What is the impact of intellectual property rules on access to medicines? A systematic review

BACKGROUND: It is widely accepted that intellectual property legal requirements such as patents and data exclusivity can affect access to medicines, but to date there has not been a comprehensive review of the empirical evidence on this topic. The World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires Member States to implement minimum standards of intellectual property protection including patents for pharmaceutical products, but also contains ‘flexibilities’ designed to address barriers to access to medicines. National intellectual property laws can also include TRIPS-plus rules that go beyond what is required by TRIPS. We aimed to systematically review literature that measures the impact of intellectual property rules on access to medicines, whether implemented as a result of TRIPS, TRIPS-plus provisions in other trade agreements, or unilateral policy decisions. METHODS: We searched Proquest, SCOPUS, Web of Science, PubMed, JSTOR, Westlaw and Lexis Nexis. Peer reviewed articles, government reports and other grey literature were included. Articles were eligible for inclusion if they were quantitative, in English, included a measure of cost, price, availability of or access to medicines, were about intellectual property or data exclusivity rules and published between January 1995 and October 2020. Ninety-one studies met our inclusion criteria. We systematically reviewed the studies’ findings and evaluated their quality using a modified quality assessment template. RESULTS AND CONCLUSION: Five broad overarching themes and 11 subthemes were identified based on the articles’ foci. They were: trade agreements (divided into EU FTAs and those that include the USA); use of TRIPS flexibilities (divided into compulsory licencing and parallel importation); patent expiry/generic entry/generic pathway (divided into comparative studies and single country studies); patent policies (also divided into comparative studies and single country studies) and TRIPS-plus rules (divided into data exclusivity, patent term extensions and secondary patenting). Most studies focused not on specific trade agreements, but on TRIPS-plus provisions, which can also be found within some trade agreements. The main finding of this review is that the stronger pharmaceutical monopolies created by TRIPs-plus intellectual property rules are generally associated with increased drug prices, delayed availability and increased costs to consumers and governments. There is evidence that TRIPS flexibilities can facilitate access to medicines although their use is limited to date. There were few studies that included resource poor settings, signalling a need for greater research in such settings where the impact on access to medicines is likely to be more damaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12992-022-00826-4

Translational strategies in drug development for knee osteoarthritis.

Osteoarthritis (OA) is a common disease worldwide with large unmet medical needs. To bring innovative treatments to OA patients, we at Merck have implemented a comprehensive strategy for drug candidate evaluation. We have a clear framework for decision-making in our preclinical pipeline, to design our clinical proof-of-concept trials for OA patients. We have qualified our strategy to define and refine dose and dosing regimen, for treatments administered either systemically or intra-articularly (IA). We do this through preclinical in vitro and in vivo studies, and by back-translating results from clinical studies in OA patients

Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats

ABSTRACT Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration of isavuconazole in rats following single and repeated oral-dose administration of radiolabeled isavuconazonium sulfate, the prodrug of isavuconazole. Following a single-dose administration of radiolabeled isavuconazonium sulfate (labeled on the active moiety), radioactivity was detectable within 1 h postdose in 56 of 65 tissue/fluid specimens. The highest maximum concentrations ( C max ) were observed in bile and liver (66.6 and 24.7 μg eq/g, respectively). The lowest C max values were in bone and eye lens (0.070 and 0.077 μg eq/g, respectively). By 144 h postdose, radioactivity was undetectable in all tissues/fluids except liver (undetectable at 336 h) and adrenal gland tissues (undetectable at 672 h). Following daily administration for up to 21 days, 1-h-postdose C max values were the highest on or before day 14 in all except seven tissues/fluids, of which only rectum mucosa and small intestine mucosa had C max values &gt;25% higher than all other 1-h-postdose values. For 24-h-postdose C max values, only large intestine, large intestine mucosa, and urine had the highest C max values at day 21. The penetration of single oral doses of unlabeled isavuconazole (25 mg/kg of body weight isavuconazonium sulfate) and voriconazole (50 mg/kg) into rat brain (assessed using liquid chromatography-tandem mass spectrometry) was also compared. Brain concentration/plasma concentration ratios reached approximately 1.8:1 and 2:1, respectively. These data suggest that isavuconazole penetrates most tissues rapidly, reaches a steady state in most or all tissues/fluids within 14 days, does not accumulate in tissues/fluids over time, and achieves potentially efficacious concentrations in the brain. </jats:p

Attitudes towards the use and acceptance of eHealth technologies : a case study of older adults living with chronic pain and implications for rural healthcare

Acknowledgements The research described here is supported by the award made by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. MC’s time writing the paper is funded by the Scottish Government’s Rural and Environmental Science and Analytical Services Division (RESAS) under Theme 8 ‘Vibrant Rural Communities’ of the Food, Land and People Programme (2011–2016). MC is also an Honorary Research Fellow at the Division of Applied Health Sciences, University of Aberdeen. The input of other members of the TOPS research team, Alastair Mort, Fiona Williams, Sophie Corbett, Phil Wilson and Paul MacNamee who contributed to be wider study and discussed preliminary findings reported here with the authors of the paper is acknowledged. We acknowledge the feedback on earlier versions of this paper provided by members of the Trans-Atlantic Rural Research Network, especially Stefanie Doebler and Carmen Hubbard. We also thank Deb Roberts for her comments.Peer reviewedPublisher PD

Review of Nuclear Physics Experiments for Space Radiation

Human space flight requires protecting astronauts from the harmful effects of space radiation. The availability of measured nuclear cross section data needed for these studies is reviewed in the present paper. The energy range of interest for radiation protection is approximately 100 MeV/n to 10 GeV/n. The majority of data are for projectile fragmentation partial and total cross sections, including both charge changing and isotopic cross sections. The cross section data are organized into categories which include charge changing, elemental, isotopic for total, single and double differential with respect to momentum, energy and angle. Gaps in the data relevant to space radiation protection are discussed and recommendations for future experiments are made

An evaluation of the psychometric properties of the Indicator of Relative Need (IoRN) instrument

BACKGROUND: The Indicator of Relative Need (IoRN) instrument is designed for both health and social care services to measure function and dependency in older people. To date, the tool has not undergone assessment of validity. We report two studies aimed to evaluate psychometric properties of the IoRN. METHODS: The first study recruited patients receiving social care at discharge from hospital, those rehabilitating in intermediate care, and those in a rehabilitation at home service. Participants were assessed using the IoRN by a single researcher and by the clinical team at baseline and 8 weeks. Comparator instruments (Barthel ADL, Nottingham Extended ADL and Townsend Disability Scale) were also administered. Overall change in ability was assessed with a 7 point Likert scale at 8 weeks. The second study analysed linked routinely collected, health and social care data (including IoRN scores) to assess the relationship between IoRN category and death, hospitalisation and care home admission as a test of external validity. RESULTS: Ninety participants were included in the first study, mean age 77.9 (SD 12.0). Cronbach’s alpha for IoRN subscales was high (0.87 to 0.93); subscales showed moderate correlation with comparator tools (r = 0.43 to 0.63). Cohen’s weighted kappa showed moderate agreement between researcher and clinician IoRN category (0.49 to 0.53). Two-way intraclass correlation coefficients for IoRN subscales in participants reporting no change in ability were high (0.88 to 0.98) suggesting good stability; responsiveness coefficients in participants reporting overall change were equal to or better than comparator tools. 1712 patients were included in the second study, mean age 81.0 years (SD 7.7). Adjusted hazard ratios for death, care home admission and hospitalisation in the most dependent category compared to the least dependent IoRN category were 5.9 (95 % CI 2.0–17.0); 7.2 (95 % CI 4.4–12.0); 1.1 (95 % CI 0.5–2.6) respectively. The mean number of allocated hours of care 6 months after assessment was higher in the most dependent group compared to the least dependent group (5.6 vs 1.4 h, p = 0.005). CONCLUSIONS: Findings from these analyses support the use of the IoRN across a range of clinical environments although some limitations are highlighted

The TEMPO Survey I: Predicting Yields of the Transiting Exosatellites, Moons, and Planets from a 30-day Survey of Orion with the Nancy Grace Roman Space Telescope

We present design considerations for the Transiting Exosatellites, Moons, and Planets in Orion (TEMPO) Survey with the Nancy Grace Roman Space Telescope. This proposed 30-day survey is designed to detect a population of transiting extrasolar satellites, moons, and planets in the Orion Nebula Cluster (ONC). The young (1-3 Myr), densely-populated ONC harbors about a thousand bright brown dwarfs (BDs) and free-floating planetary-mass objects (FFPs). TEMPO offers sufficient photometric precision to monitor FFPs with ${\rm M}\geq1{\rm M}_{\rm J}$ for transiting satellites. The survey is also capable of detecting FFPs down to sub-Saturn masses via direct imaging, although follow-up confirmation will be challenging. TEMPO yield estimates include 14 (3-22) exomoons/satellites transiting FFPs and 54 (8-100) satellites transiting BDs. Of this population, approximately $50\%$ of companions would be "super-Titans" (Titan to Earth mass). Yield estimates also include approximately $150$ exoplanets transiting young Orion stars, of which $>50\%$ will orbit mid-to-late M dwarfs and approximately ten will be proto-habitable zone, terrestrial ($0.1{\rm M}_{\oplus} - 5{\rm M}_{\oplus}$) exoplanets. TEMPO would provide the first census demographics of small exosatellites orbiting FFPs and BDs, while simultaneously offering insights into exoplanet evolution at the earliest stages. This detected exosatellite population is likely to be markedly different from the current census of exoplanets with similar masses (e.g., Earth-mass exosatellites that still possess H/He envelopes). Although our yield estimates are highly uncertain, as there are no known exoplanets or exomoons analogous to these satellites, the TEMPO survey would test the prevailing theories of exosatellite formation and evolution, which limit the certainty surrounding detection yields.Comment: Submitted to PAS

Understanding implementation of maternal acute illness management education by measuring capability, opportunity and motivation : a mixed methods study in a low-income country

A major cause of maternal death in low-income countries is a lack of adequate healthcare. The dominant approach to improving care involves continuing professional development but little is known about their impact on practice. Less still is known about the determinants of practice change and barriers to implementation. This study investigated the implementation of an acute illness management course on Ugandan health professionals’ practice and determinants of practice change. Before and after training, 51 nurses, midwives, doctors and clinical officers completed tests of knowledge. Immediately post-course and 1-month later, participants completed questions assessing intention to change practice, practice and determinants of change. Post course, participants took part in focus groups. Post-course, participants reported that they were capable and were motivated to use their knowledge and skills in practice and a lower belief in opportunity to change practice. Behavioural intention was very high and behaviour 1 month later was statistically significantly lower. Three themes emerged: 1) systematic approach changing clinical practice, 2) inter-professional communication, and 3) barriers and facilitators to implementation. Educators should consider behaviour change determinants as important assessments of outcome because they provide crucial implementation of training into practice

A scoping review of antimicrobial resistance in the Australian dairy cattle industry

INTRODUCTION: Quantification of antimicrobial resistance (AMR) is beneficial to inform policies and direct prudent antimicrobial use. AIM: This study aimed to assess the current published evidence of AMR from passive and active ad hoc surveillance activities within the Australian dairy cattle industry. METHODS: Following a scoping review framework 373 articles published before January 2023 were retrieved using the keyword search function from two online databases (PubMed® and Web of Science™ Core Collection). The duplicate articles were removed and the title, abstract, and full text of the remaining articles were reviewed following the study objectives and inclusion criteria (location, subject/theme, and data). Data from the remaining articles were extracted, summarised, interpreted and the study quality assessed using the Grades of Recommendations, Assessment, Development, and Evaluation guidelines. RESULTS: A total of 29 articles dating from the 1960 s until 2022 were identified to meet the study criteria (passive: n = 15; active: n = 14). Study characteristics such as sampling type, sampling method, and AMR assessment were all common characteristics from both passive and active surveillance articles, being milk samples, individual sampling, and phenotypic assessment respectively. Passive surveillance articles had a wider range in both the type of bacteria and the number of antimicrobials investigated, while active surveillance articles included a higher number of bacterial isolates and sampling from healthy populations. There was an overall low level of clinical AMR across all articles. Higher prevalence of non-wildtype Escherichia coli, Salmonella spp., and Staphylococcus spp., although limited in data, was suggested for commonly used Australian veterinary antimicrobials for these bacteria. The prevalence of phenotypic AMR varied due to the health and age status of the sampled animals. The articles reviewed in this study suggest the prevalence of AMR genes was higher for commonly used antimicrobials, although genes were not always related to the phenotypic AMR profile. CONCLUSIONS: Published evidence of AMR in the Australian dairy cattle industry is limited as demonstrated by only 29 articles included in this review following selection criteria screening. However, collectively these articles provide insight on industry AMR prevalence. For example, the suggestion of non-wildtype bacteria within the Australian dairy cattle indicating a risk of emerging or increasing industry AMR. Therefore, further surveillance is required to monitor the development of future AMR risk within the industry. Additionally, evidence suggesting that animals varying in health and age differ in prevalence of AMR imply a requirement for further research into animal population demographics to reduce potential bias in data collated in both national and global surveillance activities

Why less may be more: a mixed methods study of the work and relatedness of 'weak ties' in supporting long-term condition self-management

Background: The distribution of the roles and responsibilities of long-term condition management (LTCM) outside of formal health services implicates a wide set of relationships and activities of involvement. Yet, compared to studies of professional implementation, patient systems of implementation remain under-investigated. The aim of this paper is to explore the work, meaning and function attributed to ‘weaker’ ties relative to other more bonding relationships in order to identify the place of these within a context of systems of support for long-term conditions. Methods: This is a mixed methods survey with nested qualitative study. A total of 300 people from deprived areas in the North West of England with chronic illnesses took part in a survey conducted in 2010 to 2011. A concentric circles diagram was used as a research tool with which participants identified 2,544 network members who contributed to illness management. Notions of ‘work’ were used to describe activities associated with chronic illness and to identify how weaker ties are included and perceived to be involved through social network members (SNM) contributions. Results: The results provide an articulation of how SNMs are substantially involved in weak tie illness management. Weaker ties constituted 16.1% of network membership involved in illness work. The amount of work undertaken was similar but less than that of stronger ties. Weaker ties appeared more durable and less liable to loss over time than stronger ties. The qualitative accounts suggested that weak ties enabled the moral positioning of the self-managing ‘self’ and acted on the basis of a strong sense of reciprocity. Conclusions: Weak ties act as an acceptable bridge between a sense of personal agency and control and the need for external support because it is possible to construct a sense of moral acceptability through reciprocal exchange. Access to weak tie resources needs to be taken into account when considering the ways in which systems of health implementation for chronic illness are designed and delivered