Trends in prescription medicine use by older people in New Zealand 2010- 2015: a national population-based study.

BACKGROUND: Research investigating trends in the general prescription medicine use of older people in New Zealand is limited. AIM: To examine trends in the use of outpatient medicines by older adults and assess changing patterns in use from 2010 to 2015. METHODS: A retrospective cohort study including all New Zealand primary care patients over 65 years of age utilising data from the national pharmaceutical claims database. We calculated the prevalence of use within three age groups and by sex in each year by anatomical therapeutic class, therapeutic group and individual medicine. Rate ratios were calculated to compare the prevalence of use in 2010 and 2015. RESULTS: The study included 829,026 patients with a mean of 4.4 years of potential drug exposure. Overall prevalence of medicine use was 92% in 2010 and 93% in 2015. The mean number of prescriptions per patient-year for patients >=85 years of age (39.2) was almost double that of patients 65-74 years (21.8). Prevalence of use was similar between females (94%) and males (92%). Antibacterials, analgesics, cardiovascular drugs and proton pump inhibitors were the most widely used medicines. The use of systemic antibiotics increased by 2% between 2010 and 2015, but there were significant decreases in use of antithrombotics (6%), beta blockers (6%), diuretics (19%), nitrates (19%) and antiarrhythmics (24%). CONCLUSION: Our findings indicate both positive changes in response to guidance on safe and appropriate medicine use and several areas of concern. Continued monitoring of changing patterns in the medicine use of older people will be important, particularly with regard to the use of combinations of medicines that increase their risk of adverse events.

Medicinal products for geriatric patients in Germany : Current status of regulatory requirements and clinical reality.

BACKGROUND: Geriatric patients are the main users of medicinal products, although this patient group is most commonly excluded from clinical trials. Several guidelines from the International Conference on Harmonisation (ICH) and the European Medicines Agency (EMA) have tried to ensure the development and the safe use of medicines for geriatric patients. OBJECTIVE: This article aims to evaluate geriatric information provided by the summary of product characteristics (SmPC) to prescribers using relevant medicinal products in Germany for patients older than 65 years. MATERIAL AND METHODS: Based on the annually published drug prescription report (Arzneiverordnungsreport), medication which was prescribed mainly (above 80%) or at a high defined daily dose (DDD [doses per day] > 400) to patients older than 65 years in 2016 was reviewed regarding relevant geriatric information. RESULTS: The average compliance for the investigated drugs regarding geriatric information according to EMA guidelines is 27%. At least older patients are mentioned in the SmPC most frequently (68%). Information about doses or dose adjustments for patients with certain stages of frailty was not provided by the pharmaceutical companies. CONCLUSION: Current information in the SmPC for a safe and effective use of medicines for older patients is insufficient and does not conform to EMA guidelines. Compared to drug authorization in pediatrics where the industry is obliged to submit a special pediatric investigation plan (PIP) to cover the needs of this certain patient group, a mandatory geriatric investigation plan (GIP) similar to the PIP would be an appropriate measure to provide safe and effective medicines for older patients.

[Expectations of an Academic Detailer from a Pharmaceutical Industry Perspective].

In the pharmaceutical industry, a Medical Affairs ("MA") professional collects, organizes and transmits information about a health care product based on the judgment of science, medicine and ethical values, thereby optimizing the product's value, improving corporate value, and assuring quality medical care. The role of the MA is to construct a "medical strategy" through the process of collecting, analyzing and evaluating information. On the other hand, Academic Detailing is "a new approach to drug information that actively disseminates drug comparison information from a pharmacological viewpoint, linking the drug's foundation to clinical practice." Cooperation between Academic Detailing and a pharmaceutical company's MA will be an essential relationship in realizing advanced prescribing proposals in the future, with the ultimate goal of optimal medication regimes for patients.

Gender differences in utilization of services and tobacco cessation outcomes at a state quitline.

Research suggests that women may have poorer tobacco cessation outcomes than men; however, the literature is somewhat mixed. Less is known about gender differences in cessation within quitline settings. This study examined gender differences in the utilization of services (i.e., coaching sessions, pharmacotherapy) and tobacco cessation among callers to the Arizona Smokers' Helpline (ASHLine). The study sample included callers enrolled in ASHLine between January 2011 and June 2016. We tracked number of completed coaching sessions. At the 7-month follow-up, callers retrospectively reported use of cessation pharmacotherapy (gum, patch, or lozenge), as well as current tobacco use. Associations between gender and tobacco cessation were tested using logistic regression models. At month 7, 36.4% of women (3,277/9,004) and 40.3% of men (2,960/7,341) self-reported 30-day point prevalence abstinence. Compared to men, fewer women reported using pharmacotherapy (women: 71.4% vs. men: 73.6%, p = .01) and completed at least five coaching sessions (women: 35.1% vs. men: 38.5%, p < .01). After adjusting for baseline characteristics, women had significantly lower odds of reporting tobacco cessation than men (OR = 0.91, 95% CI: 0.84 to 0.99). However, after further adjustment for use of pharmacotherapy and coaching, there was no longer a significant relationship between gender and tobacco cessation (OR: 0.96, 95% CI: 0.87 to 1.06). Fewer women than men reported tobacco cessation. Women also had lower utilization of quitline cessation services. Although the magnitude of these differences were small, future research on improving the utilization of quitline services among women may be worth pursuing given the large-scale effects of tobacco.

Predicting ICU readmission using grouped physiological and medication trends.

BACKGROUND: Patients who are readmitted to an intensive care unit (ICU) usually have a high risk of mortality and an increased length of stay. ICU readmission risk prediction may help physicians to re-evaluate the patient's physical conditions before patients are discharged and avoid preventable readmissions. ICU readmission prediction models are often built based on physiological variables. Intuitively, snapshot measurements, especially the last measurements, are effective predictors that are widely used by researchers. However, methods that only use snapshot measurements neglect predictive information contained in the trends of physiological and medication variables. Mean, maximum or minimum values take multiple time points into account and capture their summary statistics, however, these statistics are not able to catch the detailed picture of temporal trends. In this study, we find strong predictors with ability of capturing detailed temporal trends of variables for 30-day readmission risk and build prediction models with high accuracy. METHODS: We study physiological measurements and medications from the Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) clinical dataset. Time series of each variable are converted into trend graphs with nodes being discretized measurements of each variable. Then we extract important temporal trends by applying frequent subgraph mining on the trend graphs. The frequency of a subgraph is a good cue to find important temporal trends since similar patients often share similar trends regarding their pathophysiological evolution under medical interventions. Important temporal trends are then grouped automatically by non-negative matrix factorization. The grouped trends could be considered as an approximate representation of patients' pathophysiological states and medication profiles. We train a logistic regression model to predict 30-day ICU readmission risk based on snapshot measurements, grouped physiological trends and medication trends. RESULTS: Our dataset consists of 1170 patients who are alive 30 days after discharge from ICU and have at least 12 h of data. In the dataset, 860 patients were not readmitted and 310 were readmitted, within 30 days after discharge. Our model outperforms all comparison models, and shows an improvement in the area under the receiver operating characteristic curve (AUC) of almost 4% from the best comparison model. CONCLUSIONS: Grouped physiological and medication trends carry predictive information for ICU readmission risk. In order to build predictive models with higher accuracy, we should add grouped physiological and medication trends as complementary features to snapshot measurements.

Large differences in neonatal drug use between NICUs are common practice: time for consensus?

AIMS: Evidence for drug use in newborns is sparse, which may cause large differences in drug prescriptions. We aimed to investigate the differences between neonatal intensive care units (NICUs) in the Netherlands in currently prescribed drugs. METHODS: This multicentre study included neonates admitted during 12 months to four different NICUs. Drugs were classified in accordance with the Anatomical Therapeutic Chemical (ATC) classification system and assessed for on/off-label status in relation to neonatal age. The treatment protocols for four common indications for drug use were compared: pain, intubation, convulsions and hypotension. RESULTS: A total of 1491 neonates (GA range 23+6 -42+2 weeks) were included with a total of 32 182 patient days, 181 different drugs and 10 895 prescriptions of which 23% was off-label in relation to neonatal age. Overall, anti-infective drugs were most frequently used with a total of 3161 prescriptions, of which 4% was off-label in relation to neonatal age. Nervous system drugs included 2500 prescriptions of which 31% was off-label in relation to neonatal age. Nervous system drugs, blood and blood forming organs, and cardiovascular drugs showed the largest differences between NICUs with ranges of 919-2278, 554-1465, and 238-952 total prescriptions per 1000 patients per ATC class, respectively. CONCLUSIONS: We showed that drug use varies widely in neonatal clinical practice. The drug classes with the highest proportion of off-label drugs in relation to neonatal age showed the largest differences between NICUs, i.e. cardiovascular and nervous system drugs. Drug research in neonates should receive high priority to guarantee safe and appropriate medicines and optimal treatment.

Benzodiazepine and Z-drug prescribing in Ireland: analysis of national prescribing trends from 2005 to 2015.

AIMS: The aim of this study was to examine prescribing trends for benzodiazepines and Z-drugs to General Medical Services (GMS) patients in Ireland. METHODS: A repeated cross-sectional analysis of the national pharmacy claims database was conducted for GMS patients aged ≥16 years from 2005 to 2015. Prescribing rates per 1000 eligible GMS population were calculated with 95% confidence intervals (CIs). Negative binomial regression was used to determine longitudinal trends and compare prescribing rates across years, gender and age groups. Duration of supply and rates of concomitant benzodiazepine and Z-drug prescribing were determined. Age (16-44, 45-64, ≥65 years) and gender trends were investigated. RESULTS: Benzodiazepine prescribing rates decreased significantly from 225.92/1000 population (95% CI 224.94-226.89) in 2005 to 166.07/1000 population (95% CI 165.38-166.75) in 2015 (P < 0.0001). Z-drug prescribing rates increased significantly from 95.36/1000 population (95% CI 94.73-96.00) in 2005 to 109.11/1000 population (95% CI 108.56-109.67) in 2015 (P = 0.048). Approximately one-third of individuals dispensed either benzodiazepines or Z-drugs were receiving long-term prescriptions (>90 days). The proportion of those receiving >1 benzodiazepine and/or Z-drug concomitantly increased from 11.9% in 2005 to 15.3% in 2015. Benzodiazepine and Z-drug prescribing rates were highest for older women (≥65 years) throughout the study period. CONCLUSIONS: Benzodiazepine prescribing to the GMS population in Ireland decreased significantly from 2005 to 2015, and was coupled with significant increases in Z-drug prescribing. The study shows that benzodiazepine and Z-drug prescribing is common in this population, with high proportions of individuals receiving long-term prescriptions. Targeted interventions are needed to reduce potentially inappropriate long-term prescribing and use of these medications in Ireland.

Medication usage change in older people (65+) in England over 20 years: findings from CFAS I and CFAS II.

Background: medical practice has changed over the last decades reflecting the ageing population, when multi-morbidity requiring multiple medications is more common. Objective: describe and quantify self-reported medicine use including both prescription and over the counter medicines in two comparable population-based studies of older people (65+) in England and to assess the nature and scale of polypharmacy. Methods: data used were from two separate population-based studies; the Cognitive Function Ageing Study I and II. Descriptive analyses were performed to summarise and quantify general medicine use. Negative binomial regression models were fitted to determine factors associated with the number of medicines used. Results: medication use, including both prescribed medicines and over the counter products has increased dramatically over the last 2 decades. The number of people taking five or more items quadrupled from 12 to 49%, while the proportion of people who did not take any medication has decreased from around 1 in 5 to 1 in 13. Cardiovascular drugs were the most frequently taken medication. Polypharmacy is associated with increases in the number of diagnosed long-term conditions. Conclusions: comparison between CFAS I and II reveals marked increases in medication usage and polypharmacy in the older population. The influence of healthcare organisation, introduction of new guidelines and technology changes leading to diagnosis of earlier, milder chronic diseases and treatment may be contributing to this changing pattern. Further research is needed to develop practical solutions to optimise medication management in older people, reducing the harming associated with medication.

WHO standards for biotherapeutics, including biosimilars: an example of the evaluation of complex biological products.

The most advanced regulatory processes for complex biological products have been put in place in many countries to provide appropriate regulatory oversight of biotherapeutic products in general, and similar biotherapeutics in particular. This process is still ongoing and requires regular updates to national regulatory requirements in line with scientific developments and up-to-date standards. For this purpose, strong knowledge of and expertise in evaluating biotherapeutics in general and similar biotherapeutic products, also called biosimilars, in particular is essential. Here, we discuss the World Health Organization's international standard-setting role in the regulatory evaluation of recombinant DNA-derived biotherapeutic products, including biosimilars, and provide examples that may serve as models for moving forward with nonbiological complex medicinal products. A number of scientific challenges and regulatory considerations imposed by the advent of biosimilars are described, together with the lessons learned, to stimulate future discussions on this topic. In addition, the experiences of facilitating the implementation of guiding principles for evaluation of similar biotherapeutic products into regulatory and manufacturers' practices in various countries over the past 10 years are briefly explained, with the aim of promoting further developments and regulatory convergence of complex biological and nonbiological products.

Do Paediatric Investigation Plans (PIPs) Advance Paediatric Healthcare?

Since 2007, new drugs need a paediatric investigation plan (PIP) for EU registration. The PIPs' justifications can be traced back to concerns expressed by Shirkey that label warnings against paediatric use made children "therapeutic orphans", and the American Academy of Pediatrics' claim that all children differ considerably from adults. US legislation first encouraged, then also required, separate, adult-style safety and efficacy studies in all paediatric subpopulations. This triggered paediatric regulatory studies by the pharmaceutical industry. There were also negative outcomes, as a result of using the legal definition of childhood as a medical/physiological term. The "therapeutic orphans" concept became dogma that supported/expanded adult-style regulatory testing into all age groups even when poorly justified in adolescents or where other methods are available to generate needed data. PIPs are especially problematic because they lack the limitations imposed on the Food and Drug Administration's (FDA's) regulatory actions and more practical approaches used in the USA. Many PIP studies are medically senseless or even questionable and/or unfeasible with poor risk/benefit ratios. For example, physiologically mature adolescents have been exposed to treatments and doses known to be suboptimal in adults. Unfeasible PIP studies in rare diseases may harm patients by preventing their participation in more beneficence-driven studies. PIP-required studies can prevent effective treatment of allergic rhinitis during years of placebo treatment, exposing minors to the risk of disease progression to asthma. The PIP system should be revised; more should be done by key players, including institutional review boards/ethics committees, to ensure that all paediatric clinical studies are medically justified, rather than legislation driven, and can produce scientifically valid results.

Medicine and the future of health: reflecting on the past to forge ahead.

The development of new therapies has a rich history, evolves quickly with societal trends, and will have an exciting future. The last century has seen an exponential increase in complex interactions between medical practitioners, pharmaceutical companies, governments and patients. We believe technology and societal expectations will open up the opportunity for more individuals to participate as information becomes more freely available and inequality less acceptable. Corporations must recognize that usual market forces do not function ideally in a setting where health is regarded as a human right, and as modern consumers, patients will increasingly take control of their own data, wellbeing, and even the means of production for developing their own treatments. Ethics and legislation will increasingly impact the processes that facilitate drug development, distribution and administration. This article collection is a cross-journal collaboration, between the Journal of Pharmaceutical Policy and Practice (JoPPP) and BMC Medicine that seeks to cover recent advances in drug development, medicines use, policy and access with high clinical and public health relevance in the future.The Medicine and the Future of Health article collection is a joint collection between BMC Medicine and Journal of Pharmaceutical Policy and Practice. Therefore, this Editorial by the guest editors has been published in both journals.

Forecasting US ivacaftor outcomes and cost in cystic fibrosis patients with the G551D mutation.

Ivacaftor, a breakthrough treatment for cystic fibrosis (CF) patients with the G551D genetic mutation, lacks long-term clinical and cost projections. This study forecasted outcomes and cost by comparing ivacaftor plus usual care versus usual care alone.A lifetime Markov model was conducted from a US payer perspective. The model consisted of five health states: 1) forced expiratory volume in 1 s (FEV1) % pred ≥70%, 2) 40%≤ FEV1 % pred <70%, 3) FEV1 % pred <40%, 4) lung transplantation and 5) death. All inputs were extracted from published literature. Budget impact was also estimated. We estimated ivacaftor's improvement in outcomes compared with a non-CF referent population.Ivacaftor was associated with 18.25 (95% credible interval (CrI) 13.71-22.20) additional life-years and 15.03 (95% CrI 11.13-18.73) additional quality-adjusted life-years (QALYs). Ivacaftor was associated with improvements in survival and QALYs equivalent to 68% and 56%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $3 374 584. The budget impact was $0.087 per member per month.Ivacaftor increased life-years and QALYs in CF patients with the G551D mutation, and moved morbidity and mortality closer to that of their non-CF peers. Ivacaftor costs much more than usual care, but comes at a relatively limited budget impact.

Trends in end-of-life cancer care in the Medicare program.

OBJECTIVES: To examine contemporary trends in end-of-life cancer care and geographic variation of end-of-life care aggressiveness among Medicare beneficiaries. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare data, we identified 132,051 beneficiaries who died as a result of cancer in 2006-2011. Aggressiveness of end-of-life care was measured by chemotherapy received within 14 days of death, >1 emergency department (ED) visit within 30 days of death, >1 hospitalization within 30 days of death, ≥1 intensive care unit (ICU) admission within 30 days of death, in-hospital death, or hospice enrollment ≤3 days before death. Using hierarchical generalized linear models, we assessed potentially aggressive end-of-life care adjusting for patient demographics, tumor characteristics, and hospital referral region (HRR)-level market factors. RESULTS: The proportion of beneficiaries receiving at least one potentially aggressive end-of-life intervention increased from 48.6% in 2006 to 50.5% in 2011 (P<.001). From 2006 to 2011, increases were apparent in repeated hospitalization (14.1% vs. 14.8%; P=.01), repeated ED visits (34.3% vs. 36.6%; P<.001), ICU admissions (16.2% vs. 21.3%; P<.001), and late hospice enrollment (11.2% vs. 12.9%; P<.001), whereas in-hospital death declined (23.5% vs. 20.9%; P<.001). End-of-life chemotherapy use (4.4% vs. 4.5%) did not change significantly over time (P=.12). The use of potentially aggressive end-of-life care varied substantially across HRRs, ranging from 40.3% to 58.3%. Few HRRs had a decrease in aggressive end-of-life care during the study period. CONCLUSIONS: Despite growing focus on providing appropriate end-of-life care, there has not been an improvement in aggressive end-of-life cancer care in the Medicare program.

Pharmacotherapy for Neurodegenerative Diseases: Are We Approaching the Tipping Point?

Neurodegenerative diseases continue to represent major unmet medical and public health needs and will increasingly strain the healthcare system as people live longer due to medical advances in other diseases. Hopefully the emergence of increased understanding of the biology of these conditions coupled with novel clinical pharmacology tools, clinical trial designs, and regulatory innovation will allow the emergence of highly effective symptomatic and disease modifying pharmacotherapies.