Pharmaceutical Scientists' Perspectives on Capacity Building in Pharmaceutical Sciences

With the anticipated health challenges brought by demographic and technological changes, ensuring capacity in underlying workforce in place is essential for addressing patients' needs. Therefore, a timely identification of important drivers facilitating capacity building is important for strategic decisions and workforce planning. In 2020, internationally renowned pharmaceutical scientists (N = 92), largely from the academia and pharmaceutical industry, with mostly pharmacy and pharmaceutical sciences educational background were approached (through a questionnaire) for their considerations on influencing drivers to facilitate meeting current capacity in pharmaceutical sciences research. From a global view, based on the results of the questionnaire, the top drivers were better alignment with patient needs as well as strengthening education - both through continuous learning and deeper specialisation. The study also showed that capacity building is more than simply increasing the influx of graduates. Pharmaceutical sciences are being influenced by other disciplines, and we can expect more diversity in scientific background and training. Capacity building of pharmaceutical scientists should allow flexibility for rapid change driven by the clinic and need for specialised science and it should be underpinned by lifelong learning

Unmet medical need as a driver for pharmaceutical sciences - a survey among scientists

Historical antecedents of pharmaceutical sciences are sound on product orientation based on (analytical) chemistry, drug delivery and basic pharmacology. Over the last decades we have seen a transition towards a stronger disease orientation. This raises questions on whether, how and to what extent unmet medical need (UMN) is important in priority setting, funding and impact in pharmaceutical sciences. An online survey in 2020 collected perspectives of internationally recognised pharmaceutical scientists (N=92), mainly from academia and industry, on drivers and influencing factors in pharmaceutical sciences. The study offers a unique global perspective, demonstrating a solid command of the global needs in pharmaceutical sciences. The survey revealed that UMN is currently seen as one of the three most important drivers, also in addition to emerging trends in science and opportunities driven by collaboration. There are expectations that UMN's impact becomes more influential. This was consistent for both industry and academic respondents. The majority of respondents also indicated that anticipated lessons learned from COVID-19 will strengthen the impact of UMN on science and leadership. This is important as prioritisation of research towards UMN can address the clinical needs where needed the most

Adverse events related to biologicals used for patients with multiple sclerosis: a comparison between information originating from regulators and information originating from the scientific community

Publisher's version (útgefin grein)Background and purpose: Clinical decision making is facilitated by healthcare professionals’ and patients’ adequate knowledge of the adverse events. This is especially important for biologicals used for treating multiple sclerosis (MS). So far, little is known about whether different information sources report adverse events consistently. Methods: Biologicals authorized by the European Medicines Agency for the treatment of MS were included in this study. Information on adverse events derived from phase 3 clinical trials from European Public Assessment Reports (EPARs) and from scientific publications was compared. Results: In the study, eight biologicals used for the treatment of MS were included for which the EPAR and/or scientific publication reported a total of 707 adverse events. Approximately one-third of the adverse events was reported in both the EPAR and scientific publication, one-third was only reported in the EPAR and one-third only in the scientific publication. Serious adverse events and adverse events that regulators classified as ‘important identified risk’ were significantly more often reported in both sources compared to adverse events not classified as such (respectively, 38% vs. 30% and 49% vs. 30%). Adverse events only reported in the EPAR or in the scientific publication were, in general, not described in the benefit–risk section or abstract, which were considered to be the most important sections of the documents. Conclusions: This study showed that there is substantial discordance in the reporting of adverse events on the same phase 3 trials between EPARs and scientific publications. To support optimal clinical decision making, both documents should be considered.It is confirmed that no specific funding was receivedfor this study.Peer Reviewe

Use of Dipeptidyl Peptidase-4 Inhibitors and the Reporting of Infections: A Disproportionality Analysis in the World Health Organization VigiBase

OBJECTIVE - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. They inactivate incretin hormones but also have many other effects throughout the body, among which are effects on the immune system. This might result in an increased infection risk. This study assessed the association between use of DPP-4 inhibitors and the reporting of infections. RESEARCH DESIGN AND METHODS - A nested case-control was conducted using VigiBase, the World Health Organization-Adverse Drug Reactions (WHO-ADR) database. The base cohort consisted of ADRs for antidiabetic drugs (Anatomical Therapeutic Chemical code A10). Cases were defined as ADRs of infection according to the Medical Dictionary for Regulatory Activities (MedDRA) classification system. All other ADRs were considered controls. Reporting odds ratios (RORs) were calculated to estimate the strength of the association between different classes of antidiabetic drugs and the reporting of infections. RESULTS - We identified 305,415 suspected ADRs involving antidiabetic drugs in 106,469 case reports, of which 8,083 involved DPP-4 inhibitors monotherapy. Overall, the reporting of infections was higher for patients using DPP-4 inhibitors compared with users of biguanides (ROR 2.3 [95% CI 1.9-2.7]). Reporting of upper respiratory tract infections (ROR 12.3 [95% CI 8.6-17.5]) was significantly associated with use of DPP-4 inhibitors. CONCLUSIONS - This study indicates an increased reporting of infections, in particular upper respiratory tract infections, for users of DPP-4 inhibitors compared with users of other antidiabetic drugs. However, the limitations of spontaneous reporting systems (e.g., underreporting, the Weber-effect, reporting bias) should be taken into account. Therefore, further research is needed to evaluate this suspicion and the underlying mechanism

The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney. Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson’s correlation coefficient and linear regression were used to assess relations between parameters.Results: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 μm2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.β = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.β = 0.31, p = 0.01) and at five years (St.β = 0.30, p = 0.01) after donation, independent of age.Conclusions: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors. Graphical abstract: [Figure not available: see fulltext.]</p

Pre-approval and post-approval availability of evidence and clinical benefit of conditionally approved cancer drugs in Europe: a comparison with standard approved cancer drugs

Aims: Cancer drugs are increasingly approved through expedited regulatory pathways including the European conditional marketing authorization (CMA). Whether, when taking CMA post-approval confirmatory trials into account, the level of evidence and clinical benefit between CMA and standard approved (SMA) drugs differs remains unknown. Methods: We identified all CMA cancer indications converted to SMA in 2006–2020 and compared these to similar SMA indications with regard to pivotal trial and CMA post-approval confirmatory trial design, outcomes and demonstrated clinical benefit (per the European Society for Medical Oncology Magnitude of Clinical Benefit Scale). We tested for differences in clinical benefit and whether substantial clinical benefit was demonstrated. To account for the clinical benefit of unconverted CMA indications, we performed sensitivity analyses. Results: We included 15 SMA and 15 converted CMA cancer indications (17 remained unconverted). Approval of 11 SMA (73%) and four CMA indications (27%) was supported by a controlled trial. Improved overall survival (OS) was demonstrated for four SMA indications (27%). Improved quality of life (QoL) was demonstrated for three SMA (20%) and one CMA indication(s) (7%). Of subsequent CMA post-approval confirmatory trials, 11 were controlled (79%), one demonstrated improved OS (7%) and five improved QoL (36%). After conversion, CMA indications were associated with similar clinical benefit (P =.31) and substantial clinical benefit as SMA indications (risk ratio 1.4, 95% confidence interval 0.57–3.4). Conclusion: While CMA cancer indications are initially associated with less comprehensive evidence than SMA indications, levels of evidence and clinical benefit are similar after conversion from CMA to SMA

Зміни активності NO-синтаз та аргінази у тканині підшлункової залози при введенні L-аргініну або аміногуанідину за умов стрептозотоцин-індукованої гіперглікемії

При стрептозотоцин-индуцированной гипергликемии у крыс изучали влияние L-аргинина и селективного блокатора индуцибельной NO-синтазы аминогунидина на активность NO-синтаз и аргиназы в ткани поджелудочной железы. Показано, что как L-аргинин, так и аминогуанидин снижают активность индуцибельной NO-синтазы, при этом L-аргинин выражено понижает концентрацию глюкозы в крови и повышает активность аргиназы, что свидетельствует об усилении неокислительного пути его метаболизма.The influence of L-arginine and selective inducible NO-synthase blocker aminoguanidine on the activity of NO-synthases and arginase in pancreatic tissue in rats under conditions of streptozotocin-induced hyperglycemia was investigated. It was shown, that both L-arginine and aminoguanidine decrease the activity of inducible NO-synthase, whereas L-arginine supplementation significantly decreases the glucose concentration in blood and increases the activity of arginase, giving evidence about the enhancement of nonoxidative pathway of its metabolism

Нові явища у функціонально-стилістичному вживанні протиставних сполучників в українській літературній мові кінця ХХ — початку ХХІ століть

У статті досліджено зміни у функціонуванні найуживаніших протиставних сполучників у мові української преси та художньої літератури кінця ХХ — почат ку ХХІ століть, обґрунтовано слабку семантико-синтаксичну спеціалізацію протиставних сполучників та визначено їхні транспозиційні можливості.In the article the changes in the functioning of the most used adversative conjunctions in the language of Ukrainian press and artistic literature of the end of the XX — the beginning of the XXI centuries have been investigated, weak semantic-syntactic specialization of adversative conjunctions has been explained and their transisting resources have been determined