Potential Life-Years Lost: The Impact of the Cancer Drug Regulatory and Funding Process in Canada.

BACKGROUND: Canada has an established publicly funded health care system with a complex drug approval and funding process. After proof of efficacy (POE; key publication/presentation) and before becoming publicly accessible, each drug undergoes a Health Canada approval process, a health technology assessment (HTA), a pricing negotiation, and finally individual provincial funding agreements. We quantified potential life-years lost during this process. METHODS: We analyzed drugs for advanced lung, breast, and colorectal cancer that underwent the HTA process between 2011 and 2016. Life-years lost were calculated by multiplying documented improvement in progression-free and overall survival, number of eligible patients, and time from POE to first public funding. For conservative calculation, we assumed all eligible patients in Canada had access at the time of first public funding, whereas in reality provinces fund at different time points. RESULTS: We analyzed 21 drugs. Of these, 15 have been funded publicly. The time from POE to first public funding ranged from 14.0 to 99.2 months (median 26.6 months). Total overall life-years lost from POE to first public funding were 39,067 (lung 32,367; breast 6,691). Progression-free life-years lost from POE to first public funding were 48,037 (lung 9,139, breast 15,827, colorectal 23,071). CONCLUSION: The number of potential life-years lost during the drug regulatory and funding process in Canada is substantial, largely driven by delays to funding of colorectal cancer drugs. Recognizing that interprovincial differences exist and that eligible patients may not all receive a given drug, if even a fraction does so, the impact of delays remains substantive. Collaborative national initiatives are required to address this major barrier to treatment access. IMPLICATIONS FOR PRACTICE: Patients may spend lengthy periods of time awaiting access to new and effective cancer drugs. Patients with private drug insurance or personal funds or who reside in certain Canadian provinces may obtain some drugs sooner than others, potentially creating a two-tiered access system. The cancer drug access and public funding system must be expedited to improve equity.

Shadows in the current management of hepatocellular carcinoma in Spain - An embarrassing truth.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Up to 80% of patients with HCC have concomitant cirrhosis as a result of hepatitis B or C virus, alcohol abuse, or non-alcoholic steatohepatitis.

Determining the Comparative Value of Pharmaceutical Risk-Sharing Policies in Non-Small Cell Lung Cancer Using Real-World Data.

BACKGROUND: Risk-sharing arrangements (RSAs) can be used to mitigate uncertainty about the value of a drug by sharing the financial risk between payer and pharmaceutical company. We evaluated the projected impact of alternative RSAs for non-small cell lung cancer (NSCLC) therapies based on real-world data. METHODS: Data on treatment patterns of Dutch NSCLC patients from four different hospitals were used to perform "what-if" analyses, evaluating the costs and benefits likely associated with various RSAs. In the scenarios, drug costs or refunds were based on response evaluation criteria in solid tumors (RECIST) response, survival compared to the pivotal trial, treatment duration, or a fixed cost per patient. Analyses were done for erlotinib, gemcitabine/cisplatin, and pemetrexed/platinum for metastatic NSCLC, and gemcitabine/cisplatin, pemetrexed/cisplatin, and vinorelbine/cisplatin for nonmetastatic NSCLC. RESULTS: Money-back guarantees led to moderate cost reductions to the payer. For conditional treatment continuation schemes, costs and outcomes associated with the different treatments were dispersed. When price was linked to the outcome, the payer's drug costs reduced by 2.5% to 26.7%. Discounted treatment initiation schemes yielded large cost reductions. Utilization caps mainly reduced the costs of erlotinib treatment (by 16%). Given a fixed cost per patient based on projected average use of the drug, risk sharing was unfavorable to the payer because of the lower than projected use. The impact of RSAs on a national scale was dispersed. CONCLUSIONS: For erlotinib and pemetrexed/platinum, large cost reductions were observed with risk sharing. RSAs can mitigate uncertainty around the incremental cost-effectiveness or budget impact of drugs, but only when the type of arrangement matches the setting and type of uncertainty.

"The difference is in the tomato at the end": Understanding the motivations and practices of cannabis growers operating within Belgian Cannabis Social Clubs.

BACKGROUND: In Belgium, Cannabis Social Clubs (CSCs) collectively organize the cultivation and distribution of cannabis for the personal use of their members. In this paper we seek to improve understanding of the motivations and practices of cannabis growers operating within CSCs, shedding light on the cultivation process. METHODS: We draw on data gathered through face-to-face semi-structured interviews with the directors of seven active Belgian CSCs (n = 21) and CSC growers (n = 23). These data are complemented by additional fieldwork and a review of policies relating to CSCs', including bylaws and growing protocols. FINDINGS: The Belgian CSCs rely on single and multiple in-house grower arrangements. Most CSC growers had been cultivating cannabis prior to joining their current CSC, albeit growing in different contexts (non-commercial and commercial). The CSC growers discussed both ideological and pragmatic motives for operating within a CSC. Cultivation took place indoors and followed organic practices. Despite their small-scale (20 plants on average), the grow sites used specialized equipment. The growers reported receiving financial compensation to cover production costs. CONCLUSION: This paper offers new insights into a particular sector of domestic cannabis cultivation - CSC growers and their practices within those collectives - which has not been studied previously. The Belgian CSCs have decentralized production among small-scale grow sites, at a size comparable to that found in other small-scale cultivation studies. In terms of motivations and practices, CSC growers share some features typically ascribed to small-scale cannabis cultivators. At the same time, CSC growers seemed particularly engaged with the CSC model and willing to adhere to the (self-)regulated practices developed by the organizations. This had implications for the way cultivation was organized and for the role of the grower within the CSC.

Legal high industry business and lobbying strategies under a legal market for new psychoactive substances (NPS, 'legal highs') in New Zealand.

BACKGROUND: The establishment of a regulated legal market for new psychoactive substances (NPS, 'legal highs') under New Zealand's Psychoactive Substances Act (PSA) 2013 created a new commercial sector for psychoactive products, previously limited to alcohol and tobacco. AIM: To explore how the newly-recognised 'legal high' industry (LHI) viewed and responded to the changing regulatory and market environment. METHODS: In-depth interviews with six key informants (KI) from the LHI: a leading entrepreneur, chemist, industry spokesperson, retailer, product buyer and a researcher commissioned by the LHI - were conducted, transcribed and analysed thematically. Formative work for the study included review of official LHI documents (websites, public submissions, self-regulation documents). RESULTS: The LHI stakeholders espoused an idealistic mission of shifting recreational users of alcohol, tobacco and illegal drugs towards "safer alternatives". Passage of the PSA was viewed as a success after years of lobbying led by pioneering LHI actors. The growth and professionalisation of the LHI resulted in an increasingly commercial market which challenged idealistic views of the original operators. LHI KI reported the targeting of young and low income customers, price cutting and increasing the strength of products as business strategies. Attempts by the LHI to self-regulate did not prevent escalation in the strength of products and fall in retail prices. The LHI reported outsourcing of manufacturing and exporting of their products to other countries, demonstrating an international business model. CONCLUSION: There was a tension between profit and idealistic motivations within the LHI and this increased as the sector became more commercialised. While the LHI distanced itself from both alcohol and tobacco, they reported the use of similar marketing, business and political lobbying strategies. Rules for engagement with new 'addictive consumption industries' are required to clarify the role they are permitted to play in the development of regulatory regimes for new psychoactive substances.

Modeling the structure and operation of drug supply chains: The case of cocaine and heroin in Italy and Slovenia.

Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible biases in how respondents describe their drug dealing activities.

Transitioning to a national health system in Cyprus: a stakeholder analysis of pharmaceutical policy reform.

OBJECTIVE: To review the pharmaceutical sector in Cyprus in terms of the availability and affordability of medicines and to explore pharmaceutical policy options for the national health system finance reform expected to be introduced in 2016. METHODS: We conducted semi-structured interviews in April 2014 with senior representatives from seven key national organizations involved in pharmaceutical care. The captured data were coded and analysed using the predetermined themes of pricing, reimbursement, prescribing, dispensing and cost sharing. We also examined secondary data provided by the Cypriot Ministry of Health; these data included the prices and volumes of prescription medicines in 2013. FINDINGS: We identified several key issues, including high medicine prices, underuse of generic medicines and high out-of-pocket drug spending. Most stakeholders recommended that the national government review existing pricing policies to ensure medicines within the forthcoming national health system are affordable and available, introduce a national reimbursement system and incentivize the prescribing and dispensing of generic medicines. There were disagreements over how to (i) allocate responsibilities to governmental agencies in the national health system, (ii) reconcile differences in opinion between stakeholders and (iii) raise awareness among patients, physicians and pharmacists about the benefits of greater generic drug use. CONCLUSION: In Cyprus, if the national health system is going to provide universal health coverage in a sustainable fashion, then the national government must address the current issues in the pharmaceutical sector. Importantly, the country will need to increase the market share of generic medicines to contain drug spending.

Cannabis social clubs in Belgium: organizational strengths and weaknesses, and threats to the model.

BACKGROUND: Cannabis Social Clubs (CSCs) are private organizations or clubs of users that produce cannabis for non-profit distribution to adult members to meet their personal needs without having to turn to the black market. CSCs can be found in many countries, but the term often covers very different empirical realities. Inspired by the Spanish CSCs and similarly taking advantage of a grey area in the Belgian cannabis legislation, Belgian cannabis activists set up the first Belgian CSC in 2006, and there are now at least 5 Belgian CSCs. The paper's main objective is to analyse the (internal) strengths and weaknesses and the (external) opportunities and threats of the model, as it exists today. METHODS: The paper draws on a review of international literature and qualitative data on the Belgian cannabis social clubs. Field visits and interviews were conducted with each club. We analysed membership application forms, cultivation protocols and contracts with growers, cannabis ownership certificates of members, information leaflets, the clubs' websites, and all media articles and documentaries on the clubs in the Belgian media. RESULTS: The paper describes the membership criteria and house rules, the members' profile, the organization and protocols for cannabis production, the distribution of cannabis through 'exchange fairs', the administrative features of the clubs and their contacts with other CSCs and with local authorities, the drug sector and the media. Belgian CSCs seem not profit-driven, and operate as a system in which cannabis is not too easily available. The clubs have fairly direct control over the quality and the potency of the cannabis they distribute. The model offers important potential opportunities, in terms of economic advantages and monitoring consumption patterns. The main threats to Belgian CSCs consist of attempts to criminalize the model, the emergence of profit-driven clubs and systemic violence from criminal entrepreneurs. Weaknesses of the model relate to the unstable or transient nature of the clubs, the transparency of their operational procedures, the superficiality of their quality control strategies, and the risk of morphing into marketing enterprises. CONCLUSIONS: The CSC model could be a safe and feasible option for policymakers to move a meaningful distance along the spectrum towards legally regulated cannabis markets without crossing over to full commercial availability. Governmental regulation could convert weaknesses and threats to the model into strengths and opportunities to ensure best practice. If authorities refrain from action, the model might dilute and evolve in a similar way as the Spanish CSCs did recently, with the establishment of large, commercial clubs.

Attitudes of cannabis growers to regulation of cannabis cultivation under a non-prohibition cannabis model.

BACKGROUND: How cannabis cultivation is dealt with under various examples of cannabis legalization or regulation is an important consideration in design of such schemes. This study aimed to (i) investigate support among current or recent cannabis growers, for various potential policy options for cannabis cultivation if prohibition were repealed, and (ii) explore the support for these options across countries, scale of growing operations, demographics, drug use and cannabis supply involvement variables. METHODS: This study utilized data from the online web survey of largely 'small-scale' cannabis cultivators, aged 18yrs and over, in eleven countries conducted by the Global Cannabis Cultivation Research Consortium (GCCRC). Data from 1722 current and recent cannabis growers in Australia, Denmark and the UK, who were all asked about policy, were included in the analysis. It investigated support for various frameworks for cultivation: (no regulation (free market); adult only; growing licenses; restrictions on plant numbers; licensed business-only sale; approved commercial growing; etc.). Among current growers, support for these options were compared across countries, across scale of growing operations, and by demographics, drug use and crime variables. RESULTS: Although there were some between country differences in support for the various policy options, what was striking was the similarity of the proportions for each of the eight most popular policy options. Among current growers, many of these positions were predicted by demographic, drug use and cannabis growing variables which were conceptually congruent with these positions. CONCLUSION: The results have relevance for the provisions regarding cannabis cultivation in the design of new non-prohibitionist models of cannabis which are increasingly under consideration. It should be of interest to policy makers, drug policy researchers, law enforcement and cannabis cultivators.

Teva Pharmaceuticals v. Sandoz: availability of generic glatiramer acetate and the impact to patent litigation claim construction.

In the upcoming case of Teva Pharmaceuticals v. Sandoz, the U.S. Supreme Court will address how much deference the appellate court should afford to a trial court's claim construction ruling. The effect of this decision will be far-reaching, as how claims are construed can determine whether a patent is infringed or not infringed, valid or invalid.

Production, perceptions, and punishment: restrictive deterrence in the context of cannabis cultivation.

BACKGROUND: American authorities have invested extraordinary resources to keep up with the growth in cannabis cultivation, and state-level cannabis laws have been changing rapidly. Despite these changes, little research on the relationship between criminal justice sanctions and grower behaviours exist, in particular research that examines restrictive deterrence - the altering of an illegal behaviour as opposed to desisting from it completely. METHODS: We examine restrictive deterrence in the context of cannabis cultivation by modelling the relationship between the threat of sanctions and the size of cultivation site and number of co-offenders. We use data from an anonymous web survey where participants were recruited through advertisements on websites related to cannabis use and cultivation. Negative binomial regression were used on 337 cases that contain valid data on size of cultivation site and 338 cases that contain valid data on the number of co-offenders. RESULTS: Our study found some evidence that the severity of state sanctions reduces the size of cultivation sites among growers who reside in the state. However, the number of contacts with the police had the opposite effect. In addition, we did not find a restrictive deterrent effect for the number of co-offenders, suggesting that different factors affect different decision points. Interestingly, objective skill and subjective skill had positive and independent effects on size of site. CONCLUSIONS: Results suggest that state-level sanctions have a structuring effect by restricting the size of cultivation sites but further increases in sanctions or enforcement are unlikely to deter more individuals from growing cannabis. In fact, there may be some potential dangers of increased enforcement on cannabis growers.

[Dynamic monitoring risk of anti-hepatoma new drug development].

Risk monitoring of new Chinese patent anti-hepatoma drugs is tracking recognized risks and residual risks, identifying emerging risk and ensure the implementation of the plan, estimating the process of reducing effectiveness. The paper is mainly through understanding the status of Chinese patent anti-hepatoma drugs, the content, characteristic and analysis method of dynamic risk monitoring, and then select the risk control indicators, collect risk information. Finally, puts forward the thought of anti-hepatoma drugs listed evaluation in our country, and try to establish the model of dynamic risk management of anti-hepatoma drugs.

Does generic entry lower the prices paid for pharmaceuticals in Australia? A comparison before and after the introduction of the mandatory price-reduction policy.

OBJECTIVE: We investigated the relationship between the number of generic medicines and pharmaceutical prices over time in Australia. METHODS: A dataset was utilised containing 76 items for 4 years (2003-2007) on the national subsidy scheme - the Pharmaceutical Benefits Scheme (PBS) - for which a generic brand is available. The PBS price was used as the dependent variable, and the number of generics available the key explanatory variable. The ordinary least-squares estimator was adopted for estimation. In the robustness analysis, an instrumental-variables method was used to account for potential endogeneity. RESULTS: Results suggested that the effect of increased generic medicine sellers on reducing the prices paid for generics is marginal but statistically significant. CONCLUSIONS: It is suggested that structural changes to the way generic prices are determined needs to be reconsidered by the Australian government if the policy aim of using increased 'competition' to lower prices is to be maximised.

Drug control and public health: getting beyond stalemate. Interview with Robin Room by Fiona Fleck.

Robin Room is a member of a drugs policy modelling group that uses data to project what would happen to the harm caused by illicit drugs if policies or conditions changed. He talks to Fiona Fleck about alternative scenarios to today's illicit trade in drugs and the implications of different scenarios for public health.

The economics of polypharmacology: fixed dose combinations and drug cocktails.

The history of Fixed Dose Combination (FDC) oral drug products has been tumultuous over its history. Some FDCs were prepared for marketing purposes and others for clinical improvements. Often, the products prepared for marketing advantage ended up causing negative outcomes. However, in recent years, there has been a resurgence of FDCs as clinicians have found them adventitious for treatment of AIDS/HIV and for oral contraceptives, just to name two examples. International regulatory Agencies and most major drug regulatory agencies have established guidelines along with regulations concerning preparation, labeling and marketing for FDCs. The advantages of FDCs are said to be in the clinical realm where simplified therapy regimens are thought to enhance patient's medication taking compliance. On the financial side, health insurers and other payers normally save money from a decreased number of dispensing fees, the use of fewer bottles, labels, etc., and from the possible situation where the price of the FDC is less than the medication price of the two separate ingredients dispensed individually. Overall, there is a great deal of evidence in favor of appropriate FDCs.