2012) [42]

√ √ √ √

Hamann et al.(2012) [49]

√ √ √

Shrank et al. (2011)[43]

√ √ √ √

Chua et al. (2010)[39]

√ √ √ √ √

Toklu et al. (2012)[46]

√ √ √

Jamshed et al.(2011) [26]

√ √ √ √

Sharrad et al.(2009) [35]

√ √ √ √ √

Gossell-Williams(2007) [45]

√ √ √

.

tempmgrcdtam

thbwcbumg

a √means the particular variable(s) is explored in the respective study

hat include educational interventions to improve knowl-dge and confidence of physicians in prescribing genericedicines [7]. On contrast, the lack of part or all of these

olicies especially the educational interventions in LMICsay account for the mixed views of physicians towards

eneric medicines. Moreover, lack of confidence in the drugegistration system, lack of communication between healthare professionals and drug regulatory authorities, lack ofrug information, guidelines, and regulatory informationhat document the bioequivalence and therapeutic equiv-lency contribute to the negative perceptions of genericedicines among physicians [24].From the present review, there were five articles (i.e.

wo from middle-income countries [35,39] and three fromigh-income countries [38,44,50]) in which knowledge ofioequivalence acceptability criteria for generic medicineas accessed. In general, all studies reported that physi-

ians have a low level of knowledge of the basis of

ioequivalence testing. Lack of knowledge on the reg-latory requirement of generic medicines will result inisconceptions about the quality, safety and efficacy of

eneric medicines [38,39,57].

The findings from this present review show that thecost of generic medicine was the main factor encouragingphysicians to prescribe generic medicines regardless of thecountry income group. This finding showed that physicianswere aware of the escalating health care costs and poten-tial savings that generic medicines can offer. In fact, wideutilization of generic medicines can lead to substantial costsavings to the healthcare system [7–10,42,58]. The moneybeing saved can be better used elsewhere [47,59,60]. More-over, empowering the physicians with the appropriateknowledge about generic medicines and increasing theirprescribing rate of these products will not only lead tocost savings and financial benefits, but it can lead to betterhealth outcomes via improving medicine access and afford-ability and hence patient adherence to essential medicines[61–63].

Another interesting issue was that physicians, regard-less of country income group, expressed concerns over

the safety and quality of generic medicines although inmany of these countries strict bioequivalence acceptabilitycriteria for generic medicines were set by their respectivedrug regulatory bodies. One plausible explanation is lack of

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awareness of physicians towards roles and responsibilitiesof drug regulatory body in respective countries.

In addition, the effect of pharmaceutical sales repre-sentatives in changing physicians’ prescribing habit shouldnot be neglected. A few papers in this review investigatedthe roles of pharmaceutical sale representatives in pro-viding drug information [35,43,47]. Physicians mentionedthat pharmaceutical sales representatives were among themajor sources of drug information and some of them men-tioned that visits from these representatives affected theirchoice of drugs when prescribing [47]. In fact, other stud-ies showed that pharmaceutical sales representative visitshad an influence on prescribing patterns [58,64,65]. Onestudy also reported that physicians were not informed withundesirable side effects by pharmaceutical sales represent-atives [66]. Patients’ health may be negatively affected ifphysicians are not informed about the side effects. Otherthan that, physician claimed they received visits mostlyfrom original pharmaceutical companies. This scenario ofbiased drug information obtained from drug companies, ifleft unattended may have a negative impact on prescribingof generic medicines. Thus, there is a need for a regula-tory body to monitor and audit drug information providedby pharmaceutical sales representatives since they are oneof the main drug information sources for physicians [31].Moreover, it is an important to provide the physicians withevidence-based information about generic medicines andtheir therapeutic equivalence with their counterpart origi-nal brands. This could be done by publishing a formulary ofinterchangeable medicines that documents the bioequiva-lence and suitability of generic substitution [67].

5. Conclusion

The present literature review revealed that physiciansfrom LMICs tend to have mixed views regarding genericmedicines. This may be due to differences in the healthcare systems and drug approval and regulatory systems,medicine policies, the level of educational interventionsand drug information sources in countries of differentincome levels. Based on the present review, in order toimprove utilization of generic medicines in LMICs, thefollowing recommendations were made. First, more edu-cation and promotional efforts should be carried outto promote the bioequivalence acceptability criteria forgeneric medicines to physicians. Second, evidence-basedinformation is needed to convince the physicians about thesafety, quality and efficacy of generic medicines especiallythose physicians practising in LMICs. Third, drug regulatorybodies need to monitor and audit drug information pro-vided by pharmaceutical sales representatives as they areone of the main drug information sources used by physi-cians.

6. Limitations

The review has a number of limitations. The litera-

ture search was carried out based on electronic databasesto which the authors’ university library subscribed. As aresult, it is possible that some important studies might nothave been retrieved. However, the review was not intended

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to be exhaustive, but merely an attempt to examine thegeneral perspectives of physicians in LMICs regardinggeneric medicines. Besides that, papers that were pub-lished in languages other than English were excluded fromthe review. Moreover, the review focused on the recentliterature, i.e., from 2001 and onwards. However, this is jus-tified because older studies might not be relevant to currentpractices. Perceptions and views do change over time, anda large number of generic medicines have been marketed inthe last two decades. Moreover, many initiatives, policies,and promotion programs have been introduced in recentyears, which might have an effect on physicians’ percep-tions and views [68]. Also, information technology and easyaccess to information about generic medicines (e.g., via theInternet) has become more common in recent years. Thus,including the recent literature makes this review more con-temporary and more relevant to today’s practice [68].

Conflicts of interest

None.

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