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This study aimed to analyze worldwide sales of new therapeutic agents and to estimate the time it takes for product sales to exceed industry-wide average drug development costs. Data obtained from company reports were analyzed to track worldwide sales of new medicines approved by the US Food and Drug Administration from 1995 to 2014. All sales figures were reported in 2019 US dollars. Kaplan-Meier curves were used to evaluate the time it took for discounted product sales to exceed the average costs associated with developing 1 new drug (accounting for the costs of failed trials), using published estimates of these costs. Based on data for 361 of 558 new therapeutic agents approved over the study period (median follow-up 13.2 years), mean sales revenue per product was $15.2 billion through the end of 2019; the median was $6.7 billion. These products jointly generated global sales of $5.5 trillion since approval. Revenues were highly skewed, with the 25 best selling products (7%, 25 of 361) accounting for 38% of this amount ($2.1 trillion of $5.5 trillion). Approximately 47% of products had discounted sales that exceeded the estimated industry-wide average costs of development within 5 years of approval, and 75% within 10 years. After attributing potential production, marketing, and other costs, these numbers dropped to 21% of products within 5 years of approval, and 46% within 10 years. Sales of new medicines approved from 1995 to 2014 were highly skewed, but many products had net discounted sales that exceeded the industry-wide average costs of development within 10 years of approval. An understanding of how sales revenues accrue in the years after initial approval, alongside data on business costs, can inform discussions about how to incentivize private investment in innovation while ensuring affordable prices for patients and the healthcare system. • Little is known about how much drug companies earn in sales revenues for new medicines and how long it takes them to recover the costs of research and development. • Based on data for 361 of 558 new therapeutic agents approved by the US Food and Drug Administration from 1995 to 2014, median worldwide sales per product was $6.7 billion through 2019 (median follow-up 13.2 years). Approximately 2 in 10 drugs had net discounted sales that exceeded the industry-wide average cost of development within 5 years of approval, and 1 in 2 within 10 years of approval (after accounting for production, marketing, and other costs). • Companies generated large revenues on sales of new drugs approved from 1995 to 2014, although sales were highly skewed. An understanding of the revenues earned by pharmaceutical companies on brand-name drugs, alongside data on business costs, can inform discussions about how to incentivize private investment in innovation while ensuring affordable prices for patients and the healthcare system. [ABSTRACT FROM AUTHOR]

Using data from A-share pharmaceutical manufacturing listed companies between 2011 and 2021, this paper constructs a difference in differences (DID) model to systematically analyze the impact of China's Marketing Authorization Holder (MAH) system pilot policy on pharmaceutical enterprise innovation. Our findings indicate that implementing the MAH system can significantly stimulate innovation in pharmaceutical enterprises, both in terms of input and output. Additionally, local intellectual property protection positively moderates the incentive effect of MAH system on pharmaceutical innovation. The results of our heterogeneity analysis further demonstrate that the pilot policy of the MAH system exerts a stronger incentive effect on the innovation behavior of non-state-owned enterprises and enterprises in the growth and mature stage. Moreover, we provide evidence for the long-term impact of MAH system on innovation within pharmaceutical companies. [ABSTRACT FROM AUTHOR]

The departure of the UK from the European Union (EU) and affiliated European regulatory bodies, including the European Medicines Agency, on Dec 31, 2020, has resulted in the Medicines and Healthcare products Regulatory Agency becoming an independent national regulator. This change has required a fundamental transformation of the UK drug regulatory landscape, creating both opportunities and challenges for future development of oncology drugs. New UK pharmaceutical policies have sought to make the UK an attractive market for drug development and regulatory review, by offering expedited review pathways coupled to strong collaborative relations with other leading international medicines regulators, outside of Europe. Oncology is a key global therapy area for both drug development and regulatory approval, and the UK Government has been keen to show regulatory innovation and international collaboration through approval of new cancer medicines. In this Policy Review, we examine the new UK regulatory frameworks, policies, and global collaborations affecting new oncology drug approvals after departure from the EU. We explore some of the challenges that might lie ahead as the UK creates new and independent regulatory review and approval processes for the next generation of cancer medicines. [ABSTRACT FROM AUTHOR]

The zero-price conundrum occurs when a clinically effective drug can justify no greater than a price of zero based on cost-effectiveness criteria from a health system perspective. This is relevant for health systems that require evidence of cost-effectiveness, in addition to safety and efficacy for drug approval and other analyses that may shape drug coverage policies, such as budget impact and comparative effectiveness. This study aimed to clarify and explore the zero-price conundrum to provide a resource in the development of practical and methodological solutions. We specified equations representing previously identified zero-price scenarios and used them to elucidate factors contributing to the zero-price conundrum and explore relationships between them. We present real-world considerations and discuss solutions from the literature. The analyses demonstrated that a primary cause of the zero-price problem for a new drug that increases quality-adjusted survival pertains to healthcare costs beyond the influence of the new drug, specifically, disease background costs, costs of existing drugs used in a combination regimen, and costs of future health interventions patients may become eligible to receive. Pragmatic solutions have been to exclude such costs from cost-effectiveness analyses. Proposed modifications to cost-effectiveness analysis include assessing each drug in a combination regimen based on its relative contribution to improved health. The zero-price dilemma may arise more frequently as the number of drugs in high-cost disease areas continues to grow. As cost-effectiveness methods evolve, there is the opportunity to develop robust solutions that can be applied consistently. • Drugs that increase quality-adjusted survival might not be cost-effective even at a price of zero because of costs beyond the influence of the drug. • The zero-price conundrum is relevant for healthcare systems that require evidence of cost-effectiveness at a given price, in addition to evidence of safety and efficacy for drug approval, and other analyses that may shape drug coverage policies, such as budget impact and comparative effectiveness. • Some proposed modifications to cost-effectiveness analysis include excluding disease background costs and assessing each drug in a combination regimen based on its relative contribution to improved health. [ABSTRACT FROM AUTHOR]

Over the past two decades, China has introduced significant changes to drug regulations through regulatory innovations to accelerate drug review and approvals, keeping in line with the rapidly growing scientific innovation in drug research and development (R&D). In this study, we outlined the revolution of drug regulation in China since the establishment of the State Drug Administration in 1998. More particularly, we performed a comprehensive analysis of newly approved anticancer drugs in China from the year 2005 to May 2021, as a powerful illustration of how the revolution has changed the drug R&D landscape. Innovative drug development in China has boomed, benefiting in particular from pro-innovation policies as well as expedited program designations by the authority. We found a significant increase in the number of both imported and domestic new anticancer drugs from 2005 to 2021, with the emergence of drugs with novel mechanisms of action, including immune checkpoint inhibitors and cell therapy products. Drug lag has also been dramatically shortened by more than 70% for imported drugs in years 2016–2020 compared to years 2006–2010. Furthermore, we provide an insight into the potential approaches to further optimize the science-based and clinical value-based regulatory and R&D drug ecosystem in China. This review provides evidence of significant impacts of regulations and policies on drug R&D and suggests that the constantly adapting regulatory ecosystem will speed up drug development in China and worldwide. This review is an overview of newly approved cancer drugs in China between 2005 and 2021, as a powerful illustration of how revolution in drug regulation has influenced the drug R&D in China. [Display omitted] [ABSTRACT FROM AUTHOR]

The World Health Organization provides 10 specific guidelines for managing the prices of pharmaceutical products. Many of those are widely known and used such as reference pricing, value-based pricing, price transparency, and tendering. Less attention and knowledge is concentrated in markup regulation across the pharmaceutical supply chain and distribution and in tax exemptions or reductions. This article quantifies the impact of these price components in the Latin American (LatAm) region and places the findings in the context of economic theory and international policy experiences. 2020 retail pharmaceutical sales data from 8 major LatAm markets covered in the IQVIA database were decomposed into ex-factory, distributor markups, and taxes using price build up information and the Price Decipher Methodology developed by the Novartis Global Pricing Governance and Negotiation team. The findings were reviewed by an international panel representing academia, health policy, health economics, patient, and industry. The ex-factory market value of the analyzed markets was $49 billion. Distribution markups added $20 billion and taxes a further $10.5 billion. This represented a 63% increase over ex-factory prices, considered high if compared with 24% for an international benchmark of 35 ex-LatAm countries. Reducing markups for these LatAm countries to 24% would represent up to $19 billion in savings for payers and patients. There is potential for significant cost reductions associated with tax and distribution markup refinements in the LatAm retail pharmaceutical market. National policies should be informed by additional context-specific research for effective implementation. • The World Health Organization provides 10 specific guidelines about settling, managing, and influencing the price of prescription pharmaceutical products. Many of those are well studied, known, and used, such as reference pricing, value-based pricing, price transparency, and tendering. Less attention has been paid on and relatively little is known about distribution markup regulation across the pharmaceutical supply chain (recommendation #4) and taxation (including exemptions or tax reductions) of pharmaceutical products (recommendation #10). • This research quantifies the role of taxes and distribution markups for retail prescription pharmaceuticals in key Latin American markets and assesses policy implications. Distribution markups added $20 billion and taxes a further $10.5 billion to ex-factory prices. This represented a 63% increase in ex-factory price levels, compared with 24% based on an international benchmark. Significant out-of-pocket and/or payer expenditure reductions could be expected by reducing markups and taxes, bringing these in line with international benchmarks. • Tax reductions or exemptions for prescription pharmaceuticals can be justified for public/social goods. Trade-offs due to the limited fiscal space, tax efficiency considerations (favoring uniform tax rates across the broadest basked of goods and services) and local context (including patient information and education) will need to be considered. Improvements in the performance of the distribution market, such as stronger competition and vertical and horizontal integration to promote economies of scale, could also be considered. [ABSTRACT FROM AUTHOR]

Research has recognized Adult Drug Treatment Courts (DTCs) as benefitting participants, with a wide body of research demonstrating lower levels of recidivism and drug use. A budding community-level body of research, however, has returned mixed results, some studies showing increases in arrests and crime relative to DTC initiation. Since DTCs cover over three-fourths of the US population, results showing such unintended consequences must be validated and rectified if held. This study estimated effects for DTCs for community-level crime effects from 1990 to 2018 using a stacked event study identification strategy. Most results indicated no significant effects. However, for population groups between 10,000 and 50,000, DTCs were associated with reductions in some crime categories. Violent index offenses offered the most robust results, and there was a small increase in non-index crimes in communities with populations between 50,000 and 100,000. • A stacked event study is appropriate when studying programs/policies like drug treatment courts (DTCs). • DTCs showed an association with reduced crime in communities between 10,000-50,000. • DTCs may have a preventative effect regarding violent crime. • Communities may also be shifting priorities in multiple areas when initiating DTCs. [ABSTRACT FROM AUTHOR]

Estimating antimalarial drug efficacy requires differentiating treatment failures from new infections arising during the several-week follow-up period in drug trials. Genetic profiling of malaria infections can guide this decision but is notoriously difficult in practice. Previous World Health Organisation (WHO) guidelines were based on assumptions with an inherently high risk of underestimating failure rates. A recent update to WHO guidelines recognises a wider range of analyses to overcome these limitations. We discuss these new analyses and their underlying logic. Drug failure rate estimates in moderate to high transmissions areas will become more accurate but will likely rise twofold due to better detection of treatment failures, and the malaria community needs to anticipate and prepare for potentially large increases in estimated failure rates. The World Health Organisation (WHO) 2008 guidelines for molecular correction in malaria drug trials assumed unrealistic 'perfect' genotyping performance (i.e., perfect detectability of all clones present in a blood sample) resulting in underestimates of the true drug failure rates. Revised guidelines were recently published which now acknowledge alternative methodologies for molecular correction. The estimates from these alternatives will likely be much more accurate but will result in estimated failure rates increasing twofold. These revised estimates will often exceed the WHO recommendation for replacing drugs whose failure rates exceed 10%. The malaria community needs to anticipate these reports of higher failure rates, understand the rationale behind them, and put policies in place to accommodate the increased estimates within existing drug deployment policies. [ABSTRACT FROM AUTHOR]

International conservation efforts and prohibitionary drug intersect in unexpected ways throughout the Mesoamerican Biological Corridor (MBC). US-led counterdrug interdiction of transnational cocaine trafficking, or 'narco-trafficking', is increasingly pushing narco-traffickers and their associated environmental destruction into protected areas (PAs) to establish new smuggling routes. These locations are also where the greatest densities of jaguars (Panthera onca), an iconic and declining species, are found in Central America. Intersecting two geospatial datasets estimating 1) jaguar densities and 2) changes in landscape suitability for drug trafficking following counterdrug interdiction pressure, we estimated that roughly 69 % of the estimated population of jaguars in the MBC were found in areas of increased suitability for narco-traffickers. Moreover, jaguar populations within PAs were 2.5 and 34 times more likely to be in increased narco-trafficking suitability areas than those in jaguar corridors or other area without conservation designations, respectively. These findings illustrate the full costs of continuing current counterdrug interdiction policies alongside conventional conservation strategies and suggest that community-based conservation governance may more effectively discourage narco-trafficking activities and enhance conservation outcomes. • Supply-side counterdrug interdiction pushes cocaine trafficking, or 'narco-trafficking', activities into remote areas • Jaguars in protected areas and corridors are at greater risk from clandestine activities than those in non-protected areas • Full accounting of collateral damages from U.S. drug policy would significantly raise the cost estimates of the War on Drugs • Renewed investment in community-based conservation approaches is an alterative to militarized drug control policy [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPS) are uncontrolled analogues of existing drugs or newly synthesized chemicals that exhibit psychopharmacological effects. Due to their diverse nature, composition, and increasing prevalence, they present significant challenges to the healthcare system and drug control policies. In response, healthcare system laboratories have developed analytical methods to detect NPS in biological samples. As a Regional Reference Centre, the Sicilian CRQ Laboratory (Regional Laboratory for Quality Control) developed and conducted an External Quality Assessment (EQA) study to assess, in collaboration with the Istituto Superiore di Sanità (ISS), the ability of different Italian laboratories to identify NPS and traditional drugs of abuse (DOA) in biological matrices. Two blood samples were spiked with substances from various drug classes, including synthetic cannabinoids, cathinones, synthetic opiates, and benzodiazepines, at concentrations ranging from 2 to 10 ng/mL. The blood samples were freeze-dried to ensure the stability of DOA and NPS. Twenty-two laboratories from the Italian healthcare system participated in this assessment. The information provided by the laboratories during the registration in an in-house platform included a general description of the laboratory, analytical technique, and the chosen panels of analytes. The same platform was employed to collect and statistically analyze the data and record laboratory feedback and comments. The evaluation of the results revealed that the participating laboratories employed three different techniques for analyzing the samples: GC-MS, LC-MS, and immunoenzymatic methods. Approximately 90 % of the laboratories utilized LC-MS techniques. Around 40 % of false negative results were obtained, with the worst results in the identification of 5-chloro AB PINACA. The results showed that laboratories that used LC-MS methods obtained better specificity and sensitivity compared to the laboratories using other techniques. The results obtained from this first assessment underscore the importance of external quality control schemes in identifying the most effective analytical techniques for detecting trace molecules in biological matrices. Since the judicial authorities have not yet established cut-off values for NPS, this EQA will enable participating laboratories to share their analytical methods and expertise, aiming to establish common criteria for NPS identification. • NPS pose challengesto healthcare and drug control policies due to their diverse nature and increasing prevalence. • EQA study to evaluate the identification NPS and traditional drugs of abuse in biological matrices in Italian laboratories. • GC-MS, LC-MS, and immunoenzymatic methodswere reported, with LC-MS showing higher specificity and sensitivity. • The absence of cut-off values for NPS emphasizes the need to establish common criteria for their identification. [ABSTRACT FROM AUTHOR]

Health and human rights organizations have endorsed drug decriminalization to promote public health-oriented approaches to substance use. In the US, policymakers have begun to pursue this via prosecutorial discretion—or the decision by a prosecutor to decline criminal charges for drug possession in their jurisdiction. This study characterizes drivers of adoption, policy design and implementation processes, and barriers to impact and sustainability of this approach to inform evolving policy efforts promoting the health of people who use drugs (PWUD). We conducted n=22 key informant interviews with policymakers and national policy experts representing 13 jurisdictions implementing de facto drug policy reforms. Analyses were informed by the Exploration, Preparation, Implementation and Sustainment (EPIS) framework and analyzed using a hybrid inductive-deductive approach. Drivers of policy adoption included racial inequities, perceived failures of criminalization, and desires to prioritize violent crime given resource constraints. Three distinct policy typologies are described with varying conditions for eligibility, linkage to services, and policy transparency and dissemination. Public misinformation, police resistance and political opposition were seen as threats to sustainability. Given evidence that criminalization amplifies drug-related harms, many policymakers are adopting de facto drug policy reforms in the absence of formal legislation. This is the first study to systematically describe relevant implementation processes and emerging policy models. Findings have implications for designing rigorous evaluations on health outcomes and informing sustainable evidence-based policies to promote health and racial equity of PWUD in the US. • Arrest and incarceration of people who use drugs are linked to negative health outcomes. • Prosecutorial discretion can be used to enact de facto decriminalization of drug possession. • Little is known about how these nascent policies are developed and implemented in the U.S. • We describe shared and distinct features of emerging policies in 14 jurisdictions nationally. • Findings have implications for evaluating impacts on health and racial equity. [ABSTRACT FROM AUTHOR]

• Plasmodium falciparum and Plasmodium vivax isolates from the Philippines were analysed. • Varying mutations were found in markers linked to resistance to antimalarial drugs. • None of the mutations were particularly of high prevalence. • Clear temporal patterns in these mutations were observed within the past 15 years. • Decrease in pfcrt and pfmdr mutations are in line with antimalarial policy change. This study provides 2016 data on the prevalence of key single nucleotide polymorphisms (SNPs) associated with antimalarial drug resistance in Palawan, Philippines. Findings were combined with historical data to model temporal changes in the prevalence of these SNPs in Plasmodium isolates. Plasmodium isolates were genotyped using drug resistance markers pfmdr1, pfcrt, pfdhfr, pfdhps , kelch-13, pvmdr1, pvdhfr , and pvdhps. Temporal trends in the probability of mutations were estimated as a function of time using a binomial generalised linear model. All samples sequenced for Plasmodium falciparum chloroquine markers pfmdr1 and pfcrt had wild-type alleles. Varying mutation patterns were observed for the sulphadoxine/pyrimethamine markers pfdhps and pfdhfr ; complete quintuplet mutations were not found. No SNPs were observed for the artemisinin marker kelch-13. For Plasmodium vivax , differing patterns were detected for pvmdr1, pvdhfr , and pvdhps. The study findings suggest that the current drugs remain effective and that there is limited importation and establishment of resistant parasites in the area. Clear temporal trends were recognised, with prominent decreases in the proportions of pfcrt and pfmdr mutations detected within the past 15 years, consistent with a change in antimalarial drug policy. Continuous surveillance of antimalarial drug resistance is important to support malaria elimination efforts. [ABSTRACT FROM AUTHOR]

Objectives: To describe the main features of a pharmaceutical market in which the duration of guaranteed monopoly periods would correspond to a new pharmaceutical product's value.Methods: After reviewing patent and regulatory exclusivity-based mechanisms for protecting prescription drug markets from competition to incentivize drug innovation in developed countries, we model market protection mechanisms within the current framework to give the longest-lasting market protections to drug developers that bring the most affordable products to market with highest public health and clinical value.Results: An approach tying pharmaceutical market exclusivity to value would have 3 main features. First, it would be based on regulatory exclusivity (ie, the drug regulator refrains from authorizing generic entry for a certain amount of time), rather than patents. Second, the duration of exclusivity period would be pegged to the magnitude of a product's anticipated health impact and its proposed price by using modified methods from the field of health technology assessment. Third, the duration of the value-based exclusivity period would be reassessed routinely 3 years after the product's launch to account for its real-world effectiveness.Conclusions: Linking a drug's proposed price to the duration of its regulatory-based exclusivities would both incentivize the development of high impact, low-cost products and motivate drug developers to introduce these products at lower prices. [ABSTRACT FROM AUTHOR]

Optimizing drug dosages is essential for effective treatment. Clinical protocols may not suit all types of patients evenly, due to many drug trials not being designed to account for all comorbities or clinically relevant outcomes. Methodologies to optimize drug policies with observational data exist, but struggle due to limited data completeness in clinical settings. Computational methods can help overcome these challenges by leveraging field knowledge. This paper proposes an Individualized Doser (IDoser), a core dosing model that links drug dose to relevant covariates via a set of coefficients and includes a loss function to code needed assumptions and requirements. Coordinate descent is used to obtain a fitted model with minimal loss. The loss function also measures performance when validating the model with unseen data. We validated the proposed approach using the case of follicle-stimulating hormone (FSH) dosing for controlled ovarian stimulation (COS). When compared to clinical practice, IDoser achieved a net improvement of up to 31.97% in the validation cases. We present a simple but effective method to bridge the gap between current clinical dosing policies and gold policies based on the true underlying and often unknown dose–response functions. [Display omitted] • IDoser allows to incorporate domain knowledge in the dosing model. • The search for policy solutions is customizable depending on the dosing problem. • For FSH dosing, up to 31.97% improvement was observed against a clinical practice. • Its flexible capabilities indicate potential applicability for similar problems. [ABSTRACT FROM AUTHOR]

• Resistance to artesunate + sulfadoxine-pyrimethamine (AS+SP) has been flagged for Plasmodium falciparum malaria in India. • Meta-analysis on SP-resistance markers in India reveals high likelihood of drug failure. • Malaria genetic surveillance is urgently needed to generate evidence for drug policy change. • 12 states and 58 districts identified as hot spots for surveillance of SP-resistance markers. India is on track to eliminate malaria by 2030 but emerging resistance to first-line antimalarials is a recognised threat. Two instances of rapid development, spread, and natural selection of drug-resistant mutant parasites in India (chloroquine across the country and artesunate + sulfadoxine-pyrimethamine [AS+SP] in the northeastern states) translated into drug policy changes for Plasmodium falciparum malaria in 2010 and 2013, respectively. Considering these rapid changes in the SP drug resistance-conferring mutation profile of P. falciparum , there is a need to systematically monitor the validated mutations in Pfdhfr and Pfdhps genes across India alongside AS+SP therapeutic efficacy studies. There has been no robust, systematic countrywide surveillance reported for these parameters in India, hence the current study was undertaken. Studies that reported data on WHO-validated SP resistance markers in P. falciparum across India from 2008 to January 2023 were included. Five major databases, PubMedⓇ, Web of ScienceTM, ScopusⓇ, EmbaseⓇ, and Google Scholar, were exhaustively searched. Individual and pooled prevalence estimates of mutations were obtained through random- and fixed-effect models. Data were depicted using forest plots created with a 95% confidence interval. The study is registered with PROSPERO (CRD42021236012). A total of 37 publications, and 533 Pfdhfr and 134 Pfdhps National Centre of Biotechnology Information (NCBI) DNA sequences were included from >4000 samples. The study included information from 80 districts, 21 states and 3 union territories (UTs) from India. The two PfDHFR mutations, C59R (62%) and S108N (74%), were the most prevalent mutations (pooled estimates 61% and 71%, respectively) and appeared to be stabilised/fixed. Although rarest overall, the prevalence of I164L was observed to be as high as 32%. The Pf DHFR double mutants were the most prevalent overall (51%; pooled 42%). The prevalence of triple and quadruple mutations was 6% and 5%, respectively, and is an immediate concern for some states. The most prevalent Pf DHPS mutation was A437G (39%), followed by K540E (25%) and A581G (12%). There was a low overall prevalence of Pf DHFR/ Pf DHPS quintuple and sextuple mutations but surveillance for these mutations is critical for some areas. The analyses span the two critical policy changes, highlight the areas of concern, and guide policymakers in strategising and refining the anti-malaria drug policy for malaria elimination. The results of the analyses also highlight the SP-resistance hot spots, critical gaps and challenges, and indicate that focal and local malaria genetic surveillance (including drug-resistance markers) is needed until malaria is successfully eliminated. [Display omitted] [ABSTRACT FROM AUTHOR]

Using the 'war on drugs' in Colombia as its case study, this paper reflects on the recent findings and recommendations of Colombia's Truth Commission to make a case for a transformative approach to end ongoing cycles of drugs-related violence. In Colombia, the armed conflict and repressive prohibitionist drug policies are deeply entangled, and violence is ongoing. A peaceful future, we contend, requires thinking about a world in which we can live well with drugs. This would be a clear break from the goal of a 'drug free' world that has prevailed under the repressive prohibitionist regime. Legal regulation of drug markets is proposed here as a form of long-overdue reparations for victim groups in Colombia, which could address and repair past inequality and harms engendered by prohibition, and improve the living conditions of people involved in, and impacted by, illegal drug markets. Colombia, with its unique historical trajectory, has much to contribute towards future projections on the global legal regulation of drug markets. By positioning legal regulation of drug markets as reparation, this paper contributes to debates on drug policy reform and reparative justice, arguing that the two are very much connected. • The Colombian truth commission (CEV) concluded that the county's conflict has been transformed by the 'war on drugs'. • This chapter analyses the CEV's recommendation to transition towards a legally regulated drug market to end violence in Colombia. • Drug policy reform is not an end in itself; it should help to create a fairer and more inclusive world. • This chapter makes an important contribution from the Global South to debates about drug legalisation. [ABSTRACT FROM AUTHOR]

Dimenhydrinate (DMH) is an antihistamine used to treat nausea and vomiting. Although widely available in pharmacies as an over the counter medication, there have been reports of potential DMH tolerance and dependence and a possible euphoric potential accompanying heavy use (>100 mg/day). Despite the potential for misuse, there is a gap in the literature concerning patterns, characteristics, and potential mechanisms of DMH misuse. This review aimed to synthesize evidence on the pharmacology, clinical effects, and management of DMH misuse and dependence to inform clinical decision making and relevant drug policy. We conducted a systematic review in accordance with the PRISMA guidelines and using Cochrane collaboration methods. We searched seven databases from their inception through July 2019. To be included in the review, studies needed to measure or focus on one or more dimensions of morbidity or mortality related to the misuse of DMH. Quantitative, qualitative and mixed-method studies were included in order to capture the breadth of possible studies. Studies were excluded if they did not fit into the conceptual framework of the study of if they focused primarily on the misuse of other substances. A narrative synthesis of study findings was pursued given the limited capacity for a quantitative meta-analysis. We identified 24 studies, which described a range of neuropsychiatric sequelae related to DMH consumption, including seizures, psychosis, depression, intoxication (resembling anticholinergic syndrome) and withdrawal. The sedative and euphoric properties, readily available nature, and low cost of DMH appear to facilitate DMH dependence, which were more commonly reported among individuals who had concurrent psychiatric disorders, displaying symptoms such as low motivation, poor concentration, and delirium. The overall quality of studies identified by this review was low—largely because the majority of studies were case reports or review articles, with few intervention or cohort studies. There is some evidence to suggest the existence of DMH-related syndromes involving intoxication, withdrawal, and dependence, more commonly among long-term, heavy DMH consumers. However, higher quality studies are needed to confirm preliminary findings that there may be a biological basis for such syndromes. [ABSTRACT FROM AUTHOR]

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs.Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis.Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001).Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs. [ABSTRACT FROM AUTHOR]

Background: Drug price transparency is defined as readily available information on the price of pharmaceutical drugs to either authorities or consumers. Price transparency, together with other information, helps define the value of drugs and enables informed decision making. It has also been used as a reference in drug price setting mechanisms in some countries' pricing policies.Objective: To investigate the evidence available: 1) on government initiatives to mandate transparency in drug pricing worldwide, 2) on the reported effects of drug pricing transparency initiatives on drug price, and 3) on the limitations and barriers of the implementation of drug pricing transparency.Methods: Databases such as Medline-Ovid, Cochrane Central Register, PubMed, and Science Direct were used to search for relevant literature from inception to February 2018. A manual search of grey literature such as policy papers, governmental publications, and websites was also performed to obtain the information that was not available in the articles. Using narrative synthesis, the results were critically assessed and summarized according to its context of drug pricing approaches.Results: Of the 4382 relevant articles located, 12 studies met the inclusion criteria for drug price transparency initiatives. Only 3 studies reported the outcomes on the regulation of drug prices. Two studies in South Africa showed that price transparency initiatives did not necessarily reduce drug prices. Another study in the Philippines indicated a reduction in medicines' price based on the effects of government-mediated access prices. The limitations and barriers in price transparency initiatives include fragmentation of the healthcare system and nondisclosure of discounts and rebates by pharmaceutical companies.Conclusion: Drug pricing transparency initiatives have been implemented in many countries and commonly coexist with a country's pricing policies. Nevertheless, due to sparse evidence, the effect of drug price transparency initiatives on price control is still inconclusive. [ABSTRACT FROM AUTHOR]

Objectives: Hepatitis C virus (HCV) antivirals have been shown to be highly effective with minimal adverse effects, but they are costly. Little is known about the national spending on this drug class in either Canada or the United States, 2 countries with different drug pricing regulations. Thus the objective of this study was to compare drug expenditure on HCV medications in the United States and Canada.Methods: This was a retrospective cross-sectional study using the IQVIA National Sales Perspectives (United States) and Geographic Prescription Monitor (Canada) databases, which contains prescription transactions from American and Canadian pharmacies. All prescription claims for the period between January 1, 2014, and June 30, 2018, were used to describe HCV antiviral expenditure in both countries.Results: The United States and Canada spent $59.7 billion and $2.8 billion on HCV medications, respectively. Population-adjusted HCV medication costs were higher in the United States ($1 million per 100 000 population) compared with Canada ($0.4 million per 100 000 population).Conclusions: Although the rates of HCV infection are similar in the 2 countries, these findings highlight the differences in both the reimbursement utilization policy for HCV treatments in the countries and the major differences in drug pricing policies. As policies to reduce drug spending in the United States are explored, this article highlights the potential cost implications of implementing Canadian index pricing. [ABSTRACT FROM AUTHOR]

Medicine price transparency initiatives provide public or government on information about the product's prices and the components that may influence the prices, such as volume and product quality. In Malaysia, medicine price transparency has become part of the government's strategies in ensuring adequate, continuous and equitable access to quality, safe, effective and affordable medicines. Since the effect of medicine price transparency depend critically on how prices are presented, this study aims to evaluate the stakeholders' perspective of medicine price transparency practice in the private healthcare system in Malaysia. This study was conducted as face-to-face, semi-structured interview. Respondents from private pharmaceutical industries, community pharmacists, general practitioners, private hospital pharmacists, governments, academicians and senior pharmacist were recruited using purposive sampling. Using phenomenological study approach, interviews were conducted, and audio recorded with their consent. Data were transcribed verbatim and analysed using thematic analysis with Atlas.ti 8 software and categorised as strengths, weaknesses, opportunities and threats (SWOT). A total of 28 respondents were interviewed. There was a mixed perception regarding the price transparency implementation in Malaysia's private healthcare settings. The potential strengths include it will provide price standardization, reduce price manipulation and competition, hence allowing the industry players to focus more on patient-care services. Moreover, the private stakeholders were concerned that the practice may affect stakeholders' business and marketing strategy, reduce profit margin, increase general practitioner's consultation fees and causing impact on geographical discrepancies. The practice was viewed as an opportunity to disseminate the truth price information to consumer and strengthen collaboration between healthcare industries and Ministry of Health although this may become a threat that affect the business survival. Price transparency initiatives would benefit the pharmaceutical industries, consumer and countries, but it needs to be implemented appropriately to prevent price manipulation, market monopoly, and business closure. Future study may want to evaluate the impact of the initiatives on the business in the industry. [ABSTRACT FROM AUTHOR]

Increasing pressure on healthcare demand and delivery has resulted in the development of new roles and services for pharmacists. As current models of pharmacy practice continue to be evaluated, pharmacists must be involved in identifying new areas that may require research. In order to do so, the current vision of the future of pharmacy practice is discussed in this commentary. Issues such as adequate funding, professional competency and building strong interprofessional relationships are still identified as major barriers to change. These barriers have been grouped into the themes that form a conceptual model of the factors affecting the future of pharmacy practice, which have led to the development of key questions for the future. [ABSTRACT FROM AUTHOR]

Background: The U.S. Congress has proposed numerous bills and resolutions in response to the opioid epidemic unfolding over the past decade. Although this legislative response has been the subject of considerable media attention and commentary, very little research has systematically analyzed congressional opioid-related legislation in terms of primary goals, focal populations, and the extent to which it includes punitive mechanisms.Methods: To address this gap in research, we conducted a policy mapping content analysis of all opioid-related bills and resolutions (N = 188) proposed in Congress between 2009-2017 (111th - 115th Congresses). Two researchers independently coded basic characteristics (e.g. type, status, sponsorship, funding); goals, using a taxonomy developed by the researchers; focal populations; and punitive intent. Researchers compared codes and addressed discrepancies through consensus.Results: Legislation addressed a wide range of goals, but frequently did not advance beyond the introduction stage (80.3%). Goals most often centered on treatment (43.1% of legislation), research (36.7%), and supply reduction of licit (34.0%) and illicit opioids (21.3%). Relatively little legislation addressed long-term recovery, avenues of safer drug consumption, or stigma reduction. Youth (21.3%) and veterans (17.0%) were the most common population categories toward which legislation was directed. Explicit attention toward racial/ethnic minorities, low-income populations, and sexual minorities was rare to nonexistent. Legislation was largely coded as not directly punitive (91.0%).Conclusion: This study represents the first systematic analysis of key features of the U.S. congressional response to the opioid epidemic. Results indicate that the legislative response has largely focused on acute intervention, with limited attention to upstream social determinants and goal areas such as long-term recovery support. While the legislative response is primarily non-punitive, most opioid-specific policy does not explicitly address the intersection of opioid misuse and addiction with salient social factors such as economic disinvestment and social isolation. [ABSTRACT FROM AUTHOR]

Background: We analyze the ongoing debate surrounding supervised injection sites in Ontario, Canada and changing policies that impact host communities. Despite a plethora of evidence proving the effectiveness of supervised injection sites on harm reduction strategy, the topic remains highly controversial with constantly changing rhetoric in the Ontario drug policy landscape.Methods: We reviewed government reports, policies, and media sources spanning from prior to the establishment of the first Canadian supervised injection site in 2000 to early 2019, adopting an advocacy coalition framework approach to this policy analysis. Various advocacy coalitions emerge from this analysis, including all three levels of government, law enforcement, health practitioners, and community groups. We describe the narratives constructed by these coalitions, analyzing the supervised injection site model as a harm reduction strategy within a continually shifting socio-political landscape.Results: Emerging from the analysis are competing narratives put forward by various stakeholders within the policy subsystem. We find policy-makers tend to leverage scientific uncertainty as a tool to defend the interests of the most powerful actor in the subsystem. Despite an increase in the number of deaths due to the opioid crisis and evidence highlighting the efficacy of supervised injection sites as a harm reduction tool, various stakeholders are locked in a battle of claims and counter-claims about the appropriate policy response to opioids.Conclusions: These findings have broad implications for drug policy in other contexts. Our case study demonstrates the strength of stopgap measures, like supervised injection, to reduce harm from controlled substances. [ABSTRACT FROM AUTHOR]

Evaluation of costs and benefits of substance use treatment programs through a standard economic framework is necessary for optimal policy making. However, drug policy making is seldom supported by economic justification. Measurement of willingness to pay is a tool to provide better understanding of intangible substance use treatment outcomes and to help a balanced policy in treatment of substance use between maintenance treatment and abstinence-based approach. To assess the reciprocal association between economic indexes and attitudes about substance use and its treatment as indicators of tendency toward the two different treatment. Willingness to pay for treatment was measured by contingency valuation method among 109 treatment cost payers of which 78 subjects were from outpatient methadone maintenance clinics and 31 were from abstinence-based residential facilities. To analyze predictors of willingness to pay, we used income to capture heterogeneity of purchasing power among subjects. Further, we checked bivariate correlation of different attitudes of cost payers with willingness to pay. In the next step using backward regression equation we tried to reach the best specification of the model. Selected variables include cost payers' attitudes toward substance use and its treatment, effectiveness of treatment, social attitude toward the condition of substance use in Iran, fairness of treatment prices, and government financial support for addiction treatment. In methadone maintenance clinics the payers' income had a pivotal role in determining willingness to pay for substance use treatment by 50% (p <0.001). On the other hand, in abstinence-based residential facilities positive attitude toward substance use (61%, p <0.01) was the major direct determinant of willingness to pay for treatment. Attitude to public financial support for substance use treatment (55%, p <0.01) and consumption experience (45%, p <0.01) showed an inverse association with WTP in regression equation. This study expanded the understanding of the nature of payment in different substance use treatment modalities. The suggestion to policy makers is that before taking position on different types of treatment services, it is necessary to pay attention to factors that determine values cost payers put on treatment. In other words, economic indexes, payers' views about substance use and its treatment, and their opinion about effectiveness of substance use treatment programs may jeopardize the success of the policy. [ABSTRACT FROM AUTHOR]

Cannabis policies are changing globally, and medical marijuana programs are part of these changes. Drawing from the examples of two high-income (Canada, an early adopter of medical marijuana, and Germany, a late adopter) and one middle-income (Thailand) countries, we illustrate two main pressures underlying these recent changes. First, in many high-income countries, cannabis has been used to self-medicate for different ailments and diseases, even though there is no evidence of effectiveness for many of these conditions. Second, the cannabis industry is pressuring governments and decision-makers to allow for medical marijuana use with lenient regulations-without specifying medical conditions (indications) and requiring only a prescription from a health professional to obtain it. As a result, demand is likely to increase, even in countries with low prevalence of use. Cannabis policy-makers need to consider a balance between the medical benefits of medical marijuana and the potential public health consequences and cost. [ABSTRACT FROM AUTHOR]

Background: There is increasing support to include people who use drugs (PWUD) into debates about drug policy reform in order to improve policy legitimacy and outcomes. The aim of this paper is thus to critically analyse the perspectives of PWUD on UK drug policy and the law. This is the first empirical study to apply the four philosophical positions that underpin drug policy debates: Millian liberalism, legal moralism, strict libertarianism and paternalism (MacCoun and Reuter, 2001) to understand opinions and ideology.Methods: Forty interviews were conducted with PWUD about the meaning of and motivation for their substance consumption and about their opinions on drug policy and the law. The responses were analysed using the sociocognitive approach pioneered by van Dijk 2014; 2015 from the field of critical discourse studies. The analysis involved connecting personal experiences, knowledge and opinions to broader values, attitudes and ideology, specifically the analysis focused upon the extent to which participants challenged or supported prohibitionist ideology.Results: The opinions of those PWUD studied were diverse and complex. There was some support for prohibition, but overwhelmingly there was resistance and challenge to it. We theorise the challenge to prohibitionist ideology on a continuum from anti-prohibition to pro-reform. Key themes from the analysis included: knowledge gaps regarding terminology; uncertainty about and lack of consideration of policy and reform; political dissonance; apprehension about public attitudes and behaviours; reform rooted in social welfare and human rights ideology; and apathy through counter-culture.Conclusion: The findings demonstrate a lack of clarity amongst some PWUD regarding drug policy and reform. Educational initiatives outlining the different reform approaches would therefore provide PWUD with invaluable knowledge and help facilitate their enagement into reform debates. Despite a lack of clarity and consistency within opinions, participants were united in their discussion of human rights, health, economics and education; therefore these topics could help frame future approaches that seek to include PWUD into debates about drug policy. [ABSTRACT FROM AUTHOR]

Canada and the United States (U.S.) face an opioid use disorder (OUD) and opioid overdose epidemic. The most effective OUD treatment is opioid agonist therapy (OAT)-buprenorphine (with and without naloxone) and methadone. Although federal approval for OAT occurred decades ago, in both countries, access to and use of OAT is low. Restrictive policies and complex regulations contribute to limited OAT access. Through a non-systematic literature scan and a review of publicly available policy documents, we examined and compared OAT policies and practice at the federal (Canada vs. U.S.) and local levels (British Columbia [B.C.] vs. Oregon). Differences and similarities were noted between federal and local OAT policies, and subsequently OAT access. In Canada, OAT policy control has shifted from federal to provincial authorities. Conversely, in the U.S., federal authorities maintain primary control of OAT regulations. Local OAT health insurance coverage policies were substantively different between B.C. and Oregon. In B.C., five OAT options were available, while in Oregon, only two OAT options were available with administrative limitations. The differences in local OAT access and coverage policies between B.C. and Oregon, may be explained, in part, to the differences in Canadian and U.S. federal OAT policies, specifically, the relaxation of special federal OAT regulatory controls in Canada. The analysis also highlights the complicating contributions, and likely policy solutions, that exist within other drug policy sub-domains (e.g., the prescription regime, and drug control regime) and broader policy domains (e.g., constitutional rights). U.S. policymakers and health officials could consider adopting Canada's regulatory policy approach to expand OAT access to mitigate the harms of the ongoing opioid overdose epidemic. [ABSTRACT FROM AUTHOR]

Medicines are essential therapeutic strategies for health systems, thus, it is essential to verify whether the use of herbal medicines is equally distributed among the Brazilian population. A cross-sectional study was conducted with the Brazilian population. Those over 18 years of age, residing in the country for at least 12 months and with regular access to the internet, were included. The information showed the profile of the individuals, health conditions and characteristics of phytotherapy use. Data were submitted to Binary Logistic Regression (P < 0.05). The research was approved by the Research Ethics Committee of the University of Pernambuco (4880,872). Among 1 421 individuals, 727 (51.2%) used herbal medicines. The chance of this use was higher among those who did not identify as female (OR adjusted = 1.4/95% CI = 1.0–1.9; P = 0.028); white (OR adjusted = 1.4/95% CI = 1.0–1.8; P = 0.019); exclusive user of the private care sector (OR adjusted = 1.8/95% CI = 1.1–2.8; P = 0.009); with health problems (OR adjusted = 1.4/95% CI = 1.0–1.9; P = 0.010); and with product prescription (OR adjusted = 7.3/95% CI = 5.4–9.9; P < 0.001). There must be professional training, health education for users and readjustment of public policies to reduce inequalities in the use of herbal medicines. [ABSTRACT FROM AUTHOR]

Background: As soon as President Rodrigo Duterte assumed office in 2016, the Philippine government launched a nationwide antidrug campaign based on enforcement-led anti-illegal drugs policies primarily implemented by the national police. This was followed by a spate of killings resulting from both acknowledged police operations and by unidentified assailants. This study assembles a victim-level dataset of drug-related killings covered by the media during the Philippine government's antidrug campaign, and presents a spatial and temporal analysis of the killings.Methods: The dataset covers information on 5021 people killed from May 10, 2016 to September 29, 2017. Data collected systematically through online search procedures and existing listings of media organizations detailing information about incidences of drug-related police operations and drug-related killings in 'vigilante-style' manner reveal patterns for who were being killed, where, and how.Results: Over half of the killings were due to acknowledged police operations, and the rest were targeted in so-called 'vigilante-style' killings. The first three months after Mr. Duterte was sworn in were the deadliest months. Those who were killed were mostly low-level drug suspects. The analysis of temporal pattern reveals the scale of killings in the country, with rapid escalation starting in July 2016 and lasting throughout the rest of that year. Observable declines occurred during periods when the 'drug war' was suspended and operations were moved to a non-police enforcement unit and rose again when police were brought back into operations. The spatial analysis indicates a large concentration of deaths in the National Capital Region (40%) compared to the rest of the country with wide variations across cities and regions.Conclusions: Overall, the Philippine 'drug war' exhibits similarities with violent wars on drugs waged in other countries such as Thailand, with heavily police-led interventions leading to fatalities in the thousands over a span of under two years. Findings of this study point to important policy adjustments that need to be made, including the role that local governments play in drug policy implementation, the disproportionate negative impacts of enforcement-led policies against drugs on urban and poor areas, the targeting of low-level suspected drug dealers and users, and the importance of proper data monitoring and transparency by the government to inform policy adjustments in the face of high costs to human life. We also discuss the importance of independent monitoring systems when the government reports conflicting information. [ABSTRACT FROM AUTHOR]

Introduction: 'New recovery' can be conceptualised as both a social movement and a broader policy agenda to restructure treatment service systems towards 'recovery-oriented systems of care'. Emerging initially out of the United States, new recovery has gained currency as a policy agenda in other jurisdictions - perhaps most distinctly in the United Kingdom. In 2012, the ideas behind 'new recovery' were debated in the Australian alcohol and other drug field as the Victorian government sought to incorporate recovery principles into policy and service design. This paper uses the policy transfer and policy translation literature to understand how international policy ideas about 'new recovery' were negotiated in the Australian context, focusing specifically on the role of non-government actors in the process.Methods: This paper draws on an analysis of policy documents, organisational documents and interviews with representatives from the Australian non-government alcohol and other drug sector to consider how new recovery was translated into Victorian drug policy.Results: The interactions between organisations and actors - including bureaucrats, governmental agencies and policy entrepreneurs - facilitated the circulation and translation of policy ideas in the Victorian context. Despite this, the analysis suggests that policy transfer was largely a symbolic exercise: overall, some of the key features of new recovery policy from the United States and the United Kingdom, such as encouraging peer-led recovery and mutual aid, were not incorporated in the Victorian policy. NGOs resisted what they considered to be some of the more problematic elements of 'new recovery', and informed the local translation of the policy.Discussion: The results have implications for understandings of the relationship between social movements, non-government organisations and the state, as well as the dynamics of knowledge transfer in drug policy. [ABSTRACT FROM AUTHOR]

The United States continues to face a public health crisis of opioid-related harm, the effects of which could be dramatically reduced through increased access to opioid agonist therapy with the medications methadone and buprenorphine. Despite overwhelming evidence of their efficacy, unduly restrictive federal, state, and local regulation significantly impedes access to these life-saving medications. We outline immediate, concrete steps that federal, state, and local governments can take to change law from barrier to facilitator of evidence-based treatment for opioid use disorder. These include removing onerous restrictions on the prescription and dispensing of buprenorphine and methadone for opioid agonist therapy, requiring insurance coverage of these medications, and mandating that they be provided in correctional settings and promoted by drug courts. Finally, we argue that jurisdictions should proactively offer opioid agonist therapy to individuals at high risk of overdose, remove barriers to establishing methadone treatment facilities, and address underlying social determinants and barriers to treatment. These changes have the ability to save thousands of lives annually. [ABSTRACT FROM AUTHOR]

Background: Most comparative drug policy analyses utilise measures of drug use, often from general population surveys (GPS). However, the limitations of GPS are well-recognised, including the small numbers of people who use illicit drugs sampled. Web surveys offer a potential solution to such issues. Therefore EMCDDA conducted a study to assess the potential for using such surveys to supplement information obtained from GPS.Methods: The European Web Survey on Drugs (EWSD) asked about use of cannabis, amphetamines, cocaine and MDMA in 14 countries from 2016 to 2018. Each participant country translated the questionnaire as necessary and devised its own sampling strategy. Individuals aged 18+, resident in the participant country, who had used one or more of the drugs covered by the survey in the past 12 months were included in the analysis. Participation was anonymous and voluntary.Results: More than 40,000 people completed the survey, with recruitment mostly through social media. Larger samples of users of all drug types than found in GPS were generally obtained. However, the respondent profiles differed markedly between countries, e.g. the proportion aged 18-24 ranged from 30% to 80%. The results relating to use showed both inter-country similarities and differences, e.g. mean daily amounts of cocaine used varied between countries but increases in amounts used with increased frequency of use were similar. Price data showed good external validity.Conclusion: Web surveys offer the possibility of collecting information from large numbers people who use illicit drugs quickly and cheaply and can fill important gaps in our knowledge of patterns of use, particularly by recreational users. However, they also have limitations. Standardising questionnaires and approaches to data cleaning and analysis facilitates comparisons between countries but obtaining comparable samples may be challenging. Multinational surveys need to balance standardisation of methods with responsiveness to differing country contexts; our collaborative model does this. [ABSTRACT FROM AUTHOR]

Background: The Nordic countries - Denmark, Finland, Norway, and Sweden - have traditionally had different approaches to drug control policies. From the late 1980s to the early 1990s, Sweden and Norway were the most restrictive countries. Prior research has described how Nordic control policies became more repressive after this, but no research has examined this claim using the intensity of implementation as a measure.Methods: This study uses data collated by the EMCDDA to examine drug control intensity from 2000 to 2016. The four countries are compared on three measures: seizure numbers relative to total population, seizures numbers by type of drug relative to population, and cannabis seizures relative to the number of annual cannabis users. Standard bivariate tests for statistical significance are used to compare control intensity over time and between countries.Results: Compared to an earlier period from the late 1980s to the early 1990s, Denmark maintained the level of drug seizures to population from 2000 to 2016. Finland increased intensity by 176 percent but remained at the lowest level in the region. Norway increased by 18 percent and is currently the country with the highest enforcement intensity. Sweden reduced overall intensity by 57 percent, which decreases the level for the region by 22 percent. Sixty to seventy percent of all seizures in every country was for cannabis. Accounting for cannabis prevalence rates changes the ranking of enforcement intensity in the countries.Conclusion: Drug control intensity in the Nordic countries has harmonized over time. The disparity between the extremes of low control intensity in Finland and high intensity in Sweden has been reduced. Denmark is still comparatively lenient to users when considering high cannabis prevalence rates and Norway has taken the position as the strictest country on all control intensity measures. [ABSTRACT FROM AUTHOR]

We alert readers to the value of using unsolicited online data in drug policy research by highlighting web-based content relevant to drug policy generated by distinct types of actor: people who consume, supply or produce illicit drugs, online news websites and state or civil society organisations. These actors leave 'digital traces' across a range of internet platforms, and these traces become available to researchers to use as data - although they have not been solicited by researchers, and so have not been created specifically to fulfil the aims of research projects. This particular type of data entails certain strengths, limitations and ethical challenges, and we aim to assist researchers in understanding these by drawing on selected examples of published research using unsolicited online data that have generated valuable drug policy insights not possible using other traditional data sources. We argue for the continued and increased importance of using unsolicited online data so that drug policy scholarship keep pace with recent developments in the global landscape of drug policies and illicit drug practices. [ABSTRACT FROM AUTHOR]

Background: Even though Indonesia has not ratified the Framework Convention on Tobacco Control (FCTC), district and provincial stakeholders are increasingly adopting smoke-free policies (SFPs). This study aimed to 1) assess whether local SFP adoption in Indonesia followed a horizontal or vertical diffusion pattern and 2) identify district characteristics that are associated with the SFP adoption.Methods: Policy documents enacted during 2004-2015 were compiled from 33 provinces and 510 districts in Indonesia. First, we described the geographical distributions of the policy adoption. Second, we ran logistic regression to assess the associations of district SFP adoption with having adjacent districts that had adopted SFPs (i.e. horizontal diffusion) and being situated in a province that had adopted SFPs (i.e. vertical diffusion). Third, the associations between district characteristics (population density, GDP, tobacco production) and SFP adoption were assessed using logistic regression.Results: By 2015, a total of 17 provinces and 143 districts had adopted SFPs. Districts with SFPs were more concentrated in the western part of Indonesia. Adoption was more likely in districts of which adjacent districts had already adopted SFPs (OR: 2.02; 95%CI: 1.26-3.23), and less likely when the province had already adopted SFPs (OR: 0.19; 95%CI: 0.11 - 0.34). Adoption was more likely in districts with higher GDP (OR high vs low GDP: 3.28; 95%CI: 1.80-5.98) and higher population density (OR high vs low density: 6.57; 95%CI: 3.63-11.9). High tobacco production showed a strong inverse association with SPF adoption (OR high vs. no production: 0.36; 95%CI: 0.17-0.74).Conclusions: Smoke-free policy adoption in Indonesian districts followed a horizontal diffusion pattern, with poorer and rural districts lagging behind in their policy adoption. Our results indicate that local-level policy development is important for smoke-free policy adoption in countries with decentralised governments, but that effective advocacy is needed to counteract tobacco industry interference. [ABSTRACT FROM AUTHOR]

Background: Cannabis policies should be relevant to communities most impacted by them. Home cultivation policies can engage people who grow cannabis and build on their motivation to supply a safe product. This paper aims to examine the laws pertaining to "home" (i.e. personal, small-scale) cannabis cultivation internationally and their different aspects, and to discuss the potential of these policies to be expanded into community-level cannabis supply models.Methods: We reviewed relevant laws and regulations in states/countries that legalised, decriminalised or applied other non-prohibitive approaches to home cannabis cultivation.Findings: Non-prohibitive approaches to home cannabis cultivation have been adopted in at least 27 jurisdictions. Twelve jurisdictions "de jure" legalised home cultivation (three U.S. states and Antigua and Barbuda legalised only home cultivation; six U.S. states, Uruguay and Canada legalised commercial sales as well). Eight states/countries "de facto" (Belgium, the Netherlands) or "de jure" decriminalised it (Czech Republic, Spain, Jamaica, and three Australian states). "De jure" depenalisation was in place in Chile and Brazil and recent court rulings yielded "de facto" depenalisation or "de facto" legalisation in five other jurisdictions (South Africa, Mexico, Colombia, Costa Rica and Georgia). Varying number of plants (per person and per property) and the circumstances of cultivation were in place. The key limitations of the regulations included (i) possession thresholds for the produce from home cultivations, (ii) rules about sharing the produce, and (iii) potentially disproportionate sanctions for non-authorised behaviours. Despite currently being limited, home cultivation policies might have the capacity to engage cannabis networks that already exist in the community and like that, enhance their participation in legitimate policy schemes.Conclusions: Rules around pooled cultivation and sharing could be made fit for purpose to accommodate community supply of cannabis. Home cultivation policies could serve as a basis for community-level cannabis supply models and as such, for more inclusive cannabis policies. [ABSTRACT FROM AUTHOR]

This paper explores the social inclusion of the illicit drug user. It does this through a comparative examination of policy orientations to the social inclusion of people who use drugs. Six policy documents from Canada and Scotland produced in the years 2000 and 2001 were systematically sampled from 42 known documents. A poststructural content analysis adapted from the work of Maarten Hajer and mapped onto an analytic frame derived from Nikolas Rose's Governing the Soul: The Shaping of the Private Self is conducted. Within the years considered, drug policy texts from Scotland signaled a more punitive approach to drug use and a less socially inclusive approach to people who used drugs than drug policy texts from Canada. The differences in policy directions identified were in keeping with a priori interpretations of each country's broad approach to illicit drug use and to the social inclusion of the illicit drug user, if not to social inclusion itself. Methodologically, combining the approaches of Hajer and Rose proved complimentary and useful as well as promising for future application to the content analysis of public discourse. [ABSTRACT FROM AUTHOR]

Recently, United States Food and Drug Administration (FDA) and European Commission (EC) approved Alnylam Pharmaceuticals' RNA interference (RNAi) therapeutic, ONPATTRO™ (Patisiran), for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. This is the first RNAi therapeutic all over the world, as well as the first FDA-approved treatment for this indication. As a milestone event in RNAi pharmaceutical industry, it means, for the first time, people have broken through all development processes for RNAi drugs from research to clinic. With this achievement, RNAi approval may soar in the coming years. In this paper, we introduce the basic information of ONPATTRO and the properties of RNAi and nucleic acid therapeutics, update the clinical and preclinical development activities, review its complicated development history, summarize the key technologies of RNAi at early stage, and discuss the latest advances in delivery and modification technologies. It provides a comprehensive view and biotechnological insights of RNAi therapy for the broader audiences. [ABSTRACT FROM AUTHOR]

In spite of having a remarkable anti tumor activity against a wide variety of cancers, the clinical effectiveness of the major chemotherapeutic drug paclitaxel is often limited by the issues of drug resistance that hampers the therapeutic effectiveness of the drug. The combination of proton pump inhibitor with paclitaxel is an effective approach to overcome therapeutic resistance caused by the acidic microenvironment (Warburg effect) in tumor. In the present study a new simple, precise and selective liquid chromatography tandem mass spectrometry method was developed for quantification of paclitaxel and lansoprazole using esomeprazole as an internal standard and applied for the pharmacokinetic study of investigational paclitaxel - lansoprazole loaded PLGA nanoparticles. The developed method quantifies both the drugs simultaneously irrespective of their dissimilar stability concerns. The detection was exercised with multiple reaction-monitoring mode in positive ionization that yielded highly intense response of parent-product (m/z) transition pair 854.4 → 286.1, 370.1 → 251.9 and 346 → 198 for paclitaxel, lansoprazole and Esomeprazole respectively. The chromatographic separation was achieved using phenomenex Kinetex 5 μ C18 100A 50 × 3.0 mm column and a gradient mobile phase combination of ammonium acetate in deionized water (pH 6.8, 2 mM, w/v) and acetonitrile spiked with formic acid (1:1000, v/v). This method showed good linearity over a concentration range of 10–320 ng/mL and 100–3200 ng/mL with correlation coefficient (R2) 0.98 and 0.94 for paclitaxel and lansoprazole respectively. Using liquid liquid extraction process both the drugs were extracted from rat plasma. The intra- and inter-day precision and accuracy values were within the variability limits and both the analytes were found to be stable throughout the freeze-thaw, auto-sampler, bench top and long term stability studies. The liquid chromatography tandem mass spectrometry method was successfully validated in accordance with United States Food and Drug administration guidelines and the results were within the acceptable limits. The liquid chromatography tandem mass spectrometry method was successfully utilized for the pharmacokinetic investigation of experimental paclitaxel - lansoprazole loaded PLGA nanoparticles in rat plasma. Development and validation of LC-MS/MS method for simultaneous detection of PTX-LAN in preclinical pharmacokinetics of a newly developed chemotherapeutics. Unlabelled Image • The first developed bioanalytical method for simultaneous detection of paclitaxel and lansoprazole • The validated method quantifies dissimilar analytes simultaneously. • The method offers a sensitive, accurate and precise measurement of analytes in a wide calibration range. • The method utilized minimum amount of plasma for pharmacokinetics determination. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate expenditures and sources of payment for prescription drugs in the United States from 1997 to 2015.Methods: The Medical Expenditures Panel Survey (MEPS) was used for this analysis. Individuals with one or more prescription medicines were eligible for inclusion. Outcomes were the inflation-adjusted cost per prescription across all payment sources (self or family, public, private, and other sources) before and after the Medicare Part D benefit and the Affordable Care Act.Results: The cost per prescription increased from $38.56 in 1997 to $73.34 in 2015. Nevertheless, consumers' out-of-pocket expenditures decreased from $18.19 to $9.61, whereas public program expenditures per prescription increased from $5.61 to $34.43 over this time. Out-of-pocket expenditures of individuals in the low-income group and near-poor group had larger declined percentages from 51.4% to 20.4% and 46.5% to 17.2% relative to individuals in higher-income groups before and after implementation of the Medicare Part D, respectively. Over 90% prescription purchases were covered by medical insurance by 2015. The per-prescription cost for medications consumed by uninsured individuals increased at a lower rate from $31.83 to $54.96 versus $40.12 to $75.58 for privately insured and $36.00 to $70.96 for publicly insured (P < .001).Conclusions: Prescription drugs expenditures have increased over the past 2 decades, but public sources now pay for a growing proportion of prescription drugs cost regardless of health insurance coverage or income level. Out-of-pocket expenditures have significantly decreased for persons with lower incomes since the implementation of Medicare Part D and the Affordable Care Act. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the relationship between supersaturation and precipitation and the effect of a supersaturated state on drug membrane permeation. Stock solutions of albendazole (ALB) and ketoconazole (KTZ) dissolved in dimethyl sulfoxide (0.1-50 mg/mL) were diluted 100-fold with buffer solution (pH 6.8, 37°C). In the case of ALB, a supersaturated state and immediate precipitation were observed at 10 μg/mL or less and 20 μg/mL or higher, respectively. When KTZ was used, at an initial concentration of 200 μg/mL or higher, precipitation was observed, although the dissolved concentration remained at approximately 120 μg/mL for at least 30 min. These dissolved concentrations of ALB and KTZ related to approximately 10-fold and 14-fold over the saturated solubility from respective bulk powder. An in vitro permeation study implied that the rate of drug permeation across a biological membrane increased with increasing supersaturation. These results suggested favorable strategies for development of a supersaturable formulation could depend on the precipitation properties of the drug. Immediate- and controlled-release forms might be suitable for supersaturable formulations for KTZ and ALB, respectively. [ABSTRACT FROM AUTHOR]

Background: Alternative cannabis regulation models are discussed and implemented worldwide. A baseline scenario under the assumption of no policy or market changes may prove useful to forecast cannabis use and treatment demand and evaluate changes in legislation.Methods: Based on data of the Continuous Rolling Survey of Addictive Behaviours and Related Risks on cannabis use, age, gender and nationality from 2011 to 2015, we used general estimating equation analysis to model lifetime and 30-days prevalence from 2015 to 2045 in Switzerland accounting for demographic trends.Results: Lifetime prevalence of cannabis use is projected to grow from 28.3% (CI 95% 27.8-28.8) in 2015 to 42.0% (CI 95% 41.0-43.0) in 2045. 30-days prevalence would increase slightly from 2.70% (CI 95% 2.53-2.88) to 3.39% (CI 95% 3.11-3.66). Due to population growth, absolute numbers with past 30-day cannabis use are estimated to increase from 202,784 (CI 95% 189,534-216,035) to 314,302 (CI 95% 288,504-340,100). Among those aged under 30 years no substantial change in lifetime and 30-days prevalence of cannabis use is projected. Larger changes are estimated to occur in the age group 30+. The mean age of past 30-day cannabis users would increase for men with Swiss nationality from 30.3 to 38.7 years.Discussion: Population-based survey data and demographic projections can be used to develop baseline scenarios of future cannabis use. Assuming no changes in cannabis legislation, growing absolute numbers of users will likely increase treatment demand. Cannabis use is estimated to increase among the group aged >30 years, which is currently underrepresented in clinical treatment and research. Our findings highlight the need for prospective baseline scenarios to evaluate the impact of legislative changes on cannabis use. Moreover, in Switzerland effective prevention and treatment interventions for cannabis use disorders are required even if cannabis legislation remains unchanged. [ABSTRACT FROM AUTHOR]

Objectives: To determine the opinions of pharmacists who supervise immunizing pharmacy technicians regarding initial trust of immunizing technicians, perceived quality of the training program, need for additional on-the-job training, frequency of technician utilization, and recommendations for other pharmacists who are considering implementation of an immunizing technician.Setting: Albertsons pharmacies located in the state of Idaho in May 2017.Practice Description and Innovation: Qualitative descriptive study of semistructured key informant interviews with Idaho pharmacists who currently supervise a pharmacy technician trained to administer immunizations.Evaluation: Informant interviews were recorded, transcribed, and coded to evaluate key themes.Results: Nineteen individual pharmacist interviews were conducted at different Albertsons pharmacy locations in the state of Idaho. Pharmacists in this study felt that their immunizing technicians were properly trained to administer immunizations, capable of giving immunizations, and empowered by their new role within the pharmacy. Participants expressed challenges with initial comfort in allowing a technician to immunize, support of this new advanced technician role, and additional on-the-job training for individual technicians. Findings also included a pharmacist-perceived increase in vaccination rates and recommendation for other technicians to be trained to administer immunizations.Conclusion: Community pharmacists who supervise pharmacy technicians trained to administer immunizations were receptive to this new advanced technician role. Pharmacists' opinions revealed that working with newly trained immunizing pharmacy technicians has not only positively affected the morale of their team, but can help to increase the number of vaccinations given by the pharmacy. Understanding pharmacist perceptions about technicians as immunizers may lead to regulation changes and adoption of this advanced technician role. [ABSTRACT FROM AUTHOR]

Self-administration of ethanol (E) and nicotine (N) occurs frequently in tandem orders (i.e., N→E vs. E→N) and thereby produces differing interoceptive profiles of subjective effects in humans. If the interoceptive stimulus characteristics of N→E differ from E→N, it is possible that such differences contribute to their co-dependence. The rationale for the present investigation was to determine whether ethanol, when preceded or followed by nicotine, produces different discriminative stimulus effects in rats. In two experiments, using a one-manipulandum operant drug discrimination procedure, rats were trained to discriminate temporal sequential administrations of ethanol (1.0 g/kg) that was followed or preceded by nicotine (0.3 mg/kg). Sessions alternated between food-reinforcement sessions on a variable interval 30-sec schedule (i.e., SD) and non-reinforcement sessions (i.e., SΔ). In Experiment 1, administrations of ethanol were followed or preceded by a 10-min interval of nicotine. Training sessions took place 10 min following the second drug injection. Four groups of rats were trained to discriminate only one sequence from sequential administrations of saline, and each drug sequence was counterbalanced across groups for their roles as SD or SΔ. There was robust stimulus control. N→E and E→N functioned equally well as SD or SΔ. Experiment 2 used two groups of rats. For one group, the E→N sequence functioned as the SD and the N→E sequence functioned as the SΔ. The drug sequences were counterbalanced for the other group. Brief non-reinforcement tests revealed significantly greater responding during the SD sequence compared to the SΔ sequence for both groups. These results suggest that different drug sequences of ethanol followed or preceded by nicotine established reliable discriminative stimulus control over operant responding, potentially because of characteristic differences in the overlapping pharmacokinetic profiles of the NE compound. The results are discussed in terms of: 1) conditional stimulus control among two interoceptive drug states; and 2) the clinical modulation of human alcohol consumption and tobacco smoking. [ABSTRACT FROM AUTHOR]