Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity
Prescription pattern analysis plays an important role in monitoring the rational use of medicines. Irrational prescribing is the most common cause of inappropriate use of medicines over the globe. Irrational prescribing cannot be controlled without a decisive evaluation of prescribing pattern of medicines and assessing the event rate. Prescription research is also a vital part of pharmacoepidemiology where it provides information regarding the extent and nature of drug exposure. According to the World Health Organization (WHO), evaluating the quality, extent, and trend of drug utilization; the pattern of use of drugs with generic names, fixed-dose combinations (FDCs), and those from the national list of essential medicines (NLEM), in compliance with standard national guidelines, the completeness of prescription in terms of dose, formulation, duration, frequency, etc., constitute the common elements of prescription research. The art of writing of a prescription plays an important role in the health-care system of the country. Prescription research is needed to find gaps in prescription writing. There is a need to find out common mistakes committed while prescribing medicines. These errors may be due to the omission of certain aspects of the prescription. This can include omissions such as not writing in the correct format, or omitting the dosage form, dose, frequency, duration of medicine, special instructions and warnings, or not informing the patient about follow-up, or the investigations that are to be done before follow-up. In addition, there may be errors of commission like prescribing too many drugs, or unnecessary use of antibiotics, or unnecessarily prescribing injectable forms, or selecting costly drugs when cheaper alternatives are available. Errors of the commission also include selecting drugs when not indicated, prescribing medicines that can increase adverse drug reactions (ADRs), medicines that lead to adverse drug interactions, irrational use of FDCs, etc., Most prescription audits emphasize on errors of omission rather than commission, as the information regarding detailed diagnosis and signs and symptoms are often not recorded. Hence, it becomes difficult to determine the rationality of prescribed medicines. Globally, as well as in a systematic review of literature from India, inappropriate prescriptions, leading to ineffectiveness, ADRs, increase in cost and antimicrobial resistance have been noted. In the UK, 7%–10% of prescriptions of junior doctors have been found to be inappropriate. The authors conducted a workshop on “Prescribing skills assessment and Training” as part of the South Asian Chapter of the American College of Clinical Pharmacology 2017, which was attended by pharmacologists from major institutes in India. They discussed the challenges regarding irrational prescribing in India and opined that the training imparted during 2 nd year of the medical curriculum was inadequate. Students at this stage cannot correlate with prescriptions because of limited clinical exposure. They are also unable to comprehend the potential impact of using brand names or the influence of medical representatives from pharmaceutical companies. Besides, the prescription review is not a part of the training curriculum, and problems of drug–drug or drug–food interaction are not adequately addressed. It was recommended that the hospital may have a special team performing prescription audits. Errors should be detected, rectified, and reported anonymously. Assessment should be made and feedback should be given. An initiative by the Indian Council of Medical Research (ICMR), New Delhi, Government of India, was commenced to harmonize the rational use of medicines across the country. A PAN India program was started in different regions of the country as a part of the ICMR-Rational Use of Medicines Centers (ICMR-RUMC) network under the National Virtual Centre Clinical Pharmacology (NvCCP)'s activity. Although previous studies conducted among Indian patients have reported the prescription analysis as per WHO indicators, however, the small sample size, narrow range of diversity, etc., did not reflect the overall real scenario of the country. Therefore, a large multicentric study involving various tertiary health-care centers from different zones of the country was designed to assess the prescribing pattern of drugs and completeness of prescription as per WHO prescribing indicators by employing a common methodology among all the selected Rational use of medical centers. Further, data will facilitate prescribing skill courses developed by the ICMR-RUMC network under NvCCP's activity for providing real-life examples to Indian medical graduates.   Study objectives The primary objective of this study was to evaluate the prescriptions for completeness and deviations from standard treatment guidelines for patients attending departments of specified specialties. The secondary objectives were to evaluate the percentage of prescriptions with antibiotics, prescriptions with brand names, prescriptions with injections, and prescriptions with multivitamins and/or iron. Methodology An observational cross-sectional analysis of prescriptions was carried out from August 2019 to August 2020 as part of the prescription research/skill program by the ICMR-RUMC network under NvCCP's activity. Thirteen tertiary care institutions across four different zones of India participated in the study. A common protocol was made available to these centers by the coordinating committee from ICMR, New Delhi, India. All the participating centers obtained approval from their respective Institutional Ethics Committees. Informed consent was obtained from patients whose prescriptions were included (except in centers where a waiver for written informed consent was obtained). Selection criteria Inclusion criteria Prescriptions for patients of any age from outpatient clinics in the participating tertiary care hospitals Prescriptions for patients undertaking new visits (visiting the department for the first time) and review visits (visiting the department more than once either for review or for follow-up). Exclusion criteria Prescriptions where information from the medical charts regarding clinical features or relevant investigations or provisional diagnosis were not mentioned Patient who were critically ill Patient unwilling to give informed consent. Sample size and sampling Each center aimed to collect a minimum of 600 prescriptions from the outpatient clinics as suggested in the WHO guidance document. Prescriptions were analyzed from the departments of Internal medicine, General Surgery, Pediatrics, Obstetrics and Gynecology, Dermatology, Ophthalmology, ENT (Otolaryngology), Psychiatry, Community medicine, or General Practice. The number of prescriptions analyzed from each department was based on the overall proportion of outpatients seen by these departments. The proportion of patients withfirst visits and follow-up visits was 1:1. Data collection Patients were contacted after their outpatient consultation in the respective department clinic or at the hospital dispensary (pharmacy). All consecutive patient prescriptions fulfilling the criteria were included till the sample size was achieved. A photocopy or a photograph of each prescription was maintained for digital records. A case record form was used for entering data from the prescription and the medical chart of the patient. Details, such as demographics, signs and symptoms, findings from clinical examination, results of investigations, provisional or definitive diagnosis, and medication details, were collected. Care was taken to maintain the confidentiality of patients. The data collected from all the centers were aggregated and analyzed centrally. Prescriptions from health-care professionals of varying years of experience (interns, postgraduates, and consultants/faculty) were included. The data were analyzed using WHO prescription indicators. Prescription assessment Prescriptions were analyzed for drug utilization patterns and medicated-related factors. For drug utilization pattern, the prescription was analyzed as per WHO criteria for the following: The average number of drugs per prescription Percentage of patients receiving monotherapy (single drug) or polytherapy (more than one drug) Percentage prescriptions with all drugs prescribed by generic name/brand name Percentage of prescriptions with FDCs Percentage of prescriptions with all drugs from the hospital formulary list Percentage of prescriptions with drugs prescribed from the National Essential Drugs List Percentage of prescription with antibiotics, injectables, vitamins/iron, etc. For medication-related factors, the act of omissions such as the percentage of complete or incomplete prescriptions, and details of incompleteness such as dose, dosage form, frequency, and duration of each drug prescribed were examined. Instructions regarding how to use the drugs were also evaluated based on whether it was available and adequate, and whether in the English or local language. Numbers of prescriptions which have instructions in the patient's vernacular language were also noted. Finally, after the discussion with the pharmacologist and subject experts and RUMC committee members, the scoring (ranging from 1 to 3) was done depending on the adherence to the guidelines. The complete prescriptions with no deviations from standard treatment guidelines were given Score 3. The score 2, i.e., partial adherence, was designated to the prescriptions (both complete and incomplete) with acceptable deviations from standard treatment guidelines. However, the prescriptions (both complete and incomplete) with unacceptable deviations from standard treatment guidelines were given score 1 for low adherence to guidelines.   The primary objective of this study was to evaluate the prescriptions for completeness and deviations from standard treatment guidelines for patients attending departments of specified specialties. The secondary objectives were to evaluate the percentage of prescriptions with antibiotics, prescriptions with brand names, prescriptions with injections, and prescriptions with multivitamins and/or iron.   An observational cross-sectional analysis of prescriptions was carried out from August 2019 to August 2020 as part of the prescription research/skill program by the ICMR-RUMC network under NvCCP's activity. Thirteen tertiary care institutions across four different zones of India participated in the study. A common protocol was made available to these centers by the coordinating committee from ICMR, New Delhi, India. All the participating centers obtained approval from their respective Institutional Ethics Committees. Informed consent was obtained from patients whose prescriptions were included (except in centers where a waiver for written informed consent was obtained).   Inclusion criteria Prescriptions for patients of any age from outpatient clinics in the participating tertiary care hospitals Prescriptions for patients undertaking new visits (visiting the department for the first time) and review visits (visiting the department more than once either for review or for follow-up). Exclusion criteria Prescriptions where information from the medical charts regarding clinical features or relevant investigations or provisional diagnosis were not mentioned Patient who were critically ill Patient unwilling to give informed consent.   Prescriptions for patients of any age from outpatient clinics in the participating tertiary care hospitals Prescriptions for patients undertaking new visits (visiting the department for the first time) and review visits (visiting the department more than once either for review or for follow-up).   Prescriptions where information from the medical charts regarding clinical features or relevant investigations or provisional diagnosis were not mentioned Patient who were critically ill Patient unwilling to give informed consent.   Each center aimed to collect a minimum of 600 prescriptions from the outpatient clinics as suggested in the WHO guidance document. Prescriptions were analyzed from the departments of Internal medicine, General Surgery, Pediatrics, Obstetrics and Gynecology, Dermatology, Ophthalmology, ENT (Otolaryngology), Psychiatry, Community medicine, or General Practice. The number of prescriptions analyzed from each department was based on the overall proportion of outpatients seen by these departments. The proportion of patients withfirst visits and follow-up visits was 1:1.   Patients were contacted after their outpatient consultation in the respective department clinic or at the hospital dispensary (pharmacy). All consecutive patient prescriptions fulfilling the criteria were included till the sample size was achieved. A photocopy or a photograph of each prescription was maintained for digital records. A case record form was used for entering data from the prescription and the medical chart of the patient. Details, such as demographics, signs and symptoms, findings from clinical examination, results of investigations, provisional or definitive diagnosis, and medication details, were collected. Care was taken to maintain the confidentiality of patients. The data collected from all the centers were aggregated and analyzed centrally. Prescriptions from health-care professionals of varying years of experience (interns, postgraduates, and consultants/faculty) were included. The data were analyzed using WHO prescription indicators.   Prescriptions were analyzed for drug utilization patterns and medicated-related factors. For drug utilization pattern, the prescription was analyzed as per WHO criteria for the following: The average number of drugs per prescription Percentage of patients receiving monotherapy (single drug) or polytherapy (more than one drug) Percentage prescriptions with all drugs prescribed by generic name/brand name Percentage of prescriptions with FDCs Percentage of prescriptions with all drugs from the hospital formulary list Percentage of prescriptions with drugs prescribed from the National Essential Drugs List Percentage of prescription with antibiotics, injectables, vitamins/iron, etc. For medication-related factors, the act of omissions such as the percentage of complete or incomplete prescriptions, and details of incompleteness such as dose, dosage form, frequency, and duration of each drug prescribed were examined. Instructions regarding how to use the drugs were also evaluated based on whether it was available and adequate, and whether in the English or local language. Numbers of prescriptions which have instructions in the patient's vernacular language were also noted. Finally, after the discussion with the pharmacologist and subject experts and RUMC committee members, the scoring (ranging from 1 to 3) was done depending on the adherence to the guidelines. The complete prescriptions with no deviations from standard treatment guidelines were given Score 3. The score 2, i.e., partial adherence, was designated to the prescriptions (both complete and incomplete) with acceptable deviations from standard treatment guidelines. However, the prescriptions (both complete and incomplete) with unacceptable deviations from standard treatment guidelines were given score 1 for low adherence to guidelines.   Data were collected from thirteen different centers of India. A total of 4838 prescriptions were analyzed from different departments of the institutes. The maximum number of patients that participated in the study was from the department of General Medicine comprising about 31.52% of the total patients. In addition, the patients from General Surgery and Obstetrics and Gynecology each comprised more than 10% of the total participants. On the other hand, the least number of the study participants were from ophthalmology constituting only 2.93% of the total patients . Out of the 4838 prescriptions, 83.05% had been prescribed with more than one drug for their treatment. Furthermore, in 57.42% of the prescriptions, at least one of the drugs were prescribed by their brand names. In the present study, FDCs were prescribed in 43.26% of the prescriptions. Moreover, 22.44% of the prescriptions were containing drugs not available in the list of their hospital formulary. On the other hand, the prescriptions with drugs not from NLEM were 55.33% from the total prescriptions. The results of the prescription summary in the present study also revealed the prescriptions of antimicrobial drugs, injectables, vitamins, and iron salts, etc., It has been found that 17.63% of the prescriptions had at least one antimicrobial drug and only 4.98% of the prescriptions had injectables. However, the vitamins and iron salts were prescribed in 53.95% of the total collected prescriptions . On an average, about three drugs (3.34) were prescribed to patients per prescription. The average number of branded drugs in a prescription was 1.74. In addition, the average number of FDCs per prescription was about 0.76. Moreover, the number of drugs per prescription that were not from the hospital formulary was 0.56 and not from NLEM were about 1.08. The number of the antimicrobial drugs was calculated to be 0.28 per prescription and injectables were prescribed on an average of 0.103 per prescription. It has been found that more than 50% of the patients were prescribed vitamins and minerals with an average of 0.45 per prescription . Out of the total prescriptions, 1870 (38.65%) prescriptions were found to be incomplete. The completeness of prescriptions was assessed based on parameters such as failure to mention the proper instructions such as dose, frequency, or duration of time of the medication, not mentioning the formulation, or the follow-up visit. Among total prescriptions, the commonly identified reasons for the incompleteness of prescriptions included not mentioning the follow-up visits (27.26%), followed by the omission of dose (22.86%) and duration of medication (15.69%). In contrast, not mentioning the frequency and formulation were the least likely reasons for incomplete prescriptions . The prescriptions had more than one errors of omission. Moreover, instructions not mentioned (48.74%) were not considered omissions since these are provided by the pharmacist. Hence, it was exempted from the reasons of incomplete prescriptions. Regarding the scoring of the adherence to guidelines, it was observed that about 55.1% of the total prescriptions had complete adherence to the relevant standard treatment guidelines, thus obtaining a score of 3. Then, about 35.1% of the prescriptions had a score of 2 indicating partial adherence to the guidelines. These prescriptions may have errors of omission and/or errors of commission, but the deviations in these prescriptions were found to be acceptable after discussion with expert committee members. However, 9.8% of prescriptions were with a score of 1 depicting low adherence to the guidelines, i.e., having unacceptable deviations from standard treatment guidelines .   The process of drug utilization in the outpatient setting is considered a multifaceted approach of the prescriber, the patient, and the pharmacist. The WHO has designed a battery of indicators to evaluate the prescription pattern/drug utilization according to the facilities available. The WHO has divided the drug use indicators into three categories: prescription indicators, patient care indicators, and health facility indicators. Inappropriate prescribing has affected the rational use of drugs, especially in developing countries. After critical analysis of the prescriptions collected in the present study, results would be used as real-life examples for all the practitioners and Indian medical graduates, and to provide suitable feedback to the online prescribing skills course being conducted by ICMR NvCCP RUMCs. The average number of drugs prescribed per prescription, i.e., 3.34 was found to be higher than prescription studies conducted in other countries such as Ethiopia (1.8–2.4), Kenya (2.7), and lesser than the study conducted in Ghana where the average number of drugs per prescriptions was 4.8. Moreover, data of 3.11 drugs per prescription were reported by a single-centric study conducted in India in the year 2014 in a tertiary care center which is comparable to the present multicentric study. All these studies observed a much higher “drugs prescribed per prescription rate” than the WHO recommended range of 1.6–1.8. The high rate of polypharmacy in the present study can lead to the increased likelihood of drug-drug interactions, augmented side effects, chances of noncompliance, high cost, etc., The collection of prescriptions of patients attending tertiary care centers with co-morbid conditions can be one of the contributing factors to the higher average number of drugs per prescription in the current study. In addition, more than one-third of the prescriptions were from General Medicine which included patients of Cardiology, Neurology, etc., followed by General Surgery where polypharmacy is common, perhaps due to multiple comorbidities. The prescription of generic drugs determines the quality of the prescription. According to the WHO, the prescription should be in a generic name. However, the results of this study had shown only 42.58% of prescriptions used generic names, which is much lesser than the prescription pattern in other Asian countries such as Pakistan (71.6%), Nepal (59.02%), and Jordan (57.6%). It must also be noted that 96.88% and 85.78% of generic prescribing was reported in India and Ethiopia, respectively. Even 100% generic prescribing was observed in a study conducted in UAE. High rate of polypharmacy with the low number of generic prescriptions demonstrated the poor quality of the prescriptions, which in turn would contribute to irrational prescribing. Such data could be helpful to formulate the national guidelines of the rational use of medicines. A critical appraisal of prescriptions is required to curtail irrational prescribing in the country. The assessment of the prescription pattern of drugs as per WHO criteria could encourage rational use of drugs. A study in Nigeria had shown overuse of antibiotics and injectables in public sector health facilities, including polypharmacy of the remaining medicines. However, in the present study, only 4.98% of the prescriptions had injectables. It is assumed that most of the injectables are administered for indoor patient departments except insulin, penicillin, etc., As the prescriptions in the present study were collected from outpatients departments of the hospital, the number of prescriptions containing injectables was found to be less as compared to other studies. In the present study, 17.63% of the patients were prescribed antimicrobials which are below the recommendations of the WHO (20%–26.8%). Even the average number of antibiotics per prescription is < 1 which is relatively lower than the recommended range (1.6–1.8) by the WHO. However, in Ethiopia, 52.3% of the total prescriptions were of antibiotics which were double of the upper limit of the WHO Most of the antibiotics prescribed were from the NLEM. The trend of prescription of mutivitamins and mineral supplements has greatly increased in past few years. Most of them are prescribed as a part of nutrient supplements in multiple disease conditions such as stroke, diabetes mellitus, and pregnant women and also used as preemptive therapy. Most of the preparations are FDCs with numerous active constituents. Initially, multivitamins were prescribed for those who were not able to obtain sufficient essential nutrients from their food. However, these prescriptions have been amplified by various pharmaceutical companies and have led to an increase in the overall cost of the prescriptions. Multi-vitamin preparations usually include Vitamin A, Vitamin B complex, Vitamin C, Vitamin D (D2 and D3), Vitamin E (alpha-tocopherol), and Vitamin K and various minerals such as Iron, Zinc, Magnesium, Calcium, Potassium, Phosphorus. In the present study, 2610 (53.95%) prescriptions comprised at least one multivitamin formulation. A study conducted in the United States also demonstrated a similar trend of 52% use of dietary supplements along with other medications. On the other hand, a study had also reported the incidence of 12% of adverse effects with the use of dietary supplements. However, some researchers have also revealed the improvement in the quality of life of individuals on multivitamins. The studies conducted in different parts of India like Bhardwaj et al.  in Haryana reported 35.76%–48.57% and Hussain et al.  in Uttar Pradesh had shown 23.12% of the prescriptions with vitamins and supplements. According to the WHO, the prescription of the drugs should be complete in terms of dose, formulation, frequency, duration, follow-up visits, instructions in local languages, etc. The aim of our study was to evaluate the reasons for incomplete prescriptions as per WHO indicators. In the present study, multiple reasons contributed to incompleteness. Majorly were failures to mention follow-up visits, followed by dose of the drugs, duration of treatment, etc., Although more than 48% of the prescriptions have not defined the instructions in the local language, it has not been considered a reason for incomplete prescriptions, as important instructions have often been given in the English language and by the concerned pharmacist. A study has reported 8.3% omission of dosage forms and 37.3% omission of drug dose during the evaluation of completeness of the prescription. The results of various other studies conducted in different countries such as India, Egypt, and Jordan had also not reached the optimum value for WHO indicators of completeness of prescription. Thus, there is a need to critically evaluate the prescription patterns and implement the necessary steps in all health-care settings. Prescription pattern studies have been found to evaluate the compliance of treatment with regional or national standard treatment guidelines. Although the WHO indicated 100% adherence to treatment guidelines, in the present study, about half (55.1%) of the prescriptions were found to have complete adherence to guidelines, as compared to about 35.1% of the prescriptions with partial adherence and 9.8% of the prescriptions had low adherence of standard treatment guidelines. As there are many new drugs entering the market, periodic surveys of the prescription pattern would facilitate the understanding of the prescription trends which can subsequently be used in the improvement of rational and appropriate use. All these can together promote the appropriate use of medicine, which means that the patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period, and at the lowest cost to them and their community. Suggestions and future directions According to prescribing indicators of the WHO, the rational use of medicines should be improved in clinical practice as prescription assessment revealed inappropriateness in the standard criterion of prescribing. The major areas of concern are polypharmacy, limited generic prescribing, prescriptions of FDCs, and drugs not from NLEM. Thus, there is an urgent requirement to revise the standards of prescriptions in various aspects. The policymakers and governing bodies should encourage the use of generics and medicines from NLEM, and limit the use of FDCs to rational combinations only. The results of this study would be used to develop the prescribing skill course by providing practical examples of the complete and incomplete prescriptions as per WHO indicators. Furthermore, being a multicentric study, data would be analyzed to interpret the regional differences in prescribing pattern of drugs across the country. A well-formulated action plan should be constituted over the country based on adherence to standard treatment guidelines, antibiotics stewardship, NLEM and FDC strategies, etc., The ongoing clinical practices should be updated and training programs or workshops need to be organized to educate and communicate the importance of WHO indicators in prescribing skills. Financial support and sponsorship This study was supported by the Indian Council of Medical Research through its Task Force Project on Rational Use of Medicines. Conflicts of interest There are no conflicts of interest.   According to prescribing indicators of the WHO, the rational use of medicines should be improved in clinical practice as prescription assessment revealed inappropriateness in the standard criterion of prescribing. The major areas of concern are polypharmacy, limited generic prescribing, prescriptions of FDCs, and drugs not from NLEM. Thus, there is an urgent requirement to revise the standards of prescriptions in various aspects. The policymakers and governing bodies should encourage the use of generics and medicines from NLEM, and limit the use of FDCs to rational combinations only. The results of this study would be used to develop the prescribing skill course by providing practical examples of the complete and incomplete prescriptions as per WHO indicators. Furthermore, being a multicentric study, data would be analyzed to interpret the regional differences in prescribing pattern of drugs across the country. A well-formulated action plan should be constituted over the country based on adherence to standard treatment guidelines, antibiotics stewardship, NLEM and FDC strategies, etc., The ongoing clinical practices should be updated and training programs or workshops need to be organized to educate and communicate the importance of WHO indicators in prescribing skills.   This study was supported by the Indian Council of Medical Research through its Task Force Project on Rational Use of Medicines.   There are no conflicts of interest.   