The role of drug regulatory authorities and health technology assessment agencies in shaping incentives for antibiotic R&D: a qualitative study.

BACKGROUND: Few antibiotics have entered the market in recent years despite the need for new treatment options. Some of the challenges of bringing new antibiotics to market are linked to the marketing authorization and health technology assessment (HTA) processes. Research shows great variation in geographic availability of new antibiotics, suggesting that market introduction of new antibiotics is unpredictable. We aimed to investigate regulatory authorities' and HTA agencies' role in developing non-financial incentives to stimulate antibiotic research and development (R&D). METHODS: We conducted individual, semi-structured, stakeholder interviews. Participants were recruited from regulatory authorities (EMA and FDA) and HTA agencies in Europe. Participants had to be experienced with assessment of antibiotics. The data were analyzed using a deductive and inductive approach to develop codes and identify key themes. Data were analyzed using thematic analysis including the constant comparison method to define concepts, and rival thinking to identify alternative explanations. RESULTS: We found that (1) interpretation of key concepts guiding the understanding of what type of antibiotics are needed vary (2) lack of a shared approach on how to deal with limited clinical data in the marketing authorization and HTA processes is causing barriers to getting new antibiotics to market (3) necessary adaptations to the marketing authorization process causes uncertainties that transmit to other key stakeholders involved in delivering antibiotics to patients. CONCLUSIONS: A shared understanding of limited clinical data and how to deal with this issue is needed amongst stakeholders involved in antibiotic R&D, marketing authorization, and market introduction to ensure antibiotics reach the market before resistance levels are out of control. Regulatory authorities and HTA agencies could play an active role in aligning the view of what constitutes an unmet medical need, and direct new economic models towards stimulating greater diversity in the antibiotic armamentarium.

A cross-sectional survey to map Clinical Pharmacy Education and Practice in Europe.

Background Clinical activities provided by pharmacists are increasing worldwide, including in Europe. However, an overview of clinical pharmacy education and practice is needed. Aim To map clinical pharmacy (CP) education and practice among European countries. Method A cross-sectional web-based survey led by the Education Committee of the European Society of Clinical Pharmacy (ESCP) was conducted. The survey comprised three domains focusing on: undergraduate education, postgraduate education, and practice. A multi-phased validation process was undertaken, attributing levels of evidence according to the number of information sources for each country. Triangulation was used to seek within country consensus. Main outcome measures included the number of hours of education in CP; existence of a specialization in CP and activities delivered in practice. Results Data from 40 European countries were included (response rate 95.2%). Most respondents (86.8%) agreed with the ESCP definition of CP. Almost every country (94.9%) reported CP topics at the undergraduate level [median number = 65 h/semester (IQR: 2.0-5.6)], including practical teaching [median = 30.0% (IQR: 17.0-42.0)]. At postgraduate level, 92.5% of countries reported PhD programmes including CP and 65.0% mentioned the existence of specific CP master/diploma degrees. Continuous professional development (CPD) courses were also reported by 63.9% of respondents. More than half the countries (52.5%; n = 21) recognized CP as an area of specialization, which for 60.0% of participants was applied solely in the hospital setting. Conclusion Although CP is embedded in education and practice in European countries, there is wide variability in education and practice patterns.

Sex differences in psychotropic and analgesic drug use before and after initiating treatment with acetylcholinesterase inhibitors.

BACKGROUND/AIMS: The aim was to explore the impact of sex on prevalence, patterns and trends in the prescription of psychotropics and analgesics in users of acetylcholinesterase inhibitors (AChEIs), before and after AChEI initiation, compared to the general population. METHODS: A prospective study applying data from the Norwegian Prescription Database (NorPD) in the period 2004-2016. Prescription of antidepressants, antipsychotics, analgesics including opioids, benzodiazepines and z-hypnotics in persistent AChEI users was studied in a follow-up period from four years before to two years after AChEI initiation in men and women of four age groups: 37-64, 65-72, 73-80 and 81-88 years. RESULTS: Use of antidepressants, antipsychotics and weaker analgesics increased in both sexes during the follow-up period in 11.764 persistent AChEI users. Women with pre-dementia and dementia stages of AD showed a prescription pattern with more use of psychotropics and opioids than men, except for antipsychotics. CONCLUSION: Female sex showed to have a significant influence on the prescriptions of psychotropics and analgesics in AD patients in a pre-dementia and dementia stage. The exception is for antipsychotics, that men used more than women. The prescription pattern showed a higher extent of polypharmacy of psychotropics and/or opioids in women than in men. The total prescription pattern of analgesics could indicate an undertreatment of pain in pre-dementia and dementia stages, most pronounced in men.

The effect of generic market entry on antibiotic prescriptions in the United States.

When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)-aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin-and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.

Epidemiology and Antimicrobial Susceptibility of Invasive Bacterial Infections in Children-A Population-Based Study From Norway.

OBJECTIVE: To describe epidemiology and antimicrobial susceptibility testing (AST) data of bacteria causing invasive infections in Norwegian children (0-18 years). METHODS: Population-based observational study using prospectively collected AST data from the Norwegian Surveillance System of Antimicrobial Resistance from 2013 to 2017. We included all clinically relevant bacterial isolates (blood and cerebrospinal fluid), and compared incidence of invasive infections and AST data in isolates from children and adults. RESULTS: We included 1173 isolates from children and 44,561 isolates from adults. Staphylococcus aureus accounted for 220/477 (46.2%, 95% CI: 41.6-50.7) of all isolates in schoolchildren (6-18 years). Compared with Streptococcus pneumonia isolates from adults (N = 2674), we observed higher nonsusceptibility rates to penicillin in isolates from children (N = 151), 11.9% versus 5.8%, P < 0.01; also higher resistance rates to erythromycin (11.3% vs. 4.9%, P < 0.01), clindamycin (9.3% vs. 3.6%, P < 0.001), and trimethoprim/sulfamethoxazole (17.9% vs. 6.4%, P < 0.001). Compared with Escherichia coli isolates in adults (N = 9073), we found lower rates of ESBL in isolates from children (N = 212), 2.4% versus 6.4%, P < 0.05. CONCLUSION: The study indicates the importance of microbiologic surveillance strategies in children and highlights the need for pediatric AST data. The high rates of nonsusceptibility to commonly used antibiotics among S. pneumoniae in children and the high burden of invasive S. aureus infections in schoolchildren calls for modifications of Norwegian guidelines.

Challenges in Antibiotic R&D Calling for a Global Strategy Considering Both Short- and Long-Term Solutions.

A recent analysis of antibiotics approved between 1999 and 2014, conducted by researchers at the Norwegian Institute of Public Health; the University of Oslo; the Center for Disease Dynamics, Economics & Policy (CDDEP); and Boston University, showed a lack of novelty and diversity regarding target pathogens and indications and a failure to address the most urgent resistance threats, including resistant Gram-negative bacteria. A global research and development strategy should incentivize development of broad-spectrum antibiotics for critically ill patients, as well as therapeutic alternatives to antibiotics, decreasing our dependence on traditional, small-molecule antibiotics.

Introduction and geographic availability of new antibiotics approved between 1999 and 2014.

BACKGROUND: Despite the urgent need for new, effective antibiotics, few antibiotics of value have entered the market during the past decades. Therefore, incentives have been developed to stimulate antibiotic R&D. For these incentives to be effective, geographic availability for recently approved antibiotics needs to be better understood. In this study, we analyze geographic availability and market introduction of antibiotics approved between 1999 and 2014. MATERIAL AND METHOD: We identified antibiotics, considered new chemical entities (NCEs) for systemic use approved globally between 1999 and 2014, from national medicine agencies' lists of approved drugs, and data from the WHO Collaborating Center for Drug Statistics. Geographic availability was mapped using sales data from IQVIA, and analyzed with regards to class, indication, safety, and origin. RESULTS: Of the 25 identified NCEs, only 12 had registered sales in more than 10 countries. NCEs with the widest geographic availability had registered sales in more than 70 countries within a ten-year timeframe and 30 countries within a three-year timeframe, spreading across five different geographic regions and three country income classes. Half (52%) of the NCEs had an indication for infections caused by antibiotic- resistant bacteria, little diversity was seen regarding target pathogen and indication. Antibiotics originated from and/or marketed by companies from the US or Europe had greater geographic availability compared to Japanese antibiotics, which seldom reached outside of Asia. For 20 NCEs developers chose to fully or partially sublicense marketing rights to a number of companies of different sizes. CONCLUSION: Our findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization. Sublicensing agreements between multiple companies was common practice. Moreover, differences were seen between countries regarding benefit/risk evaluations and company behavior. These findings could be a potential source of uncertainties, and create barriers to assure that working antibiotics are developed and made available according to public health needs.