Drug Regulation Research Articles

Validation study on the assay method for anti-factor IIa potency of enoxaparin sodium

Enoxaparin sodium is a low molecular mass heparin essential for effective anticoagulation therapy. However, significant variations in testing methods across different manufacturers have led to poor reproducibility of results, increasing the risks associated with drug quality evaluation by manufacturers and regulatory oversight. This study integrates the strengths of various testing methods to establish a reproducible assay that has been thoroughly validated. The validation results demonstrate that the method exhibits excellent specificity, linearity, robustness, precision, and accuracy, with recovery rates ranging from 98.0% to 102.0%. The new method demonstrated high consistency and reproducibility, with an RSD value of less than 2.0%, and showed the potential to replace the European Pharmacopoeia method by reducing reagent usage, experimental costs, and equipment requirements. The reliable results of this method facilitate its adoption across different laboratories, enhance the quality control of enoxaparin sodium, and provide a reference for new manufacturers and drug regulatory authorities, thereby ensuring medication safety.

FormulationBCS: A Machine Learning Platform Based on Diverse Molecular Representations for Biopharmaceutical Classification System (BCS) Class Prediction.

The Biopharmaceutics Classification System (BCS) has facilitated biowaivers and played a significant role in enhancing drug regulation and development efficiency. However, the productivity of measuring the key discriminative properties of BCS, solubility and permeability, still requires improvement, limiting high-throughput applications of BCS, which is essential for evaluating drug candidate developability and guiding formulation decisions in the early stages of drug development. In recent years, advancements in machine learning (ML) and molecular characterization have revealed the potential of quantitative structure-performance relationships (QSPR) for rapid and accurate in silico BCS classification. The present study aims to develop a web platform for high-throughput BCS classification based on high-performance ML models. Initially, four data sets of BCS-related molecular properties: log S, log P, log D, and log Papp were curated. Subsequently, 6 ML algorithms or deep learning frameworks were employed to construct models, with diverse molecular representations ranging from one-dimensional molecular fingerprints, descriptors, and molecular graphs to three-dimensional molecular spatial coordinates. By comparing different combinations of molecular representations and learning algorithms, LightGBM exhibited excellent performance in solubility prediction, with an R2 of 0.84; AttentiveFP outperformed others in permeability prediction, with R2 values of 0.96 and 0.76 for log P and log D, respectively; and XGBoost was the most accurate for log Papp prediction, with an R2 of 0.71. When externally validated on a marketed drug BCS category data set, the best-performing models achieved classification accuracies of over 77 and 73% for solubility and permeability, respectively. Finally, the well-trained models were embedded into the first ML-based BCS class prediction web platform (x f), enabling pharmaceutical scientists to quickly determine the BCS category of candidate drugs, which will aid in the high-throughput BCS assessment for candidate drugs during the preformulation stage, thereby promoting reduced risk and enhanced efficiency in drug development and regulation.

Trends in Proton Pump Inhibitor Use in Sweden by Sex and Age: A Drug Utilisation Study.

Proton pump inhibitors (PPIs) are among the most popular drugs worldwide. Yet, there are concerns on long-term safety and poor adherence to prescription guidelines. Off-label use in children and increasing maintenance use in older adults may be particularly worrisome. To assess differences in PPI use by age, sex calendar year and PPI type, and to explore potential underlying indications (ulcerogenic drugs, and indications) in Sweden. Proton pump inhibitor drug utilisation study based on the Swedish nationwide prescribed drug (2006-2023) and patient registries (2006-2022). Proton pump inhibitors were used by 14.4% (women) and 10.5% (men) of adults; and 1.0-1.5% of children and adolescents (aged < 20 years). Proton pump inhibitor use was higher in women in all age-groups except small children (aged < 5 years). Proton pump inhibitor use has increased in all age groups, especially in young children (aged < 10 years) and the oldest groups (aged > 65 years). Proton pump inhibitor users aged > 85 years filled most prescriptions with an annual average of 9.5 (men), 11.6 (women) prescriptions. Most prescriptions were for omeprazole and esomeprazole: 63.7% and 23.5% in adults; 23.5% and 44.7% in children (2023). Prescriptions for other drugs for peptic ulcers/reflux became rare, with 99% of prescriptions in this category being PPIs by 2023. Gastro-intestinal diagnoses were predominantly recorded in men, became less prevalent and only explained part of PPI use, while ulcerogenic drugs were common (particularly in women), suggesting PPIs are regularly used for gastroprotection. Proton pump inhibitor use has doubled in children and increased 50% in adults over the study period, in both sexes, while recorded gastrointestinal indications decreased. Alternative therapies were rarely prescribed in Sweden.

Does regulatory and reimbursement parallel processing provide swifter funded access to medicines for patients? Evaluation of cancer medicines using the Australian parallel process.

To assess the impact of a parallel regulatory and reimbursement process on (1) direction of funding decisions, 2) time-lag until funding recommendation, and (3) type of evidence submitted, for cancer medicines. Public regulatory and reimbursement decision documents were reviewed for cancer medicines considered by the Pharmaceutical Benefits Advisory Committee (PBAC) since the introduction of parallel processing. Medicine-indication pairs were identified from these documents and data extracted on the type and quality of evidence submitted, funding decisions and timelines, by type of review process. Associations were explored using univariate and multivariable logistic regression analysis. 182 cases were selected from the 1590 screened. Compared to sequential evaluation, a higher proportion of parallel review submissions presented a cost-effectiveness/cost-utility analysis (67.0% vs 79.7% p < 0.01) and used the same pivotal evidence as used for market authorisation (77.5% vs 90.0%, p = 0.08). There was no difference in the quality of supporting evidence and other decision-relevant predictors used for either process. Submissions undergoing parallel review were not more likely to receive a negative public funding decision (ORadj =0.46, 95%CI 0.14, 1.39; p = 0.17). Under parallel processing, the lag between drug registration and PBAC funding recommendation was drastically reduced (67 weeks) when compared to the sequential process. The type of evidence supplied to regulators and HTA bodies, and the funding decisions that ensue, have not been affected by the introduction of parallel processing in Australia. The parallel process has, however, drastically reduced the time taken to the initial funding decision.

Knowledge, Attitude and Perception of Research Ethics and Research Ethics Committees among Post-Graduate Residents of Neurosciences - A Nationwide Analysis from Pakistan

Objectives: To assess the knowledge, attitude and perception of post-graduate residents of neurosciences towards research ethics (RE) and research ethics committees (RECs). Methods: This prospective cross-sectional survey-based study was conducted by the Punjab Institute of Neurosciences, targeting post-graduate neuroscience residents throughout Pakistan during January and February, 2024. An English-language general questionnaire, designed to assess knowledge, attitudes, and perceptions of RE and RECs, was adapted to reflect local conditions. The collected responses were analyzed using the Statistical Package for Social Sciences (SPSS) to determine measures of central tendency, percentages, and frequencies. Results: Out of 241 residents, 64.3% were males. Sixty-eight percent respondents were from neurosurgery and 32% were from the field of neurology. Approximately 47% responses were from the province of Punjab. More than half (51.5%) of participants acknowledged the existence of a REC within their institution. A similar proportion (52.3%) claimed familiarity with ethical guidelines for research involving human subjects, only a slight majority (48.5%) demonstrated awareness of the specific functions carried out by RECs. Meanwhile, 44.5% expressed concerns that undergoing review by a REC could potentially delay research and pose additional challenges for researchers. Additionally, 27.4% of respondents admitted to considering the fabrication of data or results as acceptable. Conclusion: Our research uncovered a significant correlation between participants’ perceptions of RE and RECs and their comprehension of ethical principles. These findings indicate that medical postgraduates with a deeper understanding or awareness of research ethics principles and RECs tend to hold more robust attitudes toward these aspects. List of Abbreviations: AAHRPP: Association for the Accreditation of Human Research Protection Program, DME: Department of Medical Education, DRAP-CSC: Drug Regulatory Authority of Pakistan-Clinical Studies Committee, FCPS: Fellow of College of Physicians and Surgeons, IRBs: Institutional Review Boards, LMICs: Low-Middle-Income Countries, MCQs: Multiple Choice Questions, MD: Master of Medicine, MS: Master of Surgery, NBC-REC: National Bioethics Committee-Research Ethics Committee, PMDC: Pakistan Medical and Dental Council, RE: Research Ethics, RECs: Research Ethics Committees, SPSS: Statistical Package for Social Sciences. doi: https://doi.org/10.12669/pjms.40.12(PINS).11116 How to cite this: Qadri HM, Shahid R, Fatima SB, Naveed N, Khizar A, Siraj ul Haq, et al. Knowledge, Attitude and Perception of Research Ethics and Research Ethics Committees among Post-Graduate Residents of Neurosciences - A Nationwide Analysis from Pakistan. Pak J Med Sci. 2024;40(12):S55-S62. doi: https://doi.org/10.12669/pjms.40.12(PINS).11116 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Patterns and social factors associated with non-prescription use of Tramadol: a cross-sectional study among youth in urban informal settlements in Ghana

BackgroundNon-prescription use of Tramadol is increasingly becoming common among vulnerable populations. This study examines the factors associated with non-prescription use of Tramadol among youth in urban informal settlements in the Asokore Mampong Municipality, Ghana.MethodsCross-sectional data from Tramadol users aged 15 to 35 years living in urban informal settlements were analyzed. Non-prescription use of Tramadol was assessed using the item “Have you ever used Tramadol for any reason without a prescription from a healthcare professional?”. The responses were dichotomized as yes = 1, otherwise = 0. Multivariable logistic regression models evaluated the factors associated with non-prescription use of Tramadol.ResultsData on 200 Tramadol users were obtained. Family/friends (52.3%), were the main source of knowledge on Tramadol. Energy boost (43%) was the most cited reason for Tramadol use. Approximately 52% indicated a continuing non-prescription use of Tramadol for energy boost. Multivariable logistic regressions showed that those who lived alone (OR = 6.34: 95% CI = 2.03–19.82), migrants (OR = 3.97, 95% CI = 1.31–12.05) and the unemployed (OR = 3.57, 95% CI = 1.02–12.58) were significantly more likely to report non-prescription use of Tramadol.ConclusionsNon-prescription use of Tramadol is a threat to the youth in urban informal settlements in the Asokore Mampong Municipality. Interventions such as strict drug monitoring and regulation, drug use education, strict parental supervision, and sustainable jobs may contribute to controlling non-prescription use of Tramadol.

Understanding the socioeconomic dimensions of antibiotic resistance: a critical marketting perspective of healthcare stakeholders.

To explore the socioeconomic dimensions of antimicrobial resistance, emphasising the risks associated with imprudent use of antibiotics and the consequent emergence of drug-resistant "superbugs." The study employed constructivist grounded theory to investigate the perspectives of stakeholders, including physicians, patients, pharmacists, sales managers, and Drug Regulatory Authority of Pakistan (DRAP) employees. In-depth interviews were conducted with these stakeholders at their workplaces in 2022 and 2023, and transcripts were meticulously transcribed for analysis. The process of data analysis consists of open coding, then axial coding, and finally, selective coding to integrate categories into theories while the constant comparison of data was exercised to develop a cohesive theory. Data analysis revealed a dominant theme: "Navigating the Socioeconomic Terrain of Antimicrobial Resistance." Subsequently, several categories emerged, such as pharmaceutical marketting transgression, materialism among physicians and marketers, imprudent antibiotic usage, self-medication practices, lack of awareness among patients and the general public, and malpractice by unqualified and illicit practitioners. The results of the study demonstrated that critical marketting could mitigate the socioeconomic repercussions of AMR by encouraging ethical practices among the healthcare stakeholders, and hence benefit the entire society.

Regulation of mark-up on medicine prices in Zimbabwe: a pilot survey from 92 community pharmacies in the metropolitan area of Harare

BackgroundMedicine pricing in the community pharmacy sector in Zimbabwe significantly influences accessibility to health care. In this pilot survey, we investigated how community pharmacies in Zimbabwe apply various mark-up strategies to essential and non-essential medicines, and gathered community pharmacists’ perspectives on mark-up regulation.MethodsUsing an adapted methodology endorsed by the World Health Organization and Health Action International for studying medicine prices and availability, we conducted a quantitative cross-sectional pilot survey for 46 medicines (31 essential and 15 non-essential) identified using the Zimbabwe Essential Medicines List and classified according to the Vital, Essential, and Non-essential (VEN) tool. We conducted the pilot survey in 92 community pharmacies in the metropolitan area of Harare, Zimbabwe. ResultsWe gathered a total of 92 responses from 167 distributed questionnaires. The most prevalent mark-up strategy was the cost-plus fixed percentage.The median mark-up for all medicines in the community pharmacies was 60% (interquartile range 50- 82%). We found a statistically significant difference in the median mark-up by essentiality of medicines (p < 0.001), essential medicines had a median mark-up price of 62% while non-essential medicines had a mark-up of 56%. Antipsychotics had the highest mark-up at 82%, while anti-neoplastic medicine had the lowest at 36%. Overall, 55% of the community pharmacists did not support mark-up regulation.ConclusionMark-up strategies varied across community pharmacies in the metropolitan area of Harare. Without mark-up regulation, essential medicines remain significantly expensive in Zimbabwe. We recommend mark-up regulation in Zimbabwe’s community pharmacy sector and emphasize the effective use of multiple pricing strategies to reduce medicine prices. .

Pharmacological Innovations in Space: Challenges and Future Perspectives.

Since the first human experience in space, the interest in space research and medicine to explore universe is growing day by day. The extreme space conditions mainly radiation and microgravity effects on human physiology, antimicrobial susceptibility, and efficacy, safety, and stability of drugs. Therefore, the aim of this review is to address the impact of extreme space conditions, mainly microgravity and radiation, on human physiology and highlights the need for future approaches by evaluating the effectiveness of strategies to prevent or mitigate health problems. Published papers and NASA technical documents were searched in Pubmed and Google Scholar databases using the keywords ''antimicrobial susceptibility or drug resistance or drug stability or innovations or pharmacokinetic or pharmacodynamics'' and ''radiation or microgravity or space environments or space medicine or space pharmacy'' to prepare this review. In this review, the challenges regarding physiological effects and drug-related problems are examined through the evaluation of extreme conditions in space. Medications used in spaceflight are summarized, and the role of pharmacists specializing in space medicine is briefly explained. Last but not least, to overcome the aforementioned issues, novel approaches have been addressed, such as personalised treatments, development of space-resistant formulations and various microbial applications. Further research in the space medicine is required to facilitate the safe and healthy travel of humans to the Moon, Mars and other extraterrestrial destinations. One bear in mind that space research will contribute not only to the exploration of the universe, but also to the advancement of health and technological discoveries on Earth.

Time from approval to reimbursement recommendations in healthcare systems with centralized HTA processes. Focus on the Polish HTA agency

ABSTRACT Background To analyze the time from drug registration to reimbursement recommendations, we examined medicinal products, including new clinical indications, registered by the EMA between 2014 and 2019 across various therapeutic areas. Materials and Methods The Polish Agency for Health Technology Assessment and Tariffication (AOTMiT) was compared with 11 agencies in England, Wales, Ireland, Scotland, the Netherlands, Norway, France, Germany, New Zealand, Canada, Australia. A total of 1,942 recommendations published by 12 HTA agencies were analyzed. Results The time from registration to recommendation in Poland was statistically significantly longer than for the other countries. The analysis revealed noticeable differences in the time it takes from drug registration to recommendation across the countries included in this analysis. Analyzing trends from 2014 to 2019 across individual countries, there appears to be a slight tendency toward a decrease in the median time from registration to recommendation in many agencies. Conclusions This may suggest improvements in the processes of the recommending authorities and the companies responsible for providing data for assessment. Despite Poland having one of the longest times from registration to recommendation among the countries analyzed, there has been a clear year-over-year decrease in the time to publication of reimbursement recommendations.

Pharmaceutical care for patients with coronary heart disease: transformation of pharmaceutical practice

The implementation of the National Recovery Plan of Ukraine in the field of “Health Care”, namely the restoration of the pharmaceutical sector, improving the population’s access to medicines and their proper use, taking into account the regulatory and legal field harmonized with European legislation, in the context of providing the qualified pharmaceutical care and pharmaceutical services requires application of modern approaches based on evidence-based medicine and implementation in pharmaceutical practice. Patients with cardiovascular diseases, who are provided with medication under the Reimbursement Program and prescriptions from doctors, must be accompanied by pharmaceutical care based on evidence-based medicine to ensure proper use of drugs and rational pharmacotherapy. The aim of the study was to investigate Ukrainian information and scientific databases, scientometric databases, i. e.: Embase, Web of Science, PubMed, and Cochrane Library to identify, generalize, and systematize scientific sources of medical and pharmaceutical data on providing patient-oriented pharmaceutical care to patients with coronary heart disease and predict the future vector of research on the specified topic. Results. The analysis of the main strategies of providing pharmaceutical care to patients with cardiovascular diseases, in particular, coronary heart disease in pharmaceutical practice was carried out; the most researched clusters of providing pharmaceutical care were identified; modern trends and tendencies in the provision of pharmaceutical care to patients with coronary heart disease were summarized. Conclusions. The development of providing qualified pharmaceutical care to patients with cardiovascular diseases is based on the principles of patient-oriented pharmacy and evidence-based medicine, which requires the design and implementation into the pharmaceutical practice of a sustainable conceptual model of providing patient-oriented pharmaceutical care by clinical pharmacists and pharmacists of pharmacy institutions with the expansion of the main roles, respectively the standards of Good Pharmacy Practice.

Synergistic Epistasis and Systems Biology Approaches to Uncover a Pharmacogenomic Map Linked to Pain, Anti-Inflammatory and Immunomodulating Agents (PAIma) in a Healthy Cohort

The global public health addiction crisis has been stark, with over 932,400 deaths in the USA and Canada from opioid overdose since 1999–2020, surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations exhibit opioid consumption rates significantly above the norm for developed countries. Analgesic type of opioids present both therapeutic benefits and substantial health risks, necessitating balanced drug regulation, careful prescribing, and dedicated opioid stewardship. The role of the cytochrome P450 2D6 (CYP2D6) system (Enzymatic functions) in metabolizing opioids highlights the potential of genotype-guided analgesia. By integrating Pharmacogenomics (PGx), this approach aims to optimize pain management, enhance safety, and reduce addiction risks. This understanding prompted the utilization of multifactor dimensionality reduction (MDR) to explore a range of phenotypes including PGx and gene–gene interactions (GGI) in a healthy cohort, thereby personalizing pain management strategies. The study sampled 100 unrelated healthy Western Iranians and 100 individuals from the 1000 Genome Project. Pre-testing involved searching for PGx annotations (variants associated with drug-gene-diseases) related to pain sensitivity and inflammation using the PharmGKB database, which identified 128 relevant genes. A questionnaire helped select 100 participants who had never used potent opioids but also other psychoactive agents (e.g., nicotine, amphetamines, etc.) and disease-related drugs. Whole-exome sequencing (WES) was then employed to analyze these genes in an Iranian cohort. Further analyses included MDR for identifying synergistic gene annotations and GGI for exploring complex gene interactions through the Visualization of Statistical Epistasis Networks (ViSEN). The study identified a Pain, Anti-Inflammatory, and Immunomodulating agents (PAIma) panel from the 128 genes, resulting in 55,590 annotations across 21 curated pathways. After filtering, 54 significant structural or regulatory variants were identified. This research also highlighted novel gene relationships involving the CYP3A5 gene, hsa-miR-355-5p, Paliperidone, and CYP2D6, which warrant further investigation. This study offers a novel pharmacogenetic framework that could potentially transform opioid prescribing practices to mitigate misuse and enhance personalized pain management. Further validation of these findings from multi countries and ethnic groups could guide clinicians in implementing DNA-based opioid prescribing, aligning treatment more closely with individual genetic profiles.Graphical abstract

FDA Analysis of Race and Ethnic Enrollment of Clinical Trials for Drug Registration in Adult Patients for Leukemia and Myelodysplastic Syndrome

FDA Analysis of Race and Ethnic Enrollment of Clinical Trials for Drug Registration in Adult Patients for Leukemia and Myelodysplastic Syndrome

Pediatric drug regulations: A global perspective and the imperative for implementation in India

The pediatric population differs from adults in various ways, including physiological factors, pharmacokinetics, pharmacodynamics, and dosage administration. However, many medications prescribed for children are formulated for adults, necessitating dose adjustments throughout childhood. This underscores the need for pediatric drug formulations and regulations worldwide. This review delves into the intricate landscape of international pediatric drug regulations to elucidate key initiatives, challenges, and advancements shaping this field. Commencing with a historical backdrop, the review outlines the evolution of regulatory frameworks across major regions, including the United States (US), Europe, Japan, and China, while underscoring the imperative for the implementation of pediatric drug regulations in India. These regulations mandate age-appropriate dosing, rigorous clinical trials, and thorough labeling to prevent misuse. They require pediatric-specific studies to understand drug effects and dosages and enforce guidelines for off-label use. Agencies such as the US Food and Drug Administration oversee these regulations, ensuring pediatric drugs meet safety standards before approval. In addition, regulations often include provisions for informed consent and parental involvement in treatment decisions, aiming to protect children from adverse effects while providing effective therapeutic options tailored to their developmental needs. In summary, this review emphasizes the importance of global cooperation and harmonized regulations in advancing pediatric drug research. It highlights recent progress while acknowledging ongoing challenges and opportunities in this critical area.

Careers of chloroquine and hydroxychloroquine as “miraculous” anti-Covid-19 drugs

In early January 2024, a widely publicized article in the journal Biomedicine and Pharmacology estimated that approximately 17,000 COVID-19 patients in France, Italy, Spain, Turkey, and the US died as a result of hydroxychloroquine treatment. The publication of this article is a fitting closure to nearly three years of controversy about the possible use of chloroquine and hydroxychloroquine to treat COVID-19. Repurposed in early 2020 as miracle answers to the COVID-19 pandemic, they had a brief moment of worldwide celebrity, despite the doubts expressed by many experts. Hydroxychloroquine’s career ended in September 2020, when a series of clinical trials showed not only inefficacy to treat COVID-19 but also safety concerns. However, the use of chloroquine and hydroxychloroquine continued in Brazil, where the government continued to promote their use as the first therapeutic choice against COVID-19. Our study outlines the employ of these drugs in France and Brazil. Grounded in the methodology developed by social studies of science, our article reconstructs the trajectories of hydroxychloroquine in France and Brazil. It aims to elucidate the reasons for the Brazilian exception, illuminating the disastrous consequences of the exercise of a monolithic political power and of anti-democratic practices on drug regulation and proposes new reflections on a topic that has been visible in the media and widely discussed in society, but attracted much less attention in the academic sphere.

Minimizing the risk of ethylene glycol and diethylene glycol poisoning in medications: A regulatory and pharmacopoeial response

Pharmaceutical and personal care products, including syrups and toothpastes, extensively use glycerin, sorbitol, and propylene glycol. However, past incidents of ethylene glycol (EG) and diethylene glycol (DEG) contamination in these products have raised serious health concerns. Recently, several child deaths linked to contaminated cough syrup consumption have heightened concerns regarding the safety of Indian pharmaceuticals. In response, Indian drug regulatory authorities and the Indian Pharmacopoeia have implemented several measures to enhance the quality, safety, and efficacy of pharmaceuticals manufactured in India. These measures encompass risk-based inspections of manufacturing facilities, rigorous quality control checks of medicinal products intended for export, and increased transparency in the supply chain of excipients prone to EG and DEG contamination. Further, the Indian Pharmacopoeia has updated monographs for five high-risk excipients: glycerin, propylene glycol, sorbitol solution (70%, both crystallizing and non-crystallizing), and liquid maltitol. These efforts are consistent with global regulatory standards and aim to ensure the overall quality and safety of pharmaceuticals produced in India.

A Review on Genotoxic Impurities in Pharmaceutical Dosage Forms and Strategies for Identification

Abstract: Genotoxic pollutants can be broadly defined as pollutants that, regardless of the mechanism, cause significant changes in genetic material. People all over the world suffer from various health problems due to genotoxic pollutants. Recent recommendations from drug regulatory agencies in Europe and the United States (USA) require the monitoring of genotoxic and potentially genotoxic contamination in drug formulations at the ppm level. Therefore, this review evaluates several regulatory agency guidelines for monitoring genotoxic contamination, impurity levels, and toxicity in pharmaceutical products. The review also discusses analytical considerations for measuring genotoxic pollutants at trace levels and concludes with several examples of measuring several important classes of genotoxic pollutants. We will also explain our results. The article provides detailed information on genotoxicity studies of waste solutions, metal wastes, and isolated pollutants.

Evaluation and redesign of an internal medicine pharmacy practice model at a tertiary care hospital.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Clinical pharmacists are embedded into the care for patients admitted to internal medicine floors at Cleveland Clinic. The existing practice model utilized by the internal medicine pharmacy team had an uneven distribution of clinical activities among the various pharmacist roles. A study was completed to evaluate a potential adjustment to the pharmacy practice model. The objective of this study was to assess the type and quantity of clinical activities performed by each pharmacist role. These data were then utilized to evaluate the need for redistribution of care activities among the pharmacist roles and to determine the need for additional pharmacist full-time equivalents. From January to February 2023, data pertaining to the amount and type of clinical activities completed by the 9 internal medicine pharmacist roles was either manually collected or extracted from the electronic medical record. The data were then utilized to calculate a responsibility score for each role. Descriptive statistics were also calculated to assess the results. Each pharmacist role cared for an average of 34.4 patients (minimum, 24.4; maximum, 57.7) during the study period. The average responsibility score for each pharmacist role was 309.8 (minimum, 237.5; maximum, 447.8). On the basis of the data collected during the 4-week study period, a new pharmacy practice model was developed that incorporated 2 additional full-time equivalents. This model balanced patient care responsibilities among the pharmacist roles and moved the practice model from a location-based to a team-based coverage model.

Pharmacodynamic and Clinical Effects of Ginkgo Biloba Extract EGb 761 and Its Phytochemical Components in Alzheimer's Disease.

Extracts made from plants are complex mixtures of substances with varying compositions depending on the plant material and method of manufacture. This complexity makes it difficult for scientists and clinicians to interpret findings from pharmacological and clinical research. We performed a narrative review summarizing information on ginkgo biloba leaf extract, its composition, pharmacological data and clinical evidence supporting its administration for the treatment of Alzheimer's disease (AD). Medicinal products containing ginkgo biloba leaf extract which are manufactured in compliance with the requirements of the European Pharmacopoeia are approved as medicinal products for the treatment of dementia and related conditions by drug regulatory agencies in Europe, Asia and South America. As multicomponent mixtures, they may affect various targets in the pathogenesis of AD, the most common form of dementia. Pharmacodynamic studies demonstrate the effects of EGb 761 and individual constituents on various pathophysiological features of experimentally induced cognitive impairment and neurodegeneration that could contribute to its clinical efficacy. The safety and efficacy in the treatment of AD and cognitive decline has been studied in randomized, placebo-controlled clinical trials. Most of the studies that investigate the effects of ginkgo biloba extract (GbE) used the special extract EGb 761, which makes it the best-researched plant preparation worldwide. It is therefore the only herbal alternative to standard-of-care anti-dementia drugs. However, the mechanism of action has not been fully elucidated yet, and the clinical studies in AD show heterogeneity.

Survival time in Alzheimer's disease: An overlooked measure of safety and efficacy of disease-modifying therapies.

It is of vital importance to patients and physicians, as well as administrators and drug regulators, that the treatment for a disease has been shown to be safe and clinically meaningful in long-term use. Recent literature has highlighted 3 major categories of arguments for and against modification of the underlying disease process in Alzheimer's disease (AD): pathophysiology, biomarkers and data from clinical trials. We argue that the Alzheimer's arena is over-reliant on theories of disease modification based solely on brain positron emission tomography (PET) imaging and blood biomarkers of tau and Aβ peptides. Here, we instead focus on a historically-grounded empirical criterion from other fields of medicine to overcome the weak interpretations of short Alzheimer's trials: survival time (ST). Our analysis has identified 3 key points. First, if anti-amyloid therapies are AD-modifying treatments, then we argue that they should increase ST more than the standard "symptomatic" care with memantine and acetylcholinesterase inhibitors. Second, we question memantine and cholinesterase inhibitors being labeled simply as "symptomatic" Alzheimer's drugs since long-term use of them can produce disease modification, that is, increase ST. Third, we make a case for memantine or cholinesterase inhibitors being used as controls in clinical trials with amyloid-lowering and other drugs, and argue against their current under-use in care of Alzheimer's patients.