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Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease‐related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice. [ABSTRACT FROM AUTHOR]

Membrane transport proteins are involved in the absorption, disposition, efficacy, and/or toxicity of many drugs. Numerous mechanisms (e.g., nuclear receptors, epigenetic gene regulation, microRNAs, alternative splicing, post‐translational modifications, and trafficking) regulate transport protein levels, localization, and function. Various factors associated with disease, medications, and dietary constituents, for example, may alter the regulation and activity of transport proteins in the intestine, liver, kidneys, brain, lungs, placenta, and other important sites, such as tumor tissue. This white paper reviews key mechanisms and regulatory factors that alter the function of clinically relevant transport proteins involved in drug disposition. Current considerations with in vitro and in vivo models that are used to investigate transporter regulation are discussed, including strengths, limitations, and the inherent challenges in predicting the impact of changes due to regulation of one transporter on compensatory pathways and overall drug disposition. In addition, translation and scaling of in vitro observations to in vivo outcomes are considered. The importance of incorporating altered transporter regulation in modeling and simulation approaches to predict the clinical impact on drug disposition is also discussed. Regulation of transporters is highly complex and, therefore, identification of knowledge gaps will aid in directing future research to expand our understanding of clinically relevant molecular mechanisms of transporter regulation. This information is critical to the development of tools and approaches to improve therapeutic outcomes by predicting more accurately the impact of regulation‐mediated changes in transporter function on drug disposition and response. [ABSTRACT FROM AUTHOR]

The Medicines and Healthcare products Regulatory Agency was established in April 2003 by the merger of the Medicines Control Agency (MCA) and the Medical Devices Agency (MDA). This paper describes the scientific and organizational basis for the merger and describes the various challenges facing this new Agency. [ABSTRACT FROM AUTHOR]

The medicalisation of marijuana has occurred rapidly, albeit nonuniformly, across the US and around the world over the past 3 decades. This paper centres on the medicalisation of marijuana in Minnesota—which has one of the most restrictive programs in the country—as a case for evaluating the negotiation of institutional boundaries with the shift from criminalisation to medicalisation after nearly a century of criminal prohibition. Drawing upon Foucauldian discourse analyses of the medical and law enforcement associations' position statements and legislative hearings that shaped medical marijuana policy in Minnesota, this paper demonstrates a symbiotic convergence between medicine and law enforcement through the deployment of shared discursive strategies in their opposition to medical marijuana that reinforce marijuana's criminalised status by solidifying the boundaries between proper medicine and dangerous drugs. Criminal justice and medical institutions draw upon one another's definitions, logics, and practices in a mutually constitutive manner, while still maintaining distinct user subjects and institutional interventions for each based on the user's access to state‐approved forms of marijuana. The consequences for the governing of marijuana in Minnesota are explored, as well as the broader implications for the sociological study of medicalisation and criminalisation with respect to the governance of drugs and health. [ABSTRACT FROM AUTHOR]

Inflammation is a possible cause of variability in drug response and toxicity due to altered regulation in drug‐metabolizing enzymes and transporters (DMETs) in humans. Here, we evaluate the clinical and in vitro evidence on inflammation‐mediated modulation of DMETs, and the impact on drug metabolism in humans. Furthermore, we identify and discuss the gaps in our current knowledge. A systematic literature search on PubMed, Embase, and grey literature was performed in the period of February to September 2020. A total of 203 papers was included. In vitro studies in primary human hepatocytes revealed strong evidence that CYP3A4 is strongly downregulated by inflammatory cytokines IL‐6 and IL‐1β. CYP1A2, CYP2C9, CYP2C19, and CYP2D6 were downregulated to a lesser extent. In clinical studies, acute and chronic inflammatory diseases were observed to cause downregulation of CYP enzymes in a similar pattern. However, there is no clear correlation between in vitro studies and clinical studies, mainly because most in vitro studies use supraphysiological cytokine doses. Moreover, clinical studies demonstrate considerable variability in terms of methodology and inconsistencies in evaluation of the inflammatory state. In conclusion, we find inflammation and pro‐inflammatory cytokines to be important factors in regulation of drug‐metabolizing enzymes and transporters. The observed downregulation is clinically relevant, and we emphasize caution when treating patients in an inflammatory state with narrow therapeutic index drugs. Further research is needed to identify the full extent of inflammation‐mediated changes in DMETs and to further support personalized medicine. [ABSTRACT FROM AUTHOR]

The human absorption, distribution, metabolism and elimination study administering radiolabeled drugs to human volunteers is an important clinical study in the development program of new drug candidates. The manufacture of radiolabeled Active Pharmaceutical Ingredients is covered by national drug laws and may come within the scope of regulatory GMP requirements. Additionally, authorities may request an appropriate environmental zoning to minimize the risk of microbiological contaminations particularly during the synthesis of radiolabeled Active Pharmaceutical Ingredients intended for parenteral application. Thus, a radioactive clean room lab facility in line with both GMP and radiation safety regulations was installed and the environmental zoning validated by appropriate testing of technical parameters and microbial and particle monitoring. The considerations detailed in this paper cover only GMP aspects related to the synthesis of radioactive drug substance. The subsequent, final formulation step in the overall process for manufacturing of radioactive drug product for any kind of administration is not within the scope of this paper. Under these qualified and controlled environmental conditions, we are now in a position to provide radiolabeled drug substances for all kinds of drug administration including both po and iv. [ABSTRACT FROM AUTHOR]

A balanced approach using an integrated combination of strategies, namely, demand reduction, supply reduction and harm reduction, was suggested to be implemented in a balanced way to the policy vision of a South Africa 'free of substance abuse'. Responding on the call for a comprehensive review of the National Drug Master Plan 2013–2017 to ensure consistency in policy approach, this article explores the integrative propositional analysis (IPA)‐based analysis to evaluate 'how systemic' and integrated were the policy strategies applied. The analysis draws insights from the internal consistency of the policy and provides complementary evidence on the systemic breakdown of the policy, which correlates with previous studies. The findings are indicative of the usefulness of the IPA‐based tools to more pragmatically develop policy that better reflects the systemic/integrated relationship of the three strategies based on their conceptual systemic integrity. This research has implications for interdisciplinary scholars and practitioners, of policy and theory. [ABSTRACT FROM AUTHOR]

This paper takes a critical look at progress and prospects regarding the sociology of pharmaceuticals over the years. Key themes examined include: (i) medicalisation and pharmaceuticalisation; (ii) regulation; (iii) consumption and consumerism; (iv) expectations and innovation. Papers in the monograph are also introduced and discussed in relation to these themes. The paper concludes with some further comments and reflections on progress and prospects in this field, emphasising the continuing importance of sociological engagement with these personal and political issues in the 21st century. [ABSTRACT FROM AUTHOR]

Context Until the last decade of the 20th century, France had no equivalent to the US Food and Drug Administration. In this paper we describe and interpret the complex series of events that led to the passage by the French Parliament in December 1992 of a law incorporating such an agency, the Agence du Médicament (literally, 'medicines agency'). The broad aim of this project was to learn how public health policy change comes about by detailed analysis of a specific instance. More specifically, we aimed to better understand the circumstances under which public health crisis leads to significant public health policy reform. Methods This paper is based on detailed analysis of primary documents (eg, archived French health ministry papers, recorded parliamentary debates, government reports, newspaper articles) and oral history interviews covering a period from 1988 to 1993. Thematic analysis of these materials was initially grounded in theories of organizational change, moving to constructs that emerged from the data themselves. Findings Policy entrepreneurs positioned to frame adverse events and seize opportunities are key to public health policy reform. However, whether these entrepreneurs will have the requisite institutional power is contingent both on political structure and on the power of competing institutional actors. Health crises may catalyze institutional reform, but our analysis suggests that whether reform occurs, or even whether adverse episodes are labeled as crises, is highly contingent on circumstances of history, political structure, and political ideology and is extremely difficult to predict or control. Conclusions Actors positioned to shape public health policy need to have a detailed understanding of the circumstances that facilitate or impede policy reform. Health crises are now more often global than not. Comparative, theoretically grounded, cross-national research that looks in detail at how different countries respond to similar health crises would be extremely valuable in informing both policymakers and researchers. [ABSTRACT FROM AUTHOR]

The recent benefit–risk framework (BRF) developed by the Food and Drug Administration (FDA) is intended to improve the clarity and consistency in communicating the reasoning behind the FDA's decisions, acting as an important advancement in US drug regulation. In the PDUFA VI implementation plan, the FDA states that it will continue to explore more structured or quantitative decision analysis approaches; however, it restricts their use within the current BRF that is purely qualitative. By contrast, European regulators and researchers have been long exploring the use of quantitative decision analysis approaches for evaluating drug benefit–risk balance. In this paper, we show how quantitative modelling, backed by decision theory, could complement and extend the FDA's BRF to better support the appraisal of evidence and improve decision outcomes. After providing relevant scientific definitions for benefit–risk assessment and describing the FDA and European Medicines Agency (EMA) frameworks, we explain the components of and differences between qualitative and quantitative approaches. We present lessons learned from the EMA experience with the use of quantitative modelling and we provide evidence of its benefits, illustrated by a real case study that helped to resolve differences of judgements among EMA regulators. [ABSTRACT FROM AUTHOR]

Background: This paper provides a critical review of the decision‐making process of the Ontario Ministry of Health and Long‐Term Care (MOHLTC) regarding which migraine treatment drugs will be covered under the Ontario Drug Benefit Formulary (ODB). Main Text: Under MOHLTC policy, triptans and OnabotulinumtoxinA are available to patients only through the Exceptional Access Program (EAP). This policy, and justifications for it, are examined with reference to clinical guidelines, patient experiences, and health policy literature. The contexts and consequences of compromised access are outlined. Improvements in access to these treatments are suggested by highlighting how a country with similar healthcare infrastructure – Australia – employs policies that more adequately meet the needs of migraine patients as they secure treatments. Conclusions: Despite clinically significant gains in the discovery of safe and effective migraine‐specific treatments the ODB thus far has failed to align its practice with current clinical recommendations. This forces patients to rely heavily on medication that, while still effective for some, is potentially suboptimal. This review concludes it is prudent, at minimum, to follow clinical recommendations that advocate for the removal of triptans from EAP and recategorize them as Limited Use drugs. Ideally, moving them to a general benefit would further remove the barriers experienced by patients attempting to access this treatment. [ABSTRACT FROM AUTHOR]

This paper presents a review of the recent economics literature in the area of illicit drug use. Particular attention is paid to the economics of addiction and the rational addiction model, the welfare economics framework for analysing the social costs of drug use, and the attempts that have been made by economists to evaluate recent or proposed policy interventions. A dominant theme in this review is the problem of poor data availability. This is particularly true when it comes to implementing the Rational Addiction model, but it is also apparent in the literature on estimating the costs of illicit drug use to society as a whole. One of the main conclusions of this review is that until recently public policy has not been particularly influenced by research carried out by economists. It is not clear whether this is because economists have had to grapple with inadequate data, and hence their conclusions are couched in uncertainty, or whether it is because drugs researchers have assumed a very limited role for economists in their analysis. [ABSTRACT FROM AUTHOR]

Model‐informed drug development (MIDD) refers to the application of a wide range of quantitative models in drug development to facilitate the decision‐making process. MIDD was formally recognized in Prescription Drug User Fee Act (PDUFA) VI. There have been many regulatory applications of MIDD to address a variety of drug development and regulatory questions. These applications can be broadly classified into four categories: dose optimization, supportive evidence for efficacy, clinical trial design, and informing policy. Case studies, literature papers, and published regulatory documents are reviewed in this article to highlight some common features of these applications in each category. In addition to the further development and investment in these established domains of application, new technology, and areas, such as more mechanistic models, neural network models, and real‐world data/evidence, are gaining attention, and more submissions and experiences are being accumulated to expand the application of model‐based analysis to a wider scope. [ABSTRACT FROM AUTHOR]

Background and aims: The short‐lived regulated legal market for new psychoactive substances (NPS) in New Zealand marked a radical departure from the traditional prohibition‐based approach to drugs. This paper aimed to enhance understanding of this policy change using Punctuated Equilibrium Theory (PET). Methods: The analysis draws on 3 years of evaluative research, including interviews with key stakeholders, analysis of legislation and policy documents and academic and grey literature. Results: The reframing of the NPS issue from one of drug control to the need for stricter market regulation was achieved by the efforts of strategic policy entrepreneurs, including the legal high industry, drug law reform advocates, influential politicians and an independent legal advisory institution. This reframing was aided by the perceived saliency of the NPS problem and ineffectiveness of previous prohibition‐based responses. In the absence of any political opposition to the regulatory approach, the Psychoactive Substances Act rapidly progressed through the Parliament. However, once the interim legal market was established, portrayal of the issues shifted away from experts and lobbyists to critique from local communities, local government, animal rights activists and the media, who viewed the new regime as a source of social and health problems. The mobilization of criticism ('Schattschneider mobilization') drew on ideas of animal welfare and community safety. With a looming national election, the government responded by ending the interim market with the urgent passage of amendment legislation. Conclusions: Punctuated Equilibrium Theory (PET) helps explain how New Zealand's Psychoactive Substances Act (PSA) policy first emerged on the political agenda and how the initial positive tone of expert support for reform shifted to a tide of popular criticism during the interim regime. However, with its emphasis on explaining agenda‐setting, PET does not account for the legislative design shortcomings of the PSA. [ABSTRACT FROM AUTHOR]

Real world evidence (RWE) has the potential to inform drug discovery, development, and regulatory decision making. The emergence and availability of large population‐based datasets around the globe have stoked enthusiasm in the research community. However, much work remains to refine research methodologies, evolve the science, and define the place of RWE as a complementary source of evidence to randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: The US Food and Drug Administration (FDA) has expanded the use of surrogate markers in drugs approved for oncology/hematology indications. This has likely resulted in a greater number of approvals and possibly drugs coming to market faster, but it is unknown whether these drugs also improve overall survival (OS) for patients taking them. Methods: We sought to estimate the percentage of oncology drugs that have shown to improve OS in a cross‐sectional analysis of US FDA oncology drug approvals (2006–2023). We searched for OS data in registration trials and the peer‐reviewed literature. Results: We found 392 oncology drug approvals. Eighty‐seven (22%) drug approvals were based on OS, 147 drug approvals were later tested for OS benefit (38% of all approvals and 48% of drugs approved on a surrogate), and 130 (33%) have yet to be tested for OS benefit. Of the 147 drug approvals later tested for OS, 109 (28% of all approvals and 74% of drugs later tested for OS) have yet to show OS benefit, whereas 38 (10% of all approvals and 26% of drugs later tested for OS benefit) were later shown to have OS benefit. In total, 125 out of 392 (32%) drugs approved for any indication have been shown to improve OS benefit at some point, and 267 (68%) have yet to show approval. Conclusion: About 32% of all oncology drug approvals have evidence for an improvement in OS. Higher standards are needed in drug regulation to ensure that approved drugs are delivering better patient outcomes, specifically in regards to survival. [ABSTRACT FROM AUTHOR]

Since the 1980s, the pharmaceutical industry has benefited substantially from a series of policy changes that have strengthened the patent protection for brand-name drugs as a result of the industry's political influence. This paper incorporates special interest politics into a quality-ladder model to analyze the policy-makers' tradeoff between the socially optimal patent length and campaign contributions. The welfare analysis suggests that the presence of a pharmaceutical lobby distorting patent protection is socially undesirable in a closed-economy setting but may improve social welfare in a multi-country setting, which features an additional efficiency tradeoff between monopolistic distortion and international free riding on innovations. [ABSTRACT FROM AUTHOR]

Windows of opportunity for changing drug laws open infrequently and they often close without legislative change being affected. In this paper the author, who has been intimately involved in the process, describes how evidence-based recommendations to 'decriminalize' cannabis have recently been progressed through public debate and the political process to become law in Western Australia (WA). The Cannabis Control Bill 2003 passed the WA Parliament on 23 September. The Bill, the legislative backing behind the Cannabis Infringement Notice (CIN) Scheme, came into effect on 22 March 2004. This made WA the fourth Australian jurisdiction, after South Australia, the Australian Capital Territory and the Northern Territory, to adopt a prohibition with civil penalties scheme for minor cannabis offences. This paper describes some of the background to the scheme, the process by which it has become law, the main provisions of the scheme and its evaluation. It includes reflections on the role of politics and the press in the process. The process of implementation and evaluation are outlined by the author, foreshadowing an ongoing opportunity to understand the impact of the change in legislation. GUEST EDITOR: RICHARD MATTICK [ABSTRACT FROM AUTHOR]

Background and aims Prohibitions on producing, distributing and selling cannabis are loosening in various jurisdictions around the world. This paper describes the diversification of cannabis supply laws and discusses the challenges to and opportunities for learning from these changes. Methods We document changes in cannabis supply laws that de jure legalized cannabis production for medical and/or non-medical purposes (excluding industrial hemp) in Australasia, Europe, North America and South America. We also highlight challenges to evaluating these legal changes based on our experiences studying cannabis laws and policies in the United States. Findings As of August 2016, two countries have passed laws to legalize large-scale cannabis production for non-medical purposes at the national (Uruguay) or subnational level (four US states). At least nine other countries legally allow (or will soon allow) cannabis to be supplied for medicinal purposes. Most of the changes in cannabis supply laws have occurred since 2010. The data available in most countries are inadequate for rigorously evaluating the changes in cannabis supply laws. Conclusion The evidence base for assessing changes in cannabis supply laws remains weak. Efforts should focus upon collecting information about quantities consumed and market transactions as well as validating self-report surveys. [ABSTRACT FROM AUTHOR]

Objective With growing access to the Internet, people who use drugs and traffickers started to obtain information about novel psychoactive substances (NPS) via online platforms. This paper aims to analyze whether a decreasing Web interest in formerly banned substances-cocaine, heroin , and MDMA-and the legislative status of mephedrone predict Web interest about this NPS. Methods Google Trends was used to measure changes of Web interest on cocaine, heroin, MDMA, and mephedrone. Google search results for mephedrone within the same time frame were analyzed and categorized. Results Web interest about classic drugs found to be more persistent. Regarding geographical distribution, location of Web searches for heroin and cocaine was less centralized. Illicit status of mephedrone was a negative predictor of its Web search query rates. The connection between mephedrone-related Web search rates and legislative status of this substance was significantly mediated by ecstasy-related Web search queries, the number of documentaries, and forum/blog entries about mephedrone. Conclusions The results might provide support for the hypothesis that mephedrone's popularity was highly correlated with its legal status as well as it functioned as a potential substitute for MDMA. Google Trends was found to be a useful tool for testing theoretical assumptions about NPS. [ABSTRACT FROM AUTHOR]

The medicines regulatory environment is evolving rapidly in response to the changing environment. Advances in science and technology have led to a vast field of increasingly complicated pharmaceutical and medical device products; increasing globalization of the pharmaceutical industry, advances in digital technology and the internet, changing patient populations, and shifts in society also affect the regulatory environment. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines, medical devices and blood products to protect and improve public health, and supports innovation through scientific research and development. It works closely with other bodies in a single medicines network across Europe and takes forward UK health priorities. This paper discusses the range of initiatives in the UK and across Europe to support innovation in medicines regulation. The MHRA leads a number of initiatives, such as the Innovation Office, which helps innovators to navigate the regulatory processes to progress their products or technologies; and simplification of the Clinical Trials Regulations and the Early Access to Medicines Scheme, to bring innovative medicines to patients faster. The Accelerated Access Review will identify reforms to accelerate access for National Health Service patients to innovative medicines and medical technologies. PRIME and Adaptive Pathways initiatives are joint endeavours within the European regulatory community. The MHRA runs spontaneous reporting schemes and works with INTERPOL to tackle counterfeiting and substandard products sold via the internet. The role of the regulator is changing rapidly, with new risk-proportionate, flexible approaches being introduced. International collaboration is a key element of the work of regulators, and is set to expand. [ABSTRACT FROM AUTHOR]

All the while, Dick calmly explained the improvements underway at the FDA in more than 50 congressional hearings, many of which were made difficult by harsh but often unfair public criticism of the FDA. Dick will long be remembered by the drug development and drug regulatory communities for his highly influential role as Director of the US Food and Drug Administration (FDA) Bureau of Drugs from 1971-1982, a time during which much of what we now recognize as the essential features of a well-controlled study were identified and incorporated into drug development. Even these regulations had little impact on FDA review practices until the 1970s during Dick's tenure at the FDA. [Extracted from the article]

First, this paper attempts an assessment of recent developments in British drug policies. In the 1980s British drug policies are in a state of transformation in which it appears that medicine is being displaced from a central role, and being replaced by a more extensive and diffuse response involving a broader range of agencies and ideas about drug problems. A more active role is being played by central government, the debate on drugs is becoming politicized, and there is a new emphasis on law enforcement, and legal and penal control It is now questionable whether the British approach to drug problems is as distinctive as it once was. Given that research on contemporary drug policy is negligible, the second task of this paper is to identify a number of areas and issues worthy of policy analysis. [ABSTRACT FROM AUTHOR]

In their paper, Istvan and colleagues hint at the similarities between the regulation policies of flunitrazepam and zolpidem to draw conclusions about zolpidem's use. Indeed, of the about 1400 cases of hospitalization for addiction to high doses of benzodiazepines and the like in our institution, none were due to flunitrazepam, while more than half of them were due to lormetazepam. Https://doi.org/10.1007/s11739-020-02538-2 5 Lugoboni F, Bertoldi A, Casari R, Mantovani E, Morbioli L, Tamburin S. Adult attention-deficit/hyperactivity disorder and quality of life in high-dose benzodiazepine and related Z-drug users. [Extracted from the article]

Background New Zealand has recently attempted to address the underlying drivers of the escalating new psychoactive substances ( NPS) ('legal highs') problem by establishing the world's first pre-market approval regulatory regime for NPS. NPS products which can be shown with clinical trial data to pose a 'low risk' of harm will be approved for legal manufacture and sale. Aims and method This paper critically assesses the new regime, drawing on experience of the pharmaceutical sector and legal BZP market. Findings A number of characteristics of the recreational use of NPS may not be well addressed by standard medical clinical trials, including binge use, polydrug use, use by vulnerable groups and high-risk modes of administration. The overt advertising and covert promotion of approved NPS products on the internet may make them fairly visible to young people. The black market for unapproved NPS may be difficult to suppress given that unapproved NPS will be physically identical to approved NPS. If the legal market for NPS encourages the use of NPS, alcohol and other drugs there may be an increase in drug-related harm. Alternatively, if the legal NPS market reduces the use of more harmful drugs, there may be a considerable public health benefit. Conclusions The clinical trials required for NPS products should address the characteristics of recreational NPS use. Enforcement resources and technical solutions are required to clearly distinguish legal NPS products. The impact the new NPS regime has on other drug use is a key issue and demands further study. [ABSTRACT FROM AUTHOR]

This paper considers the variation in entry, stay, and residence travel restrictions for people living with HIV/AIDS in the World Health Organization's Eastern Mediterranean region and the wider Muslim world. If these travel restrictions are associated with human rights violations, why do some countries maintain restrictions while others repeal them? In particular, why do countries with a secular governmental regime like Egypt maintain restrictions, while non-secular countries like Iran do not? We argue that in the Eastern Mediterranean region this variation is explained not by the characteristics of a country's particular form of Islam, its level of development, or its adherence to human rights norms, but by the characteristics of the epidemic in a given country. Countries in which the main mode of transmission is sex maintain restrictions because of stigma associated with sex outside marriage in Islam. Countries in which the main mode of transmission is injecting drug use are less likely to maintain restrictions because of Islam's more lenient approach towards drugs. Using firth logistic regression, we show that this holds for countries in the Eastern Mediterranean, but not for Muslim countries globally. We discuss possible reasons for this and the implications for future research. [ABSTRACT FROM AUTHOR]

I read with interest the excellent paper by Powell I et al i .1 entitled "Drug Dosing Recommendations for All Patients: A Roadmap for Change", wherein they discuss "adjusting drug development and regulation to enable effective dosing for all." If drug developers studied wide dose ranges throughout drug development, and regulators subsequently approved wide dose ranges, we would have a pragmatic framework for delivering personalized dosing based on dose titration for each patient. Personalized Dosing = Approved Wide Dose Ranges + Dose Titration. [Extracted from the article]

This paper draws on theories of nodal governance and discursive framing to investigate the rhetorical strategies adopted by campaigners in the ongoing contest over access to medicines and the protection of intellectual property rights in Kenya. It focuses specifically on debates surrounding the implementation of the WTO's TRIPs Agreement in 2001 and the passage of anti‐counterfeit legislation in 2008. A survey of parliamentary debates and media sources, as well as interviews conducted with key participants, indicates that “the nation” provided a common overarching frame for arguments made by opposing sides to these debates. The salience of specifically national considerations confirms our view that studies of framing and health governance need to extend their focus beyond developments in international and developed country fora. It also highlights the continued purchase of the national interest as a means of mobilizing the key state institutions needed to implement global legal regimes in Africa. [ABSTRACT FROM AUTHOR]

In September 1989, amid an emotional and ideological debate regarding problematic drug use in the United States and the 'war on drugs', RAND's Drug Policy Research Center (DPRC) was created through private foundation funds. The purpose of this new research center was to provide objective empirical analysis on which to base sound drug policy. Twenty years later, RAND's DPRC continues its work, drawing on a broad range of analytical expertise to evaluate, compare and assess the effectiveness of a similarly broad range of drug policies. More than 60 affiliated researchers in the United States and Europe make up the Center, which attempts to provide objective empirical analyses to better inform drug policies within the United States and abroad. This paper provides a look back at the creation, evolution and growth of the Center. It then describes how the Center operates today and how it has maintained its clear identity and focus by drawing on the analytical capabilities of a talented group of researchers from a broad range of academic disciplines. [ABSTRACT FROM AUTHOR]

The article presents the interview summary with epidemiologist Ingeborg Rossow who discusses her experience helping patients and meeting all sorts of people, and conducting dental research. Also her participation in the alcohol and suicide prevention project aimed researchers to look at whether the association between alcohol consumption and suicide rates varied throughout different drinking cultures.

Reports on the introduction of a draft policy paper on the distribution of medicines in Great Britain. Emphasis on animal health and welfare and of public safety; Proposal of the maintenance of a three-tier system of medicines; Policy governing the training and monitoring standards of veterinary prescriptions.

Introduction and Aims. A large legal market for party pills containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) developed in New Zealand after 2004. The use of these party pills has been associated with adverse health effects. The purpose of this paper was to assess a general population sample of party pill users to investigate the relationship between (1) patterns of use of BZP/TFMPP party pills and concurrent use of other drug types, and (2) adverse side effects from BZP/TFMPP party pill use. Design. A national household survey of the use of BZP/TFMPP party pills was conducted using a computer-assisted telephone interviewing (CATI) facility. The quantity of BZP and TFMPP in each brand of party pill was obtained from the National Poisons Centre. Multiple logistic regression analysis was used to identify independent predictors of having experienced adverse side effects from party pills. Results. The mean quantity of BZP/TFMPP taken on an occasion of greatest use was 533 mg (median 400 mg, range 43 - 2500 mg). Being female, using cannabis and other drugs concurrently with BZP/TFMPP party pills, taking large quantities of party pills in a single session and taking 5-hydroxytryptophan (5-HTP) recovery pills at the same time as party pills were independent predictors of having experienced an adverse problem from party pills. Conclusions. Females may be at greater risk of experiencing problems from BZP/TFMPP party pills due to their smaller physical size. Taking 5-HTP 'recovery' pills with party pills may increase the risk of adverse effects as both substances increase users' levels of serotonin. [ABSTRACT FROM AUTHOR]

Background Δ9-Tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis and its various preparations. Increasing use of cannabis for recreational purposes has created a problem for road-traffic safety. This paper compares age, gender and the concentrations of THC in blood of individuals apprehended for driving under the influence of drugs (DUID) in Sweden, where a zero-tolerance law operates. Measurements Specimens of blood or urine were subjected to a broad screening analysis by enzyme immunoassay methods. THC positives were verified by analysis of blood by gas chromatography-mass spectrometry (GC-MS) with a deuterium-labelled internal standard (d3-THC). All toxicology results were entered into a database (TOXBASE) along with the age and gender of apprehended drivers. Findings Over a 10-year period (1995–2004), between 18% and 30% of all DUID suspects had measurable amounts of THC in their blood (> 0.3 ng/ml) either alone or together with other drugs. The mean age [± standard deviation (SD)] of cannabis users was 33 ± 9.4 years (range 15–66 years), with a strong predominance of men (94%, P < 0.001). The frequency distribution of THC concentrations ( n = 8794) was skewed markedly to the right with mean, median and highest values of 2.1 ng/ml, 1.0 ng/ml and 67 ng/ml, respectively. The THC concentration was less than 1.0 ng/ml in 43% of cases and below 2.0 ng/ml in 61% of cases. The age of offenders was not correlated with the concentration of THC in blood ( r = −0.027, P > 0.05). THC concentrations in blood were higher when this was the only psychoactive substance present ( n = 1276); mean 3.6 ng/ml, median 2.0 ng/ml compared with multi-drug users; mean 1.8 ng/ml, median 1.0 ng/ml ( P < 0.001). In cases with THC as the only drug present the concentration was less than 1.0 ng/ml in 26% and below 2.0 ng/ml in 41% of cases. The high prevalence of men, the average age and the concentrations of THC in blood were similar in users of illicit drugs (non-traffic cases). Conclusions The concentration of THC in blood at the time of driving is probably a great deal higher than at the time of sampling (30–90 minutes later). The notion of enacting science-based concentration limits of THC in blood (e.g. 3–5 ng/ml), as discussed in some quarters, would result in many individuals evading prosecution. Zero-tolerance or limit of quantitation laws are a much more pragmatic way to enforce DUID legislation. [ABSTRACT FROM AUTHOR]

Previous empirical studies that have examined the links between pharmaceutical price controls, profits, cash flows, and investment in research and development (R&D) have been largely based on retrospective statistical analyses of firm- and/or industry-level data. These studies, which have contributed numerous insights and findings to the literature, relied upon ad hoc reduced-form model specifications. In the current paper we take a very different approach: a prospective micro-simulation approach. Using Monte Carlo techniques we model how future price controls in the US will impact early-stage product development decisions in the pharmaceutical industry. This is done within the context of a net present value (NPV) framework that appropriately reflects the uncertainty associated with R&D project technical success, development costs, and future revenues. Using partial-information estimators calibrated with the most contemporary clinical and economic data available, we demonstrate how pharmaceutical price controls will significantly diminish the incentives to undertake early-stage R&D investment. For example, we estimate that cutting prices by 40–50% in the US will lead to between 30 and 60% fewer R&D projects being undertaken (in early-stage development). Given the recent legislative efforts to control prescription drug prices in the US and the likelihood that price controls will prevail as a result, it is important to better understand the firm response to such a regulatory change. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Many civil society organisations (CSOs) have been at the forefront of identifying new ideas and implementing innovative models regarding health and health systems around the world. Their activities become highly charged, however, when they engage in advocacy efforts designed to influence change in policies and systems linked with more controversial or complicated public health issues. Policies, laws and regulations regarding illicit drugs and tobacco fall directly into that category. There is no doubt that the use of both kinds of substances can have the same health consequences—including ill health and death—yet they are approached in widely different ways. Smoking is legal to some extent in every country in the world, and is generally considered a matter of personal choice. Many people believe that efforts to limit tobacco use are coercive and impede on individual rights. Those who use illicit drugs such as heroin, meanwhile, are with few exceptions considered social deviants, misfits and lawbreakers. Many CSOs support comprehensive, government-funded prevention strategies coupled with non-punitive, non-judgemental programmes designed to help users change behaviour. Such strategies are designed to reflect and respond to the medically addictive nature of both tobacco and many illegal drugs. Proponents argue that not only are the public health benefits of expansive, well-conceived interventions potentially vast, but so too are the social and economic benefits accruing from lower rates of debilitating disease and premature death. To that end, many international, national and local CSOs are identifying the direct and indirect health consequences of tobacco and illegal drug use; proposing and advocating for strategies to limit their impact; and sharing information and resources with like-minded organisations elsewhere. This leadership role has helped influence and shape policy, especially in recent years. This paper examines civil society's involvement in efforts to change drug and tobacco policy in selected countries in Central and Eastern Europe and the former Soviet Union (CEE/FSU). It concludes that in Poland and Kazakhstan, in terms of tobacco control, and increasingly in Ukraine and parts of Central Asia in terms of harm reduction, multi-sectoral approaches are the most effective way to engage citizens and to implement comprehensive strategies to change behaviour by supportive measures, not punitive ones. [Malinowska-Sempruch K, Bonnell R, Hoover J. Civil society—a leader in HIV prevention and tobacco control. Drug Alcohol Rev 2006;25:625 – 632] [ABSTRACT FROM AUTHOR]

In this paper Moore & Dietze use data from their study of street-based injecting drug users and sex workers in the Melbourne suburb of St Kilda to challenge the dominant emphasis of drug policy in Australia. They remind us that while existing harm reduction strategies that encourage individual behaviour change should be continued, these measures need to be complemented and extended by further attention to the environmental aspects of drug-related harm. This is a timely call. Responses targeting individual behaviour change are relatively easy to implement and less politically challenging. However, if we are really serious about reducing drug-related harm in the Australian community, then broader systemic and structural barriers which undermine these efforts must be addressed.Simon LentonEditor, Harm Reduction Digest. [ABSTRACT FROM AUTHOR]

Following increasing concern in the UK about the mortality and morbidity associated with self-poisoning with analgesics, especially paracetamol (Tylenol, acetaminophen), legislation was introduced in 1998 to modify packs sold over-the-counter. The most important change was a reduction in the maximum size of packs. In this paper the background to the legislation, the rationale behind it, and its early impact are reviewed. The changes have had significant positive initial benefits on the mortality and morbidity associated with self-poisoning with analgesics. [ABSTRACT FROM AUTHOR]

Breast cancer with bone metastasis accounts for serious cancer-associated pain which significantly reduces the quality of life of affected patients and promotes cancer progression. However, effective treatment using nanomedicine remains a formidable challenge owing to poor drug delivery efficiency to multiple cancer lesions and inappropriate management of cancer-associated pain. In this study, using engineered macrophage membrane (EMM) and drugs loaded nanoparticle, we constructed a biomimetic nanoplatform (EMM@DJHAD) for the concurrent therapy of bone metastatic breast cancer and associated pain. Tumor tropism inherited from EMM provided the targeting ability for both primary and metastatic lesions. Subsequently, the synergistic combination of decitabine and JTC801 boosted the lytic and inflammatory responses accompanied by a tumoricidal effect, which transformed the tumor into an ideal decoy for EMM, resulting in prolonged troop migration toward tumors. EMM@DJHAD exerted significant effects on tumor suppression and a pronounced analgesic effect by inhibiting μ-opioid receptors in bonemetastasismousemodels.Moreover, the nanoplatformsignificantly reduced the severe toxicity induced by chemotherapy agents. Overall, this biomimetic nanoplatform with good biocompatibility may be used for the effective treatment of breast cancer with bone metastasis. [ABSTRACT FROM AUTHOR]

Physiologically based pharmacokinetic modeling could be used to predict changes in exposure during pregnancy and possibly inform medicine use in pregnancy in situations in which there is currently limited or no available clinical PK data. The Medicines and Healthcare Product Regulatory Agency has been evaluating the available models for a number of medicines cleared by hepatic clearance mechanisms. Models were evaluated for metoprolol, tacrolimus, clindamycin, ondansetron, phenytoin, caffeine, fluoxetine, clozapine, carbamazepine, metronidazole, and paracetamol. The hepatic metabolism through cytochrome P450 (CYP) contributes significantly to the elimination of these drugs, and available knowledge of CYP changes during pregnancy has been implemented in the existing pregnancy physiology models. In general, models were able to capture trends in exposure changes in pregnancy to some extent, but the magnitude of pharmacokinetic change for these hepatically cleared drugs was not captured in each case, nor were models always able to capture overall exposure in the populations. A thorough evaluation was hampered by the lack of clinical data for drugs cleared by a specific clearance pathway. The limited clinical data, as well as complex elimination pathways involving CYPs, uridine 5′‐diphospho‐glucuronosyltransferase and active transporter for many drugs, currently limit the confidence in the prospective use of the models. Pregnancy‐related changes in uridine 5′‐diphospho‐glucuronosyltransferase and transport functions are emerging, and incorporation of such changes in current physiologically based pharmacokinetic modeling software is in progress. Filling this gap is expected to further enhance predictive performance of models and increase the confidence in predicting PK changes in pregnant women for hepatically cleared drugs. [ABSTRACT FROM AUTHOR]

Rapid detection and identification of opioids are of great significance and an urgent need in drug regulation and forensic science. Fentanyl is an extremely potent synthetic drug of abuse that unfortunately cannot be accurately detected. Therefore, techniques combining fast, highly sensitive and portable for fentanyl detection need to be developed. Surface‐enhanced Raman spectroscopy (SERS) has emerged as a promising detection technique owing to its high sensitivity and selectivity. Here, we reported a nonmetal SERS substrate used for trace fentanyl detection. The lowest detectable concentration was 10−7 M, and the MoO2 substrate exhibited excellent thermal and chemical stability, which could even ensure high‐temperature heating, laser irradiation, and corrosion of strong acid or alkali. [ABSTRACT FROM AUTHOR]

Drug use by young people is widespread and increasing. Attempts to prevent or reduce young people's drug use have focused on school-based education, This paper examines some of these strategies. There is wide agreement that providing information about drugs is necessary but insufficient; in addition, you rig people need to be given the opportunity to examine attitudes about drug use, develop skills in making decisions about use and look at ways to reduce the harms that are associated with their own and others' use of both legal and illegal drugs. Most commentators are also agreed that drug education needs to start early and should take account of what young people already know about drugs. Peer-led approaches are promising but not yet adequately evaluated. Because there are basic differences in philosophies and equivocal research on the effectiveness of drug education there is little consensus on a number of issues. [ABSTRACT FROM AUTHOR]

Policy PointsPeople are dying at record numbers from overdose in the United States.Concerted action has led to a number of successes, including reduced inappropriate opioid prescribing and increased availability of opioid use disorder treatment and harm‐reduction efforts, yet ongoing challenges include criminalization of drug use and regulatory and stigma barriers to expansion of treatment and harm‐reduction services.Priorities for action include investing in evidence‐based and compassionate policies and programs that address sources of opioid demand, decriminalizing drug use and drug paraphernalia, enacting policies to make medication for opioid use disorder more accessible, and promoting drug checking and safe drug supply. [ABSTRACT FROM AUTHOR]

This article analyses how two key instruments of European Union pharmaceuticals legislation—good manufacturing practices and environmental risk assessment of pharmaceuticals—address known risks posed by the release of pharmaceuticals in the environment to human health and the environment and identifies the challenges that they face in regulating global manufacturing supply chains. The analysis reveals that these instruments fail to address the environmental challenges posed by pharmaceuticals within global manufacturing supply chains. Based on these findings, we propose to revise European pharmaceuticals legislation by expanding the scope and information requirements of both human and veterinary environmental risk assessment and increasing its weight in the risk–benefit analysis for human pharmaceuticals; by including direct environmental requirements for certain prioritized pharmaceuticals; and by integrating environmental considerations and related verification mechanisms into good manufacturing practices. [ABSTRACT FROM AUTHOR]

The article explores what addiction specialists in the United States might learn from Estonia regarding their response to problems relating to drug addiction and overdose. Particular focus is given to the use of fentanyl, which has been a major contributor to the overdose death epidemic in both Estonia and the United States. Other topics discussed include methodologies for harm reduction, the development of early warning systems (EWS) that can inform users of the dangers and harms of new fentanyl analogues, and the effectiveness of naloxone.

Zelentsova et al. utilized NMR metabolomic profiling to quantify and compare biomarkers in human serum, aqueous humor (AH), and vitreous humor (VH). SP [ sp [10] SP ] sp They identified promising targets that correlated well with PMI and proposed a model based on several metabolites in AH and VH. Nuclear magnetic resonance (NMR) spectroscopy has a long history in structure elucidation of molecules both small and large. With the reemergence of lower field strength, permanent magnet, benchtop NMR systems operating at 40-100 MHz, there has been a renewed interest in NMR for routine drug analysis as evident in articles discussed in the previous section. In their article " I Benchtop nuclear magnetic resonance spectroscopy in forensic chemistry i ", Draper and McCarney provide an excellent literature review of the use of benchtop NMR systems in forensic chemistry applications largely spanning the last 5 years of developments. SP [ sp [2] SP ] sp This review covers a broad range of methods now being explored to push the application limits of benchtop NMR in forensic as well as other applications. [Extracted from the article]

Amphetamine and cathinone derivatives are abused recreationally due to the sense of euphoria they provide to the user. Methodologies for the rapid detection of the drug derivative present in a seized sample, or an indication of the drug class, are beneficial to law enforcement and healthcare providers. Identifying the drug class is prudent because derivatisation of these drugs, to produce regioisomers, for example, occurs frequently to circumvent global and local drug laws. Thus, newly encountered derivatives might not be present in a spectral library. Employment of benchtop nuclear magnetic resonance (NMR) could be used to provide rapid analysis of seized samples as well as identifying the class of drug present. Discrimination of individual amphetamine‐, methcathinone‐, N‐ethylcathinone and nor‐ephedrine‐derived fluorinated and methylated regioisomers is achieved herein using qualitative automated 1H NMR analysis and compared to gas chromatography–mass spectrometry (GC–MS) data. Two seized drug samples, SS1 and SS2, were identified to contain 4‐fluoroamphetamine by 1H NMR (match score median = 0.9933) and GC–MS (RRt = 5.42–5.43 min). The amount of 4‐fluoroamphetamine present was 42.8%–43.4% w/w and 48.7%–49.2% w/w for SS1 and SS2, respectively, from quantitative 19F NMR analysis, which is in agreement with the amount determined by GC–MS (39.9%–41.4% w/w and 49.0%–49.3% w/w). The total time for the qualitative 1H NMR and quantitative 19F NMR analysis is ~10 min. This contrasts to ~40 min for the GC–MS method. The NMR method also benefits from minimal sample preparation. Thus, benchtop NMR affords rapid, and discriminatory, analysis of the drug present in a seized sample. [ABSTRACT FROM AUTHOR]

In this article the authors present their stands on the paper of H. Kalant about drugs classification along with their scheduling. They remark on Single Convention on Narcotic Drugs of 1961 and Convention on Psychotropic Substances of 1971 that organize a body of law internationally applicable to control and ensure the availability of narcotic drugs and pyschotropic substances. They also conclude that the control of addictive substances should aim in controling its availability and supply.

Introduction and Aims: There have been many changes to cannabis laws across the globe, some dramatic but more often incremental. This study explored the experiences after an incremental cannabis law reform in the Australian Capital Territory, Australia.Method: Semi-structured interviews (n = 30) were conducted in March and April 2021, 14 months after the introduction of cannabis law reform, with people aged 18 and over who had grown and/or consumed cannabis in the previous 12 months. Participants were asked about recent and past cannabis use, growing cannabis and changes to their practices after the introduction of the legislation.Results: Incremental cannabis law change resulted in regulatory grey areas. How people interpreted and navigated such grey areas were connected to their relative privileges, circumstances and histories. Those who were highly policed were more likely to experience the grey areas negatively. Those who were not highly policed found the grey areas confusing or 'half-arse' (insufficiently executed), but mostly experienced the new laws positively through new cannabis cultivation or perceived reduction in stigma and fear of arrest. Those with self-identified privilege were unconcerned with grey areas of the legislation.Discussion and Conclusion: Incremental policy change can result in grey areas that require some navigation. Vulnerable populations appear less likely to experience the full benefits of such incremental drug law reform. It is vital to attend to the inequities that can arise from incremental law reform so that positive experiences are shared across the population regardless of relative privilege. [ABSTRACT FROM AUTHOR]

The development of specific drug therapy for children was a paradigm‐changing event that transformed paediatric medical practice. However, a series of tragedies involving drug treatment for children resulted in a gap developing between drug regulation and practice, with the majority of drugs used in child healthcare being used off‐label, rendering children therapeutic orphans. Over the past two decades changes in drug regulation led by the US Food and Drug Administration and followed by the European Union's European Medicines Agency have led to substantial changes in how new drugs with potential use in children are studied and labelled. While these changes have substantially improved labelling for new drugs, there has been much less progress with older drugs. Although the unique challenges of conducting clinical research in children have been addressed by novel clinical trial designs, many of these innovations have not been translated into approaches accepted for the drug approval process. The regulations applying to the need for paediatric studies currently are only applicable in the United States and the European Union, and there is less impetus for paediatric labelling in other jurisdictions. This impacts on a number of issues beyond labelling, including the availability of child‐friendly formulations. Finally, the impact of Brexit on paediatric drug studies in the UK remains unclear and is subject to ongoing negotiations between the UK government and the European Union. [ABSTRACT FROM AUTHOR]

Half of all pregnancies in the USA are unintended, suggesting a high incidence of either improper or nonuse of contraceptives. Emergency birth control (EBC) provides individuals with additional insurance against unplanned pregnancy in the presence of contraception failure. This study is the first to estimate the impact of switching EBC from prescription to nonprescription status in the USA on abortions and risky sexual behavior as measured by STD rates. Utilizing state-level variation in access to EBC, we find that providing individuals with over-the-counter access to EBC leads to increase STD rates and has no effect on abortion rates. Moreover, individual-level analysis using the National Longitudinal Survey of Youth indicates that risky sexual behavior such as engaging in unprotected sex and number of sexual encounters increases as a result of over-the-counter access to EBC, which is consistent with the state-level STD findings. [ABSTRACT FROM AUTHOR]