Artificial intelligence in pharmacovigilance - Opportunities and challenges.

Pharmacovigilance (PV) is a data-driven process to identify medicine safety issues at the earliest by processing suspected adverse event (AE) reports and extraction of health data. The PV case processing cycle starts with data collection, data entry, initial checking completeness and validity, coding, medical assessment for causality, expectedness, severity, and seriousness, subsequently submitting report, quality checking followed by data storage and maintenance. This requires a workforce and technical expertise and therefore, is expensive and time-consuming. There has been exponential growth in the number of suspected AE reports in the PV database due to smart collection and reporting of individual case safety reports, widening the base by increased awareness and participation by health-care professionals and patients. Processing of the enormous volume and variety of data, making its sensible use and separating "needles from haystack," is a challenge for key stakeholders such as pharmaceutical firms, regulatory authorities, medical and PV experts, and National Pharmacovigilance Program managers. Artificial intelligence (AI) in health care has been very impressive in specialties that rely heavily on the interpretation of medical images. Similarly, there has been a growing interest to adopt AI tools to complement and automate the PV process. The advanced technology can certainly complement the routine, repetitive, manual task of case processing, and boost efficiency; however, its implementation across the PV lifecycle and practical impact raises several questions and challenges. Full automation of PV system is a double-edged sword and needs to consider two aspects - people and processes. The focus should be a collaborative approach of technical expertise (people) combined with intelligent technology (processes) to augment human talent that meets the objective of the PV system and benefit all stakeholders. AI technology should enhance human intelligence rather than substitute human experts. What is important is to emphasize and ensure that AI brings more benefits to PV rather than challenges. This review describes the benefits and the outstanding scientific, technological, and policy issues, and the maturity of AI tools for full automation in the context to the Indian health-care system.

Treatment outcome of different antiretroviral drug regimens in HIV-positive pregnant women.

OBJECTIVE: The objective of the study was to compare the maternal and fetal outcomes of currently preferred tenofovir-based regimen with previous zidovudine-based regimen and also to determine whether the time of starting antiretroviral therapy (ART), whether it can affect the pregnancy and fetal outcome. MATERIALS AND METHODS: Pregnant patients prescribed any of the above regimens were followed up every month till delivery and newborns for initial 6 months. Maternal endpoints were body weight, hemoglobin, and CD4 count, whereas fetal endpoints were birth weight, Apgar score, body weight, and HIV status at 6 months. Data were analyzed using ANOVA and unpaired t-test. P <0.05 was considered statistically significant. RESULTS: A significant increase in CD4 count was observed in patients treated with both the regimens at 12 months as compared to baseline (P < 0.001 and 0.05). Moreover, a significant increase in CD4 count was observed at 12 months as compared to baseline, whether treatment was started before or after the diagnosis of pregnancy (P < 0.05 and 0.001). A significant difference in mean body weight at the end of 9 months was observed in patients wherein ART was started before or after the diagnosis of pregnancy (P < 0.005). Majority of patients had a favorable maternal outcome, while fetal birth weight, Apgar score, body weight, and HIV status were comparable at 6 months irrespective of treatment and time of starting ART. CONCLUSION: All ART regimens are equally effective in terms of increase in CD4 count, gestational gain in body weight, and pregnancy and fetal outcome. Furthermore, there is no significant difference in efficacy, pregnancy, and fetal outcome in women who were already on ART when diagnosed pregnancy or who were started ART later in antenatal period.

Pharmacovigilance and assessment of drug safety reports during COVID 19.

The speed and volume of clinical research to discover effective drug against novel corona virus has been remarkable. To address the unmet medical need, the regulations are made flexible and convenient without any relaxation in drug safety reporting. The pharmacovigilance activities, especially adverse event reporting regardless of clinical trials or clinical practice should continue as usual because patient safety is the priority. The exposure to experimental drugs with limited evidence of risk - benefit makes it more crucial to adapt robust safety monitoring, accuracy in adverse event reporting, and timely assessment. With the current restriction on physical contact, travel and free movements, isolation, quarantine, and huge clinical workload during pandemic, causality assessment will be more challenging. It may not be possible to capture details of all adverse events, thereby affecting completeness and quality of safety reports. A substantial number of COVID 19 patients will receive investigational drugs along with multiple other medications for clinical manifestations and drug therapy for lifestyle diseases. Causality assessment will be a challenge due to overlapping toxicities, multiple confounding, contributory factors, and insufficient data on safety and risk profile of combining drugs. Assessment will be unable to precisely determine the causality as certain or unlikely, although, it will be valuable in categorizing the causal association as "possible" adverse drug reactions and their scientific basis. Several of these detailed reports, when collated, can identify risk factors for possibilities of prevention or avoid harm. In the current situation of pandemic and uncertainty of experimental new and old repurposed drugs, causation needs to be viewed for the study drug with a public health perspective. After all, this is the best time tested approach to generate evidence and drug evaluation to prevent damage to prospective patients.

Early treatment outcome of bedaquiline plus optimised background regimen in drug resistant tuberculosis patients.

AIMS: Bedaquiline (BDQ) has been recently approved for drug resistant tuberculosis with active drug safety monitoring under programmatic condition. The present study was conducted to evaluate safety, tolerability and efficacy of bedaquiline plus optimised background regimen. METHODS: A prospective study was conducted on cohort of pre-extensively drug resistant (XDR) and XDR pulmonary TB patients. Eligible patients were closely monitored for cardiac safety, adverse events (AEs), clinical and microbiological improvement during BDQ (6 months) and post BDQ phase for twelve months. RESULTS: Of 127 patients enrolled, a significant increase in mean QTc interval was observed on 13th day and 3rd week as compared to baseline (p < 0.0001). Mean maximum increase of QTc was 37.92ms (95% CI, 14.1-61.74ms). Concomitant anti-TB medications, age, gender, low body mass index (BMI) had significant effect on QTc prolongation (p < 0.0001, p < 0.05). However, none of the patient required discontinuation of BDQ. Majority of AEs (86.3%) were non-serious and not preventable 108 (87.1%). The median time for sputum-culture conversion was 40.89 ± 3.5 days (95% CI, 34-48 days) and the treatment outcome was successful in 102 (80.3%) patients with negative sputum culture conversion. CONCLUSIONS: Bedaquiline containing regimen achieved favourable outcome. Although, bedaquiline along with concomitant anti-TB medications has the potential to prolong QTc interval, the benefit certainly outweighs the risk. This calls for a through pre-treatment cardiovascular and biochemical evaluation as a preventive measure and appropriate selection of patients for safe use of BDQ and successful outcome.

An analysis of the use of antimicrobial agents in outdoor patients of ophthalmology.

OBJECTIVES: The study was aimed to analyze commonly used antimicrobials in outdoor patients of ophthalmology department. MATERIALS AND METHODS: The study was an observational, cross-sectional study carried out in the Department of Pharmacology and Ophthalmology after approval from the head of departments and Institutional Ethics Committee. All the patients age 18 years and above who were prescribed antimicrobials and gave consent were included in study. Data were recorded in a case study form containing relevant patient information and results of general, ocular, and special examinations along with the details of antimicrobials prescribed. Data were analyzed according to the World Health Organization/International Network for Rational Use of Drugs indicators and appropriate statistical tests. RESULTS: A total of 900 patients who were prescribed antimicrobial agents (AMAs) were included in the study. The most common chief complaint was diminution of vision (25.78%). The most common indication of use of AMAs was for treating ocular infections (50.22%). The most commonly prescribed antimicrobial group was fluoroquinolone (FQ) (63.8%) and the most common drug was moxifloxacin (35.95%). The most common dosage form of AMAs was eye drops (68.55%). The average number of drugs per encounter was 4.41. The percentage of encounters with injectables prescribed was 0.67%. The percentage of use of antibiotics was 100%. The percentage of total drugs and AMAs prescribed by generic name was 41.5 and 11.92, respectively. The percentage of antimicrobial drugs prescribed from essential drugs list was 34.24%. The mean duration of antimicrobial therapy was 7.2 ± 4.54 days. CONCLUSION: More than half of the patients are prescribed multiple AMAs. Moxifloxacin, a newer generation FQ , was the most commonly prescribed AMA in our study. Educational interventions and strict adherence to hospital antimicrobial use policy are needed to restrict the use of AMAs and increase rational prescribing.

Analysis of Cutaneous Adverse Drug Reactions Reported at the Regional ADR Monitoring Center.

INTRODUCTION: Skin is one of the major target organ for adverse drug reactions (ADRs). The incidence of dermatological ADRs among indoor patients in developed countries ranges from 1-3%, whereas in developing countries such as India, it is 2-5%. AIMS: To analyze the clinical spectrum, seriousness, outcome, causality, severity, and preventability of the cutaneous ADRs. MATERIAL AND METHODS: All cutaneous ADRs reported at the Regional Adverse Drug Reaction Monitoring Center between January 2013 to May 2016 were identified and evaluated. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and the Naranjo'a reactions (ADRs) Severity (Hartwig and Seigel scale), and preventability (Schumock and Thornton criteria) of a said drug. RESULTS: Out of 2171 ADRs reported during study period, 538 were cutaneous ADRs (24.78%). The most common clinical presentation was maculopapular rash (58.92%) followed by itching (10.59%), and Stevens-Johnson syndrome (4.83%). The time relationship of cutaneous ADRs to drug therapy revealed that they can develop within 1 week to 1 year of treatment. Most common causal drug groups were antimicrobials (46%), non-steroidal anti-inflammatory drugs (NSAIDs) (18%), and antiepileptics (10%). Polypharmacy was observed in 7% of the cases. Most of the cutaneous ADRs were non-serious (91%), however, 10 were life-threatening and 1 was resulted in death due to the Stevens-Johnson syndrome. Causality category for majority of cutaneous ADRs was possible. Although majority of cutaneous ADRs were moderately severe (81%), however, not preventable (89%). CONCLUSION: The occurrence of cutaneous ADRs is common and they developed within 1 week of therapy. Antimicrobial agents and NSAIDs are the most common implicated drug class. Hence, physicians should closely monitor the patient in the first week while using such therapy for early detection and prevention of cutaneous ADRs.

An analysis of adverse drug reactions in extremes of age group at tertiary care teaching hospital.

OBJECTIVES: To analyze clinical spectrum, seriousness, outcome, causality, severity and preventability of ADRs in geriatrics and pediatric patients. MATERIALS AND METHODS: All ADRs reported in geriatrics (≥ 65 years) and pediatrics (≤ 12 years) indoor as well outdoor patients from January, 2010 to April, 2016 at ADR monitoring centre, Department of Pharmacology, B. J. Medical College and Civil Hospital were identified. A retrospective analysis was carried out for clinical presentation, causality (as per WHO-UMC scale and Naranjo's algorithm), severity (Hatwig and Seigel scale) and preventability (Schaumock and Thornton criteria). RESULTS: Out of 3690 ADRs, 160 were in geriatric patients (4.33%) while 231 in pediatric patients (6.26%). The most commonly affected body system was gastrointestinal (53, 33.13%) followed by neurological disorders (26, 16.25%) in geriatric patients. While in pediatric patients, the most commonly affected body system was skin and appendages (73, 31.60 %) followed by gastrointestinal disorders (58, 25.11%). The most common causal drugs in geriatric patients was cardiovascular (38, 23.75%) followed by antimicrobials (28, 13.25%). While in pediatric patients, the most common causal drug group was antimicrobials (85, 33.46%) followed by blood products (36, 14.12%). Total 17 ADRs reported following vaccination, 7 (41.17%) were injection site abscess and 11 (64.70%) were due to pentavalent vaccine. Polypharmacy was common in geriatrics (31, 19.37%). Causality assessment for majority of ADRs in geriatrics (83, 52.5%) and pediatrics (171, 67.32%) were probable. CONCLUSION: ADRs are common in geriatric and pediatric patients usually within four weeks of oral therapy. Active surveillance of drug safety monitoring in these vulnerable population is recommended.

An Evaluation of Efficacy and Safety of Commonly Prescribed Drugs and Effect of These Drugs on Quality of Sleep in Patients Suffering From Zoster-Associated Pain.

This observational, prospective, single-center study was conducted to evaluate the efficacy and safety of commonly prescribed drugs for zoster-associated pain and their impact on quality of sleep at a tertiary care hospital in western India. Patients ≥18 years of age, newly diagnosed with zoster-associated pain were evaluated on days 0, 7, 14, 30, 60, 90, 120, 150, and 180 or until resolution of pain, whichever was earlier, using the Wong Baker FACES Pain Rating Scale, Neuropathic Pain Scale, and Insomnia Severity Index for intensity of pain, quality of pain, and quality of sleep, respectively. A total of 78 patients (46.0 [16.3] years) completed the study. They received nonsteroidal anti-inflammatory drugs (65), gabapentin (30), amitriptyline (27), and amitriptyline + gabapentin (21) for mean durations of 7.7 (3.0), 89.2 (7.2), 107.6 (46.3), and 104.5 (46) days, respectively. Improvement in the Wong Baker FACES Pain Rating Scale and Neuropathic Pain Scale score was similar among treatment groups except for a greater fall in Wong Baker FACES Pain Rating Scale score at days 7 and 120 and that in deep pain score at day 7 in combination treatment group vs the amitriptyline group. Clinically significant insomnia was detected in 35 patients at baseline and demonstrated progressive and similar improvement among groups. Treatment modification was required in 20 patients. Zoster-associated pain resolved in 69 patients. Nine adverse drug reactions, mostly mild, nonserious, and nonpreventable, were reported. To conclude, drugs commonly used for zoster-associated pain are effective and well tolerated. These have a similar effect on pain and quality of sleep, except for a possible greater effect of combination treatment in the early phase of intense and deep pain.

A safety analysis of different drug regimens used in human immunodeficiency virus-positive patients.

BACKGROUND: Long-term toxicity of antiretroviral agents is rarely addressed in initial clinical trials. Effective pharmacovigilance is essential for long-term safety of antiretroviral therapy (ART). MATERIALS AND METHODS: All adverse drug reactions (ADRs) reported due to ART between January 2014 and September 2016 were analyzed as per different drug regimens used. ADRs were also analyzed for system organ classification, seriousness, time relationship of ADRs with drug therapy, causality (as per the World Health Organization-Uppsala Monitoring Centre scale and Naranjo algorithm), and severity (Hartwig and Siegel scale). Comparison was done between (tenofovir + lamivudine + efavirenz [TLE]) and (zidovudine + lamivudine + nevirapine [ZLN]) regimens. RESULTS: During a study period, 2983 patients were on ART. The most common drug regimen prescribed was TLE (1805) followed by ZLN (326). A total of 325 (10.89%) ADRs were reported in which 150 ADRs were reported in TLE regimens (46%) and 130 in ZLN regimens (40%). The mean age of patients with ADRs was 40 ± 12.56 years and men (58.1%) were more affected than women (41.8%). The most common system organ involved in ZLN regimen was blood (50, 39%) and skin (35, 27%), while it was neurological (63, 42%) and renal disorder (27, 18%) in TLE regimen. Most of ADRs were observed after 1 month of therapy (79.5%) and showed possible causal relation with drug therapy (78.15%). Majority of ADRs were mild in nature (86.7%). The serious ADRs were reported more in ZLN (18%) regimen as compared to TLE (9%) (P < 0.05). CONCLUSION: Both ART regimens are associated with ADRs affecting all body system; however, the frequency and severity of ADR are high with ZLN regimen.

Transfusion-related adverse reactions in pediatric and surgical patients at a tertiary care teaching hospital in India.

BACKGROUND: Use of blood and its components is lifesaving. However, their use is often associated with adverse events. OBJECTIVE: To analyze the pattern of adverse reactions associated with transfusion of blood and its components in pediatric and surgical patients at a tertiary care teaching hospital. MATERIALS AND METHODS: Patients receiving transfusion of blood or its components in a randomly selected unit each from Departments of Pediatrics, including thalassemia OPD and surgery, were monitored intensively for a period of 6 months. Clinical course, management, outcome, causality, severity, seriousness, and preventability of observed transfusion reactions (TRs) were analyzed. RESULTS: A total of 411 pediatric and 433 surgical patients received 594 and 745 transfusions respectively during the study period. Of these, TRs were observed in 69 (11.6%) children and 63 (8.4%) surgical patients. Majority of reactions in children (48, 69.5%) and surgical patients (51, 80.9%) were acute, developing within 24 h of transfusion. TRs were observed with packed cells (13.2%), cryoprecipitate (10%), platelet concentrate (14.3%) and fresh frozen plasma (1.3%) in pediatric patients and with packed cells (7.2%), whole blood (25%) and platelet concentrate (62.5%) in surgical patients. Most common TRs included febrile nonhemolytic TRs (FNHTRs) and allergic reactions. Reactions were more frequent in patients with a previous history of transfusion or those receiving more than one transfusion and in children, when transfusion was initiated after 30 min of issue of blood component. Majority of reactions were managed with symptomatic treatment, were nonserious, moderately severe, probably preventable and probably associated with the suspect blood component in both populations. CONCLUSION: Transfusion reactions in children and surgical patients are commonly observed with cellular blood components. Majority of reactions are acute and nonserious. FNHTRs and allergic reactions are the most common transfusion reactions. Risk of transfusion reactions is more in patients receiving multiple transfusions.

Treatment Outcome of Ovulation-inducing Agents in Patients with Anovulatory Infertility: A Prospective, Observational Study.

OBJECTIVE: To compare different treatment regimens on pregnancy rate and outcome in patients with anovulatory infertility. PATIENTS AND METHODS: A prospective observational study was conducted on patients with infertility due to anovulation. Patients treated with clomiphene citrate (CC) 50/100 mg/day from 2nd to 6th day of menstrual cycle (MC) (n = 38), short gonadotropin-releasing hormone (GnRH) agonist regimen (leuprolide [0.5 mg subcutaneous] + recombinant follicle-stimulating hormone [rFSH] [225 IU intramuscular [IM] from 2nd to 10th day of MC [n = 32]), long GnRH agonist regimen (leuprolide from 21st day followed by leuprolide + rFSH from 2nd to 10th day of MC [n = 19]), and antagonist regimen (human menopausal gonadotropin [hMG] [150 IU IM] from 2nd day followed by hMG + cetrorelix from 7th to 10th day of MC) (n = 6) were recruited and followed up for follicular size, endometrial thickness, and pregnancy test. Data were analyzed using appropriate statistical test andP < 0.05 was considered statistically significant. RESULTS: A significant increase in follicular diameter and endometrial thickness was observed in patients treated with gonadotropin regimens as compared to CC alone (P < 0.0001). The highest number of positive pregnancy test with ultrasonographic evidence of gestational sac was observed with leuprolide + rFSH (long regimen) (10/19, 52.6%) followed by leuprolide + rFSH (short regimen) (13/32, 40.6%) while least in antagonist regimen (2/6, 33.3%) and CC (1/38, 2.63%). All regimens were well tolerated. CONCLUSION: Treatment outcome was better with long agonist regimen.

Treatment outcome of patients having extensively drug-resistant tuberculosis in Gujarat, India.

BACKGROUND: To investigate the factors affecting treatment outcome of extensively drug resistant tuberculosis (XDR-TB) in Gujarat, India. METHODS: A prospective, observational study was conducted on patients with XDR TB from January 2012 to October 2016. Details of demography, clinical symptoms, sputum/culture and radiological examination, drug treatment, adverse drug reactions (ADRs) and treatment outcome were recorded in pretested case record form (CRF). Data was analyzed using Fisher's exact test and paired student's t test. RESULTS: Out of 112 patients, 83 (74%) were men and 29 (26%) were women and majority of belonged to age group of 16 - 45 years. Majority of patients (79%) received standardized treatment. A total of 61 (54%) patients converted to sputum culture negative by 12 months and out of these, 49 turned sputum culture negative within initial 6 months of treatment. Successful treatment outcome was seen in 29 (25.89 %). Age ≤40 years (P<0.05), body mass index > 18.5 (P<0.05) and sputum/culture conversion at three month (P<0.001) were positive predictors for successful treatment outcome, while tobacco chewing habit (P<0.05) and alcohol consumption (P<0.05) were negative predictors for the successful treatment outcome. Out of 83 (74.1 %) patients with unsuccessful treatment outcome, 58 (51.78 %) died, 11 (9.82 %) were defaulter and 10 (8.92 %) were treatment failure. Factors positively associated with death were very low BMI (< 18.5), concomitant diseases and harmful personal habits. CONCLUSIONS: Treatment outcome of XDR TB patients is extremely poor with high mortality rate.

Comparison of Effect of Antidepressants on Psychomotor Functions.

OBJECTIVE: The comparison of the effect of antidepressants on psychomotor functions in patients with endogenous depression. MATERIALS AND METHODS: This prospective interventional study was carried out at a tertiary care teaching hospital on 95 literate patients with newly diagnosed endogenous depression matching inclusion and exclusion criteria. Patients were prescribed either desvenlafaxine (50 mg) or fluoxetine (40 mg) or sertraline (50 mg). Psychomotor functions were assessed by digit letter substitution, six letter cancellation, choice reaction time, hand steadiness and flicker fusion test at the baseline 1st month and 3rd month. Efficacy of drugs was also measured by Hamilton rating scale for depression. Data were analyzed by using ANOVA and P < 0.05 was considered as statistically significant. RESULTS: A total of 95 patients were enrolled. Fluoxetine, desvenlafaxine, and sertraline were prescribed in 32, 32, and 31 patients, respectively. At the end of 3 months, a significant improvement in psychomotor functions was observed in patients treated with sertraline (P < 0.05), while desvenlafaxine-treated patients did not show any significant change in any of the tests. Surprisingly, fluoxetine-treated patients showed deterioration in all psychomotor tests (P < 0.05). Hamilton rating score improved at the end of 3 months treatment as compared to baseline. Most commonly observed adverse reactions in all three drug groups were nausea (n = 20), dizziness (n = 3), headache (n = 20), and diarrhea (n = 3). CONCLUSION: Sertraline significantly improves psychomotor function as compared to desvenlafaxine while fluoxetine impairs.

A study of medication errors in a tertiary care hospital.

OBJECTIVE: To determine the nature and types of medication errors (MEs), to evaluate occurrence of drug-drug interactions (DDIs), and assess rationality of prescription orders in a tertiary care teaching hospital. MATERIALS AND METHODS: A prospective, observational study was conducted in General Medicine and Pediatric ward of Civil Hospital, Ahmedabad during October 2012 to January 2014. MEs were categorized as prescription error, dispensing error, and administration error (AE). The case records and treatment charts were reviewed. The investigator also accompanied the staff nurse during the ward rounds and interviewed patients or care taker to gather information, if necessary. DDIs were assessed by Medscape Drug Interaction Checker software (version 4.4). Rationality of prescriptions was assessed using Phadke's criteria. RESULTS: A total of 1109 patients (511 in Medicine and 598 in Pediatric ward) were included during the study period. Total number of MEs was 403 (36%) of which, 195 (38%) were in Medicine and 208 (35%) were in Pediatric wards. The most common ME was PEs 262 (65%) followed by AEs 126 (31%). A potential significant DDIs were observed in 191 (17%) and serious DDIs in 48 (4%) prescriptions. Majority of prescriptions were semirational 555 (53%) followed by irrational 317 (30%), while 170 (17%) prescriptions were rational. CONCLUSION: There is a need to establish ME reporting system to reduce its incidence and improve patient care and safety.

An analysis of serious adverse drug reactions at a tertiary care teaching hospital.

OBJECTIVE: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs) such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. MATERIALS AND METHODS: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization -Uppsala Monitoring Center (WHO-UMC) criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and Siegel scale), and preventability (Schumock and Thornton criteria). RESULTS: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of the serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%), and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature. CONCLUSION: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.

Evaluation of impact of teaching clinical pharmacology and rational therapeutics to medical undergraduates and interns.

OBJECTIVES: To find out the impact of teaching clinical pharmacology and rational therapeutics (CPT) to medical undergraduates (UGs) and interns. MATERIALS AND METHODS: This cross-sectional, prospective study was conducted on three UGs batches and interns using two pretested validated structured questionnaires, modified from the work of Tobaiqy et al. The study was approved by the Institutional Ethics Committee. ANOVA and Chi-square test were used for statistical analysis. The value of P < 0.05 was considered statistically significant. RESULTS: A total of 379 UGs and 96 interns participated in this study. Mean knowledge score of interns was significantly reduced as compared to UGs (P < 0.0001). A significant increase in confidence for unsupervised prescribing of nonsteroidal anti-inflammatory drugs (99%), oral rehydration salt, iron salts was perceived among interns as compared to UGs (P < 0.05). However, 63.5% confessed problems in selection of drugs, drug-drug interactions, prescribing in special patient population. Although they were confident prescribing fixed dose combination for adult patients (89.5%), majority were hesitant to prescribe opioids (77%), steroids (76%), vaccines (75%), and antihypertensives (62%). CONCLUSION: The theoretical CPT teaching transfers knowledge to UGs; however, it is not retained in internship and does not adequately prepare interns to prescribe safe and rational drugs.

An evaluation of drug promotional literatures published in scientific medical journals.

OBJECTIVES: Evaluation and comparison of ethical standards of published drug promotional literatures (DPLs) between different Indian and non-Indian scientific medical journals regarding compliance to the World Health Organization (WHO) and International Federation of Pharmaceutical Manufacturers and Associations (IFPMAs) guidelines. MATERIALS AND METHODS: A cross-sectional, observational study was carried out at pharmacology department. DPLs published in Indian and non-Indian scientific medical journals available at central library of medical college during the period of 6 months were collected according to selection criteria. DPLs were evaluated and compared for compliance to ethical standards of drug promotion laid by the WHO and IFPMA. Data were analyzed using Fisher's exact test. RESULTS: Out of total 178 DPLs, 103 DPLs were from Indian journals and 75 DPLs were from non-Indian journals. When compared regarding compliance to all the 11 ethical criteria of WHO, no significant difference was found between DPLs published in Indian and non-Indian journals. However, DPLs from indian journals contained significantly less information regarding dosage regimen (P = 0.0096), adverse drug reactions (P = 0.0028), warnings (P = 0.0104) and major drug interactions (P < 0.0001) as compared to non-Indian journals. Compliance to all the five IFPMA criteria was significantly higher in DPLs of non-Indian journals (88%) than Indian journals (39%) (P < 0.0001). CONCLUSION: Noncompliance to ethical standards of WHO and IFPMA guidelines is more common in DPLs of Indian journals as compared to non-Indian journals. Thus strict implementation of regulatory measures regarding DPLs published in Indian medical journals is recommended.

Critical Analysis of Cardiovascular and Central Nervous System Fixed Dose Combinations Available in Indian Market.

INTRODUCTION: Fixed Dose Combinations (FDCs) are being increasingly used to improve compliance and achieve greater benefits of the two or more active ingredients given together than the corresponding individual drug components given separately. AIM: To analyse the rationality of Cardiovascular (CV) and Central Nervous System (CNS) FDCs available in Indian market. MATERIALS AND METHODS: CVS and CNS FDCs, enlisted in Indian Drug Review, 2014, were analysed by a pretested validated eight point criteria tool. Each FDC was assessed for number of active pharmacological ingredients, approval by regulatory authority, listing in WHO Essential Medicine List. While efficacy, safety, pharmacokinetic, pharmacodynamic interactions and advantages of each FDC were analysed by literature search. The total score of the tool was 12 and score ≥7 was considered rational. FDCs were divided in four groups as per rationality and DCGI approval. ANOVA was used for statistical analysis and p<0.05 was considering statistically significant. RESULTS: Out of 152 FDCs, 107 were CV and 45 belonged to CNS group and 40 had documented evidence of efficacy and safety. Majority of FDCs showed advantage of being convenient by reducing pill count and only 32 showed reducing adverse drug reactions. Out of 107 CV FDCs, 46 were rational and 61 were irrational with a mean rationality score of 6.72±2.82 (CI- 95 %, 3.90 - 9.54). While out of 45 CNS FDCs, 8 were rational and 37 were irrational with a mean rationality score of 6.22±2.08 (CI - 95 %, 4.14 - 8.30). A significant difference in mean rationality score of group A (DCGI approved + rational) was observed as compared to group B (DCGI approved + irrational) and group C (DCGI unapproved + rational) as compared to group D (DCGI unapproved + irrational) (p<0.05). CONCLUSION: The absence of watertight pre-requisite, critical analysis of the scientific validity of the formulations and 'convenience' category has resulted into proliferation of irrational FDCs. This calls for strict regulatory approval process to avoid miserable FDC scenario in the country.