Pharmacoepidemiological studies of prescribing practices of health care providers of Pakistan : A cross-sectional survey

Half of all medicines are prescribed or sold inappropriately and half of all patients fail to take their medicines correctly worldwide. The present study was conducted to evaluate the pattern and practice of drugs within the modern medical system by investigating the prescription pattern, drug use in private and public health care facilities, assessment of the magnitude of the problem, identifying factors responsible for the problem, suggesting measures in Pakistan. There were marked differences between the qualities of consultation indicators between general practitioners (GPs) and public health care providers. The average number of drugs per prescription was 2.92 for all types of health care providers, mean number of drugs dispensed was 2.41 and 50% of the dispensed drugs were adequately labeled. Five categories of drugs comprised around 70% of all drugs prescribed. Injections prescribed per prescription were 0.32, infusions 0.07, capsules/tablets 1.85, syrups/suspensions 0.8. Number of drugs prescribed by GP’s was 4.3 and was 2.9 (P = 0.001) for public health care providers and antibiotics prescribed per prescription were 0.9 and 0.8 (P = 0.176) for the GP’s and public health care providers. The availability of drugs at public health care facilities influenced prescription in 88% of cases as compared to 57% (P = 0.001) at GPs clinics. Prescribing and dispensing practices are irrational both in public and private sector in Pakistan like many developing countries. Workable and appropriate interventions need to be developed and implemented in countries to improve trends of prescribing. The essential drug list and standard treatment guidelines should be disbursed to all medical, dental and pharmacy students.


INTRODUCTION
The Islamic Republic of Pakistan, with an area of 796095 km² is the sixth largest country and has a population of 160 million.Of these, 43.2% are less than 15 years, 53.4% are from 15 to 64 years and 3.4% are 65 years and above, with a per capita income of US$ 492.33 % of the population lives in the urban areas and 67.0%lives in the rural areas.Its population growth rate is 2.06% (NIPS, 2003).In Pakistan, the number and type of drugs *Corresponding author.E-mail: shshaikh2001@yahoo.com. is on the rise every year while the resources for health care services especially medicines remain meager.
It is estimated that over half of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients fail to take their medicines correctly worldwide (Hogerzeil, 1995).The medicines are used rationally when patients receive the appropriate medicines in doses that meet individual requirements, for an adequate period of time, and at the lowest cost both to them and their community (WHO, 2001(WHO, , 1995)).Irrational use occurs when one of the conditions is not met.Inappropriate use of medicines, related illness and deaths are restricted not not in the low-income countries but studies in Australia, Kuwait and USA, as well in middle-income countries like Thailand, have revealed that inappropriate medicines are widespread in teaching hospitals (WHO, 2001).In many countries, the problem extends beyond hospitals.Two third of all antibiotics are sold without prescription, though under regulated private sectors.A recent review of the adverse events in the USA (White et al., 1999) shows these to be the fourth to sixth ranked cause of death in the country, with economic costs of between US$ 30 to 130 billion per year.The usage of antibacterial drugs was reviewed in 16 European countries being very similar economically and epidemiologically, the use varied by a factor of 2.5 between countries (Ronning et al., 2003).
Ensuring appropriate prescribing is a major challenge for the health services.Variation in the volume and cost of prescribing in different parts of the country, between practices and between individual doctors, has been a concern to many clinicians and policy-makers (Watkins et al., 2003;Hansen, 2003;Whitford, 2003).Attempts to characterize high and low prescribing have been made with inconsistent results (Lagerlov et al., 2001;Prosser et al., 2003).Incorrect antibiotic prescription exposes patients to the risk of side effects with little therapeutic benefit.It may encourage the emergence of drug resistance which has increased dramatically across a wide range of important antimicrobial chemotherapeutic groups including those used to treat tuberculosis (Prosser et al., 2003).It is worth mentioning that factors like doctor characteristics, hospital consultants, the pharmaceutical industry and patient characteristics lie behind the prescription decisions among general practitioners (Das et al., 2001).A number of studies have been carried out in Pakistan from time to time, but study to estimate the prescription and dispensing practices covers few hospitals or one district or one city, but this study is so comprehensive that it covers the four districts of Pakistan (Siddiqi et al., 2002;Najmi et al., 1998;Riaz et al., 2011).A cross sectional survey of the four districts of Pakistan was carried out within the modern medical system by investigating the prescription pattern and drug use in the health care facilities in the formal health sector of Pakistan to assess the magnitude of the problems, identifying underlying factors responsible for the problem and suggesting measures to control drug misuse in the country.

METHODOLOGY
The primary objective of the study was to evaluate the pattern and practice of drug's use (and misuse) in the modern allopathic health sector in Pakistan, with respect to assessing the extent and magnitude of the problem and suggesting corrective measures for its control.

Survey
A survey methodology was adopted which was developed by WHO Hussain et al. 1485 and has so far been implemented in 12 developing countries and is based on the application of selected drug use indicators.The sampling unit was the patient prescribed encounter (P-P encounter).The sample size was estimated using quality of prescription as the outcome variable.Studies on GPs from Karachi and Attock (Hogerzeil et al., 1993, Siddiqi et al., 2002) have shown that in cases of diarrhea in children, the quality of prescription is inadequate in over 50% of P-P encounters.Using this figure as an indicator of the overall quality of prescription with a precision level of ± 2.0% at 95% confidence level, the estimated sample size was around 5,000 P-P encounters.Survey instruments were developed and pre-tested in another district.The pharmacist and some students visited each facility to collect information.In case it was not possible to collect adequate prescriptions on the first visit, the same health facilities were visited again.A program was written in EPIINFO version 5 and entered by a trained person.The quality of prescription and the quality of consultation were computed for the four indicator disease, acute respiratory infections (ARI), childhood diarrhea, fever in children and adults.The quality of prescription whether adequate or inadequate, was assessed by a team of interviewers for each patient-provider encounter, which was especially trained for this purpose.Based on the likely diagnosis and the standard treatment for the health problem in question, the treatment given, that is, drug(s) group, their mode of administration (type), dosage and duration given to the patient was then compared with the standard treatment for the likely ailment to determine the quality of prescription.An additional variable quality of consultation was also computed using in addition to the quality of prescription, patient's reception, adequacy of history, relevance of physical examination, consultation time, dispensing time and patient's satisfaction with consultation.

Demographic profile of patients
Out of 10120 prescriptions for whom age was available, 4508 (45.28%) were prescribed for age group of 19 to 45 years, followed by 2358 (23.68%) for age group of 45 years, 1884 (18.92%) for age group of 6 to 18 years and 728 (7.31%) for children under 5 years.Among all the prescriptions assessed, 55.44% were given to females and 44.56% to males (Figure 1).Quality of consultation indicators are not related to prescription practices and were studied for all health care providers.This included adequacy of history, relevance of physical examination, whether diagnosis was informed to the patient, whether diagnosis was written on the prescription, whether laboratory tests were required and were they appropriately ordered and whether the patient required referral and was it appropriately carried out.The results were compared amongst the groups of public providers and general practitioners.The practices patterns of the general practitioners (GPs) and public facility personnel were also compared.Major differences in the quality of consultation amongst public providers and GPs were observed (Figure 2).There was marked difference between the quality of consultation indicators between GPs and public health care providers and there were significant differences statistically and clinically as well (93.93% versus 70.18%).The percentage of physical examination by general practitioners was higher than public health care provider (85.22% versus 67.13%) which is statistically significant as well.The trend of informing the patients about the diagnosis and also noting it down on prescriptions was 43.64% by GPs as compared to 39.71% by public health care providers and the trend of writing it down on prescriptions was 62.26% by GPs and 52.78%, respectively which is an indication of communication approach by the GPs and public health care providers.

Laboratory test and referral practices of GPs and public health care providers
The frequency and appropriateness of laboratory tests and patient referrals were also studied in some details as well.Laboratory tests were frequently ordered by GPs (24.65%) followed by public health care providers (17.39%).

Drug prescription and dispensing practices
The total numbers of drugs prescribed were 29950 and the average number of drugs per prescription was 2.92 ± 1.6 for all categories of providers (Table 1).The total number of drugs dispensed at the facility was 20148 of the drugs prescribed.The mean number of drugs dispensed at the facilities was 2.41 ± 1.6.Out of the dispensed drugs, 5382 or 50% were adequately labeled (mean 1.53 ± 1.31).The mean number of antibiotics per

Differences in prescription practices by type of providers
Prescription practices of health care providers were compared by the type of providers.The mean number of drugs prescribed by GP was 4.3 ± 1.8, public provider 2.9 ± 0.7 (P = 0.001) and this difference is statistically significant.The mean number of antibiotics prescribed per prescription was 0.9 ± 0.8 and 0.8 ± 0.6, respectively for the GP and public provider.Steroids were also most frequently being prescribed by the GPs (0.12 ± 0.35).While for the public health care providers (0.07 ± 0.21), the mean number of steroids per prescription were almost the same.These differences were statistically significant.The GPs prescribed 0.6 ± 0.5 NSAIDs, followed by public health care providers (0.6 ± 0.5) (Table 5).The GPs and public providers are prescribing the same number of NSAIDs.A comparison of prescription practices, regarding vitamins and hematinics among health care providers, revealed that vitamins were most frequently prescribed by GPs (0.49 ± 0.76) and public providers (0.28 ± 0.5).Hematinics on the other hand were prescribed most frequently by public health care providers (0.28 ± 0.5), followed by GPs (0.06 ± 0.24).In all instances, the differences were not statistically significant (Table 5).Sources of information on pharmaceutical preparations were evaluated for all types of health care providers.The most important source of information about drugs for the GP was the medical representative of pharmaceutical companies (92%).Some of them also stated that they had consulted books on pharmacology and therapeutic indices available on the market.Other sources of information included wall charts and guidelines, scientific journals and newsletters.An interesting source of information on drugs for GPs as well as other health care providers was prescriptions of senior doctors and specialists.For public sector health care providers, the three equally important sources of information on drugs were the medical representatives, pharmacology books and prescriptions of senior doctors and specialists (Figure 3).

Potential factors that influence the prescription practices of providers
The survey relating to the potential factors that influenced the practices of health care providers was completed at the end of the survey.Factors that were considered were that of patient as well as related provider (Table 6).All the health care providers gave consideration to the age of the patient, severity of the disease, socio-economic status of the patient and previous experience of treating similar patients as important factors that determined their choice of drugs.There was no significant difference among these factors when studied by the type of provider.How frequently the drugs prescribed were influenced by patient demand were also evaluated.Patient demand was considered most frequently at the pharmacies (87.3%),where patients often resort to selfmedication.However, the public providers were influenced by patient demand in 42% of cases as compared to 62% in cases of GPs.The practitioners were also asked whether their prescribing practices were influenced by the fact that if they did not prescribe certain drugs, they may lose patients to others.In response 52% of GPs and 12.0% of public providers were admitted of being influenced by market "competition".Two potential factors regarding availability of drugs and the availability of essential drug list (EDL) at facilities were also studied.The availability of drug at public facilities influenced prescription in 88% of cases as compared to 57% at GP clinics.EDL was not available in some facilities irrespective of whether they were in the public or private sector, and did not influence the prescription practices of the providers.When asked whether medical representative influences prescription practices of providers, the response was positive with 54% of GPs and 24% public providers.The difference remained statistically significant even when considered between GPs and public providers.Review of medical literature also seemed to influence prescription practices, 45.3% for GPs and 46.9% for public health care providers (Table 6).When asked to prioritize what were the three most important factors that influenced their prescription, altogether, there were 475 responses from among the health care providers (Figure 4).The top three factors as indicated by the providers were socioeconomic status of the patient, 25.5% previous experience of treating patients, 22.30% and severity of disease, 14.2%.These were followed by patient demand for specific drugs 10.5% and availability of drugs at facility 10.4%, and

DISCUSSION
This study has assessed various aspects of prescription practices at a four districts level covering a population of 15 to 20 million peoples of varied socioeconomic strata.10120 prescriptions of 174 health care providers were studied.The only other broad-based study at a district level is from Maharashtra in India, which analyses the rationality of prescriptions in relation to the diseases for which they were prescribed (Phadge-Ar, 1996).The other study was in the district Attock in Pakistan which assessed this problem in the formal allopathic health sector and compared prescription practices of health care providers in the public and private sector, and prescriptions were collected from 60 public and 48 private health facilities.The mean (± SE) number of drugs per prescription was 4.1 ± 0.06 for private and 2.7 ± 0.04 for public providers.General practitioners (GPs) who represent the private sector prescribed at least one antibiotic in 62% of prescriptions when compared with 54% for public sector providers.Over 48% of GP prescriptions had at least one injectable drug when compared with 22.0% by public providers.13% of GP prescriptions had two or more injections.More than 11% of GP prescriptions had an intravenous infusion when compared with 1% for public providers.GPs prescribed three or more oral drugs in 70% of prescriptions when compared with 44% for public providers (Siddiqi et al., 2002).A set of drug-use indicators was produced and tested in 12 developing countries of the world (WHO, 1993).These indicators can be used for monitoring and improving drug-use practices in developing and under developed countries.These indicators were used to compare the prescription patterns of the public and private sector in the four districts of Pakistan with those from studies carried out in other 12 countries.In results from these countries, both similarities and differences in drug-use patterns were observed.Out of the special interest, were outlying values, for example, the average numbers of drugs per encounter in Indonesia and Nigeria, (3.3 and 3.8), the high percentages of prescriptions of one or more antibiotics in Uganda and Sudan (56 and 63%) and of injectable drug in Uganda, Sudan and Nigeria (36 to 48%) and the low availability of essential drugs, Ecuador (38%).The problem in the private sector is far more serious and seems to be driven by the aggressive marketing and incentive to the prescribers by the various pharmaceutical companies with no check from the Government.These indicators have also been used to identify priorities for action.For example, since 94% of drugs are prescribed by generic name in Zimbabwe, there is no need to spend more resources on this feature, whereas in Ecuador, with only 37% generic prescription, there is a clear need.In public facilities in Nepal and Tanzania, very few drugs not on the national list of essential drugs are prescribed.In Nigeria the average dispensing time per patient is extremely short (13 s) and the number of drugs per prescription is rather high; both could be topics for focused training and supervision.The same applies to the low percentage of patients in Malawi who understood the dosage schedule that they received.The data on drug use indicators from Pakistan also reveals interesting information.The average number of drugs per encounter is 3.0, drugs prescribed as generics was 25%, antibiotics was given in 55% of prescriptions and 34% prescriptions were carried out as injections.The average time for consultation was 2.9 min, 75% drugs prescribed were dispensed at facility, 85% patients had adequate knowledge of drug dosage and 83% of the essential drugs were found to be in stock at the health facilities.This data gives an overall picture of the drugs indicators in Pakistan and is comparable to such data from other developing countries.Like Nigeria and Indonesia the average number of drugs per encounter is rather high, so is the percent of prescriptions with antibiotics and injections per prescription.
In a country where a lot of prescription is being done over-the-counter (OTC) in pharmacies, prescription practices have been assessed and when compared with those of GPs and public health care providers, altogether 174 prescribers were evaluated (78 GPs and 96 public providers).Among all the prescriptions assessed, 55.44% were given to females and 44.56 % to males.Quality or consultation indicators not related to prescription practices was studied for all providers as well as when compared with GPs and public health care providers.
These included adequacy of history, relevance or physical examination, whether diagnosis was informed to the patient, whether diagnosis was written on the prescription, whether laboratory test was required and was it appropriately ordered and whether the patient required referral and was it appropriately carried out.Whereas adequacy of history taken was similar in the groups of providers and physical examination was adequately performed by GPs in 85.8 to 69% by public health care providers.An interesting feature with respect to informing the diagnosis to the patient and writing it on the prescription, reflected opposite behavior of GPs and public sector personnel.GPs verbally informed about the diagnosis in 51% of cases as compared to 42.5% for public providers.On the other hand diagnosis was written on prescription by 55% of public providers as compared to 47% GPs.This is a reflection on the difference in communicative approaches of GPs and public providers.GPs have a better communication with the patients as compared to public providers and are more likely to inform the patient about the nature of the problem they are into.Their documentation on the other hand is rather poor as compared to the staff of public facilities; probably they are answerable to their seniors, and by the end of the month, reflect their performance as well.
An indication of the seriousness of the diseases for which patients visited health care providers could be assessed by the requirement of referrals and laboratory tests.With respect to requirement for a laboratory investigation, the percentage was 18.3 and 13.6%.On the other hand, the requirement for referrals was similar in the case of GPs and public health care providers (7.1% versus 8.8%).For the appropriateness of the laboratory tests ordered and the referrals made as a measure of the quality of consultation, it was observed that laboratory tests were not ordered when required in 35.2% instances with GPs and 55% instances with public provider.Assessment of appropriateness of referrals indicated that referral was held back by GPs in 64% and public providers in 50%.The problem of referring a patient when not required was not found to be a major one.This is an area that suggests further training and monitoring of primary care providers.Antibiotics (24.6%),NSAIDs (13.2%), steroids (2.4%), vitamins (10.6%) and hematinics (3.7%) comprised 55% of all the 9,766 drugs prescribed.Antibiotics were given in 54.6% of prescriptions, NSAIDs in 32.2% prescriptions, steroids in 6.2% prescriptions, vitamins in 25.4% prescriptions and hematinics in 10.3% prescriptions.The overuse of antibiotics, NSAIDs and steroids for primary care problems has major consequences in terms of adverse effects, drugs resistance and economic burden to the patient.Almost 13% of the 9,766 drugs prescribed were either an injection (11.1%) or an intravenous infusion (1.5%).Almost every third prescription had a parenteral injection or infusion.This is a potential area for intervention for public sector as well as Pakistan Medical Association (PMA) in the country.Comparison of the prescription practices of various health care providers has revealed some useful information for potential intervention of the concerned managers and researchers.The mean number of drugs prescribed by GP was 4.3 and public health care provider was 2.9.The mean number of antibiotics prescribed per prescription was 0.8 and 0.9, steroids 12 and 5%, respectively.NSAIDs were given on 50% of prescriptions by GPs, followed by public providers 40%.The indiscriminate use of medication by the private sector GPs is a public health problem.In comparison with the 12 countries studied (Hogerzeil, 1993), GPs in the four districts where studies were carried out and are prescribing more than anywhere else Hussain et al. 1491 in the world.The practice of prescribing vitamins as a "tonic" as compared to prescription of pure hematinics (iron and folate) gives interesting findings.The GPs are prescribing much more vitamins (54%) as compared to public providers (14%).Public providers prescribed hematinics most frequently (20%) than GPs (8%).This is partly explained by individual prescription practices but also by the supply of hematinics to public health facilities from the provincial drug depots.It is suggested that in order to improve the quality of drugs prescribed, physician education and training must be improved and the role of pharmaceutical companies in physician training should be limited, emphasizing more objective sources of information, such as therapeutic guidelines (Figueiras et al., 2000;Francisco et al., 2002).On the other hand, these results highlight the need to apply primary care reforms in accordance with Alma-Ata (WHO, 1978;Bender et al., 1987).The commercial sources of information are known to have a greater influence than scientific sources on general practitioners' prescribing behavior in under developed and developing countries.It is found that although, physicians believed that drug advertisements and pharmaceutical representatives had a minimal effect on their prescribing behavior, they held advertising oriented beliefs about the efficacy of drugs, such as cerebral vasodilators and dextropropoxyphene (Avron et al., 2000).Recently, in a survey of 200 general practitioners and 230 hospital based doctors, the information on the latest new drug prescribed was derived from pharmaceutical representatives in 42% of the cases (McGetting et al., 2001).A systematic review also found that meetings with representatives were associated with requests by physicians for promoted drugs to be added to the hospital formulary, requiring changes in prescribing practice with increased prescribing costs and less rational prescription (Wazna et al., 2000).Therefore, interactions between physicians and drug companies raise scientific and ethical questions.Socioeconomic factors have some impact on antibiotic prescription in young children.Children of mothers with only basic schooling were at highest risk of receiving multiple prescriptions, whereas children of mothers with a high education, and/or high household income, had the lowest risk (Thrane et al., 2003).A systematic approach advocated by the World Health Organization can help minimize poor quality and erroneous prescription.This six-step approach to prescription suggests that the physician should: (1) evaluate and clearly define the patient's problem; (2) specify the therapeutic objective; (3) select the appropriate drug therapy; (4) initiate therapy with appropriate details and consider non-pharmacologic therapies; (5) give information, instructions and warnings; and (6) evaluate therapy regularly (e.g., monitor treatment results, consider discontinuation of the drug).Two additional steps: (7) consider drug cost when prescribing; and (8) use computers and other tools to reduce prescription errors (Thrane et al., 2003).These eight steps, along with ongoing self-directed learning, compose a systematic approach to prescription that is efficient and practical for the family physician.Using prescription software and having access to electronic drug references on a desktop or handheld computer can also improve the legibility and accuracy of prescriptions and help physicians avoid errors (Madelyn et al., 2007).A closedloop electronic prescribing, dispensing and barcode patient identification system reduced prescribing errors and medication administration errors (MAEs), and increased confirmation of patient identity before administration.Time spent on medication-related tasks increased (Bryony et al., 2007).

Conclusion
The Pakistan Medical and Dental Council, Federal Ministry of Health and the provincial departments of Health have to play a critical role in this regard, while the role of the Pakistan Medical Association in selfregulation of prescription practices cannot be over emphasized.A combination of regulatory and nonregulatory targeted interventions at health care providers as well as consumers needs to be implemented to improvise prescription practices of health care providers at public and private sector.There is need for the training of health care personnel, provision of providing up-to-date information about drugs to health care providers through regular bulletins, newsletters and other material.Regulation alone would not be effective unless it is supported by a well-established regulatory mechanism which ensures effective implementation and strengthens the role of various government and autonomous agencies.Improper prescription practices will not improve without consumer target and interventions that educate and empower communities regarding the hazards of inappropriate drug use.More research is required on different types of intervention strategies in various healthcare settings for conclusive evidence to be collected regarding the effectiveness as special intervention strategy.

Limitations of the study
The prescription practices may have changed as a result of seasonal variation.Therefore, these results can not necessarily be extrapolated to all cities of the country.
Administering the same survey instruments to other cities in the future would be useful in determining its trends of prescribers.

Figure 1 .Figure 2 .
Figure 1.Age and sex distribution of patients.

Figure 4 .
Figure 4. Potential factors that influence the prescription of providers (n = 354).

Table 1 .
Age and sex distribution of patients.

Table 2 .
Average of drugs per prescription for major groups of drugs.

Table 3 .
Percentage breakdown of 29550 drugs prescribed by major groups of drugs (n = 9954).

Table 4 .
Indicators for mode of administration and preparation of drugs prescribed.

Table 5 .
Differences in prescription practices by type of providers.

Table 6 .
Prioritization of factors that influence prescription among all respondents (number of responses = 475).