County-Level Recreational Marijuana Policies and Local Policy Changes in Colorado and Washington State (2012-2019).

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.

Public health impacts to date of the legalisation of medical and recreational cannabis use in the USA.

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.

Looking back from 2020, how cannabis use and related behaviours changed in Canada.

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.

Methamphetamine exposures reported to United States poison control centers, 2000-2019.

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 legalization of cannabinoid products and standardizing cannabis-drug development in the United States: a brief report
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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.
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Este breve informe cubre los avances recientes en la regulación del cannabis y los cannabinoides y en la aprobación de medicamentos. La popularidad del cannabis y de los productos cannabinoides continúa aumentando. Estos productos están disponibles para la mayoría de la población en los Estados Unidos y se pueden comprar tan fácilmente como el alcohol. Aunque muchos estados han aprobado programas y licencias de investigación, estas actividades y productos siguen siendo ilegales a nivel federal. La solución para Estados Unidos sería ofrecer múltiples vías para la aprobación de productos que se adaptarían a la diversidad de los productos y las necesidades del consumidor. Estas múltiples vías para la aprobación del mercado protegerían la salud pública, ya sea que el público esté utilizando cannabis y cannabinoides como medicamento, producto de bienestar o o sustancia recreativa.

Ce rapport couvre les progrès récents dans la réglementation du cannabis et des cannabinoïdes et l'approbation des médicaments. La popularité du cannabis et des dérivés cannabinoïdes continue d'augmenter, et ces produits sont disponibles pour la majorité de la population aux États-Unis, où ils s'achètent aussi facilement que l'alcool. Bien que de nombreux états aient approuvé des programmes et les licences de recherche, ces activités et produits demeurent tous illégaux au niveau fédéral. La solution pourrait être pour les États-Unis d'offrir plusieurs voies d'approbation qui s'adaptent à la diversité des produits et aux besoins du consommateur. Plusieurs voies d'approbation du marché protégeraient la santé publique, que le cannabis et les cannabinoïdes soient consommés en tant que médicament, produit de bien-être ou substance récréative.

Patent highlights April-May 2020.

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

Pharmacology and legal status of cannabidiol.

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.

Retrospective Policy Analysis of Tobacco Prevention and Control in Ethiopia.

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.

Surveillance from the high ground: sentinel surveillance of injuries and poisonings associated with cannabis. / Surveillance de niveau supérieur : surveillance par sentinelle des blessures et des intoxications associées au cannabis.

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.

[40 years of medicines policy in the Netherlands: from financial constraints to medicines shortages?] / 40 jaar geneesmiddelenbeleid.

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.

Facing the option for the legalisation of cannabis use and supply in New Zealand: An overview of relevant evidence, concepts and considerations.

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.

Análisis de la evolución en el acceso a los medicamentos huérfanos en España / Analysis of the evolution in the access to orphan medicines in Spain

OBJETIVO: Evaluar el acceso al mercado de los medicamentos huérfanos en España que a fecha de 31 de diciembre de 2017 tuvieran vigente su designación, y para aquellos comercializados en España estimar los tiempos entre la asignación de código nacional (CN) por parte de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) y la fecha de comercialización efectiva. MÉTODO: La base de datos para identificar los medicamentos huérfanos autorizados por la Agencia Europea de Medicamentos (EMA), a fecha 31 de diciembre de 2017 (n = 142), es su Registro Comunitario publicado por la Comisión Europea. La EMA publica los medicamentos huérfanos que han perdido la designación. Las fechas de asignación de CN provienen de la AEMPS, y las de comercialización, de Bot PLUS. Se llevó a cabo un análisis descriptivo de las variables de estudio. Las variables cuantitativas se describieron utilizando la media y mediana, así como la desviación estándar y su rango. Las variables cualitativas se describieron según frecuencias absolutas y relativas. La comparación de resultados se realizó mediante contrastes paramétricos y no paramétricos en función de la aplicabilidad, con un nivel de significación del 5%. RESULTADOS: Entre 2002 y 2017, la EMA autorizó (con designación vigente a 31 de diciembre de 2017) 100 medicamentos huérfanos. De ellos, 86 tienen CN asignado, y de estos, 54 se han comercializado en España (54% de los medicamentos huérfanos vigentes y 63% de aquellos con CN). Para todos los medicamentos huérfanos con fecha de comercialización (53), el tiempo (mediana) desde la asignación del CN hasta su comercialización en España es de 13,4 meses (desviación estándar: 17,0; mínimo: 2,1; máximo: 91,7). La mediana para los comercializados en 2002-2013 y 2014-2017 es de 12,4 meses y 14,0 meses, respectivamente (p = 0,46). Esta diferencia no es estadísticamente significativa, lo que cabría esperar dado el número limitado de medicamentos huérfanos en nuestra «población». CONCLUSIÓN: Numerosos factores determinan el acceso a los medicamentos huérfanos. La autorización centralizada de comercialización en Europa es un éxito; su acceso es más limitado, dadas las complejidades de evaluación de la evidencia disponible en los procesos de financiación y precio. Es necesario implementar nuevas políticas que reduzcan las desigualdades en el acceso y permitan la sostenibilidad del sistema. Para conseguir estos objetivos, podrían contemplar un proceso acelerado en la decisión de financiación y precio, y el pago por resultados con incertidumbre alta

OBJECTIVE: To assess the access to orphan medicines in Spain, focusing on those with an active "orphan" designation, as of 31st December 2017; and for those orphan medicines in the Spanish market, estimate the time between being assigned a National Code (NC) by the Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) and being approved for launch. METHOD: We used the European Commission's Public Register of orphan medicines to identify the orphan medicines authorised by the European Medicines Agency (EMA), as of 31 December 2017, while we sourced expired orphan indications from the EMA's website. Dates when NCs were assigned were sourced from the AEMPS, and commercialisation dates from Bot PLUS. A descriptive analysis of the study variables was done. The quantitative variables were described using means and medians, as well as standard deviations and ranges. The qualitative variables were described according to absolute and relative frequencies. The comparison of results was performed by parametric and non-parametric contrasts according to the applicability, at a 5% significance level. RESULTS: The EMA has approved 100 orphan medicines (with designation as of 31/12/2017) between 2002-2017. Eighty-six have a NC assigned by the AEMPS. Fifty-four have been launched in Spain (representing 54% of the full sample; 63% with NC). For the 53 orphan drugs with launch date in Spain, the median time between receiving its NC and its launch is 13.4 months (standard deviation: 17.0; minimum: 2.1; maximum: 91,7). The median time is 12.4 months and 14.0 months for those medicines launched in Spain between 2002-2013 and 2014-2017 respectively (p = 0.46). This difference is not statistically significant, which is what could be expected given the low numbers of orphan medicines in the "population". CONCLUSION: Complex factors determine the access to orphan drugs in Europe. The centralised procedure to obtain marketing authorisation at European level is a success. However, access is more limited, given the complexities of the evaluation of the available evidence for pricing and reimbursement decisions. It is therefore necessary to implement new policies that reduce inequalities in access and help achieve sustainable healthcare systems. To achieve this, they will need to offer the possibility of allowing earlier access, and using payment by results when there is high uncertainty

Adolescent treatment admissions for marijuana following recreational legalization in Colorado and Washington.

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 (ß=-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 (ß=-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.

Using MyDispense to simulate validation of controlled substance prescriptions in a pharmacy law course.

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 (ß = 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.

Legal requirements and recommendations to prescribe naloxone.

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.

FDA Approval and Regulation of Pharmaceuticals, 1983-2018.

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.