The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health.

OBJECTIVES: This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS: Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS: All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION: Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

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.

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.

From courts to markets: New evidence on enforcement of pharmaceutical bans in India.

Regulatory enforcement of product safety standards given health concerns, whether it is in romaine lettuce, smartphones or cars, is emerging to be a challenge for global public health. This is particularly true for developing economies with fragile institutions. In this context, recent studies on Indian pharmaceutical markets provide evidence suggesting that the sector is a hub for substandard quality of medicines. Departing from these prior studies which use randomly collected samples, we reinvestigate this question using novel pan-India market sales data of banned medicines from 0.75 million pharmacists and chemists in India. We find that indeed such medicines get sold in India even after bans are imposed on them in the period 2007 to 2013. However, there is a general decline in demand post ban for our focal molecules suggesting broad adherence to bans. We also observe regional heterogeneity in prevalence of banned medicines sold between rich and poor regions of India with the former counterintuitively showing more sales. That said, while Ozawa et al. (2018) argue that prevalence of substandard medicines is around 13% in low and middle-income countries, we find an infringement ratio which is more muted in India at about 5%. Finally, a regression-based examination suggests that prior firm presence in therapeutic markets and popularity of molecules positively impact the likelihood of sale of banned medicines in India. Our results are robust to alternative explanations and are substantiated with a theoretical set up examining firm trade-offs in the decision to infringe. India has recently been under the lens of the global access to medicines debate and our findings have important policy implications for global health.

Cost-Effectiveness of Reclassifying Triptans in Australia: Application of an Economic Evaluation Approach to Regulatory Decisions.

BACKGROUND: Migraine is a common, chronic, disabling headache disorder. Triptans, used as an acute treatment for migraine, are available via prescription in Australia. An Australian Therapeutic Goods Administration (TGA) committee rejected reclassifying sumatriptan and zolmitriptan from prescription medicine to pharmacist-only between 2005 and 2009, largely on the basis of concerns about patient risk. Nevertheless, pharmacist-only triptans may reduce migraine duration and free up healthcare resources. OBJECTIVES: To estimate the cost-effectiveness of reclassifying triptans from prescription-only to pharmacist-only in Australia. METHODS: The study design included decision-analytic modeling combining data from various sources. Behavior before and after reclassification was estimated using medical practitioner and patient surveys and also administrative data. Health outcomes included migraine frequency and duration as well as adverse events (AEs) discussed by the TGA committee. Efficacy and AEs were estimated using randomized controlled trials and observational studies. RESULTS: Reclassifying triptans will reduce migraine duration but increase AEs. This will result in 337 quality-adjusted life-years gained at an increased cost of A$5.9 million over 10 years for all Australian adults older than 15 years (19.6 million). The incremental cost-effectiveness ratio was estimated to be A$17 412/quality-adjusted life-year gained. CONCLUSIONS: The incremental cost-effectiveness ratio is likely to be considered cost-effective by Australian decision makers. Serotonin syndrome, a key concern of the TGA committee, had little impact on the results. Further research is needed regarding pharmacist-only triptan use by migraineurs currently using over-the-counter medicines and by nonmigraineurs, the efficacy of triptans, and the risk of cardiovascular and cerebrovascular AEs and chronic headaches with triptans.

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.

Pharmaceutical Policy Reforms to Regulate Drug Prices in the Asia Pacific Region: The Case of Australia, China, India, Malaysia, New Zealand, and South Korea.

Medicine price directly affects affordability and access to medicines particularly in countries where a major portion of pharmaceutical spending is through out-of-pocket payment, such as in the Asia Pacific region. We have undertaken a detailed appraisal of the pharmaceutical policy reforms to regulate drug prices in 3 developed (Australia, New Zealand, and South Korea) and 3 emerging (China, India, and Malaysia) economies of the Asia Pacific region. Despite continuous efforts by the authorities in adopting a wide range of reformatory pharmaceutical pricing policies to ensure affordability of medicines, these policies may not be optimal where drug prices were not lowered as expected (eg, in Korea). On the contrary, considerable price reductions of various pharmaceuticals have been observed in New Zealand and India because of the reform in pharmaceutical pricing policy. This review of pharmaceutical pricing reforms reinforces the need for constant monitoring by policy makers in Asia Pacific countries to regulate drug prices and to undertake reform in pharmaceutical pricing policies when necessary to ensure affordability and access to medicines.

Is pharmacovigilance of biologicals cost-effective?

Pharmacovigilance is an essential part of the post-marketing surveillance of new biologicals. It not only requires a substantial investment of the marketing authorization holder but also of the clinical field to provide accurate safety information. Hence, does pharmacovigilance delivers value for money? This important question needs to be discussed in the light of regulatory requirements, value and cost.

Prohibition, regulation or laissez faire: The policy trade-offs of cannabis policy.

Trade-offs are central to the cannabis policy debate. Prohibition and strict regulation may help reduce the physical, mental and social harms of cannabis consumption, but at the cost of increasing the harms from illegal markets and reducing consumption benefits. An economic model clarifies how these costs and benefits relate to policy and connects them to observable prices and tax-levels given the assumptions of the analysis. These model- based arguments are related to the ongoing academic policy debate. While some arguments from this literature modify the interpretation of the model (e.g., due to dependence, cognitive biases and market structure), the literature often fails to appropriately account for the magnitude of the policy costs and benefits identified. Taking various caveats into account, the framework indicates that a strict regulation would likely be preferable to prohibition given current estimates of excess harms (externalities and internalities) from cannabis use. While cannabis prohibition appears difficult to justify within an economic regulatory framework, risks from industry influence, policy ratchet effects, and human "decision-making flaws" speak to the need for caution and strong regulation when implementing legal regimes.