Drug Regulation Research Articles

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.

Time from approval to reimbursement recommendations in healthcare systems with centralized HTA processes. Focus on 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 in individual countries, it is noteworthy that in most agencies the median time from registration to recommendation is declining. 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.

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.

Activity Assessment of Factor Replacement Therapies to Guide Infusion Rate Protocols in Patients with Bleeding Disorders

Abstract Introduction The development of institutional protocols guiding administration of clotting factor replacements in patients with bleeding disorders requires an understanding of product stability over infusion duration. Inclusion of new factor products on formulary at our institution raised consideration for optimal administration routes, including whether a bolus intravenous push versus infusion over 4-12h provided acceptable factor activities. Here we assessed the activity of two clotting factor replacement therapies over a 24h period to guide clinical care protocols. Method This study was performed in the Special Coagulation Lab as a collaboration between pharmacy, hematology, and laboratory medicine. Two vials each of Novoeight, a recombinant antihemophilic factor used in patients with factor VIII deficiency, and Vonvendi, a recombinant von Willebrand Factor (VWF) replacement approved for prophylaxis in adults with Type 3 von Willebrand Disease, were reconstituted to clinically relevant potencies (13 IU/ml, Novoeight; 27 IU/ml, Vonvendi). Products were spiked separately into factor VIII-deficient plasma (Novoeight) or assay diluent (Vonvendi), given inability to obtain VWF-deficient plasma, and tested for activity at various timepoints. Novoeight samples were assessed by traditional one-stage FVIII assays, while Vonvendi samples were assessed for VWF antigen, ristocetin cofactor activity (RCA), and glycoprotein Ib binding activity (GP1bM). Results Novoeight samples maintained similar FVIII activities at all timepoints tested, with differences falling within the coefficient of variation of the assay. Specifically, the two samples had FVIII levels of 108% and 95% at baseline and levels of 98% and 91%, respectively, at 12h, which was the timepoint of greatest interest given plans to allow 12h infusion rates. For Vonvendi samples, measurement of VWF antigen remained fairly stable throughout the 24h period. However, VWF activity decreased in both RCA and GP1bM assays over time, including by 4h. RCA values were 193% and 190% at baseline, 113% and 95% at 4h, and 63% and 63% at 12h. GP1bM was 140% and 133% at baseline, 92% and 91% at 4h, and 56% and 70% at 12h. Together, these results supported implementation of protocols allowing for extended (up to 12h) infusion of Novoeight and short (3-5min) bolus infusion of Vonvendi. Conclusion Our study demonstrated maintained Novoeight activity over the study period, confirming infusion rates of 12h should be efficacious. Conversely, Vonvendi yielded significantly decreased activity levels in as little as 4h, indicating the need for faster infusion rates. Based on our results, current practices at our institution were adapted to include extended infusion for Novoeight only. Drug activity studies may not directly reflect patient outcomes, and additional studies of factor activities following product infusion into patients and clinical hemostasis correlates are necessary. Nevertheless, the clinical lab should continue to play a primary role in testing, monitoring, and developing patient care protocols for therapeutic drugs through multidisciplinary collaboration.

Regulatory Quality in the International Circulation of Medicinal Products

Since 2014, the World Health Organization has been implementing a large-scale project to strengthen and develop national regulatory systems, which is aimed at increasing the availability of safe, effective and high-quality medicines and medical devices for the population of all countries, but primarily low- and middle-income countries. The project analyzes the maturity of national regulatory systems using a global benchmarking tool developed based on various regulatory authority assessment systems and has undergone extensive discussion and pilot testing; the results of national authorities that have reached high levels of maturity are published. A WHO List of Regulatory Authorities is also being formed, replacing the previously used concept of "stringent regulatory authorities". This List is recommended for use in regulatory reliance procedures by national regulatory authorities, purchasing structures of various levels and status: commercial, public, state or international. The regulatory quality of drug regulation is one of the critical factors of any national healthcare system. At the global level, it is directly related to goals 1,3,8,9 and 11 of sustainable development defined by the UN. The WHO project under consideration to assess maturity) of the regulatory system of the pharmaceutical sector is fundamentally different from similarly focused projects carried out in the past. First of all, the project focuses not on legal and regulatory/methodological documents, but on institutional and procedural aspects, i.e. on the structure and functions of regulatory bodies. Along with this, the project can have a significant impact on global pharmaceutical markets.

Consensus Statement on the Outcome of the European Herbal Health Products Summit - Which Way Forward?

Herbal medicinal products are a vital part of the healthcare system in Europe and beyond. Being predominantly sold as non-prescription medicines in pharmacies, they are very popular with patients, physicians, and pharmacists and are therefore an important part of self-medication. Interest in this sector has recently gained momentum, reflecting the ongoing revision of the general pharmaceutical legislation and the recent discussion on nutrition and health claims on foods based on the implementation report of Regulation (EC) No 1924/2006 by the European Parliament 1. Therefore, on 20th February 2024, the Society for Medicinal Plant and Natural Product Research (GA), in collaboration with the German Pharmaceutical Industry Association (BPI) and the German Medicines Manufacturers' Association (BAH, now Pharma Deutschland), hosted an in-person summit in Brussels entitled 'European Herbal Health Products Summit - Which way forward?'. The summit featured a wide range of speakers, including policymakers, regulatory authorities, industry representatives, and academic experts. It was divided into several sessions covering topics such as the future and relevance of herbal medicinal products in the EU, the revision of the EU pharmaceutical legislation, and the resulting impact on herbal medicinal products. Furthermore, the discussions delved into the "Health Claims Regulation" - the European Parliament's implementation report and the related regulatory challenges of herbal medicinal products at an EU level. This consensus paper summarises the current status and provided recommendations to pave the way for future strategies to ascertain the continued use of herbal medicinal products as an important therapeutic option for patients.

Psychomodulatory substances: New legislative framework for control of psychoactive substances in Czechia

This article challenges drug prohibition advocated by UN conventions as the prevailing regulatory model for psychoactive substances, highlighting its ineffectiveness, harmfulness and outdated nature. At the same time, the conventions exclude some psychoactive substances from international regulation, leaving control to individual countries. Presenting an innovative approach, this article outlines an approach to the legal regulation of psychomodulatory substances (psychoactive substances with low health and societal risk) in non-medical contexts. Acknowledging the potential benefits of such psychoactive substances and balancing them with potential harms, it suggests stringent rules for marketing, safety, and preventing sales to minors. This approach aims to quell illicit markets, safeguard vulnerable populations, and encourage controlled use. Through a case study of the Czech Republicʼs introduction of a new category of psychomodulatory substances, this article showcases a paradigm shift from the prevailing repressive approach to drug regulation. This adaptive model effectively navigates the regulatory void, offering a viable alternative to the UNʼs prohibition framework.

Three consecutive cases of acute liver failure in young women due to acetaminophen overdose: insights into Japanese social issues and transplantation landscape.

Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.

True Benefits of Immune Checkpoint Inhibitors in the Treatment of Malignant Pleural Mesothelioma in Japan.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Storage practice and wastage of pharmaceuticals in Chinese urban-dwelling households: Description of urban-dwelling households.

At-home storage of medications could pose a threat to public health and the environment if not handled appropriately. Excessive storage also creates health care and economic burdens. This study investigated storage practices, waste, and their determinants in China. Data were collected by pharmacy staff of urban-dwelling households via online questionnaires. Descriptions at the household and medicine levels were conducted in Stata 16. Individual and family characteristics were associated with the presence of household medicine storage (84.6%, n=5290), but storage location was poor. Expiration was the primary reason for discarding medicines. Respondents were inclined to buy medicines in pharmacies without prescription for storage purposes at out-of-pocket expenses, and 60.7% of medicines were purchased at out-of-pocket expenses, despite medical insurance coverage. Regarding wastage, 11.2% of medicines had expired and 38.2% were no longer needed. Purchasing for storage purposes was related to less waste due to expiration, while purchasing for treating acute diseases rather than chronic diseases was related to more waste, due to less for use. Accounting for 12.2% of all medications, antibiotics were associated with expiration and no further need for use. Source-control measures targeting health facilities, pharmacies, and residents are needed under the combined efforts of all relevant departments.

Whole-genome Sequencing Association Analysis of Quantitative Platelet Traits in A Large Cohort of β-thalassemia.

Platelet acts as a crucial monitoring indicator for hypercoagulability and thrombosis and a key target for drug regulation. Genotype-phenotype association studies have confirmed that platelet traits are quantitatively regulated by multiple genes. However, there is currently a lack of genetic studies on the heterogeneity of platelet traits in β-thalassemia under hypercoagulable state. Here, we studied the phenotypic heterogeneity of platelet count (PLT) and mean platelet volume (MPV) in 1020 β-thalassemia patients. We further performed a functionally informed whole genome sequencing association analysis of common variants and rare variants (RVs) for PLT and MPV in 916 patients through integrative analysis of whole-genome sequencing data and functional annotation data. Extreme phenotypic heterogeneity of platelet traits was observed in β-thalassemia patients. Additionally, the common variant based gene-level analysis identified the novel gene of RNF144B associated with MPV. The RV analysis identified several novel associations in both coding and noncoding genome, including missense RVs of PPP2R5C associated with PLT and missense RVs of TSSK1B associated with MPV. In conclusion, we performed a comprehensive and systematic whole genome scan of platelet traits in the β-thalassemia cohort, demonstrating the specificity of genetic regulation of platelet traits in the context of β-thalassemia, providing potential targets for intervention.

Authors’ reply: Inadequate analysis of the budgetary impact of new label indications after initial drug registration in Brazil: A response to a published case study

Authors’ reply: Inadequate analysis of the budgetary impact of new label indications after initial drug registration in Brazil: A response to a published case study

A Review on Pharmaceutical Regulatory Authority of India, USA, UK, Australia

Medicines play an important role in saving lives, maintaining health, preventing disease, curbing epidemics and promoting national economic development. This is why people, governments, the pharmaceutical industry and research institutes pay for drugs. However, to do this, the drugs must be safe, effective and of high quality. This means that the development, production, import, export and distribution of drugs are regulated to ensure that they meet prescribed standards. To effectively regulate medicines, the government has established strong National Regulatory Authorities (NRAs) to ensure that medicines are effectively regulated to protect and promote public health. Pharmaceutical regulations around the world play an important role in ensuring the safety, quality and efficacy of medicines. Medicines regulatory agencies are responsible for enforcing regulations and issuing guidelines for the development, licensing, registration, manufacture, labelling, storage, marketing, distribution, pricing of drugs, drug importation and post marketing studies. While seeking international markets, the pharmaceutical industry must comply with the pharmaceutical regulations of other countries with different regulatory requirements. A single regulatory approach for marketing authorization (MA) applications for medicines in different countries is difficult. Therefore, the Common Technical Document (CTD) was developed to provide a common format for the electronic submission of drug registration applications.

Establishing defined daily and course doses for antimicrobials used in Pakistani broilers to enable farm-level quantification and comparison of antimicrobial use

Monitoring antimicrobial use (AMU) is crucial, as it plays a key role in driving antimicrobial resistance (AMR). Animals account for a significant share of AMU, making it essential to accurately quantify AMU exposure at the species, farm, and country levels. In Pakistan, prophylactic use of antimicrobials remains common alongside therapeutic use. This study aimed to establish defined daily and course doses for both therapeutic and prophylactic use of antimicrobials in commercial broiler production in Pakistan. A list of antimicrobial products was compiled from the daily treatment records from 100 commercial broiler farms in Punjab, Pakistan. For each active substance (AS), a defined daily dose (DDDvetPK) was assigned for treatment, prevention or both, by averaging the recommended doses of all similar AS with the same administration route. A defined course dose (DCDvetPK) was calculated by multiplying the average recommended dose by the average treatment duration for each AS, based on the Summary of Product Characteristics (SmPC). A total of 41 AS, categorized into 17 antimicrobial classes, were identified from 139 antimicrobial products. The most frequently reported AS were colistin (polymyxins) at 15.9 %, amoxicillin (aminopenicillins) at 7.5 %, neomycin (aminoglycosides) at 7.3 %, enrofloxacin (fluoroquinolones) at 6.7 %, and tylosin (macrolides) at 6.4 % of the total treatments (n = 358) reported at farms. Notably, 51 % of AS were classified as critically important for human medicine by WHO. Among AS indicated for treatment in SmPC, the defined daily doses for Pakistan (DDDvetPK) varied substantially from the European Medicines Agency (EMA) values (DDDvet), with the top deviations being Tiamulin (+147.8 %), Sulfadimidine_TMP (+111.2 %), Flumequine (+88.6 %), Spiramycin (-87.8 %), and Tylosin (-84.3 %). This study presents a list of defined daily doses and defined course doses for AMU quantification in Pakistani broilers using dose-based indicators. The observed differences between Pakistani and EMA doses, and lack of EMA doses for preventive antimicrobials, suggest using Pakistani DDDvetPK values to quantify antimicrobial usage in Pakistan. A huge variation in recommended doses was reported in SmPC. There is an urgent need to establish a list of approved veterinary antimicrobials used in Pakistan, along with harmonization in recommended doses and maintenance of standardized SmPC by the drug regulatory authorities. Setting up a national-level list of defined daily doses is crucial to accurately monitor and quantify AMU.

Evaluation of Drug and Herbal Medicinal Promotions on Social Media During the COVID-19 Pandemic in Relation to World Health Organization Ethical Criteria and South African Health Products Regulatory Authority Guidelines in South Africa: Cross-Sectional Content Analysis.

Consideration of ethics in the promotion of medications is essential to safeguard the health of consumers, particularly during health crises. The World Health Organization (WHO) and the South African Health Products Regulatory Authority (SAHPRA) have established stringent standards to ensure the integrity of pharmaceutical promotions and safeguard public health, including advertisements on the internet and social media platforms. However, the dynamic nature of online advertising poses challenges for monitoring and enforcing ethical standards. The study aimed (1) to examine the COVID-19 drug and medicinal promotions across online platforms and social media from 2020 to 2022 in South Africa and (2) to ensure that drug promotions adhere to ethical guidelines outlined by the WHO and SAPHRA. A cross-sectional content analysis was conducted to assess drug and medicinal advertisements across various internet and social media platforms. A systematic approach was used to identify and analyze promotional content, focusing on adherence to ethical guidelines outlined by WHO and SAPHRA. Data were collected and analyzed to determine the extent of compliance and identify any potential violations or areas for improvement. A total of 14 online drug advertisements were included in this analysis. Our findings show that most of the drugs advertised did not meet the regulations and guidelines provided by WHO and SAHPRA. There were omissions about active ingredients, proprietary names, adverse drug responses, precautions, and overdosage and adverse drug reactions. Traditional medicines were not fully consistent with the approved WHO ethical criteria data sheet. Our analysis highlights the critical importance of ensuring compliance with ethical guidelines in drug promotions on the internet and social media platforms. There is a need for continued vigilance and enforcement efforts to uphold ethical standards and protect the health of the public. Ongoing monitoring and collaboration between national drug regulatory agencies, pharmaceutical companies, and online platforms will be essential for promoting responsible advertising. In addition, safety monitoring and pharmacovigilance systems for herbal medicinal products are yet to be established.

RNA-Binding Small Molecules in Drug Discovery and Delivery: An Overview from Fundamentals.

RNA molecules, similar to proteins, fold into complex structures to confer diverse functions in cells. The intertwining of functions with RNA structures offers a new therapeutic opportunity for small molecules to bind and manipulate disease-relevant RNA pathways, thus creating a therapeutic realm of RNA-binding small molecules. The ongoing interest in RNA targeting and subsequent screening campaigns have led to the identification of numerous compounds that can regulate RNAs from splicing, degradation to malfunctions, with therapeutic benefits for a variety of diseases. Moreover, along with the rise of RNA-based therapeutics, RNA-binding small molecules have expanded their application to the modification, regulation, and delivery of RNA drugs, leading to the burgeoning interest in this field. This Perspective overviews the emerging roles of RNA-binding small molecules in drug discovery and delivery, covering aspects from their action fundamentals to therapeutic applications, which may inspire researchers to advance the field.

A Review on a Drug Registration Process in United Kingdom

This review outlines the regulatory modifications in several pharmaceutical industries that have been impacted by Brexit and develops new standards-based recommendations from the Medicines and Healthcare Products Regulatory Agency (MHRA). To get insight into the regulatory changes that occurred in the pharmaceutical industry during the dissolution of Europe and Britain, retrospective and contemporaneous reviews were used. As the transition period concluded, the MHRA issued a library of new guidelines on January 1, 2021. The several pharmaceutical industries covered by this guidance include clinical trials, medical equipment, imports and exports of Pharmaceuticals and Cosmetics. The Medicines and Healthcare products Regulatory Agency (MHRA) is responsible for approving medicinal products in the UK. The agency offers various routes for marketing authorisation, including national, international, and decentralised procedures. The national routes include a 150-day assessment, rolling review, European Commission (EC) Decision Reliance Procedure, decentralised and mutual recognition reliance procedure, and unfettered access procedure for marketing authorisations approved in Northern Ireland. International routes include Project Orbis and Access Consortium. Applicants must submit their applications through the MHRA submissions portal in electronic Common Technical Document (eCTD) format. The agency verifies the technical validity of submissions using the Lorenz Docubridge validation tool. The MHRA offers fast-track marketing authorisation for products with strong public health benefits or those addressing supply shortages. Applications that do not meet guidelines will be rejected, and applicants must resubmit after correcting errors. Understanding MHRA guidelines and requirements facilitates market entry for medicinal products in the UK. Conclusion: Any medicinal agent to be marked in the United Kingdom has to follow the guidelines and regulations given by the MHRA a regulatory authority which approve drug products. The objective of the review article is to highlights information regarding the requirements. Different types routes in registration of medicinal products in a market in the United Kingdom knowing the requirements of the MHRA guidelines, it is too easy for a product to get into the UK market.

A study on the mediating-moderate effect of the types of illicit drugs on mental health in China.

In China, over 5 million people have been identified and registered by the public security institutions for using illicit drugs. The aim of this study is to compare the influence of different types of illicit drugs on the self-reported mental health of Chinese people. In particular, we want to assess the damage of Heroin, Methamphetamine and Ketamine to mental health in a social environment where drug use is strictly regulated. The study is based on survey with 6,906 people who use drugs in Guangdong province, China. Risk of mental health issue is measured using the Brief Symptoms Inventory 18 (BSI-18) Scale, and a higher BSI-18 score indicates more severe mental health problems. The data was analyzed through multilevel regression analysis, propensity score matching analysis and mediation analysis. The three major types of illicit drugs have both moderating and mediating effects on the length of drug-use history, that Heroin use leads to longer drug-use duration, while Ketamine use causes more damage on mental health per unit time of drug-use duration. Average duration of Methamphetamine use is 0.7 year shorter than average duration of Heroin use, and average duration of Ketamine use is 1.7 year shorter than average duration of Heroin use. For each year of increase of drug-use duration, Ketamine use leads to 1.2 times more of BSI score increase than Heroin use, and 2.3 times more of BSI score increase than Methamphetamine use. These three drugs are associated with severe mental health issue in a society with strict drug regulation. Attention should be paid to the mental health of people regardless of the type of drugs they use.

Factors influencing patients' decisions regarding participation in clinical trials: Review of current literature.

Obtaining timely data in clinical trials (CTs) is critical for drug registration. This depends directly on the speed at which patients are recruited. This paper provides an overview of selected scientific works and literature from different countries about patients' motivators and barriers to participating in CTs From 55 articles retrieved from PubMed, 5 were selected for the analysis. Additionally, 6 publications, including 2 by Polish authors, were reviewed. As a result, we identified 10 factors for further investigation: altruism, hope for personal benefit, access to better care, the role of a doctor, the opinions of close friends or relatives, financial compensation, side effects, the patient's role as a guinea pig, effort and time, and the use of placebo. Regardless of the therapeutic area, health status, study phase, country, geographic area, economic situation, or healthcare system, patients indicated very similar reasons when deciding to participate in a CT. Even if patients as a group had similar motives and concerns, there are individual elements or unusual factors that need to be better understood and evaluated to accelerate the recruitment process in order to avoid certain drugs or therapies being overlooked or underestimated. In this way, investigators can help patients make the best decisions and more effectively support the process of registering a new drug. Future research on factors influencing patients' decisions is still necessary: We do not know how the COVID-19 pandemic may have influenced patient motivation, how new regulations on CTs are changing patients' perceptions of CTs, and what may be important depending on the study, country, therapeutic area and other factors.

Approved medicines for paediatric solid tumours in Europe: Lessons from the life cycle of a paediatric investigation plan

BackgroundDespite the positive changes brought by the Paediatric Regulation in the European Union (EU) in 2007, drug development in children remains challenging. MethodsTo better understand the issues encountered to reach an authorisation for paediatric patients, we reviewed the pathway of the 11 Paediatric Investigational Plans (PIPs) with indications targeting paediatric solid tumours granted by the Committee for Medicinal Products for Human Use (CHMP) between 2007 and 2022. ResultsOn average 5,5 years were necessary to reach approval after a PIP was agreed. All the PIPs underwent at least one modification (median 3 modifications per PIP). The use of single arm trials, in the context of refractory/relapsed disease in absence of standard of care treatment, was supportive for granting a paediatric indication in the majority of the cases. In 6 out of 11 approved products, extrapolation from adults was used. For 2/11 the approval focused on an older population first compared to the initial age group agreed in the PIP due to the development of a suitable formulation for younger children still ongoing at the time of first approval. Scientific advice sought on paediatric development use of extrapolation from adults, major objections raised by CHMP and post-marketing requirements were examined. ConclusionAnalysing the process necessary to reach an authorisation for paediatric patients, we highlight the major challenges faced in the paediatric approval process and the positive examples of successful drug development that reached final approval. Our analysis is expected to provide useful insights to drug developers, investigators and regulators.