Advancing pediatric drug development in South Asia: Current landscape and vision for the future.

ABSTRACT: The manuscript summarizes the outcomes of a one-day conference by the South Asian College of American College of Clinical Pharmacology (SAC-ACCP) in July 2023, at Bhopal. The theme of the conference was "Advancing pediatric drug development in South Asia." SAC-ACCP organized this event in Bhopal to foster the discipline of clinical pharmacology and to motivate researchers and physicians in the in the central part of India. The conference featured presentations on regional approaches to pediatric drug development in Asia by pediatric scientific experts from the pharmaceutical industry, regulatory agencies, as well as independent consultancies. The speakers highlighted several important aspects of the evolving regulatory landscape in India and proposed numerous actionable steps in acceleration of pediatric drug development. This commentary provides insights from presentations and the panel discussion at this conference and also makes an attempt to connect to similar discussions that occurred at the SAC-ACCP drug development conference in 2017.

Drug Development Failure: How GLP-1 Development Was Abandoned in 1990.

Many factors determine whether and when a class of therapeutic agents will be successfully developed and brought to market, and historians of science, entrepreneurs, drug developers, and clinicians should be interested in accounts of both successes and failures. Successes induce many participants and observers to document them, whereas failed efforts are often lost to history, in part because involved parties are typically unmotivated to document their failures. The GLP-1 class of drugs for diabetes and obesity have emerged over the past decade as clinical and financial blockbusters, perhaps soon becoming the highest single source of revenue for the pharmaceutical industry (Berk 2023). In that context, it is instructive to tell the story of the first commercial effort to develop this class of drugs for metabolic disease, and how, despite remarkable early success, the work was abandoned in 1990. Told by a key participant in the effort, this story documents history that would otherwise be lost and suggests a number of lessons about drug development that remain relevant today.

[Managing medicine shortages: responsibilities and strategies at the Swedish Medical Products Agency]. / Restsituationer för läkemedel ­ uppdrag och ansvarsfördelning.

The paper outlines the role of the Swedish Medical Products Agency (Läkemedelsverket) in managing medicine shortages. The agency receives reports from pharmaceutical companies, investigates causes, and disseminates information to pharmacies, healthcare providers, and the public. While focusing on mitigating shortages, the agency clarifies its non-involvement in manufacturing or sales decisions. Pharmaceutical companies must promptly report shortages, with sanctions enforced for non-compliance. Various measures, including regulatory actions, interchangeable medicines, temporary dispensations, and licensing, are employed to address shortages. Additionally, the agency advocates for stable national drug supply preparedness, emphasizing collaboration and governmental intervention.

Consumer Out-Of-Pocket Drug Prices Grew Faster Than Prices Faced By Insurers After Accounting For Rebates, 2007-20.

The rising price of branded drugs has garnered considerable attention from the public and policy makers. This article investigates the complexities of pharmaceutical pricing, with an emphasis on the overlooked aspects of manufacturer rebates and out-of-pocket prices. Rebates granted by pharmaceutical manufacturers to insurers reduce the actual prices paid by insurers, causing the true prices of prescriptions to diverge from official statistics. We combined claims data on branded retail prescription drugs with estimates on rebates to provide new price index measures based on pharmacy prices, negotiated prices (after rebates), and out-of-pocket prices for the commercially insured population during the period 2007-20. We found that although retail pharmacy prices increased 9.1 percent annually, negotiated prices grew by a mere 4.3 percent, highlighting the importance of rebates in price measurement. Surprisingly, consumer out-of-pocket prices diverged from negotiated prices after 2016, growing 5.8 percent annually while negotiated prices remained flat. The concern over drug price inflation is more reflective of the rapid increase in consumer out-of-pocket expenses than the stagnated inflation of negotiated prices paid by insurers after 2016.

Is there a relationship between attitudes of general practitioners/family doctors and attitudes of their patients regarding industry-sponsored clinical investigations? A cross-sectional survey in a convenience sample of doctors and patients across nine European countries.

AIM: To assess the relationship between the attitudes of general practitioners/family medicine doctors (GP/FD) and of their patients toward industry-sponsored clinical research. METHODS: A cross-sectional survey included volunteer GPs/FDs who then enrolled and interviewed their patients. Data were analyzed in hierarchical models (patients nested in GPs/FDs, nested in countries/regions). RESULTS: A total of 201 GPs/FDs from nine European countries responded to the invitation and enrolled 995 of their patients. We observed mild associations between some of the GPs/FDs' attitudes (general opinion on sponsored clinical studies, appreciation of the general values of such studies, views about the importance of participant protection/privacy) and some of the patients' attitudes (appreciation of the general values and of risks associated with sponsored clinical studies, importance assigned to potential personal benefits from participation). We observed no association between GPs/FDs' attitudes and patients' willingness to participate in such studies. However, willingness to participate increased with higher patients' appreciation of the general values of sponsored studies, decreased with higher patients' appreciation of associated risks, and showed a quadratic trend across the levels of importance assigned by patients to potential personal benefits (willingness was higher when the assigned importance was very low or very high). More importance to GP/FD's advice in this respect was assigned by patients who assigned more importance to potential personal benefits, who were better educated, and who resided in rural/suburban dwellings. CONCLUSIONS: In the present convenience sample, lay-person attitudes about and willingness to participate in industry-sponsored clinical studies were associated with the attitudes of their GPs/FDs.

Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects.

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples.

Green accounting and reporting in Bangladesh's pharmaceutical and textile industries: A holistic perspective.

This study examined the factors influencing green accounting and reporting practices (GARPs) in Bangladesh's pharmaceutical and textile industries. Hence, it draws upon disclosure theory to disclose relevant information in the context of environmental accounting and encourages them to boost their environmental performance. It utilized content analysis from 13 pharmaceuticals and 22 textiles data from Dhaka stock exchange (DSE) listed companies of Bangladesh and applied quantitative methods for comparative analysis. The findings showed that GARPs are influenced by firm characteristics and external factors rather than organizational performance, and eleven environmental indicators (separately) have a lower mean of less than 0.50 in both industries. Firms' general characteristics (FFGC) are noteworthy factors that exhibit a negative coefficient for both the pharmaceutical and textile sectors but hold a robust impact on the GARPs, with P = 0.007 and 0.003, respectively. The statistical significance of environmental factors (EFs) applies to the textile sector p = 0.000. Implementing GARPs in the pharmaceutical industry proved more effective than in the textile sector, offering valuable support to managers in expediting environmental practices in Bangladesh's textile industry.

Conflicts of Interest of Canadian Medical School Deans: A Cross-Sectional Study.

Background: Medical school deans wield considerable influence over research, clinical and educational missions at their institutions. This study investigates conflict of interest (COI) of Canadian medical school deans. Method: The websites of all 17 Canadian medical schools were searched for any mention of relationships between deans and pharmaceutical or medical device companies. Results: No COIs were discovered for 11 of the deans. Six had COIs, including participating in research funded by pharmaceutical companies and received consulting and speaker fees. Discussion: A minority of deans had COIs with healthcare industry companies. Whether deans' COIs affect policies at the medical schools they lead should be the subject of further investigation.

[A capability to promote the utilization of human samples for improving the |clinical response predictability in the pharmaceutical company].

An issue in drug discovery research at pharmaceutical companies is the decline in the probability of market launch, and there is a need to improve the proof-of-concept (POC) acquisition rate by further improving clinical predictability. For this purpose, we need to deepen our understanding of human pathophysiology, and to make efficient of drug discovery research by utilizing human samples and data due to the change in mindset from "animals" to "humans" at the drug discovery research stage. In particular, with the aim of improving the efficiency of drug discovery research by utilizing human samples/data, we have established a human sample utilization support capability, then we are supporting the acquisition of appropriate human samples/data to meet each drug research need with collecting information on organizations that can provide various human samples and accumulating know-how on obtaining human samples/data. In addition, we have built a one-stop support system for surveying human samples/data, negotiating, and contracting with the organizations, obtaining ethical committee approvals, importing samples, and dealing with customs clearance. As results, our researchers can obtain high-quality human samples/data to meet their research needs rapidly/easily. By establishing this capability, the number of the research projects that implement target validation, pharmacological evaluation, BM identification, and patient stratification, etc. using human samples/data from the early stage of drug discovery, has increased, and then, the evidence obtained by using human samples/data contribute to create drug candidates with high probability of clinical effect. We will introduce our activities while showing the support flow that was actually constructed.

Text summarization for pharmaceutical sciences using hierarchical clustering with a weighted evaluation methodology.

In the pharmaceutical industry, there is an abundance of regulatory documents used to understand the current regulatory landscape and proactively make project decisions. Due to the size of these documents, it is helpful for project teams to have informative summaries. We propose a novel solution, MedicoVerse, to summarize such documents using advanced machine learning techniques. MedicoVerse uses a multi-stage approach, combining word embeddings using the SapBERT model on regulatory documents. These embeddings are put through a critical hierarchical agglomerative clustering step, and the clusters are organized through a custom data structure. Each cluster is summarized using the bart-large-cnn-samsum model, and each summary is merged to create a comprehensive summary of the original document. We compare MedicoVerse results with established models T5, Google Pegasus, Facebook BART, and large language models such as Mixtral 8 × 7b instruct, GPT 3.5, and Llama-2-70b by introducing a scoring system that considers four factors: ROUGE score, BERTScore, business entities and the Flesch Reading Ease. Our results show that MedicoVerse outperforms the compared models, thus producing informative summaries of large regulatory documents.