Boosting pharmaceutical innovation in the post-trips era; the real life lessons for developing world.

PhDThe process of globalization and the emergence of a rules-based multilateral trading system pose significant challenges to local pharmaceutical industries in developing countries. With the advent of global patent protection for pharmaceuticals, developing countries are facing a significant dilemma. It is necessary for these countries to comply with international intellectual property standards while simultaneously protecting their local industries and, thus, ensuring an affordable supply of drugs. A better understanding of the nature of the Agreement on Trade Related Aspects of Intellectual Property (TRIPS Agreement) and its components could help to raise awareness of the need for a comprehensive innovation policy. It is widely accepted that intellectual property rights (IPRs) are economic assets. Furthermore, they are necessary to develop world-class standards of innovation and creativity. Nevertheless, this thesis argues that innovation is not driven by the presence of strong IPRs alone; it has many other components going far beyond the IPRs regime. Nonetheless, designing policies for the promotion of R&D and the building up of innovation capacities in developing countries requires a wellconstructed patent regime. However, it also requires the implementation of broadbased science, technology and innovation policy initiatives aimed at promoting and facilitating capacity building for the enhanced absorption of new technologies. To this end, this thesis investigates the concept of innovation and illustrates the crucial role that patent strategies play within processes of pharmaceutical innovation. Drawing on extensive country and company case studies, the thesis identifies the key issues relevant to the revival of local pharmaceutical industries. Based on an understanding of the post-TRIPS environment and case studies of national innovation strategies, this thesis specifically addresses the following question - to what extent can lessons from national experiences be transferred to current policy developments for innovation in the pharmaceutical industry in a developing country context? 4 The research findings aim to contribute significantly to the body of knowledge in relation to new developmental policies. Overall, it is hoped that these findings can promote innovation and ensure the sustainability of the local pharmaceutical industry in the developing world.Centre for Commercial Law Studies Queen Mary University of London Cental Reseach Fund British council Swedish Institut

The Trans Pacific Partnership Agreement, intellectual property and medicines: Differential outcomes for developed and developing countries

The final text of the Trans Pacific Partnership Agreement (TPP), agreed between the 12 negotiating countries in 2016, included a suite of intellectual property provisions intended to expand and extend pharmaceutical company exclusivities on medicines. It drew wide criticism for including such provisions in an agreement that involved developing countries (Vietnam, Peru, Malaysia, Mexico, Chile and Brunei Darussalam) because of the effect on delaying the introduction of low-cost generics. While developing nations negotiated transition periods for implementing some obligations, all parties would have eventually been expected to meet the same standards had the TPP come into force. While the TPP has stalled following US withdrawal, there are moves by some of the remaining countries to reinvigorate the agreement without the United States. The proponents may seek to retain as much as possible of the original text in the hope that the United States will re-join the accord in future. This article presents a comparative analysis of the impact the final 2016 TPP intellectual property chapter could be expected to have (if implemented in its current form) on the intellectual property laws and regulatory regimes for medicines in the TPP countries. Drawing on the published literature, it traces the likely impact on access to medicines. It focuses particularly on the differential impact on regulatory frameworks for developed and developing nations (in terms of whether or not legislative action would have been required to implement the agreement). The article also explores the political and economic dynamics that contributed to these differential outcomes

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

Computed tomography as a predictor of the extent of the disease and surgical outcomes in ovarian cancer

Objectives: The aim of the present study is to determine the predictive value of Computed Tomography (CT), alone or in combination with serum CA-125 levels, for preoperative staging, detection of the extent of the disease, and surgical complications in patients with ovarian carcinoma. Material and methods: One hundred and fourteen patients diagnosed with ovarian carcinoma following an exploratory laparotomy with a preoperative CT scan, performed between January 2007 and June 2013, were enrolled in the study. Preoperative CT and intraoperative surgical findings were compared using 14 parameters and predictions of CT for gas­trointestinal, genitourinary, and cardiovascular complications. All radiological features and clinical characteristics were analyzed statistically. Results: CT and surgical findings correlated (sensitivity/ specificity) as follows: uterine and tubal spread (66%/89%), cervical involvement (100%/80%), peritoneal nodulesincreased density-carcinomatosis (57%/93%), omental involvement (68%/95%), retroperitoneal involvement (25%/84%), ascites (85%/87%), perirectal and perivesical fat plan obliteration (43%/94%), liver metastasis (50%/91%), small and large bowel involvement (47%/95%), adnexal mass (94%/70%), and other metastases (47%/86%). Also, CT findings were found to be statistically insignificant for prediction of mesenteric involvement, bladder metastasis, and diaphragmatic involvement. The overall CT sensitivity and specificity at detecting intraoperative findings was 91% and 71%, respectively. We found a statistically significant correlation between intestinal involvement on CT and the necessity of additional surgical procedures. Conclusions: CT is a widely used imaging method in the preoperative evaluation of ovarian cancer. However, its predictive value, sensitivity and specificity differ, depending on the anatomical region

The association between coronary flow rate and impaired heart rate recovery in patients with metabolic syndrome: A preliminary report

Background: The aim of this study is to evaluate heart rate recovery (HRR) and association between coronary flow rate and HRR in patients with metabolic syndrome (MS) who had morphologically normal coronary angiogram.Methods: Study population included 43 patients with MS and 37 control subjects without MS. All patients were selected from individuals who had recently undergone coronary angiography in our hospital and were diagnosed as having angiographically normal coronary arteries. Exercise stress test results obtained prior to coronary angiography were evaluated for calculating HRR and other parameters. In addition, coronary flow was objectively evaluated for each major coronary artery in each subject using TIMI frame count method.Results: All HRR values calculated were detected significantly lower in MS group compared to controls (HRR first: 32 ± 9 vs. 37 ± 10; p = 0.01, second: 46 ± 11 vs. 52 ± 11; p = 0.03, third: 51 ± 12 vs. 59 ± 12; p = 0.00, fourth: 54 ± 13 vs. 61 ± 2; p = 0.02). TIMI frame counts for each major epicardial coronary artery and mean TIMI frame count were also found to be significantly higher in MS group compared to controls (left anterior descending artery:51 ± 24 vs. 39 ± 15; p = 0.009, left circumflex artery: 32 ± 11 vs. 24 ± 7; p = 0.001, right coronary artery: 33 ± 14 vs. 24 ± 10; p = 0.003, mean TIMI frame count: 38 ± 15 vs. 29 ± 9;p = 0.002). Additionally, significant negative correlations were also detected between HRR first minute and coronary TIMI frame count values in patients with MS. None of MS parameters did not affect HRR values, however mean TIMI frame count independently associated with HRR first minute (p = 0.04) in patients with MS.Conclusions: Impaired coronary blood flow occurring in MS might be a clue of autonomic dysfunction in addition to previously known endothelial dysfunction.

Do patients with diabetes use the insulin pen properly?

Aim: This study was conducted to evaluate the insulin pen application knowledge and skills of patients with diabetes. Methods: In our descriptive study, 200 patients with diabetes were asked to present the insulin pen injection technique on a mannequin and the steps of the pen injection implementation were noted on the data collection form as correct/incorrect by researchers. Results: More than 3 out of 4 (79.5%) of the participants were using the insulin pen or the cartridge after the expiry date, 70.5% were not rotating the injection site, and 63.0% were massaging the skin after injection. Injection sites complications were significantly more in those who were using the insulin pen or the cartridge after the expiry date, those who don\u2019t know the proper length of the needle and the possible body injection sites, those who don\u2019t rotate the injection sites, those who massage after injection, and those who don\u2019t use a new needle at each injection (p<0.05). Conclusion: This study put into light some failures in the knowledge and skills of patients with diabetes regarding insulin pen use. Nurses should provide patients with diabetes an effective and repetitive training concerning insulin pen use. DOI: https://dx.doi.org/10.4314/ahs.v19i1.38 Cite as: Tosun B, Cinar FI, Topcu Z, Masatoglu B, Ozen N, Bagcivan G, et al. Do patients with diabetes use the insulin pen properly? Afri Health Sci. 2019;19(1). 1628-1637. https://dx.doi.org/10.4314/ahs.v19i1.3

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Boosting pharmaceutical innovation in the post-trips era : real life lessons for the developing world

The process of globalization and the emergence of a rules-based multilateral trading system pose significant challenges to local pharmaceutical industries in developing countries. With the advent of global patent protection for pharmaceuticals, developing countries are facing a significant dilemma. It is necessary for these countries to comply with international intellectual property standards while simultaneously protecting their local industries and, thus, ensuring an affordable supply of drugs. A better understanding of the nature of the Agreement on Trade Related Aspects of Intellectual Property (TRIPS Agreement) and its components could help to raise awareness of the need for a comprehensive innovation policy. It is widely accepted that intellectual property rights (IPRs) are economic assets. Furthermore, they are necessary to develop world-class standards of innovation and creativity. Nevertheless, this thesis argues that innovation is not driven by the presence of strong IPRs alone; it has many other components going far beyond the IPRs regime. Nonetheless, designing policies for the promotion of R&D and the building up of innovation capacities in developing countries requires a wellconstructed patent regime. However, it also requires the implementation of broadbased science, technology and innovation policy initiatives aimed at promoting and facilitating capacity building for the enhanced absorption of new technologies. To this end, this thesis investigates the concept of innovation and illustrates the crucial role that patent strategies play within processes of pharmaceutical innovation. Drawing on extensive country and company case studies, the thesis identifies the key issues relevant to the revival of local pharmaceutical industries. Based on an understanding of the post-TRIPS environment and case studies of national innovation strategies, this thesis specifically addresses the following question - to what extent can lessons from national experiences be transferred to current policy developments for innovation in the pharmaceutical industry in a developing country context? 4 The research findings aim to contribute significantly to the body of knowledge in relation to new developmental policies. Overall, it is hoped that these findings can promote innovation and ensure the sustainability of the local pharmaceutical industry in the developing world.EThOS - Electronic Theses Online ServiceGBUnited Kingdo