Evaluation of prescriptions from tertiary care hospitals across India for deviations from treatment guidelines & their potential consequences

Abstract

Background & objectives:

Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians.

Methods:

It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as ‘prescriptions having deviations’. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an ‘unacceptable deviation’.

Results:

Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108).

Interpretation & conclusions:

The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.

Inappropriate prescribing of medicines is a major clinical concern and can negatively impact upon efficacy, safety and economic issues for the patients. Hence, the treatment of patients in clinical practice should be individualized and based on principles of rational prescribing. The present definition of rational use was drafted by the World Health Organization (WHO) more than three decades ago at an international conference in Kenya in 19851. However, inappropriate prescribing is still a problem and worldwide over 50 per cent of the medications may be prescribed or dispensed inappropriately and 50 per cent of the patients may be non-compliant to their medication2. Inappropriate prescriptions can lead to an increase in adverse drug reactions, hospitalization and increase in cost of treatment3,4. Inappropriate use of medicines includes, but is not limited to, selecting injectable forms or expensive drugs when cheaper alternatives are available, polypharmacy, unwarranted antibiotic use, failure to adhere to clinical guidelines and non-compliance by patients to prescribed drug regimens. The rise of antimicrobial resistance is a key concern among low- and middle-income countries (LMICs)5 and various interventions have been proposed in this regard. For example, Godman et al6 have discussed strategies to improve the management of upper respiratory tract infections and reduce inappropriate antibiotic use, particularly among LMICs. WHO has also released the Access, Watch, Reserve antibiotic book, which provides specific guidance on the empiric use of antibiotics7. A systematic review and meta-analysis has further emphasized upon the same8. However, a thorough literature search failed to identify any original research on the magnitude of irrational prescribing and potential impact of inappropriate prescriptions in India and a review showed that majority of the prescription audits focussed on the errors of omission rather than commission9. In this context it is important to capture real-life examples of inappropriate prescriptions and their potential consequences and use such examples to improve prescribing practices.

We therefore designed this multi-centric study under the Indian Council of Medical Research- Rational Use of Medicines (ICMR-RUM) task force project with the objective of capturing and evaluating the prevalence of inappropriate prescriptions and assessing the potential consequences of inappropriate prescribing in terms of increased possibility of drug interaction, lack of response, increase in cost of treatment, preventable adverse drug reaction (ADR) and antimicrobial resistance. This will help in reducing inappropriate prescribing practices.

Material & Methods

Study design: This was a cross-sectional, observational, multicentric study. It was carried out from August 2019 to August 2020. The study was conducted by 13 ICMR Rational Use of Medicines Centres (RUMC) located in tertiary care teaching hospitals and medical colleges in different geographical regions of India. These RUMCs are a part of the ICMR National Virtual Centre for Clinical Pharmacology (NVCCP). At each RUMC, the study was conducted by a team of pharmacologists along with clinicians from the respective institute. Institutional ethics committee approval was obtained from each of these hospitals before the initiation of the study.

Study population and recruitment: Individuals who presented to the outpatient department (OPD) of different specialities in the hospital (community medicine, general medicine, surgery, obstetrics and gynaecology, paediatrics, dermatology, ophthalmology, otorhinolaryngology, psychiatry and other OPDs such as orthopaedics, chest medicine, dentistry and superspeciality OPDs) and fulfilled the inclusion criteria were enrolled in the study.

Individuals of any age and gender whose prescriptions mentioned the symptoms and signs with provisional or definitive diagnosis of the disease and the drugs prescribed were included. Critically ill patients and those who were not able/willing to give informed consent were excluded from the study.

Prescriptions given to patients visiting the OPDs for the first time for treatment of their conditions as well as prescriptions of patients who had come to the OPDs for follow up were collected randomly (approximately half were new cases and half were follow up cases).

The investigators approached the study participants to participate in the study while exiting from the respective OPDs after being seen by the consulting physician. Written informed consent was sought from study participants/legally authorized representatives of the participants to record the details of their prescriptions. Following their consent, their OPD papers were screened for eligibility.

The demographic details, OPD registration number, age, gender, body weight, signs and symptoms, clinical examination findings, results of investigations, diagnosis and medication details of eligible individuals were noted in the case record form. Confidentiality of data was maintained.

Sample size calculation: As per the guidelines for rational use of medicines10 sample size was calculated as minimum 600 prescriptions per centre. The stratification of the number of prescriptions to be collected from various OPDs was as follows: community medicine: 100, general medicine: 100, surgery: 100, obstetrics and gynaecology: 100, paediatrics: 80, dermatology: 30, ophthalmology: 30, Ear Nose Throat (ENT): 30 and psychiatry: 30. This proportion of study participants in each speciality was based on average per day attendance of the OPD, and likelihood of deviations, rule of 3 to capture the prevalence of 1:10-1:30 inappropriate prescriptions in different specialities.

Assessment of prescriptions: Each prescription was evaluated for appropriateness by initially reviewing whether they were complete or incomplete. A complete prescription was defined as one in which the formulation, dose, duration and frequency of administration of drugs prescribed were clearly stated in the prescription. Each complete prescription was further assessed for adherence to the local standard treatment guidelines (STGs). In the absence of local STGs, prescriptions were checked for adherence to first the national STGs/STW (Standard treatment workflow) published by the Department of Health Research, ICMR, Government of India. For certain conditions, for which there were no national STGs, prescriptions were assessed to verify whether they conformed to the guidelines developed by national professional bodies or international treatment guidelines for that given condition in that order (the guidelines to be used for assessment were confirmed with the clinicians). Prescriptions that were not compliant with the STGs or guidelines were labelled as ‘prescriptions having deviations’ or inappropriate prescriptions.

If any one of the four variables (formulation, dose, duration and frequency) was not stated in the prescription, it was considered incomplete (error of omission) and the variable that was missing was noted. All incomplete prescriptions were considered deviations from STGs.

All prescriptions with deviations were reviewed by the pharmacologists to check if the deviation could result in one or more of the following consequences, viz. drug interaction, lack of response, increase in cost, preventable ADR and antimicrobial resistance. A prescription with deviations in which the consequences listed above were unlikely to occur was considered an acceptable deviation. If the deviation in the prescription could result in any one of the above-mentioned consequences, it was labelled as an unacceptable deviation.

The prescriptions classified as acceptable and unacceptable deviation were re-reviewed by the clinicians and the RUMC committee consisting of pharmacologist, clinicians subject expert and community medicine expert. If there was a disagreement about classifying the deviation, the clinician and pharmacologist deliberated over the discrepancy and came to a consensus to finally classify the deviation as acceptable or unacceptable. In addition, clinicians were also requested to state what would be the appropriate corrective action for each prescription in which there was an unacceptable deviation.

The final step was to assign an appropriateness score to the prescription. The total number of prescriptions achieving a score of 3, 2 and 1 was calculated. Score 3 (highest score) was assigned to prescriptions that were complete and adhered to either local STGs/national or international treatment guidelines. Score 2 was assigned to those prescriptions which deviated from the local STGs/national or international treatment guidelines, but the deviations were considered acceptable, irrespective of whether the prescriptions were complete or incomplete. Score 1 was assigned to all prescriptions whose deviations from the local STGs/national or international treatment guidelines and were considered unacceptable.

Statistical analysis: Demographic variables captured for continuous data were expressed as mean and standard deviation. Categorical data were expressed as percentage. Prescriptions were analyzed for completeness, deviations, appropriateness score and corrective action given by the clinician using descriptive statistics. Data were analyzed using Microsoft Excel 365 (Microsoft Corp., Redmond, WA) and SPSS 25 version software (IBM corp., Armonk, N.Y., USA).

Results

A total of 7800 prescriptions were collected and 4838 prescriptions were analyzed from 13 RUMCs as per the protocol. The age in year with standard deviation of the participants was 37.54±18.29, and it was similar across gender. The prescriptions collected were from all the zones, north - 2879, south - 778, west - 881 and east-300. All the prescribers were postgraduates in their respective disciplines and on average were in practice for 4-18 yr.

The number of complete and incomplete prescriptions along with deviations is depicted in Figure. Of the 4838 prescriptions, 2968 (61.34%) were documented as complete, of which 2667 prescriptions (55.12%) were appropriate and in accordance with guidelines. However, 301/2968 (6.22%) had deviations (i.e. errors of commissions wherein the prescribed drug was not in accordance with the guidelines). Out of these 301 complete prescriptions with deviations, 138 (46%) prescriptions had acceptable deviations while 163 prescriptions (54%) [95% confidence interval (CI): 2.4-8.38%] had unacceptable deviations. The remaining 1870/4838 (38.65 %) prescriptions were recorded as incomplete as they had deviations (i.e. errors of omissions in terms of dose, duration, frequency and/or formulation). Of these, 1558 prescriptions (1558/1870; 83%) were noted as having acceptable deviations and 312 (17%) (95% CI: 6.38-20.81%) as having unacceptable deviations. Thus, 2171/4838 prescriptions having deviations (1870+301), 475 (163+312) (9.8%) (95% CI: 8.55-11.05%) prescriptions from complete and incomplete prescriptions had unacceptable deviations. The prescriptions were grouped according to the appropriateness score as stated in the methodology (Table I). Out of the 4838 prescriptions collected, 475 (9.81%) prescriptions had unacceptable deviations. The total number of drugs prescribed in these prescriptions was 1696, which accounted for 3.5 drugs/prescription. The unacceptable deviations were further classified according to the OPDs (Table II) and diagnoses (Table III). Of the 475 prescriptions, 102 prescriptions had stated more than one diagnosis. When the remaining 373 prescriptions were sorted on the basis of the diagnoses, there were 13 diagnoses with more than ≥5 prescriptions in each data set, whereas the rest of the diagnoses (Table III) had less than five prescriptions in each set. Table IV lists the drugs that were prescribed inappropriately and hence led to an unacceptable deviation. It was observed that pantoprazole was the most frequently prescribed drug leading to unacceptable deviation followed by the fixed-dose combination (FDC) rabeprazole with domperidone and oral enzyme preparations. Some salient examples of the unacceptable deviations are mentioned in Table V.

Figure.

Flow chart of prescription analysis. AD, acceptable deviation; UD, unacceptable deviation; DI, drug interaction; ADR, adverse drug reaction; AMR, antimicrobial resistance; STG, standard treatment guidelines.

Table I.

Grouping of prescriptions according to the appropriateness score (n=4838)

Appropriateness score	n=4838	%
1	475	9.81
2	1696	35.05
3	2667	55.12
Grand total	4838	100

Table II.

Prescriptions from different outpatient departments having unacceptable deviations

OPD	Total number of prescriptions in speciality	Number of prescriptions with unacceptable deviations	%
Community medicine	300	74	24.66
ENT	295	39	13.22
Paediatrics	454	49	10.79
Medicine	1529	148	9.67
Surgery	592	33	5.57
Dermatology	322	10	3.1
Ophthalmology	142	2	1.4
Psychiatry	219	5	2.28
OBGY	548	19	3.46
Others*	437	96	21.96
Total	4838	475

^*Others: Orthopaedics, physical medicine and rehabilitation, chest medicine, dentistry, cardiology, neurology, surgical gastroenterology. OPD, outpatient department; ENT, ear nose throat

Table III.

Diagnosis found in the prescriptions with unacceptable deviations

Diagnosis on prescription	Number of prescriptions
URTI	49
Hypertension	20
Osteoarthritis	20
Diabetes	15
Malaria	14
Functional dyspepsia	10
Migraine	10
Dental caries	8
Otitis media	8
Diarrhoea	5
Urinary tract infection	3
Tinea cruris	2
Haemorrhoids	2
Insomnia	2
Constipation	2
Herpes zoster	2
Osteoporosis	2
Anal fissure	2
Others (e.g. dacryocele, left tennis elbow, local abscess, right foot injury, ulcerated wound, aphthous ulcers, cerebrovascular ischaemia, blepharitis, post-COVID-19 fibrosis, megaloblastic anaemia, pelvic inflammatory disease, cerebellar infarct, lichen planus and tuberculosis)	299
Total	475

URTI, upper respiratory tract infection

Table IV.

List of drugs prescribed inappropriately in the prescriptions with unacceptable deviations

Drugs	Number of prescriptions (475)	% of total prescriptions with unacceptable deviations
Pantoprazole	54	11.36
Rabeprazole + domperidone	35	7.36
Trypsin or chymotrypsin	24	5.05
Serratiopeptidase	25	5.26
Azithromycin	20	4.21
Ranitidine	11	2.31
Cefixime	11	2.31
Amoxicillin+clavulanate	10	2.1
Aceclofenac	6	1.26
Others (antidiabetics, antiemetics, antihypertensives, antiepileptics, antimicrobials, antipsychotics, antispasmodics and FDCs - gabapentin + nortriptyline, montelukast + levocetirizine, diclofenac + serratiopeptidase, phenylephrine + chlorpheniramine+ dextromethorphan and multivitamins)	279	58.73
Total	475

FDC, fixed-dose combination

Table V.

Examples of unacceptable deviations

Diagnosis	Prescription details	Drug responsible for deviation (number of prescriptions)	Reason for supling as unacceptable deviation	Potential consequence/s
Herpes Zoster	Tablet acyclovir 800 mg BD for five days, tablet pantoprazole 40 mg BBF for 5 days, tablet diclofenac + paracetamol 1 mg BD for 5 days, tablet pregabalin 1 mg HS for 5 days, ointment fusidic cream L/A for 7 days +	Pantoprazole (54)	Prescription of an anti-ulcer agent with NSAID in the absence of a risk factor	Increase in the cost of therapy
URTI	Tablet montelukast sodium + levocetirizine OD, tablet paracetamol 650 mg BD, Syrup dextromethorphan BD, Tablet rabeprazole + domperidone BD	Montelukast sodium + levocetirizine; rabeprazole + domperidone (35)	Both the FDCs –montelukast + levocetirizine and rabeprazole + domperidone are not indicated	Increase in the cost of therapy
Local abscess	Tablet trypsin + chymotrypsin BD for 5 days, tablet aceclofenac + paracetamol BD for 3 days	Trypsin + chymotrypsin (24)	Poor efficacy for the efficacy of trypsin-chymotrypsin as anti-inflammatory drugs, prescribing	Increase in the cost of therapy
Dental caries infection	Tablet amoxicillin + clavulanic acid 625 mg BD for 5 days, tablet diclofenac + serratiopeptidase BD for 5 days	Diclofenac + serratiopeptidase	Existing scientific evidence for serratiopeptidase is not sufficient to support its use	Increase in the cost of therapy Increase adverse drug reaction
Chronic periodontitis	Tablet ofloxacin + ornidazole BD for 5 days, tablet diclofenac BD for 5 days, capsule becosules OD for 15 days, gel benzocaine SOS for 15 days	Ofloxacin + ornidazole (4)	Not as per guidelines, irrational combination	Can increase cost and antimicrobial resistance
Recurrent oral aphthous ulcers	Tablet amoxicillin + clavulanic acid BD for 5 days, tablet diclofenac + serratiopeptidase BD for 5 days, tablet rabeprazole + domperidone BD for 5 days, tablet multivitamin HS for 5 days, tablet cetirizine + phenylephrine OD for 30 days	Amoxicillin + clavulanic acid; diclofenac + serratiopeptidase; rabeprazole + domperidone; cetirizine + phenylephrine (14)	Lack of evidence for all the drugs prescribed First-line treatment is topical therapy	Lack of response Increase in cost Increase in AMR Increase in ADR
Tonsillitis of less than three days duration	Tablet azithromycin 500 mg OD, Tablet cetirizine OD Tablet paracetamol + SOS	Tablet azithromycin (20)	Symptom duration is less than three days so unnecessary antibiotics prescribed	Increase the cost and AMR
Dacryocele	Tablet amoxicillin + clavulanic acid 625 mg TDS×five days, Tablet ranitidine 150 mg TDS×5 days, tablet diclofenac + serratiopeptidase BD×5 days, tablet moxifloxacin BD×5 days	Ranitidine and serratiopeptidase	Gastroprotection not required with NSAID unless there is an increased risk of peptic ulcer; Existing scientific evidence for serratiopeptidase is not sufficient to support its use	Increase in cost Increase in ADR
Anal fissure	Tablet ciprofloxacin, tablet metronidazole, tablet omeprazole, tablet trypsin + chymotrypsin, tablet paracetamol, lactulose, 2% suspension Xylocaine jelly, diltigesic ointment	Metronidazole, ciprofloxacin (4)	Treatment of anal fissure is topical therapy unless it is secondary to other systemic diseases. Lack of evidence for the use of antimicrobials and enzyme preparations. The use of anti-ulcer agent is unjustified	Increase in cost Increase in AMR Increase in ADR

ADR, adverse drug reaction; AMR, antimicrobial resistance; BD, twice a day; OD, once a day; BBF, before breakfast; TDS, thrice a day; SOS, as and when required; L/A, local application; HS, night time; NSAID, non steroidal anti inflammatory drugs

The potential consequences of these deviations could be increased cost to the patient (301, 63%) and/or a probability of increase in the number of ADRs (254, 53%), drug interactions (81, 17%), AMR (72, 15%) or even a possibility of treatment failure (77, 16%). Majority of the prescriptions (310/475) had multiple overlapping impacts.

The guidelines which were used to review the 475 prescriptions labelled as having unacceptable deviations are mentioned in Table VI. The clinicians were consulted if they had any recommendation to minimize irrational prescribing with respect to the 475 prescriptions having unacceptable deviations. The major recommendation by clinicians was to issue an administrative order stating that the clinicians in the hospital should adhere to the principles of rational prescribing. The second recommendation was to conduct an online training for clinicians on the principles of rational prescribing. Few commented to give feedback to prescribers about the importance of writing drug and disease details in a prescription along with starting of antibiotic stewardship programme.

Table VI.

Most common guidelines followed for prescriptions having unacceptable deviations

Name of the guidelines	Number of prescriptions (n=475)
American Association of Family Physician	64
American College of Rheumatology	54
Standard Treatment Guidelines ICMR MoHFW, GOI	50
NICE guidelines 2019	34
American Heart Association	24
American Diabetes Association	18
American College of Gastroenterology	18
Clinical Practice Guidelines	8
American Family Physician	7
Others (Chronic Wound Care Guidelines, API, CDC, ILEA, Surgical Guidelines, American Academy of Otolaryngology HNSF, Tonsillar and Peritonsillar Abscess Guidelines, Clinical Guidelines, GINA Guidelines, American Psychiatry Association Practice Guidelines, American Urology Society ACEOM, Guidelines of Infectious Diseases Working Party AGIHO of German Society of Hematology and Oncology DGHO, Local Practice Guidelines, AAFF, IDSA, AA of Pediatrics, AA of Ophthalmology, American International Health Alliance	198
Total	475

MoHFW, Ministry of Health and Family Welfare; GOI, Government of India; NICE, National Institute for Health and Care Excellence

Discussion

In this study, outpatient prescriptions by physicians of various specialities in tertiary care, teaching government and private hospitals across India were analyzed. Prescriptions of eligible patients exiting from OPD or hospital pharmacy were captured and analyzed the prescriptions for appropriateness.

A thorough literature search revealed that the tools available to evaluate inappropriate medications, either focus on the patient population (e.g. geriatric or paediatric)11,12 or the healthcare setting (either OPD or IPD)13. There is no universally validated tool to encompass all patient age groups visiting different healthcare settings. Hence, we designed a prescription assessment tool that had both explicit and implicit items requiring consensus by the pharmacologist and the clinician. In addition, we designed the tool to focus on completeness of the prescription (errors of omission) and whether the drug prescribed was as per STGs (errors of commission). Based on this tool, prescriptions could be classified as complete and incomplete prescriptions. All complete prescriptions that did not adhere to STG and all incomplete prescriptions were labelled as inappropriate prescriptions and were further sub-classified into prescriptions having acceptable or unacceptable deviations from STGs. We also looked at errors of omission (underprescribing/incomplete) and commission (overprescribing/incorrect). Till date, none of the tools designed to study inappropriateness cover these aspects.

Kaufman et al11 in their systematic review on published assessment tools for inappropriate prescribing observed that under prescribing was mentioned only in six tools although it is an important aspect of inappropriate prescribing. They further observed that many tools evaluate the selection of a drug in accordance with treatment guidelines. Even though adherence to all applicable treatment guidelines without individualization is the best practice for ‘rational’ prescribing, for ‘appropriate’ prescribing individualization is a prerequisite11. To overcome this, prescriptions in this study that deviated from guidelines were considered acceptable if the deviation from STG was due to tailoring of the drug therapy for a given individual. In addition, an important section of our assessment tool was to gauge the potential consequences of such deviations, e.g., preventable ADR, lack of effect, drug interaction, potential for AMR and increase in cost.

Of the incomplete prescriptions, 1558/1870 (83%) were found to be acceptable when reviewed by the clinicians. Their argument in favour of this was that the hospital pharmacy had only one particular drug formulation (single strength) and the frequency and the duration of treatment were explained to the individual by the pharmacist, e.g., in case of multivitamin tablets and topical preparations, the dose was not mentioned and the likelihood of the potential consequences was minimal. The incomplete prescriptions that were considered having unacceptable deviations 312/1870 (17%) were those in which the occurrence of potential consequences of not mentioning the dose of the drug (insulin, hormonal preparations, aspirin and glimepiride) was higher. Similarly, if the prescriber had not specified the duration of therapy for chronic conditions such as hypertension, diabetes and epilepsy, the prescription was considered having an unacceptable deviation because it was felt that the occurrence of the potential consequences was higher.

When the complete prescriptions were reviewed by the clinicians, 301/2968 prescriptions deviated from the guidelines. Of these, 138 were found to be acceptable even though they did not comply with the guidelines because the clinicians felt that the drug therapy was tailored to the patients’ comorbidities. Of the 301 prescriptions, 163 were considered to be unacceptable deviations because the drugs prescribed could cause one or more of the potential consequences.

Among the potential consequences that could have occurred due to unacceptable deviations, it was observed that the likelihood of increased cost (63%) was the maximum followed by increased ADRs (53%). Studies from southeast Asian countries have shown that medication errors are relatively common, and can lead to adverse drug events14 lack of response (16%) and antimicrobial resistance (AMR: 15%). There can be waste of resources if drugs are injudiciously prescribed, and if the inappropriate drug prescribed is an antibiotic, it can lead to AMR. Similarly, when unnecessary multiple drugs are prescribed, it can cause adverse effects, impair the quality of life and increase the cost of treatment. If required drugs are not prescribed, it can lead to a lack of response and prolong the duration of the disease.

In the present study, the OPD having maximum deviations was from the community medicine OPD, followed by ENT and paediatrics. It is possible that the deviations in the community medicine OPDs were more in number as such OPDs are run by junior doctors. Dearden et al15 in his systematic review found 14 studies analyzing prescribing behaviours of junior doctors and stated that the likelihood of committing prescribing errors by them is due to their limited experience, knowledge and skills and reluctance to look up for drug doses or access other vital information. Again the study by Guma et al16 showcased that the antibiotics were less likely to be prescribed empirically by the general practitioners with more experience and working alone. Deviations were found in ENT OPD due to non-specific therapy, e.g., combinations of analgesics with either proton pump inhibitors, trypsin-chymotrypsin combinations or serratiopeptidase prescribed for dyspepsia, URTI or acute otitis media, or respiratory tract infections.

The most common diagnosis in the prescriptions was URTI (42/475) followed by hypertension, osteoarthritis and diabetes. URTI was commonly captured, as individuals with this illness are typically managed by doctors attending various OPDs such as medicine, paediatrics, community medicine and ENT. Similarly, individuals presenting with joint pains visit either the medicine or orthopaedics OPD, resulting in more number of prescriptions having the diagnosis of osteoarthritis.

The drugs identified in prescriptions with unacceptable deviations were pantoprazole, rabeprazole and domperidone combination, trypsin/chymotrypsin, serratiopeptidase, ranitidine, azithromycin, cefixime, amoxicillin and clavulanic acid combination and aceclofenac. It appears that the above drugs were prescribed to not only treat the symptoms but also to treat potential side effect of the drugs prescribed. For patients with pain as a presenting symptom, analgesics were co-prescribed with pantoprazole. Gastroprotective drugs are to be prescribed if the patient has a risk for developing peptic ulcer. Unnecessary prescribing of pantoprazole may lead to potential side effects such as abdominal bloating, oedema and rash. Similarly, it was observed that rabeprazole and domperidone combination along with antacids was prescribed for functional dyspepsia which is not recommended in national/international guidelines. In a study conducted by Biswas et al17 299/304 (98%) prescriptions mentioned domperidone, as a FDC with pantoprazole, and they can cause potential ADRs. In this study, participants presenting with bilateral knee pain (osteoarthritis) were prescribed trypsin/chymotrypsin along with analgesics and/or serratiopeptidase with antibiotics. Existing scientific evidence for serratiopeptidase is not sufficient to support its use18. Further, the FDC (trypsin+chymotrypsin) is irrational and increases the cost of therapy. A study by Elliot et al19 analyzed 237 million medication errors which cost NHS £98,462,582 per year, consumed 181,626 bed-days and leading to 1708 deaths. Azithromycin and the FDC amoxicillin + clavulanic acid were co-prescribed in URTI, which was inappropriate and can contribute to AMR in the long run19. Furthermore, cefixime was prescribed to patients suffering from acute otitis media (not the first choice as per STGs) along with an antihistaminic, an analgesic and an anti-ulcer drug resulting in an unacceptable deviation.

Most of the physicians followed the disease-specific ICMR guidelines and the adherence was found to be around 55 per cent. For those conditions where there were no Indian guidelines or recent updates in the guidelines, physicians used the international guidelines as these are not only updated regularly but also easily accessible in the public domain20. The prescriptions with unacceptable deviations could have been prescribed by the junior doctors who have to cater to a large number of patients and are not able to prioritize and multitask within the fixed time allocated for OPD duties. Besides this, inadequate emphasis on rational prescribing in medical curriculum21 and drug promotion by pharmaceutical industries22 may also have contributed to the inappropriate prescribing and non-compliance to guidelines. However, comparison was not done between prescribing practices of senior and junior doctors. Unfortunately, it is the patient who has to bear the consequences of the irrational prescribing practices. To resolve this problem, we need to inculcate rational prescribing amongst medical student right from the undergraduate days and reinforce these principles during their further professional development.

As a part of this study, we asked physicians to suggest corrective actions to minimize inappropriate prescribing. The suggestions given by the physicians were issuance of administrative order to write a complete legible prescription according to treatment guidelines, provide feedback about prescription errors to prescribers on a regular basis and/or implement online prescribing skill training modules for physicians with the help of case studies. Similar corrective actions were implemented in a study conducted in the UK, wherein feedback was provided to doctors on individual prescribing errors as well as to pharmacists, and prescribing advice emails addressing a common and/or serious error were sent fortnightly. The study observed improved experiences due to these interventions. However, a measurable reduction in prescribing errors was not observed and the authors recommended that a multifaceted approach should be implemented to reduce prescribing errors23. Worldwide many techniques including ‘Stockholm model with wise-list’24 have been employed to reduce inappropriate prescriptions, e.g. computerized provider order entries instead of a paper-based system, regular prescription monitoring programmes and writing prescriptions according to the principles of rational use of medicines. These techniques have reduced errors, but their impact on patient harm needs to be studied25,26,27. A study conducted in Namibia found that WHO/INRUD (The International Network for Rational Use of Drugs) indicators showed poor accuracy in assessing prescribing practices in ambulatory care, so appropriate models are required to optimize medicine use in ambulatory care in the future28. A systematic review conducted by Bos et al29 did not find any concrete evidence to indicate that educating prescribers in the hospital lead to a decrease in patient harm. However, this review included only 15 studies which had evaluated the effects of educational programmes for hospital physicians and of reporting outcomes on (potential) patient harm. Further, these studies had methodology issues such as small sample size with a short follow up period post-intervention and had a risk of high performance and reporting bias. The authors recommended that future research should focus on the implementation of multifaceted educational programmes, with improved patient care outcomes. Another systematic review from China evaluated the effects of various interventions, viz. educational, audit and feedback, health policy change strategies and information system support interventions, which were targeted to improve providers’ prescription behaviours in primary health centres. They observed that the interventions decreased the prescribing of antimicrobials and improved the rational use of antibiotics30. The Ministry of Health and Family Welfare of India appointed a Core Working Group to draft the National Action Plan (NAP) and released the NAP on Antimicrobial Resistance (AMR) 2017 - 2021 in April 201731.

This study was not without limitations. Being a cross-sectional study, the previous and subsequent prescriptions were not captured by us. Furthermore, our selection criteria included those prescriptions having at least a provisional diagnosis, mentioning drugs along with non-pharmacological treatment, so all prescriptions (2962) that mentioned only symptoms without stating the diagnosis were excluded. This led to the inclusion of a smaller number of prescriptions (4838). All consequences of deviations were potential and based on pharmacokinetics and pharmacodynamics of the prescribed drugs except for the cost of therapy which was based on the assumption that unnecessary drugs prescribed could increase the cost of treatment. Hence, the actual patient harm was not studied.

Recently, in 2021, the Pharmaceutical Affairs Commission of the Chinese Hospital Association formed a guideline working group consisting of multidisciplinary experts which formulated guidelines consisting of six recommendations for evaluating prescription appropriateness32. We recommend that the national and local treatment guidelines should be updated on a regular basis based on evidence, disseminated to the clinicians and prescribing according to these guidelines must be mandated by responsible local authorities. Moreover, training modules with case studies based on real-life scenarios that focus on rational prescribing and adherence to treatment guidelines need to be designed on an urgent basis for all prescribers, especially junior doctors. In fact, our network has already launched ICMR prescribing skill course for Indian Medical Graduates in September 2020, with the second cycle in June 2021 and the third cycle due in June 2022.

The most common drug prescribed inappropriately in the prescriptions with unacceptable deviations was pantoprazole. The potential consequence of the unacceptable deviations reported by the clinician was increased cost of treatment. To minimize the deviations, clinicians recommend timely prescription review and implementing continuous educational interventions on rational prescribing.

Financial support and sponsorship

This study was funded by the Indian Council of Medical Research (ICMR) through its Task Force project (65/11/2018/RUD/BMS/Centre-1) on Rational Use of Medicines.

Conflicts of interest

None.