Five-Year Sales for Newly Marketed Prescription Drugs With and Without Initial Orphan Drug Act Designation.

This study evaluates sales revenue earned in the first 5 years for newly marketed brand-name drugs with and without an initial orphan drug designation.

Distribution of Abatement Funds Arising From US Opioid Litigation.

This Viewpoint discusses the settlement agreements reached against several major pharmaceutical distributors resulting from the US opioid epidemic and how those funds will be distributed amongst the states.

Compliance to Online Retail of Electronic Nicotine Delivery Systems (ENDS) in India before and after the 2018 Ban Order of the Government of India.

Since their launch globally in 2012, electronic nicotine delivery systems (ENDS) were positioned as a harm reduction strategy and cessation device but it is yet to be proven to have clinical safety or public health benefits. Instead, recent reports suggest that the tobacco industry targeted youth and sponsored research whose evidence was used to mislead policymaking. On August 28, 2018, Ministry of Health & Family Welfare's advisory banned the sale, purchase, and trade of ENDS. A survey was done in two waves. The first survey was done between August 10 and 25 2018 all websites which sold ENDS product were mapped and documented. The survey was repeated (November 30, 2018) were after the restriction to trade on ENDS was proposed by the Department of Customs. The two waves of survey found that no website, whether comprehensive e-commerce portals or dedicated ENDS marketing platforms fully complied with government orders. National and states government enforcement agencies are currently unaware of internet-based sale of ENDS. Although some states have given specific directions to stop the sale and delivery of ENDS within the state through e-commerce, there is limited monitoring and legal compliance by seller. Public health advocates need to stay vigilant and monitor the online sale and point of sale retail of ENDS to ensure strict compliance of national and state regulations.

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.

Probiotics and the Microbiome-How Can We Help Patients Make Sense of Probiotics?

The notion of probiotics as microbes that confer health benefits has its origins in the speculative ideas that are more than a century old, yet remain largely unsubstantiated by scientific evidence. The recent advances in microbiome science have highlighted the importance of intestinal microbes in human physiology and disease pathogenesis. These developments have provided a boost to the probiotics industry, which continues to experience exponential growth driven mainly by creative marketing. Consumers, patients, and most health care providers are not able to discern the underlying science or differentiate the permitted claims that promise vague health benefits from disease-specific claims reserved for drugs. No probiotic product has been able to satisfy the regulatory requirements to be categorized as a drug, a substance intended to cure, mitigate, or prevent disease. However, patients take probiotic products in the belief that they will help to treat their intestinal or systemic diseases. Thus far, the regulators have failed to create policies that would assist to inform the public in this area. In fact, the existing regulatory regime actually creates formidable barriers to research that could provide evidence for clinical efficacy of probiotic products. We propose a potential solution to this vexing problem, where a committee created through a partnership of academia, professional organizations, and industry, but free of potential conflicts of interest, would be charged with rigorous evaluation of specific probiotic products and the evidence in support of their different claims. Companies that would submit to this process would earn the trust of consumers and healthcare providers, as well as a distinction in the marketplace.

The costs and benefits of cannabis control policies
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As is the case for most drugs, cannabis use has costs and benefits, and so do the policies that attempt to minimize the first and maximize the second. This article summarizes what we know about the harmful effects of recreational cannabis use and the benefits of medical cannabis use under the policy of prohibition that prevailed in developed countries until 2012. It outlines three broad ways in which cannabis prohibition may be relaxed, namely, the depenalization of personal possession and use, the legalization of medical use, and the legalization of adult recreational use. It reviews evidence to date on the impacts of each of these forms of liberalization on the costs and benefits of cannabis use. It makes some plausible conjectures about the future impacts of the commercialization of cannabis using experience from the commercialization of the alcohol, tobacco, and gambling industries. Cannabis policy entails unavoidable trade-offs between competing social values in the face of considerable uncertainty about the effects that more liberal cannabis policies will have on cannabis use and its consequences for better or worse.
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El consumo de cannabis, como se da con la mayoría de las drogas, tiene costos y beneficios ; igual ocurre con las políticas que intentan minimizar los primeros y maximizar los segundos. Este artículo resume lo que conocemos acerca de los daños provocados por el consumo recreativo de cannabis y los beneficios de su empleo medicinal según la política de prohibición que prevaleció en los países desarrollados hasta 2012. Se describen tres principales formas en las que la prohibición de cannabis se puede mitigar: la despenalización de la posesión y uso personal, la legalización del uso médico, y la legalización del uso recreativo en adultos. Se revisa la evidencia hasta la fecha sobre los impactos de cada una de estas formas de liberalización en los costos y beneficios del consumo de cannabis. Se hacen algunas posibles conjeturas acerca de los impactos futuros de la comercialización de cannabis utilizando la experiencia al respecto de las industrias del alcohol, el tabaco y de los juegos de azar. Se sabe poco sobre el impacto de la liberalización del consumo de cannabis, así como de sus consecuencias positivas o negativas. Cualquier política sobre este tema implica compromisos inevitables entre valores sociales opuestos.

Comme pour la plupart des drogues, la consommation de cannabis a ses coûts et ses bénéfices. Tout comme les politiques qui s'efforcent de minimiser les premiers et de maximiser les seconds.. Nous résumons dans cet article nos connaissances sur les dangers de l'usage récréatif du cannabis et les bénéfices de son usage médical dans le cadre de la politique d'interdiction qui a prévalu dans les pays développés jusqu'en 2012. Nous y décrivons trois grandes voies d'assouplissement de l'interdiction du cannabis, à savoir la dépénalisation de la possession et de la consommation personnelles, la légalisation de l'utilisation médicale et la légalisation de la consommation récréative par des adultes. Chacune de ces formes de libéralisation influe sur les coûts et les bénéfices de la consommation de cannabis, générant des données analysées ici. En nous inspirant de l'expérience acquise dans le cadre de la commercialisation de l'alcool et la légalisation des jeux de hasard, nous émettons des hypothèses sur les possibles conséquences de la commercialisation du cannabis. L'impact de la libéralisation du cannabis sur sa consommation est peu connu, de même que ses conséquences pour le meilleur ou pour le pire, et toute politique menée à ce sujet implique des compromis inévitables entre des valeurs sociales opposées.

Costs of cannabis testing compliance: Assessing mandatory testing in the California cannabis market.

Most U.S. states that have regulated and taxed cannabis have imposed some form of mandatory safety testing requirements. In California, the country's largest and oldest legal cannabis market, mandatory testing was first enforced by state regulators in July 2018, and additional mandatory tests were introduced at the end of 2018. All cannabis must be tested and labeled as certified by a state-licensed cannabis testing laboratory before it can be legally marketed in California. Every batch that is sold by licensed retailers must be tested for more than 100 contaminants, including 66 pesticides with tolerance levels lower than the levels allowable for any other agricultural product in California. This paper estimates the costs of compliance with mandatory cannabis testing laws and regulations, using California's testing regime as a case study. We use state government data, data collected from testing laboratories, and data collected from lab equipment suppliers to run a set of Monte Carlo simulations and estimate the cost per pound of compliance with California's new cannabis testing regulations. We find that cost per pound is highly sensitive to average batch size and testing failure rates. We present results under a variety of different assumptions about batch size and failure rates. We also find that under realistic assumptions, the loss of cannabis that must be destroyed if a batch fails testing accounts for a larger share of total testing costs than does the cost of the lab tests. Using our best estimates of average batch size (8 pounds) and failure rate (4%) in the 2019 California market, we estimate testing cost at $136 per pound of dried cannabis flower, or about 10 percent of the reported average wholesale price of legal cannabis in the state. Our findings explain effects of the testing standards on the cost of supplying legal licensed cannabis, in California, other U.S. states, and foreign jurisdictions with similar testing regimes.

Out-of-state cannabis purchases in the United States.

BACKGROUND: Cannabis legalization at the US state level may have implications for cross-border purchases and diversion of legal products. The current study examined the association between out-of-state purchases and 1) cannabis regulations; and 2) the length of time a state has had recreational retail sales. METHODS: Data come from US respondents who participated in Wave 1 of the International Cannabis Policy Study (ICPS), conducted in August-October 2018. Respondents were aged 16-65 years who had used cannabis in the past 12 months (n = 4320). Respondents were recruited using the Nielsen Consumer Insights Global Panel. Binary logistic regression models examined likelihood of any out-of-state cannabis purchases in the prior year, including differences by cannabis regulations, and time since recreational cannabis retail sales began. RESULTS: Overall, 15.0 % of US cannabis users had made any out-of-state cannabis purchases in the past 12 months. Respondents in states where recreational cannabis was legal were less likely to make any out-of-state purchases than respondents in states where only medical cannabis was legal (AOR = 0.45, 95 % CI: 0.34-0.60, p < 0.001) and where all cannabis was prohibited (AOR = 0.36, 95 % CI: 0.26-0.50, p < 0.001). Among respondents in 'legal' states, a longer history of legal sales was associated with a lower likelihood of out-of-state cannabis purchases (AOR = 0.82, 95 % CI: 0.72-0.93, p = 0.002). CONCLUSION: The findings demonstrate that consumers in states where recreational cannabis is legal were less likely to purchase cannabis out-of-state than consumers in states where recreational cannabis is not legal. Future research should examine which states people travel to purchase cannabis and why.

Public health implications of legalising the production and sale of cannabis for medicinal and recreational use.

We assess the current and describe possible future public health impacts of the legalisation of cannabis production, sale, and use in the Americas. First, we describe global patterns of cannabis use and their most probable adverse health effects. Second, we summarise evidence regarding the effectiveness of cannabinoids for medicinal use and describe approaches that have been used to regulate the use of medicinal cannabis and how these approaches might have affected medicinal and recreational use and harms (eg, road crashes). Third, we describe how jurisdictions that have legalised recreational use have regulated production and sale of cannabis. Fourth, we evaluate the effects of cannabis legalisation on cannabis use and harms and on the use of alcohol, tobacco, and other drugs. Fifth, we use alcohol and tobacco policy examples to identify possible long-term public health effects of cannabis legalisation. Finally, we outline policy approaches that could minimise harms to public health arising from the legalisation of a commercial cannabis industry.

The Pay-Twice Critique, Government Funding, and Reasonable Pricing Clauses.

The federal government subsidizes the research and development of prescription medications. Thus, a captivating critique of expensive medications is that prices are too high because of taxpayer co-financing. This critique is often framed in terms of "paying-twice"-first for the research and second through the above market pricing of resulting products. Reasonable pricing clauses-which place some kind of pricing limitation on the exercise of license or patent rights governing a federally funded medication-are one proposed policy tool for addressing the pay-twice critique. This article provides increased analytical clarity as well as historical context to present-day debates about the privatization of federally funded research and prescription drug pricing. It makes three arguments. First, despite its pervasiveness and intuitive plausibility, the pay-twice critique is subject to differing interpretations which has important implications for the appropriateness of proposed solutions. Second, despite their initial attractiveness, the costs, necessity, and effectiveness of reasonable pricing clauses render the wisdom of this policy tool uncertain. However, third, given continued interest in reasonable pricing clauses, the NIH's previous experience with such a policy offers some useful lessons.

The Implementation of Marijuana Legalization in New York.

In 2018, Governor Cuomo tasked the Department of Health (DOH) with studying the anticipated impact of legalizing recreational marijuana use in New York State. DOH concluded that the positive effects of a regulated marijuana market outweighed the potential negative impact but that implementation required close monitoring of usage, education of specific populations, and regular and rigorous evaluation. In states where cannabis is legal, studies have shown associated decreases in crime rates and increases in financial resources. Conversely, accidental ingestion in children and accidents following ingestion had increased. The road ahead is fraught with challenges, especially because of the nonuniformity in federal and state laws.

Recreational marijuana legalization and prescription opioids received by Medicaid enrollees.

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.

The Case for Disclosure of Biologics Manufacturing Information.

Ten years after the enactment of the Biologics Price Competition and Innovation Act (BPCIA), competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration (FDA) evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers. As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry (Industry) that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients. This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), which is administered by the Environmental Protection Agency (EPA). The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets.

Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases, and Cures.

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.

Drug Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties Regulation. Final rule; further delay of effective date.

The Health Resources and Services Administration (HRSA) administers section 340B of the Public Health Service Act (PHSA), known as the "340B Drug Pricing Program" or the "340B Program." HRSA published a final rule on January 5, 2017, that set forth the calculation of the ceiling price and application of civil monetary penalties. The final rule applied to all drug manufacturers that are required to make their drugs available to covered entities under the 340B Program. On August 21, 2017, HHS solicited comments on further delaying the effective date of the January 5, 2017, final rule to July 1, 2018 (82 FR 39553). HHS proposed this action to allow a more deliberate process of considering alternative and supplemental regulatory provisions and to allow for sufficient time for additional rulemaking. After consideration of the comments received on the proposed rule, HHS is delaying the effective date of the January 5, 2017, final rule, to July 1, 2018.