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Background: We previously reported that the 2018 Canadian Cannabis Act, allowing youth to possess up to 5 g dried cannabis or equivalent for personal use/sharing, was associated with short-term (76 days) post-legalization reduction in police-reported cannabis-related crimes among youth. To establish whether the change might be sustained, we now estimate this association during a much longer time period by including an additional three years of post-legalization data., Methods: Using national daily police-reported criminal incident data from January 1, 2015-December 31, 2021 from the Canadian Uniform Crime Reporting Survey (UCR-2), the study employed Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models to assess the associations between legalization and youth (12-17 years) cannabis-related offenses (male, n = 34,508; female, n = 9529)., Results: Legalization was associated with significant reductions in both male and female police-reported cannabis-related offenses: females, 4.04 daily incidents [95% confidence interval (CI), 3.08; 5.01], a 62.1% decrease [standard error (se), 34.3%]; males, 12.42 daily offenses (95% CI, 8.99; 15.86), a reduction of 53.0% (se, 22.7%). There was no evidence of associations between cannabis legalization and patterns of property or violent crimes., Conclusions: Results suggest that the impact of the Cannabis Act on reducing cannabis-related youth crimes is sustained, supporting the Act's objectives to reduce cannabis-related criminalization among youth and associated effects on the Canadian criminal justice system., Competing Interests: Declaration of Competing Interest This research was supported in part by a Canadian Institutes of Health Research (CIHR) Project Grant (PJT 180292) awarded to the first author (RCC). In relation to the manuscript, the authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To determine if marijuana legalization was associated with reduced opioid mortality., Study Design: The United States (US) opioid mortality trend during the 2010-2019 decade was compared in states and District of Columbia (jurisdictions) that had implemented marijuana legalization with states that had not. Acceleration of opioid mortality during 2020, the first year of the coronavirus disease 2019 (COVID-19) pandemic, was also compared in recreational and medicinal-only legalizing jurisdictions., Methods: Joinpoint methodology was applied to the Centers for Disease Control and Prevention WONDER data. Trends in legalizing jurisdictions were cumulative aggregates., Results: The overall opioid and fentanyl death rates and the percentage of opioid deaths due to fentanyl increased more during 2010-2019 in jurisdictions that legalized marijuana than in those that did not (pairwise comparison p = 0.007, 0.05, and 0.006, respectively). By 2019, the all-opioid and fentanyl death rates were 44 and 50 percent greater in the legalizing than in the nonlegalizing jurisdictions, respectively. When the COVID-19 pandemic hit in 2020, jurisdictions that implemented recreational marijuana legalization before 2019 had significantly greater increases in both overall opioid and fentanyl death rates than jurisdictions with medicinal-only legalization. For all-opioids, the mean (95 percent confidence interval) 2019-to-2020 increases were 46.5 percent (36.6, 56.3 percent) and 29.1 percent (20.2, 37.9 percent), respectively (p = 0.02). For fentanyl, they were 115.6 percent (80.2, 151.6 percent) and 55.4 percent (31.6, 79.2 percent), respectively (p = 0.01)., Conclusions: During the past decade, marijuana legalization in the US was associated at the jurisdiction level with a greater acceleration in opioid death rate. An even greater increase in opioid mortality occurred in recreational-legalizing jurisdictions with the onset of the COVID-19 pandemic. Marijuana legalization is correlated with worsening of the US opioid epidemic.

Policy Points In 2012, Colorado and Washington were the first states to legalize recreational marijuana through voter-initiated ballots. In these states, counties could restrict or ban local marijuana facilities through a variety of regulatory methods such as ordinances and zoning. County-level recreational marijuana policies in Washington and Colorado vary substantially, with 69.2% of Washington counties and 23.4% of Colorado counties allowing all types of recreational marijuana facilities as of April 1, 2019. After Colorado and Washington legalized recreational marijuana, many counties modified their marijuana policies over time, with shifts in county policy often preceded by advocacy and information-seeking activities., Context: In 2012, Colorado and Washington were the first states to legalize recreational marijuana. Both allowed local governments to further regulate the availability of marijuana facilities in their jurisdictions. As early adopters, these states are important quasi-natural experiments to examine local marijuana policy and policy change processes, including key stakeholders and arguments., Methods: We conducted a policy scan of county-level recreational marijuana ordinances and regulations in Colorado and Washington. Data collected included policy documents from counties in both states and newspaper articles. We used a mixed-methods approach to describe the types of county-level recreational marijuana policies enacted by April 1, 2019; identify key policy stakeholders involved in local policy debates; and explore arguments used in support or opposition of county policies. We also selected four counties that represent three county policy environments (all marijuana facility types allowed, some marijuana facility types allowed, all marijuana facility types prohibited) and described the policy changes within these counties since recreational marijuana was legalized., Findings: By April 1, 2019, Colorado counties were less likely than Washington counties to allow marijuana facilities-48.4% of Colorado counties prohibited recreational marijuana facilities in their jurisdiction compared to 23.1% of Washington counties. Since state legalization, several counties in both states have made substantial marijuana facility policy modifications, often preceded by information-seeking activities. Primary stakeholders involved in policy debates included elected officials, law enforcement, individual growers/farmers, marijuana business license applicants, parents, and residents. Proponents referenced local economic gain, reduced crime, and potential health benefits of marijuana as arguments in favor of permitting local facilities, whereas opponents pointed to economic loss, negative health and public health issues, public safety concerns, and existing federal law. Both sides referenced local public opinion data to support their position., Conclusions: By early 2019, a patchwork of local marijuana policies was in place in Colorado and Washington. We identify key areas of policy and public health research needed to inform future local marijuana policy decisions, including the impact of legalization on public health outcomes (particularly for youth) and public safety., (© 2021 The Authors. The Milbank Quarterly published by Wiley Periodicals LLC on behalf of The Millbank Memorial Fund.)

Objective: To investigate characteristics and trends of methamphetamine exposures reported to United States (US) poison control centers., Methods: Data from the National Poison Data System were analyzed., Results: From January 1, 2000 through December 31, 2019, US poison control centers managed 54,199 cases involving methamphetamine as the first-ranked substance. Adults 20-39 years old accounted for more than half (56.3%) of cases. There were 1,291 deaths, of which 43.0% involved multiple-substance exposures. Among multiple-substance exposures in which methamphetamine was the first-ranked substance, stimulants and street drugs (excluding methamphetamine) were most commonly also present (22.7%), followed by opioids (19.0%). The substance class associated with the most fatalities was opioids ( n  = 243, 26.6%). The rate of methamphetamine exposures per 100,000 US population increased from 0.6 to 1.1 from 2000-2005, then decreased from 1.1 to 0.4 from 2005-2007, followed by an increase from 0.4 to 2.6 from 2007-2019. From 2007-2019, the rate significantly increased in all US regions, and among all age groups, except among 6-12-year-olds. Also, the rates of single-substance and multiple-substance exposures each increased significantly (both p  < 0.0001) from 2007-2019, as did the overall methamphetamine fatality rate per 100,000 US population (0.0036 to 0.022, p  < 0.0001). From 2000-2019, the proportions of cases resulting in admission to a health care facility and serious medical outcome increased from 30.2% to 47.8% ( p  < 0.0001) and from 37.6% to 54.0% ( p  < 0.0001), respectively., Conclusions: The rate of exposure to methamphetamine in the US declined initially following passage of the Combat Methamphetamine Epidemic Act of 2005. However, since 2007, the rate and severity of exposures to methamphetamine have increased, primarily driven by individuals 20 years or older. Increased prevention efforts are needed, including prevention of methamphetamine initiation among adolescents and young adults, improved access to effective treatment for co-occurring mental health and substance use disorders, and prevention of unintentional exposures among children.

The legality of cannabis use has been changing in a number of jurisdictions around the world. In the U.S., it has been legalised for medicinal and/or recreational uses in 34 jurisdictions and counting. This study leverages the decades-long experience of legalisation in the U.S. to provide an overview of the associated changes in public attitudes, cannabis markets and adverse health effects. We found a broad-based warming of public attitudes toward legalisation, potentially influenced by the increasingly positive portrayal of cannabis in media and declines in cannabis risk perceptions. Potency of cannabis products increased significantly while prices fell sharply. Although adults were less responsive to price changes than adolescents, adults who use cannabis regularly were sensitive to prices, with an estimated 10% price reduction leading to about 2.5% increase in the rate of use. Overall, past-year cannabis use has increased in adults since 2002, and adults over 26 years old who resided in states with medicinal cannabis laws were more likely to have used cannabis in the past 30 days, to have used daily, and to have higher rates of cannabis use disorders than adults who resided in states without legalised medicinal cannabis. Traffic fatalities involving cannabis temporarily increased in some states post-legalisation, and there were more presentations to medical services related to chronic regular cannabis use. There is suggestive evidence that adverse health consequences have increased among people who use cannabis regularly since legalisation. More robust research is needed to determine whether these effects of legalisation are temporary or long-term., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The Canadian government legalized non-medical cannabis use by adults in October 2018 to minimize associated harms and redirect profits from criminals. In October 2019, a wider array of products, including edibles, was legalized, with entry into the legal market beginning in December., Data and Methods: Three quarters (the first quarters of 2018 and 2019 and the fourth quarter of 2020) of the National Cannabis Survey were used to examine changes in cannabis use (overall use and daily or almost daily (DAD) use), consumption methods, products and sources., Results: Cannabis use in the past three months was higher in late 2020 (20.0%) than in 2019 (17.5%) and 2018 (14.0%), and this was particularly the case among: females (for whom rates rose to equal male rates for the first time), adults aged 25 and older, and some provinces. Similarly, DAD use, at 7.9% also increased. Higher percentages of Canadians reported getting at least some of their cannabis from legal sources or growing it, and fewer were relying on friends and family or illegal sources in 2020., Discussion: This study spans three years-from before legalization to about two years after. It provides a more complete picture of the law's impact on cannabis use and related behaviours, given the more established legal cannabis industry better equipped to compete with the black market on price, convenience and selection. Findings demonstrate that change is continuing, and, as before, some cautions and assurances remain. The impact of the COVID-19 pandemic on cannabis use continues to be difficult to measure. Monitoring remains important, given the ever-changing provincial retail landscapes; the introduction of new products; and the pressure by the industry to remove or adjust potency limits, and allow widespread delivery, farm-gate sales and cannabis lounges.

This brief report covers recent advances in cannabis and cannabinoid regulation and drug approval. The popularity of cannabis and cannabinoid products continues to rise, and these products are available for the majority of the population in the United States to purchase as easily as alcohol. Although many states have approved programs and research licenses, these activities and products all remain federally illegal. The solution may be for the United States to offer multiple pathways for product approval that adapt to the diversity of the products and the needs of the consumer. Multiple pathways for market approval would protect public health, whether the public is using cannabis and cannabinoids as a medicine, a wellness product, or as a recreational substance.
., (© 2020, AICHServier GroupCopyright © 2020 AICH Servier Group. All rights reserved.)

A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development.

Issues: Non-medical cannabis policies are changing, including towards legalisation-with-regulation frameworks. New Zealand will hold a public referendum on cannabis legalisation in 2020. We reviewed data on cannabis use and health/social harms; policy reform options; experiences with and outcomes of reforms elsewhere; and other relevant considerations towards informing policy choices in the upcoming referendum., Approach: Relevant epidemiological, health, social, criminal justice and policy studies and data were identified and comprehensively reviewed., Key Findings: Cannabis use is common (including in New Zealand) and associated with risks for health and social harms, mainly concentrated in young users; key harms are attributable to criminalisation. 'Decriminalisation' reforms have produced ambivalent results. Existing cannabis legalisation frameworks vary considerably in main parameters. Legalisation offers some distinct advantages, for example regulated use, products and user education, yet outcomes depend on essential regulation parameters, including commercialisation, and policy ecologies. While major changes in use are not observed, legalisation experiences are inconclusive to date, including mixed health and social outcomes, with select harms increasing and resilient illegal markets. It is unclear whether legalisation reduces cannabis exposure or social harms (e.g. from enforcement) for youth., Implications/conclusions: No conclusive overall evidence on the outcomes of legalisation elsewhere exists, nor is evidence easily transferable to other settings. Legalisation offers direct social justice benefits for adults, yet overall public health impacts are uncertain. Legalisation may not categorically improve health or social outcomes for youth. Legalisation remains a well-intended, while experimental policy option towards more measured and sensible cannabis control and overall greater policy coherence, requiring close monitoring and possible adjustments depending on setting-specific outcomes., (© 2020 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

Backgrounds and Aims: Iran has 2.1 and 1.8% of its 15-64-year-old population living with illicit substance and opioid use disorders, respectively. To address these problems, Iran has been developing a large and multi-modality addiction treatment system, spanning the time before and after the Islamic Revolution., Methods: Iran's current drug treatment scene is a combination of services, ranging from medical/harm reduction services to punitive/criminal justice programs. Included in this array of services are drop-in centers providing low-threshold harm reduction services, such as distribution of sterile needles and syringes; opioid maintenance treatment clinics providing methadone, buprenorphine and opium tincture; and abstinence-based residential centers. We will review the evolution of this system in four phases., Results: In 1980, Iran's revolutionary government shut down all voluntary treatment programs and replaced them with residential correctional programs. The first shift in the addiction treatment policies came 15 years later after facing the negative consequences. Addiction is viewed as a disease, and new voluntary treatment centers offering non-agonist medications and psychosocial services were established. With an increased number of people who inject drugs and HIV/AIDS epidemics, in the second shift an extensive move towards harm reduction strategies and opioid-maintenance programs has been implemented to reduce HIV-related high-risk behavior. The emergence of a methamphetamine use crisis creating an increased number of socially marginalized addicted people resulted in public and political demands for stricter policies and ended in the third shift starting in 2010, with extended compulsory court-based residential programs. Currently, there is a new shift towards reducing the severity of criminal penalties for drug use/sales and promoting proposals for opium legalization., Conclusion: Iran's evolutionary experience in developing a large addiction treatment program in a complex combination of medical/harm reduction and punitive/criminal justice addiction treatment can be examined in its political, clinical and pragmatic context., (© 2019 Society for the Study of Addiction.)

Cannabidiol (CBD) is the second most abundant cannabinoid present in Cannabis sativa L. It is not associated with psychotropic activity and is capable to mitigate the psychotomimetic effects produced by tetrahydrocannabinol (THC). The latest cannabis decriminalization policies and the high applicability in therapeutic and technologic-industrial fields, have determined an exponential marketing growth of foods, cosmetics and in particularly medicinal products containing CBD, which are easily available for consumers. Most importantly, on 2018 United States Food and Drug Administration approved CBD oral solution with the trade name of Epidiolex® for the treatment of two rare and severe forms of epilepsy, "Lennox-Gastaut syndrome" and "Dravet syndrome", in pediatric patients. The aim of this review was to focus on pharmacology and on legal status of CBD, to highlight the lack of harmonization of international regulatory laws over the marketing authorization of CBD-based products.

Introduction: In October 2018, Canada legalized the nonmedical use of cannabis for adults. The aim of our study was to present a more recent temporal pattern of cannabis-related injuries and poisonings found in the electronic Canadian Hospitals Injury Reporting and Prevention Program (eCHIRPP) database and provide a descriptive summary of the injury characteristics of cannabis-related cases captured in a nine-year period., Methods: We conducted a search for cannabis-related cases in the eCHIRPP database reported between April 2011 and August 2019. The study population consisted of patients between the ages of 0 and 79 years presenting to the 19 selected emergency departments across Canada participating in the eCHIRPP program. We calculated descriptive estimates examining the intentionality, external cause, type and severity of cannabis-related cases to better understand the contextual factors of such cases. We also conducted time trend analyses using Joinpoint software establishing the directionality of cannabis-related cases over the years among both children and adults., Results: Between 1 April 2011, and 9 August, 2019, there were 2823 cannabis-related cases reported in eCHIRPP, representing 252.3 cases/100 000 eCHIRPP cases. Of the 2823 cannabis-related cases, a majority involved cannabis use in combination with one or more substances (63.1%; 1780 cases). There were 885 (31.3%) cases that involved only cannabis, and 158 cases (5.6%) that related to cannabis edibles. The leading external cause of injury among children and adults was poisoning. A large proportion of cannabis-related cases were unintentional in nature, and time trend analyses revealed that cannabis-related cases have recently been increasing among both children and adults. Overall, 15.1% of cases involved serious injuries requiring admission to hospital., Conclusion: Cannabis-related cases in the eCHIRPP database are relatively rate, a finding that may point to the fact that mental and behavioural disorders resulting from cannabis exposure are not generally captured in this surveillance system and the limited number of sites found across Canada. With Canada's recent amendments to cannabis regulations, ongoing surveillance of the health impacts of cannabis will be imperative to help advance evidence to protect the health of Canadians., Competing Interests: The authors have no conflicts of interest to declare.

Background: The trend of non-communicable diseases is alarmingly increasing and tobacco consumption and exposure to its smoke have been playing the leading role. Thirty-seven Ethiopians deaths per day are attributable to tobacco. Unless appropriately mitigated, this has social, economic and political impacts. Implementation of the appropriate policy is a good remedy; however, the policy process has never been straight forward and always successful. The involvement of different actors makes policy process complex hence agenda setting, policy formulation, implementation, and evaluations have been full of chaos and even may fail at any of these levels. Thus the aim of this review was retrospectively analyzing tobacco-related policies in Ethiopia that are relevant to control tobacco use and mitigate its impacts., Methods: Systematically, we searched in pub-med, Scopus, Web of Science and Embase. Additionally, we did hand search on Google scholar and national websites. The terms "tobacco", "cigar", "cigarette", "control", "prevention", "policy" and "Ethiopia" were used. Eleven of 128 records met the inclusion criteria and then included. For data analysis, we applied the health policy analysis framework developed by Walt and Gilson., Result: Lately, Ethiopia enacted and started to implement tobacco control policies and programs, but its implementation is problematic and consumption rate is increasing., Conclusion: Despite the early involvement in tobacco control initiatives and enactment of legal frameworks, Ethiopia's journey and current stand to prevent and control the devastating consequences of tobacco is very limited and unsatisfactory. Therefore, we strongly call for further action, strong involvement of private sector and non-governmental organizations., (© 2020 Teshome Tesfaye Habebo, et al.)

Introduction: There is concern that recreational marijuana legalization (RML) may lead to increased cannabis use disorder (CUD) among youth due to increased marijuana use. This study investigates whether adolescent substance use disorder treatment admissions for marijuana use increased in Colorado and Washington following RML., Methods: Annual data on 2008-2017 treatment admissions for marijuana use from the SAMHSA TEDS-A dataset for adolescents age 12-17 were used to model state treatment admissions trends. Difference-in-differences models were used to investigate whether treatment admissions increased following RML in Colorado/Washington compared to non-RML states, after adjusting for socioeconomic characteristics and treatment availability., Results: Over all states in the analysis, the rate of adolescent treatment admissions for marijuana use declined significantly over the study period (β=-3.375, 95 % CI=-4.842, -1.907), with the mean rate falling nearly in half. The decline in admissions rate was greater in Colorado and Washington compared to non-RML states following RML, though this difference was not significant (β=-7.671, 95 % CI=-38.798, 23.456)., Conclusion: Adolescent treatment admissions for marijuana use did not increase in Colorado and Washington following RML. This may be because youth marijuana use did not increase, CUD did not increase (even if use did increase), or treatment seeking behaviors changed due to shifts in attitudes and perceptions of risk towards marijuana use., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The continued toll of opioid-related overdoses has motivated efforts to expand availability of naloxone to persons at high risk of overdose, with 2016 federal guidance encouraging clinicians to co-prescribe naloxone to patients with increased overdose risk. Some states have pursued analogous or stricter legal requirements that could more heavily influence prescriber behavior., Methods: We conducted a systematic legal review of state laws that mandate or recommend that healthcare providers prescribe naloxone to patients with indicators for opioid overdose risk. We coded relevant statutes and regulations for: applicable populations, patient criteria, educational requirements, and exemptions., Results: As of September 2019, 17 states had enacted naloxone co-prescribing laws, the earliest of which was implemented by Louisiana in January 2016. If patient overdose risk criteria are met, over half of these states mandate that providers prescribe naloxone (7 states, 41.1 %) or offer a naloxone prescription (2 states, 11.8 %); the remainder encourage prescribers to consider prescribing naloxone (8 states). Most states (58.8 %) define patient overdose risk based on opioid dosages prescribed, although the threshold varies substantially; other common overdose risk criteria include concomitant opioid and benzodiazepine prescriptions and patient history of substance use disorder or mental illness., Conclusions: A growing minority of states has adopted a naloxone prescribing law, although these policies remain less prevalent than other naloxone access laws. By targeting higher-risk patients during clinical encounters, naloxone prescribing requirements could increase naloxone prescribed, destigmatize naloxone use, and reduce overdose harms. Further investigation into policy effectiveness, unintended consequences, and appropriate parameters is warranted., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

On a near daily basis, medicines make the news. Abstract topics such as international pricing policy or medicines patents, and concrete topics such as medicines shortages are regularly reported on. In this article, we summarise a 40-year-history of medicines policy in the Netherlands. Furthermore, we briefly touch upon future directions in this area.

Background and Purpose: MyDispense is an innovative, web-based program which simulates a community pharmacy. Use of this software may assist students' comprehension of validating controlled substance prescriptions by determining if prescriptions contain errors or omissions., Educational Activity and Setting: Fourteen MyDispense practice exercises were created and implemented into a required second-year pharmacy law course. Completion of the MyDispense exercises and performance on the pharmacy law midterm exam were recorded. A questionnaire was administered to students to receive feedback on the exercises., Findings: There were complete data on all 94 student pharmacists enrolled in the didactic course. Thirty-five students (37%) completed all MyDispense exercises, 15 students (16%) completed some of the exercises, and 44 (47%) did not complete any of the exercises. Linear regression results indicate that students who completed more MyDispense exercises were significantly more likely to score higher on the midterm than those who completed fewer exercises (β = 0.28, p = 0.02). Students reported moderate to high exercise value and a willingness to use the software in preparation for future pharmacy law examinations., Summary: MyDispense provided a platform for students to apply controlled substance laws to the prescription validation process in the community pharmacy setting. Completion of practice exercises in MyDispense was shown to positively impact student performance on a pharmacy law midterm. Students valued the innovative simulation tool and were willing to access the tool again to prepare for future examinations., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: US law requires testing of new drugs before approval to ensure that they provide a well-defined benefit that is commensurate with their risks. A major challenge for the US Food and Drug Administration (FDA) is to achieve an appropriate balance between rigorous testing and the need for timely approval of drugs that have benefits that outweigh their risks., Objective: To describe the evolution of laws and standards affecting drug testing, the use of new approval programs and standards, expansions of the role and authority of the FDA, and changes in the number of drugs approved from the 1980s to 2018., Evidence: Sources of evidence included principal federal laws and FDA regulations (1962-2018) and FDA databases of approved new drugs (1984-2018), generic drugs (1970-2018), biologics (1984-2018), and vaccines (1998-2018); special development and approval programs (Orphan drug [1984-2018], Fast-Track [1988-2018], Priority Review and its predecessors [1984-2018], Accelerated Approval [1992-2018], and Breakthrough Therapy [2012-2018]); expanded access (2010-2017) and Risk Evaluation and Mitigation Strategies (2008-2018); and user fees paid to the FDA by industry (1993-2018)., Findings: From 1983 to 2018, legislation and regulatory initiatives have substantially changed drug approval at the FDA. The mean annual number of new drug approvals, including biologics, was 34 from 1990-1999, 25 from 2000-2009, and 41 from 2010-2018. New biologic product approvals increased from a median of 2.5 from 1990-1999, to 5 from 2000-2013, to 12 from 2014-2018. The median annual number of generic drugs approved was 136 from 1970 to the enactment of the Hatch-Waxman Act in 1984; 284 from 1985 to the enactment of the Generic Drug User Fee Act in 2012; and 588 from 2013-2018. Prescription drug user fee funding expanded from new drugs and biologics in 1992 to generic and biosimilar drugs in 2012. The amount of Prescription Drug User Fee Act fees collected from industry increased from an annual mean of $66 million in 1993-1997 to $820 million in 2013-2017, and in 2018, user fees accounted for approximately 80% of the salaries of review personnel responsible for the approval of new drugs. The proportion of drugs approved with an Orphan Drug Act designation increased from 18% (55/304) in 1984-1995, to 22% (82/379) in 1996-2007, to 41% (154/380) in 2008-2018. Use of Accelerated Approval, Fast-Track, and Priority Review for new drugs has increased over time, with 81% (48/59) of new drugs benefiting from at least 1 such expedited program in 2018. The proportion of new approvals supported by at least 2 pivotal trials decreased from 80.6% in 1995-1997 to 52.8% in 2015-2017, based on 124 and 106 approvals, respectively, while the median number of patients studied did not change significantly (774 vs 816). FDA drug review times declined from more than 3 years in 1983 to less than 1 year in 2017, but total time from the authorization of clinical testing to approval has remained at approximately 8 years over that period., Conclusions and Relevance: Over the last 4 decades, the approval and regulation processes for pharmaceutical agents have evolved and increased in complexity as special programs have been added and as the use of surrogate measures has been encouraged. The FDA funding needed to implement and manage these programs has been addressed by expanding industry-paid user fees. The FDA has increasingly accepted less data and more surrogate measures, and has shortened its review times.

Objectives: There has been advocacy for legalization of abusable substances, but systematic data on societal beliefs regarding such legalization are limited. People who use substances may have unique beliefs about legalization, and this study assessed whether they would be in favor of drug legalization/decriminalization. It was hypothesized that those who use particular drugs (especially marijuana) would support its legalization/decriminalization, but that this would not be the case across all classes (especially opioids and stimulants)., Methods: A nationwide sample of 506 adults were surveyed online to assess demographic characteristics, substance misuse, and beliefs regarding drug legalization/decriminalization. Legalization/decriminalization beliefs for specific drugs were assessed on an 11-point scale (0, strongly disagree; 10, strongly agree)., Results: For persons with opioid misuse (15.4%), when asked about their agreement with: "heroin should be legalized," the mean score was 4.6 (SEE = 0.4; neutral). For persons with stimulant misuse (12.1%), when asked about their agreement with: "cocaine should be legalized," the score was 4.2 (0.5). However, for persons with marijuana misuse (34.0%), when asked about their agreement with: "medical marijuana should be legalized" the score was 8.2 (0.3; indicating agreement), and for "recreational marijuana" the score was also 8.2 (0.3)., Conclusions: These results suggest that persons who used marijuana strongly support the legalization of both recreational and medical marijuana, whereas persons who primarily have opioid or stimulant misuse have less strongly held beliefs about legalization of substances within those respective categories. By including those who misuse drugs, these data assist in framing discussions of drug legalization and have the potential to inform drug policy considerations.

Objectives: The objective was to identify the main texts applicable to the practice of pharmacy in Quebec, then count the specific number of recommendations and criteria and describe the evolution of the legal and normative framework., Methods: This is a descriptive and retrospective study of the main texts applicable to the legal and normative framework for the practice of pharmacy on January 1st, 2019., Results: A total of 107 texts relating to the practice of pharmacy in Quebec were identified. They come from the legislator (53.1 %), the Order of pharmacists (26.1 %) or other organizations (20.8 %). These were laws/regulations (n=59), contributing to the optimal use of drugs (n=18), relating to hospital pharmacy management (n=18), the provision of pharmaceutical care (n=11), drug preparation (n=3), oncology practice (n=2) or health and safety at work (n=1). Thirty-three texts were considered for enumeration of recommendations and explicit criteria, for a total of 235 recommendations and 3703 explicit criteria applicable to the practice of hospital pharmacy in Quebec., Conclusion: There is a significant increase in the number of texts, recommendations and criteria applicable to the practice of hospital pharmacy in Quebec. Compliance with this legal and normative framework appears to be a considerable challenge for hospital pharmacists. It seems worthwhile to further promote discussion with text-issuing agencies in order to keep the search for compliance realistic., (Copyright © 2019 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

We examine the association between opioid prescription patterns in privately insured adults and changes in state cannabis laws among five age groups (18-25, 26-35 36-45, 46-55 and 56-64 years). Using the 2016 Clinformatics Data Mart, a nationwide commercial health insurance database, we performed a cross-sectional analysis of two types of opioid prescribing (>30-day and >90-day prescriptions) among all adults aged 18-64 based on the stringency of cannabis laws. We found a significant interaction between age and cannabis law on opioid prescriptions. Age-stratified multilevel multivariable analyses showed lower opioid prescription rates in the four younger age groups only in states with medical cannabis laws, when considering both >30 day and >90 day opioid use [>30 day adjusted odds ratio (aOR) = 0.56, in 18-25, aOR = 0.67 in 26-35, aOR = 0.67 in 36-45, and aOR = 0.76 in 46-54 years; >90 day aOR = 0.56, in 18-25, aOR = 0.68 in 26-35, aOR = 0.69 in 36-45, and aOR = 0.77 in 46-54 years, P < 0.0001 for all]. This association was not significant in the oldest age group of 55-64 years. There was no significant association between opioid prescriptions and other categories of cannabis laws (recreational use and decriminalization) in any of the age groups studied., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine the association of medical marijuana legalization with prescription opioid utilization., Methods: A 10% sample of a nationally representative database of commercially insured population was used to gather information on opioid use, chronic opioid use, and high-risk opioid use for the years 2006-2014. Adults with pharmacy and medical benefits for the entire calendar year were included in the population for that year. Multilevel logistic regression analysis, controlling for patient, person-year, and state-level factors, were used to determine the impact of medical marijuana legalization on the three opioid use measures. Sub-group analysis among cancer-free adults and cancer-free adults with at least one chronic non-cancer pain condition in the particular year were conducted. Alternate regression models were used to test the robustness of our results including a fixed effects model, an alternate definition for start date for medical marijuana legalization, a person-level analysis, and a falsification test., Results: The final sample included a total of 4,840,562 persons translating into 15,705,562 person years. Medical marijuana legalization was found to be associated with a lower odds of any opioid use: OR = 0.95 (0.94-0.96), chronic opioid use: OR = 0.93 (0.91-0.95), and high-risk opioid use: OR = 0.96 (0.94-0.98). The findings were similar in both the sub-group analyses and all the sensitivity analyses. The falsification tests showed no association between medical marijuana legalization and prescriptions for antihyperlipidemics (OR = 1.00; CI 0.99-1.01) or antihypertensives (OR = 1.00; CI 0.99-1.01)., Conclusions: In states where marijuana is available through medical channels, a modestly lower rate of opioid and high-risk opioid prescribing was observed. Policy makers could consider medical marijuana legalization as a tool that may modestly reduce chronic and high-risk opioid use. However, further research assessing risk versus benefits of medical marijuana legalization and head to head comparisons of marijuana versus opioids for pain management is required.

Objectives: To examine the effect of cannabis policy liberalisation (decriminalisation and legalisation) levels of use in adolescents and young adults., Design: Systematic review and meta-analysis., Inclusion Criteria: Included studies were conducted among individuals younger than 25 years and quantitatively assessing consequences of cannabis policy change. We excluded articles: (A) exclusively based on participants older than 25 years; (B) only reporting changes in perceptions of cannabis use; (C) not including at least two measures of cannabis use; (D) not including quantitative data; and (E) reviews, letters, opinions and policy papers. PubMed, PsycINFO, Embase and Web of Science were searched through 1 March 2018., Data Extraction and Synthesis: Two independent readers reviewed the eligibility of titles and abstracts and read eligible articles, and four authors assessed the risk of bias (Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies). Extracted data were meta-analysed. The protocol was registered with PROSPERO., Results: 3438 records were identified via search terms and four via citation lists; 2312 were retained after removal of duplicates, 99 were assessed for eligibility and 41 were included in our systematic review. 13 articles examined cannabis decriminalisation, 20 examined legalisation for medical purposes and 8 examined legalisation for recreational purposes. Findings regarding the consequences of cannabis decriminalisation or legalisation for medical purposes were too heterogeneous to be meta-analysed. Our systematic review and meta-analysis suggest a small increase in cannabis use among adolescents and young adults following legalisation of cannabis for recreational purposes (standardised mean difference of 0.03, 95% CI -0.01 to -0.07). Nevertheless, studies characterised by a very low/low risk of bias showed no evidence of changes in cannabis use following policy modifications., Conclusions: Cannabis policy liberalisation does not appear to result in significant changes in youths' use, with the possible exception of legalisation for recreational purposes that requires monitoring., Trial Registration Number: CRD42018083950., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Asia Pacific (AP) region is diverse and dynamic. It comprises over 40 economies, with about 24 markets that are relatively more active in terms of promulgating and implementing regulations that impact the biopharmaceutical industry and advance drug development. Although many country- and territory-specific regulations, often driven by the local economy and market dynamics, exist, the overall trend in the AP region is toward international harmonization and global convergence. More markets are now participating in the International Council on Harmonization (ICH), and there is growing interest in identifying and incorporating best practices from competent regulatory agencies. These include expedited pathways to speed access to new medicines, and incentives and other means to encourage innovation. In this paper, we provide a summary of recent activities in select AP markets.

After decades of disregard in the Western world, phage therapy is witnessing a return of interest. However, the pharmaceutical legislation that has since been implemented is basically designed for regulating industrially-made pharmaceuticals, devoid of any patient customization and intended for large-scale distribution. Accordingly, the resulting regulatory framework is hardly reconcilable with the concept of sustainable phage therapy, involving tailor-made medicinal products in the global perspective of both evolutionary and personalized medicine. The repeated appeal for a dedicated regulatory framework has not been heard by the European legislature, which, in this matter, features a strong resistance to change despite the precedent of the unhindered implementation of advanced therapy medicinal product (ATMPs) regulation. It is acknowledged that in many aspects, phage therapy medicinal products are quite unconventional pharmaceuticals and likely this lack of conformity to the canonical model hampered the development of a suitable regulatory pathway. However, the regulatory approaches of countries where phage therapy traditions and practice have never been abandoned are now being revisited by some Western countries, opening new avenues for phage therapy regulation. As a next step, supranational and international organizations are urged to take over the initiatives originally launched by national regulatory authorities.

The cost of prescription drugs in the United States continues to be a source of concern for patients, caregivers, and policymakers. Drug prices typically decline rapidly once generic drugs receive US Food and Drug Administration (FDA) approval and enter the market, but the past decade has witnessed rising costs and shortages of generic drugs. We describe the strategies used by brand-name manufacturers to undermine generic competition and the reasons underlying the price increases of off-patent drugs, some of which continue to lack any competition from generic versions, and others that have increased in price despite having generic versions. We discuss the FDA's role in addressing drug prices and promoting competition, including recent agency policies to modify its process of reviewing generic drug applications and to prioritize applications for off-patent drugs with few competitors. We also examine proposed policy solutions and research areas that could help address the price increases of off-patent drugs., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

Objectives: Medical marijuana use may substitute prescription opioid use, whereas nonmedical marijuana use may be a risk factor of prescription opioid misuse. This study examined the associations between recreational marijuana legalization and prescription opioids received by Medicaid enrollees., Methods: State-level quarterly prescription drug utilization records for Medicaid enrollees during 2010-2017 were obtained from Medicaid State Drug Utilization Data. The primary outcome, opioid prescriptions received, was measured in three population-adjusted variables: number of opioid prescriptions, total doses of opioid prescriptions in morphine milligram equivalents, and related Medicaid spending, per quarter per 100 enrollees. Two difference-in-difference models were used to test the associations: eight states and DC that legalized recreational marijuana during the study period were first compared among themselves, then compared to six states with medical marijuana legalized before the study period. Schedule II and III opioids were analyzed separately., Results: In models comparing eight states and DC, legalization was not associated with Schedule II opioid outcomes; having recreational marijuana legalization effective in 2015 was associated with reductions in number of prescriptions, total doses, and spending of Schedule III opioids by 32% (95% CI: (-49%, -15%), p = 0.003), 30% ((-55%, -4.4%), p = 0.027), and 31% ((-59%, -3.6%), p = 0.031), respectively. In models comparing eight states and DC to six states with medical marijuana legalization, recreational marijuana legalization was not associated with any opioid outcome., Conclusions: No evidence suggested that recreational marijuana legalization increased prescription opioids received by Medicaid enrollees. There was some evidence in some states for reduced Schedule III opioids following the legalization., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This study compared young adults with and without a medical marijuana (MM) recommendation from a provider ("MM card") on their developmental trajectories of frequent marijuana use and marijuana-related problems in young adulthood., Methods: The analytic sample consists of young adult past month marijuana users (N = 671) who were part of a larger, diverse, and predominantly California cohort. Analyses are based on data from seven surveys completed from ages 13-19., Results: At age 19, 28% of participants reported having an MM card to legally purchase marijuana from an MM dispensary. A multiple group latent growth model indicated that young adults who had an MM card showed steeper increases in frequent marijuana use (i.e., 20-30 days of use in the past month) from ages 13-19 compared to young adults who did not have an MM card. Logistic regression models that matched MM cardholders and non-MM cardholders on individual sociodemographic characteristics found that MM cardholders were more likely to report marijuana negative consequences, selling marijuana/hashish, and driving under the influence of marijuana in the past year. In addition, MM cardholders were more likely to have tried cutting down or quitting in the past 3-months., Conclusions: Among young adult marijuana users, those with an MM card had a higher risk profile for marijuana use and related problems compared to those without an MM card. Given expanding state legalization of MM, this issue warrants further attention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In November 2013, a team of European regulators initiated the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Funded by the Health Programme of the European Union, and with contributions from the involved Member States, SCOPE gathered information and expertise on how regulators in Member States run their national pharmacovigilance systems to meet the requirements of the pharmacovigilance legislation that came into effect in June 2012. The SCOPE project evaluated then-current practices and developed tools to further improve the skills and capability in the pharmacovigilance network. The project was divided into eight separate work streams, five of which concentrated on pharmacovigilance topics-collecting information on suspected adverse drug reactions, identifying and managing safety issues (signals), communicating risk and assessing risk minimisation measures, supported by effective quality management systems. The other three work streams focused on the functional aspects-coordination, communication and evaluation of the project. Through the project, SCOPE delivered guidance, training in key aspects of pharmacovigilance, and tools and templates to support best practice. The deliverables provide practical guidance that those working in the European national competent authorities can take to strengthen their national systems. The SCOPE outputs can be useful for other stakeholders involved in pharmacovigilance activities, including the pharmaceutical industry, healthcare professionals, patient and consumer organisations, and academia.

Background: As of May 2017, the United States federal government renewed its prioritization for the enforcement of mandatory minimum sentences for illicit drug offenses. While the effect of such policies on racial disparities in incarceration is well-documented, less is known about the extent to which these laws are associated with decreased drug use. This study aims to identify changes in cocaine use associated with mandatory minimum sentencing policies by examining differential sentences for powder and crack cocaine set by the Anti-Drug Abuse Act (ADAA) (100:1) and the Fair Sentencing Act (FSA), which reduced the disparate sentencing to 18:1., Methods: Using data from National Survey on Drug Use and Health, we examined past-year cocaine use before and after implementation of the ADAA (1985-1990, N = 21,296) and FSA (2009-2013, N = 130,574). We used weighted logistic regressions and Z-tests across models to identify differential change in use between crack and powder cocaine. Prescription drug misuse, or use outside prescribed indication or dose, was modeled as a negative control to identify underlying drug trends not related to sentencing policies., Results: Despite harsher ADAA penalties for crack compared to powder cocaine, there was no decrease in crack use following implementation of sentencing policies (odds ratio (OR): 0.72, p = 0.13), although both powder cocaine use and misuse of prescription drugs (the negative control) decreased (OR: 0.59, p < 0.01; OR: 0.42, p < 0.01 respectively). Furthermore, there was no change in crack use following the FSA, but powder cocaine use decreased, despite no changes to powder cocaine sentences (OR: 0.81, p = 0.02), suggesting that drug use is driven by factors not associated with sentencing policy., Conclusions: Despite harsher penalties for crack versus powder cocaine, crack use declined less than powder cocaine and even less than drugs not included in sentencing policies. These findings suggest that mandatory minimum sentencing may not be an effective method of deterring cocaine use.

Background and Purpose: The purpose of this project was to impact pharmacy students' personal and professional development through simulation of a board of pharmacy disciplinary hearing regarding addiction., Educational Activity and Setting: The mock board hearing was conducted as part of the required curriculum. Faculty obtained materials from a prior board hearing. The actual respondent, lawyer, former executive director, and a board agent participated. Students served as board members and president, asked questions of the witnesses, and deliberated per board procedure. After the event, student learning and perceptions were assessed through knowledge-based, opinion-based questions, and open-ended questions., Findings: Of the 141 students who attended the event, 97% completed the assessment. The average score on the knowledge-based questions was 95%. Ratings of perceptions and reflections of the experience were used in tandem to understand the experience. In general, students indicated the experience was positive and impactful towards their education. Students indicated they felt that the experience allowed them to better understand addiction and empathize with someone called before the board. In fact, there were fundamental differences in perceptions regarding the "addicted person," going from a penalizing and stigmatized perspective to one of caring and compassion., Summary: Students were knowledgeable about the board and its regulatory process after the event. More than knowledge, students indicated fundamental changes in their views of addiction. Other institutions may consider implementing similar exercises to engender empathy and professionalism regarding drug addiction and regulatory compliance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Imagine a Minister for Addictions, not only for individuals we criminalize and stigmatize as "drug addicts" but for us all. So misunderstood is addiction, so scant is our public discourse about its scientific basis and so deep is the despair wrought by its present spread that we require a government reboot., (Copyright © 2018 Longwoods Publishing.)

Pre-clinical research supports that cannabinoids reduce opioid dose requirements, but few studies have tested this in humans. This review evaluates ecological and epidemiological studies that have been cited as evidence that medical cannabis use may reduce opioid use and opioid-related harms. Medline and Embase were searched for relevant articles. Data were extracted on study setting, analyses approach, covariates, and outcomes. Eleven ecological and 14 epidemiological studies were found. In ecological studies, states that allow medical cannabis laws have reported a slower rate of increase in opioid overdose deaths compared with states without such laws. These differences have increased over time and persisted after controlling for state sociodemographic characteristics and use of prescription monitoring programmes. Few studies have controlled for other potential confounders such as opioid dependence treatment and imprisonment rates. Some epidemiological studies provide evidence that cannabis availability may reduce opioid use, but are limited by selection bias, cross-sectional designs, and self-reported assessments of the opioid-sparing effects of cannabis. Some epidemiological and ecological studies suggest that cannabis may reduce opioid use and harms, although important methodological weaknesses were identified. Well-designed clinical studies may provide more conclusive evidence on whether cannabinoids can reduce opioid use and related harm.

Background: Half of the US states have legalized medical cannabis (marijuana), some allow recreational use. The economic and public health effects of these policies are still being evaluated. We hypothesized that cannabis legalization was associated with an increase in the proportion of motor vehicle crash fatalities involving cannabis-positive drivers, and that cannabis use is associated with high-risk behavior and poor insurance status., Methods: Hawaii legalized cannabis in 2000. Fatality Analysis Reporting System data were analyzed before (1993-2000) and after (2001-2015) legalization. The presence of cannabis (THC), methamphetamine, and alcohol in fatally injured drivers was compared. Data from the state's highest level trauma center were reviewed for THC status from 1997 to 2013. State Trauma Registry data from 2011 to 2015 were reviewed to evaluate association between cannabis, helmet/seatbelt use, and payor mix., Results: THC positivity among driver fatalities increased since legalization, with a threefold increase from 1993-2000 to 2001-2015. Methamphetamine, which has remained illegal, and alcohol positivity were not significantly different before versus after 2000. THC-positive fatalities were younger, and more likely, single-vehicle accidents, nighttime crashes, and speeding. They were less likely to have used a seatbelt or helmet. THC positivity among all injured patients tested at our highest level trauma center increased from 11% before to 20% after legalization. From 2011 to 2015, THC-positive patients were significantly less likely to wear a seatbelt or helmet (33% vs 56%). They were twice as likely to have Medicaid insurance (28% vs 14%)., Conclusion: Since the legalization of cannabis, THC positivity among MVC fatalities has tripled statewide, and THC positivity among patients presenting to the highest level trauma center has doubled. THC-positive patients are less likely to use protective devices and more likely to rely on publically funded medical insurance. These findings have implications nationally and underscore the need for further research and policy development to address the public health effects and the costs of cannabis-related trauma., Level of Evidence: Prognostic, level III.

We review recent findings on medical aspects of marijuana use in order to identify those who are at greatest risk of marijuana-related medical problems. We analyze the impact of medical marijuana laws on health, in particular the disproportionate effects on adolescents and children. Chronic marijuana use predominantly affects certain areas of the brain that overlap the default mode network, linked hubs in the brain that play a supervisory role in critical thought processes such as attention, memory, and social interactions. Disruption of the default mode network areas has been documented in schizophrenia and Alzheimer's disease, illnesses with symptoms and brain changes that parallel findings in marijuana abusers. These findings counter the claim that marijuana is a harmless drug and are a cause for alarm in persons with cannabis dependence.

Background: Marijuana use during adolescence is associated with neurocognitive deficits and poorer functioning across several domains. It is likely that more states will pass both medical and recreational marijuana legalization laws in the coming elections; therefore, we must begin to look more closely at the longitudinal effects of medical marijuana (MM) advertising on marijuana use among adolescents so that we can better understand effects that this advertising may have on their subsequent marijuana use and related outcomes., Methods: We followed two cohorts of 7th and 8th graders (mean age 13) recruited from school districts in Southern California from 2010 until 2017 (mean age 19) to examine effects of MM advertising on adolescents' marijuana use, cognitions, and consequences over seven years. Latent growth models examined trajectories of self-reported exposure to medical marijuana ads in the past three months and trajectories of use, cognitions, and consequences., Results: Higher average exposure to MM advertising was associated with higher average use, intentions to use, positive expectancies, and negative consequences. Similarly, higher rates of change in MM advertising exposure were associated with higher rates of change in use, intentions, expectancies, and consequences over seven years., Conclusions: Results suggest that exposure to MM advertising may not only play a significant role in shaping attitudes about marijuana, but may also contribute to increased marijuana use and related negative consequences throughout adolescence. This highlights the importance of considering regulations for marijuana advertising, similar to regulations in place for the promotion of tobacco and alcohol in the U.S., (Copyright © 2018. Published by Elsevier B.V.)

Purpose of Review: To review the literature on decriminalization of drug use from 2016 to 2017 and suggest the way forward., Recent Findings: The systematic review of the literature on decriminalization resulted in seven articles that discuss decriminalization as compared with 57 published articles on legalization. Decriminalization of drug use did not have an effect on the age of onset of drug use and the prices of drugs did not decrease after the implementation of drug decriminalization. Policy-based studies on decriminalization suggest shifting from criminal sanctions to a public health approach, which was endorsed by the United Nations (UN) that viewed drug addiction as a preventable and treatable health disorder. One study preferred decriminalization only for cannabis and cautioned against regulating cannabis like alcohol. Another study indicated that general medical practitioners in Ireland did not favour the decriminalization of cannabis., Summary: Scientific evidence supporting drug addiction as a health disorder and the endorsement by the UN strengthen the case for decriminalization. However, studies reporting on the positive outcomes of decriminalization remain scarce. The evidence needs to be more widespread in order to support the case for decriminalization. Furthermore, the endorsement by the UN needs to be acted upon by individual member states.

The pharmaceutical industry is one of the most regulated industries in Switzerland. Though the concept of good manufacturing practises (GMP) was implemented for chemical production in the early 1990s, the rules and regulations for our industry are in constant evolution. In this article we will highlight the impact of these changes to the industry using three recent guideline up-dates as examples: the implementation of ICH Q3D 'Guideline for elemental impurities', the EU-GMP Guideline Part III Chapter 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities' from 01. June 2015, and the new guidelines to data integrity such as 'PIC/S 041-1 Good Practices for Data Management and Integrity in regulated GMP/GDP environments'. These examples show how scientific approaches help to modernize the control strategies for our products and increase product quality for a better patient safety. The requirements of data integrity regulations are also of interest to industries and universities not working under GxP requirements as they also support the business to improve data quality (traceability) for patent applications, and reduce risk of data falsification.

A dozen or more regulatory frameworks have been proposed for legal cannabis but many of the "not-for-profit" options have yet to be developed in any detail, reducing the likelihood they will be seriously considered by policy makers. New Zealand's innovative "not-for-profit" regulatory regime for gaming machine gambling (i.e. "slot machines") has reversed the previous increase in gambling expenditure, empowered local councils to cap the number of gambling venues, and is unique in requiring the societies operating gaming machines to distribution 40% of the gross expenditure from machines (i.e. $NZ 262 million in 2015) to community purposes (e.g. sports). However, the regime has been criticised for not addressing the concentration of gaming outlets in poorer communities, and not requiring grants to be allocated in the disadvantaged communities where outlets are located. There have also been cases of gaming societies providing community grants in exchange for direct or indirect benefits. In this paper we adapt this regulatory approach to a legal cannabis market. Under the proposed regime, licensed "not-for-profit" cannabis societies will be required to distribute 20% of cannabis sales to drug treatment and 20% to community purposes, including drug prevention. Grants must be allocated in the regions where cannabis sales are made and grant committees must be independent from cannabis societies. A 20% levy will be used to cover the wider health costs of cannabis use. A further 10% levy will be used to fund the regulator and evaluate the new regime. Local councils will have the power to decide how many, and where, cannabis retail outlets are located. Other important elements include a minimum price for cannabis, effective taxation of cannabis products, regulating CBD in cannabis products, higher taxation of traditional smoking products, advertising restricted to place-of-sale, no internet sales, and restrictions on industry involvement in regulation making and research., (Copyright © 2017. Published by Elsevier B.V.)

Objectives: To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget., Methods: Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices., Results: For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)