Prescription-event Monitoring Research Articles

Adverse Drug Reaction (ADR) and Pharmacovigilance: A Current Prospectives

Unwanted medication response is defined as "a significantly undesirable or harmful reaction; side effects typically indicate a risk from additional management and contact for prevention, special care, a change in the dosage schedule, or withdrawal of the product. Generally, ADR have been divided into two types: Type-A which is dose dependent and predictable on the basis of the pharmacology of the drug. e.g. beta blocker. Type-B which is unpredictable and not dose dependent. e.g. anticonvulsant. The science and activities related to the detection, assessment, understanding and prevention of adverse events or any other drug-related problem" is the definition of pharmacovigilance. Post-marketing surveillance and additional ADR monitoring techniques include prescription event monitoring, digital medical record connection, voluntary reporting by hospitals (such as the UK's Yellow Card System), cohort/case control studies, and personal case reports from physicians. Because preventing or reducing the risk of adverse drug reactions (ADRs) continues to be a challenge in our daily clinical practice, reaching the highest level of possible results from treatments continue to be a top priority for individual clinicians.

J Guy Edwards, FRCPsych, FRCP, FRCGP (Hon), DPM, HonMFPH, Founding Editor of Human Psychopharmacology.

J Guy Edwards, FRCPsych, FRCP, FRCGP (Hon), DPM, HonMFPH, Founding Editor of Human Psychopharmacology.

Prescription Event Monitoring of Checkpoint Inhibitor-Induced Liver Injury and Outcomes of Rechallenge: A 10-Year Experience

Prescription Event Monitoring of Checkpoint Inhibitor-Induced Liver Injury and Outcomes of Rechallenge: A 10-Year Experience

OS172 - Prescription event monitoring of checkpoint inhibitor-induced liver injury and outcomes of rechallenge: a 10-year experience

OS172 - Prescription event monitoring of checkpoint inhibitor-induced liver injury and outcomes of rechallenge: a 10-year experience

Prescription-Event Monitoring Study on Safety and Efficacy of Levonadifloxacin (Oral and I.V.) in Management of Bacterial Infections: Findings of Real-World Observational Study.

Background:Levonadifloxacin is a novel broad-spectrum antibiotic belonging to the benzoquinolizine subclass of quinolones. It is available in intravenous as well as oral formulation for the treatment of infections caused by common Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus (MRSA).Patients and Methods:This study retrospectively assessed the real-world safety and efficacy of levonadifloxacin (oral and/or IV) in the treatment of 1229 patients across various clinical conditions. Study outcomes were clinical and microbiological success at the end of therapy.Results:The mean duration of levonadifloxacin therapy was 7.2 days, with a time to clinical improvement averaging at 4 days. Three hundred and three patients received oral therapy, 875 received IV, and 51 received a combination of IV followed by oral therapy. Patients were prescribed levonadifloxacin for skin and soft-tissue infections, diabetic foot infections, septicemia, catheter-related bloodstream infections, bone and joint infections, febrile neutropenia, and respiratory infections including COVID-19 pneumonia. High clinical success rates of 98.3%, 93.7%, and 96.1% with oral, IV, and IV followed by oral levonadifloxacin, respectively, were obtained. Only 11 mild adverse events were reported in 9 patients which included constipation, diarrhea, hyperglycemia, nausea, fatigue, and vomiting. Overall, 96.3% and 97.3% of investigators rated the efficacy and safety of levonadifloxacin as “good to excellent.”Conclusions:An excellent safety and efficacy profile of levonadifloxacin was observed in this study making it a suitable treatment option for management of various bacterial infections, including those caused by resistant Gram-positive pathogens such as MRSA and quinolone-resistant S. aureus.

The Role of Advanced Technologies Supplemented with Traditional Methods in Pharmacovigilance Sciences.

The immediate automatic systemic monitoring and reporting of adverse drug reactions, improving the efficacy is the utmost need of the medical informatics community. The venturing of advanced digital technologies into the health sector has opened new avenues for rapid monitoring. In recent years, data shared through social media, mobile apps, and other social websites has increased manifolds requiring data mining techniques. The objective of this report is to highlight the role of advanced technologies together with the traditional methods to proactively aid in the early detection of adverse drug reactions concerned with drug safety and pharmacovigilance. A thorough search was conducted on papers and patents regarding pharmacovigilance. All articles with respect to the relevant subject were explored and mined from public repositories such as Pubmed, Google Scholar, Springer, ScienceDirect (Elsevier), Web of Science, etc. Results: The European Union's Innovative Medicines Initiative WEB-RADR project has emphasized the development of mobile applications and social media data for reporting adverse effects. Only relevant data has to be captured through the data mining algorithms (DMAs) as it plays an important role in timely prediction of risk with high accuracy using two popular approaches; the frequentist and Bayesian approach. Pharmacovigilance at the pre-marketing stage is useful for the prediction of adverse drug reactions in the early developmental stage of a drug. Later, post-marketing safety reports and clinical data reports are important to be monitored through electronic health records, prescription-event monitoring, spontaneous reporting databases, etc. Conclusion: The advanced technologies supplemented with traditional technologies are the need of the hour for evaluating a product's risk profile and reducing risk in population especially with comorbid conditions and on concomitant medications.

Use of atomoxetine and suicidal ideation in children and adolescents: Results of an observational cohort study within general practice in England

AimTo investigate the association between atomoxetine, a drug used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and suicidal ideation, within a cohort of 2–18-year-old patients in England. MethodsThe study was conducted using the observational cohort technique of Modified prescription event monitoring (M-PEM). Patients prescribed atomoxetine were identified from dispensed prescriptions issued by primary care physicians. A customised postal GP questionnaire was used to capture outcome data for suicidal ideation. A matched pair cohort analysis was performed within patients to compare the risk of suicidal ideation in the period after starting atomoxetine with the risk prior to starting atomoxetine; this was stratified by age and concomitant use of methylphenidate. Additional information on patient characteristics, and events of interest was also collected; individual cases of suicidal ideation were qualitatively assessed for drug relatedness. ResultsOf the final cohort (n=4509); 85.5% male (n=3857), median age 11 years (IQR: 9,14). Primary prescribing indication for atomoxetine was ADHD (n=4261, 94.6%). Almost a quarter of the cohort had been co-prescribed methylphenidate. Results of the matched pair cohort analysis indicated that the period after starting atomoxetine was not associated with an increase in the incidence of suicidal ideation compared to the period prior to starting treatment (RR: 0.71; CI: 0.48–1.07; P-value: 0.104). Individual case assessment of suicidal ideation suggested a causal association within a number of cases. ConclusionsThis study found no evidence of an increased risk of suicidal ideation during treatment with atomoxetine, compared to the period prior to starting treatment. Amongst age specific subgroups, this risk may change. Nonetheless, individual case assessment suggested a causal relationship in some patients, hence physicians need to be aware of the possibility of developing this event, and furthermore consider how best to detect it in this paediatric population. This study demonstrates the importance of combining quantitative statistical analyses with a qualitative case series assessment.

Risk of seizure associated with use of acid-suppressive drugs: An observational cohort study.

Previous, large, prescription-event monitoring studies in patients receiving PPI therapy recorded instances of convulsion or seizure. The objective of this study was to quantify the relative risk of seizure associated with the use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) in a general population, overall and stratified by epilepsy status, and to determine the effects of demographics and comorbidities. In this observational study (NCT01744301), patients aged 20-84years in the study period from 1 January 2005 to 31 December 2011 were identified from The Health Improvement Network. In a nested case-control analysis, 8605 patients with seizure were matched to 40000 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. After adjustment, there were no associations between current PPI use and seizure risk in the overall population (OR: 1.05; 95% CI: 0.87-1.27), the subcohort with epilepsy (OR: 0.87; 95% CI: 0.49-1.53), and the subcohort without epilepsy (OR: 1.05; 95% CI: 0.87-1.28). There were no associations between current H2RA use and seizure risk in the overall population (OR: 1.16; 95% CI: 0.62-2.18) and the subcohort without epilepsy (OR: 1.02; 95% CI: 0.51-2.01). Seizures were less frequent in women than in men. Dementia/psychosis, anxiety, depression, and use of anxiolytics, antidepressants, and paracetamol were associated with an increased seizure risk. Our study revealed that the use of PPIs and the use of H2RAs were not associated with an increased risk of seizures in the overall population or in the cohorts stratified by epilepsy status.

Adverse drug reactions and pharmacovigilance of herbal medicines in India

The use of Ayurvedic medicines is popular in India and in recent times has become accepted in other countries. This paper discusses, in brief, the Ayurvedic concepts of adverse reactions to medicines, the need for pharmacovigilance of Ayurvedic medicines, challenges in introducing pharmacovigilance in Ayurveda, and some recommendations to successfully implementing these activities. Pharmacovigilance is the science and practice related to the detection, assessment, understanding, and prevention of adverse effects of drugs or any other possible drug-related problems. The objective of the present article is to review the recent trends and challenges posed in the practice of pharmacovigilance of herbal drugs, especially in the Indian context and to shed light on the importance of pharmacovigilance practice in establishing and maintenance of rational use of these drugs. There is increasing awareness of the need to develop pharmacovigilance for herbal medicines. Applying standard pharmacovigilance techniques (WHO guidelines) presents additional challenges, related to the ways in which herbal medicines are regulated, used, named, and perceived. Proper reporting of suspected adverse drug reactions to herbal medicines is currently the main method of detection. However, there is under-reporting for herbal medicines, since users do not seek professional advice about their use of such products, or report adverse effects. Herbal medicine practitioners are not recognized as reporters to spontaneous reporting schemes. Several other conventional pharmacovigilance tools, such as prescription-event monitoring and the use of computerized health record databases, are currently of little use for evaluating the safety of herbal medicines although modified methods have been developed. This process of pharmacovigilance of herbals in India has come a long way since its initiation. The promotion of the systematic and rational use of drugs requires the reporting of adverse events possibly caused by herbal and traditional medicines also

Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!!

Role of progesterone in reproductive medicine is evolving with its suggested clinical role for the hormonal and nonhormonal actions in reproductive medicine. The main function of progesterone is to induce 'secretory' changes in endometrium that is further complimented by its immunomodulatory and anti-inflammatory actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better implantation. MHRA recommends Serum Progesterone levels ≥14ng/ml in the mid-luteal phase for supporting pregnancy adequately. Oral Natural Micronized Progesterone SR formulation represents a therapeutic advance in this direction offering 'therapeutic compliance' with oral formulation while avoiding the local side effects related to long-term patient compliance in reproductive disorders. The formulation offers round the clock efficiency and efficacy with single dose administration thereby improving patient convenience and compliance. This formulation has been marketed globally since 1986 utilizing the well validated drug delivery system involving Methylcellulose base. The clinical utility of this formulation is further suggested especially in various conditions related with luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase support in ART. The level of evidence has been quite robust with several clinical studies including Prescription Event Monitoring and Investigator initiated studies supporting the clinical role of oral NMP SR formulation especially in 'Real world' clinic settings for Luteal phase insufficiency that may be physiological or iatrogenic.

Utilisation of extended release quetiapine (Seroquel XL™): Results from an observational cohort study in England

BackgroundA post-authorisation safety study was carried out as part of the EU Risk Management Plan to examine the long-term (up to 12 months) use of quetiapine XL as prescribed in general practice in England. AimTo present a description of the drug utilisation characteristics of quetiapine XL. MethodsAn observational, population-based cohort design using the technique of Modified Prescription-Event Monitoring (M-PEM). Patients were identified from dispensed prescriptions issued by general practitioners (GPs) for quetiapine XL between September 2008 and February 2013. Questionnaires were sent to GPs 12 months following the 1st prescription for each individual patient, requesting drug utilisation information. Cohort accrual was extended to recruit additional elderly patients (special population of interest). Summary descriptive statistics were calculated. ResultsThe final M-PEM cohort consisted of 13,276 patients; median age 43 years (IQR: 33, 55) and 59.0% females. Indications for prescribing included bipolar disorder (n=3820), MDD (n=2844), schizophrenia (n=2373) and other (non-licensed) indications (n=3750). Where specified, 59.3% (7869/13,276) were reported to have used quetiapine IR (immediate release formulation) previously at any time. The median start dose was highest for patients with schizophrenia (300mg/day [IQR 150, 450]). The final elderly cohort consisted of 3127 patients and 28.5% had indications associated with dementia. The median start dose for elderly patients was highest for patients with schizophrenia or BD (both 100mg/day [IQR 50, 300]). ConclusionsThe prevalence of off-label prescribing in terms of indication and high doses was common, as was use in special populations such as the very elderly. Whilst off-label use may be unavoidable in certain situations, GPs may need to re-evaluate prescribing in circumstances where there may be safety concerns. This study demonstrates the ongoing importance of observational studies such as M-PEM to gather real-world clinical data to support the post-marketing benefit:risk management of new medications, or existing medications for which license extensions have been approved.

Signal Detection and their Assessment in Pharmacovigilance

Signal detection and its assessment is the most important aspect in pharmacovigilance which plays a key role in ensuring that patients receive safe drugs. For detection of adverse drug reactions, clinical trials usually provide limited information as they are conducted under strictly controlled conditions. Some of the adverse drug reactions can be detected only after long term use in larger population and in specific patient groups due to specific concomitant medications or disease. The detection of unknown and unexpected safety signals as early as possible from post marketing data is one of the major challenge of pharmacovigilance. The current method of detecting a signal is predominantly based on spontaneous reporting, which is mainly helpful in detecting type B adverse effects and unusual type A adverse effects. Other sources of signals detection are prescription event monitoring, case control surveillance and follow up studies. Signal assessment is mainly performed by using Upsala Monitoring scale & Naranjo scale of probability to analyze the cause and effect analysis. Signal detection and their assessment is very vital and complex process. Thus, the main objective of this review is to provide a summary of the most common methods of signal detection and their assessment used in pharmacovigilance to confirm the safety of a drug. Recent developments, challenges, & future needs have also been discussed.

New Ways of Detecting ADRs in Neonates and Children.

Severe adverse drug reactions (ADRs) cause 5-7% of all hospital admissions, an estimated 2,000,000 severe reactions, and over 100,000 deaths each year in the USA. A recent systematic review indicated that the overall incidence of ADRs was 11% in hospitalized children and 1% in outpatients. Detecting ADRs in neonates and children is challenging, particularly because there are fewer clinical trials involving children than adults and drug use in children is common without a labeled indication. Ontogeny and significant physiological changes related to age have an impact on metabolic drug clearance and pharmacodynamics in children compared to adults, as well as on drug action. A variety of strategies have been developed for the identification and further evaluation of ADRs, starting from case reports and advancing into more structured methodologies, such as active surveillance, for accumulating the necessary information. While each approach has merit, a comprehensive surveillance approach with different methods is required to monitor drug safety in the post-market period. Among the methods that have shown value in neonates and children are anecdotal reporting, voluntary organized reporting, prescription event monitoring, pharmacoepidemiology using administrative databases, and active surveillance. There is an urgent need to improve the evaluation of paediatric drug safety in the pre- and post-market phases of drug evaluation in order to better predict in whom serious harm may occur and better ensure the safe use of drugs for neonates and children.

Implementing surgical antibiotic prophylaxis guidelines; role of clinical pharmacist

Surgical antibiotic prophylaxis (SAP) guidelines compliance evaluation of local SAP administration with surveillance of Surgical Site Infections (SSIs) incidence in patient undergoing surgery, many of the important conclusions can be carried out which leads to a substantial improvement in SAP administration practice. International recommendations include Scottish Intercollegiate Guidelines Network (SIGN), Antibiotic prophylaxis in surgery, Edinburgh: SIGN; 2008 [updated April, 2014]; and ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery, 1999 [updated September, 2013] provides evidence based regulations which can be used to establish local therapeutic guidelines for antibiotic prophylaxis administration in patients undergoing surgery. Besides establishment of evidence based SAP guidelines, implementation of these guidelines is of vital importance. Clinical pharmacist holds keystone kind of role in overall acceptance and implementation of these locally established guidelines, ultimately improving health related outcomes in patients as a result of reduction in post-operative SSIs development. As an important ally to practitioner clinical pharmacist plays a very important role in building a bridge between practitioner’s decisions and health outcomes of patients. This role fulfilled by clinical pharmacist with the help of clinical pharmacy services like Drug utilization review, Drug utilization evaluations, Prescription event monitoring, clinical research studies, Drug information services, Therapeutic drug monitoring and clinical pharmacokinetics services. At the end, complete compliance with evidence based SAP guidelines leads to decrease in overall incidence of SSIs development and improvement in health related outcomes of patients undergoing surgery.

Experiences and Lessons From Implementing Cohort Event Monitoring Programmes for Antimalarials in Four African Countries: Results of a Questionnaire-Based Survey.

IntroductionCohort event monitoring (CEM) is an intensive method of post-marketing surveillance for medicines safety. The method is based on prescription event monitoring, which began in the 1970s, and has since been adapted by WHO for monitoring the safety of medicines used in Public Health Programmes. CEM aims to capture all adverse events that occur in a defined group of patients after starting treatment with a specific medicine during the course of routine clinical practice.ObjectiveThe aims of this study were to describe the experiences of National Pharmacovigilance Centres (NCs) that have used CEM to monitor artemisinin-based combination therapy (ACT) for uncomplicated malaria in the African setting, to raise awareness of some of the challenges encountered during implementation and to highlight aspects of the method that require further consideration.MethodA questionnaire-based survey was conducted to capture the experiences of NCs that have implemented CEM for active post-marketing surveillance of antimalarial medicines in sub-Saharan Africa. Six NCs were identified as having implemented CEM programmes and were invited to participate in the survey; five NCs indicated willingness to participate and were sent the questionnaire to complete.ResultsFour NCs responded to the survey—Ghana, Kenya, Nigeria and Zimbabwe—providing information on the implementation of a total of six CEM programmes. Their experiences indicate that CEM has helped to build pharmacovigilance capacity within the participating NCs and at the monitoring sites, and that healthcare providers (HCPs) are generally willing to participate in implementing the CEM method. All of the programmes took longer than expected to complete: contributing factors included a prolonged enrolment period and unexpectedly slow data entry. All of the programmes exceeded their budget by 11.1–63.2 %. Data management was identified as a challenge for all participating NCs.ConclusionsThe reported experiences of four NCs that have undertaken CEM studies on ACTs indicate that CEM has helped to build pharmacovigilance capacity within NCs and monitoring sites and that HCPs are willing to participate in CEM programmes; however, the method was found to be labour intensive and data management was identified as a challenge. Reducing the workload associated with CEM, particularly in relation to data management, and integrating the method into the routine work of HCPs and NCs should be considered for future implementation.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-015-0331-7) contains supplementary material, which is available to authorized users.

Feature Selection in Detection of Adverse Drug Reactions from the Health Improvement Network (THIN) Database

Adverse drug reaction (ADR) is widely concerned for public health issue. ADRs are one of most common causes to withdraw some drugs from market. Prescription event monitoring (PEM) is an important approach to detect the adverse drug reactions. The main problem to deal with this method is how to automatically extract the medical events or side effects from high-throughput medical events, which are collected from day to day clinical practice. In this study we propose a novel concept of feature matrix to detect the ADRs. Feature matrix, which is extracted from big medical data from The Health Improvement Network (THIN) database, is created to characterize the medical events for the patients who take drugs. Feature matrix builds the foundation for the irregular and big medical data. Then feature selection methods are performed on feature matrix to detect the significant features. Finally the ADRs can be located based on the significant features. The experiments are carried out on three drugs: Atorvastatin, Alendronate, and Metoclopramide. Major side effects for each drug are detected and better performance is achieved compared to other computerized methods. The detected ADRs are based on computerized methods, further investigation is needed.

Strategy support for the Post‐Market Monitoring (PMM) of GM plants: Review of existing PMM strategies developed for the safety assessment of human and animal health

Strategy support for the Post‐Market Monitoring (PMM) of GM plants: Review of existing PMM strategies developed for the safety assessment of human and animal health

Short Term Safety and Tolerability of a Fixed Dose Combination of Olmesartan, Amlodipine and Hydrochlorothiazide.

To assess the short term safety and tolerability of a fixed dose combination (FDC) of olmesartan, amlodipine and hydrochlorothiazide (OAH) in real-world clinical setting in India. Physicians were requested to provide eight weeks observational clinical event data of the patients prescribed with FDC of Olmesartan (20/40mg), Amlodipine (5mg) and hydrochlorothiazide (12.5mg) in the prescription event monitoring (PEM) forms. Data on patients' demographics, indication for FDC, concomitant medication and other relevant history was also collected and was analysed with descriptive statistics. Two hundred thirty eight physicians provided data of 4763 patients. Mean age of the population was 55±7 years and males were 59.3%. The commonest indication for the FDC was uncontrolled hypertension (60.7%). Diabetes and dyslipidemia were present in 37.9% and 35.1% respectively. Concomitant medications included statins (42.3%), oral anti-diabetic (33.7%) and antiplatelet agents (24.7%). Pedal oedema (0.29%) was the most common adverse event (AE) reported followed by headache (0.16%), giddiness (0.15%), light headedness (0.15) and stroke (0.15%). Other less common (0.04%) reported AEs were tiredness, dizziness, gastritis, hypersomnia, hypoglycaemia, lower respiratory tract infection (LRTI), weakness, diarrhea, labyrinthitis, urinary tract infection, hyponatremia and hypotension. Occurrence of AEs was more common in patients with uncontrolled hypertension (60.74%). The FDC of olmesartan, amlodipine and hydrochlorothiazide prescribed most frequently for patients with uncontrolled hypertension and co-morbidities was found to be safe and well tolerated over a short period of observation.

Feature Selection in Detection of Adverse Drug Reactions from the Health Improvement Network (THIN) Database

Adverse drug reaction (ADR) is widely concerned for public health issue. ADRs are one of most common causes to withdraw some drugs from market. Prescription event monitoring (PEM) is an important approach to detect the adverse drug reactions. The main problem to deal with this method is how to automatically extract the medical events or side effects from high-throughput medical events, which are collected from day to day clinical practice. In this study we propose a novel concept of feature matrix to detect the ADRs. Feature matrix, which is extracted from high-throughput medical data from The Health Improvement Network (THIN) database, is created to characterize the medical events for the patients who take drugs. Feature matrix builds the foundation for the irregular and high-throughput medical data. Then feature selection methods are performed on feature matrix to detect the significant features. Finally the ADRs can be located based on the significant features. The experiments are carried out on three drugs: Atorvastatin, Alendronate, and Metoclopramide. Major side effects for each drug are detected and better performance is achieved compared to other computerized methods. The detected ADRs are based on computerized methods, further investigation is needed.

A prescription event monitoring study on the utility of garenoxacin, a newer fluoroquinolone in India.

Background:Prescription event monitoring (PEM) study is conducted worldwide. The main objective of such study is to monitor the adverse events when a drug is being prescribed in “real life clinical” settings. PEM studies are being looked upon as an essential observational tool of postmarketing surveillance. Garenoxacin, a newer fluoroquinolone offers an excellent spectrum of antimicrobial coverage, which includes Gram-positive, Gram-negative, anaerobes and atypical microorganism. This broad spectrum of activity is attributed to its unique structure.Aim:The aim was to assess the safety profile of garenoxacin in Indian settings.Materials and Methods:A total of 400 doctors across the country participated in the study. Data from 12,498 patients was obtained. Monitoring of each patient was done for any adverse events.Results:As an initial line of therapy garenoxacin was preferred in majority of cases of community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. Adverse events were reported in 159 patients which included 0.5% cases with nausea/vomiting, 0.1% cases with diarrhea. Central nervous system side-effects like drowsiness or dizziness was reported in 0.02% of the cases. All the adverse events were of mild to moderate severity and did not require hospitalization.Conclusion:Garenoxacin a novel desfluoroquinolone appears to be an ideal antimicrobial agent for the treatment of various respiratory tract infections including CAP. With superior safety profile, excellent antimicrobial coverage and a convenient once a day dosing garenoxacin appears to improve the patient compliance.