Regulatory enforcement of the marketing of fixed-dose combinations in India: a case study of systemic antibiotics

\ua9 2023, The Author(s).Background: In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market. Methods: Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008–2020 using PharmaTrac market dataset. Results: The regulatory initiatives permitted 68 formulations to be given de facto approvals (‘No Objection Certificates’) outside the statutory regime, banned 46 FDCs and restricted one FDC. Market data show that FDCs as a proportion of total antibiotic sales increased from 32.9 in 2008 to 37.3% in 2020. The total number of antibiotic FDC formulations on the market fell from 574 (2008) to 395 (2020). Formulations with a record of prior central approval increased from 86 (2008) to 94 (2020) and their share of the antibiotic FDC sales increased from 32.0 to 55.3%. In 2020, an additional 23 formulations had been permitted de facto approval, accounting for 10.6% of the antibiotic FDC sales. Even in 2020, most marketed formulations (70.4%, 278/395) were unapproved or banned, and comprised a 15.9% share of the antibiotic FDC sales. The share of NLEM-listed antibiotic FDC sales increased from 21.2 (2008) to 26.7% (2020). Conclusion: The initiatives had limited impact. Regulatory enforcement has been slow and weak, with many unapproved, and even banned, FDCs remaining on the market

The impact of stringent prescription-only antimicrobial sale regulation (Schedule H1) in India: an interrupted time series analysis, 2008–18

To assess the impact of Schedule H1 regulation notified and implemented in 2014 under the amended rules of the Drugs and Cosmetics Act (DCA), 1940 on the sale of antimicrobials in the private sector in India.The dataset was obtained from the Indian pharmaceutical sales database, PharmaTrac. The outcome measure was the sales volume of antimicrobials in standard units (SUs). A quasi-experimental research design—interrupted time series analysis—was used to detect the impact of the intervention.We observed a substantial rise in antimicrobial consumption during 2008–18 in the private sector in India, both for antimicrobials regulated under Schedule H1 as well as outside the regulation. Key results suggested that post-intervention there was an immediate reduction (level change) in use of Schedule H1 antimicrobials by 10% (P = 0.007), followed by a sustained decline (trend change) in utilization by 9% (P > 0.000) compared with the pre-intervention trend. Segregated analysis on different antimicrobial classes suggests a sharp drop (level changes) and sustained decline (trend changes) in utilization post-intervention compared with the pre-intervention trend. Our findings remained robust on carrying out sensitivity analysis with the oral anti-diabetics market as a control. Post-intervention, the average monthly difference between antimicrobials under Schedule H1 and the control group witnessed an immediate increase of 16.3% (P = 0.10) followed by a sustained reduction of 0.5% (P = 0.13) compared with the pre-intervention scenario.Though the regulation had a positive impact in terms of reducing sales of antimicrobials notified under the regulation, optimizing the effectiveness of such stand-alone policies will be limited unless accompanied by a broader set of interventions

Shining a light on an additional clinical burden: work-related digital communication survey study – COVID-19 impact on NHS staff wellbeing

Work-related communication volume within the United Kingdom’s National Health Service (NHS) has had little systematic research previously. The impact of communication volume on work-life balance of healthcare staff in the NHS is also not known and has not been an area of focus or governance. COVID-19 led to a shift to non-physical work, with greater reliance on digital communication for clinical decision making. We sought to elucidate the relationship between communication, work-life balance, and COVID-19. An online survey was conducted to assess the platforms used to communicate professionally, the volume of and time spent on work-related communications, how this has changed from before to during COVID-19, and the effect on work-life balance. A total of 3047 healthcare staff provided consent and evaluable data. Emails were reported as the most frequently used communication tool, and the majority of staff asked, reported increased work-related communications due to COVID-19. Staff estimated receiving 14 emails on an average day before COVID-19. During the pandemic, staff estimated getting approximately 17 emails on an average day and 29 emails on a busy day. Work communications reportedly took up increased amounts of family and home time during COVID-19. A large proportion (36%) of staff were unable to switch off from work-related communications already before COVID-19, worsening (57%) during the pandemic. Work-related digital communication is a vital component of working in the NHS. We provide the first detailed data on the types, volume, and impact of such communication on NHS staff during the COVID-19 pandemic, compared to pre-pandemic levels. We found that 82% of staff support the need for NHS guidance on work-related communications to help manage overload, protect emotional wellbeing, and increase resilience. Further work is urgently needed in this area to tackle the negative impact of communication technologies (technostress) on work-life balance to reduce staff stress, burnout, and turnover or early retirement of some staff

Antibiotic prescriptions for Oral Diseases in India: Pattern and Practices

Introduction: The key objective of this research was to describe the prescription rate of various antibiotics for dental problems in India and to study the relevance of the prescriptions by analysing antibiotic type associated with different dental diagnoses, using a large scale nationally representative dataset. Methods: We used a 12-month period (May 2015 to April 2016) medical audit dataset from IQVIA (formerly IMS Health). We coded the dental diagnosis provided in the medical audit data to International Statistical Classification of Diseases and Related Health Problems (ICD-11) and the prescribed antibiotics for the diagnosis to Anatomic Therapeutic Chemical (ATC) -2020 classification of World Health Organization. The primary outcome measure was the medicine prescription rate per 1,000 persons per year (PRPY1000). Results: Our main findings were -- 403 prescriptions per 1,000 persons per year in the year 2015 -2016 for all dental ailments. Across all ATC level 1 classification, ‘Diseases of hard tissues’ made up the majority of the prescriptions. ‘Beta-lactam’, ‘Penicillin,’ and ‘Cephalosporins’ were the most commonly prescribed antibiotics for dental diagnoses followed by ‘Macrolides’ and ‘Quinolones’. ‘Dental caries’ , ‘Discoloration of tooth’, and ‘Toothache’ were the most common reasons for ‘Beta-Lactams’ and ‘Penicillin’ prescriptions. Conclusion: To conclude our study reports first ever country (India) level estimates of antibiotic prescription by antibiotic classes, age groups, and ICD-11 classification for dental ailments

Deterioration of Parkinson's disease during hospitalization: survey of 684 patients

Abstract Background A substantial fraction of Parkinson's disease patients deteriorate during hospitalisation, but the precise proportion and the reasons why have not been studied systematically and the focus has been on surgical wards and on Accident & Emergency departments. We assessed the prevalence and risk factors of deterioration of Parkinson's disease symptoms during hospitalization, including all wards. Methods We invited Parkinson's disease patients from three neurology departments in The Netherlands to answer a standardised questionnaire on general, disease and hospital related issues. Patients who had been hospitalized in the previous year were included and analysed. Possible risk factors for Parkinson's disease deterioration were identified. Proportions were analysed using the Chi-Square test and a logistic regression analysis was performed. Results Eighteen percent of 684 Parkinson's disease patients had been hospitalized at least once in the last year. Twenty-one percent experienced deterioration of motor symptoms, 33% did have one or more complications and 26% had received incorrect anti-Parkinson's medication. There were no statistically significant differences for these variables between admissions on neurologic or non-neurologic wards and between having surgery or not. Incorrect medication during hospitalization was significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration, as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose per day was a significant risk factor for deterioration. When adjusting for different variables, wrong medication distribution was the most important risk factor for deterioration. Conclusions Incorrect medication and infections are the important risk factors for deterioration of Parkinson's disease patients both for admissions with and without surgery and both for admissions on neurologic and non-neurologic wards. Measures should be taken to improve care and incorporated in guidelines.</p

Climate and southern Africa's water-energy-food nexus

In southern Africa, the connections between climate and the water-energy-food nexus are strong. Physical and socioeconomic exposure to climate is high in many areas and in crucial economic sectors. Spatial interdependence is also high, driven for example, by the regional extent of many climate anomalies and river basins and aquifers that span national boundaries. There is now strong evidence of the effects of individual climate anomalies, but associations between national rainfall and Gross Domestic Product and crop production remain relatively weak. The majority of climate models project decreases in annual precipitation for southern Africa, typically by as much as 20% by the 2080s. Impact models suggest these changes would propagate into reduced water availability and crop yields. Recognition of spatial and sectoral interdependencies should inform policies, institutions and investments for enhancing water, energy and food security. Three key political and economic instruments could be strengthened for this purpose; the Southern African Development Community, the Southern African Power Pool, and trade of agricultural products amounting to significant transfers of embedded water

Why Um Helps Auditory Word Recognition: The Temporal Delay Hypothesis

Several studies suggest that speech understanding can sometimes benefit from the presence of filled pauses (uh, um, and the like), and that words following such filled pauses are recognised more quickly. Three experiments examined whether this is because filled pauses serve to delay the onset of upcoming words and these delays facilitate auditory word recognition, or whether the fillers themselves serve to signal upcoming delays in a way which informs listeners' reactions. Participants viewed pairs of images on a computer screen, and followed recorded instructions to press buttons corresponding to either an easy (unmanipulated, with a high-frequency name) or a difficult (visually blurred, low-frequency) image. In all three experiments, participants were faster to respond to easy images. In 50% of trials in each experiment, the name of the image was directly preceded by a delay; in the remaining trials an equivalent delay was included earlier in the instruction. Participants were quicker to respond when a name was directly preceded by a delay, regardless of whether this delay was filled with a spoken um, was silent, or contained an artificial tone. This effect did not interact with the effect of image difficulty, nor did it change over the course of each experiment. Taken together, our consistent finding that delays of any kind help word recognition indicates that natural delays such as fillers need not be seen as ‘signals’ to explain the benefits they have to listeners' ability to recognise and respond to the words which follow them