The Placebo Standard in Regulatory Market Approval: Why the Declaration of Helsinki Has Been Ignored for 35 years

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The legalization of cannabinoid products and standardizing cannabis-drug development in the United States: a brief report

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.

Development Time and Patent Extension for Prescription Drugs in Canada: A Cohort Study

The Comprehensive Economic and Trade Agreement between Canada and the European Union provides for an extension of Canadian patents for prescription drugs by up to 2 years. One of the arguments advanced for longer patent time is to compensate companies for the length of the overall drug development time (the time between patent application and market approval). This study investigates overall development time in Canada for different groups of drugs approved between January 1, 2009 and December 31, 2018 and how many of these drugs are eligible for up to 2 years of patent term extension. Based on a list of patents and dates of market approval, the change in overall development time for all drugs was calculated along with whether there were differences in development time between different groups of drugs. Using Canadian patent filing dates, overall development time for all drugs went from a mean of 2240 days (95% CI: 1832, 2648) in 2009 to 4197 days (95% CI: 3728, 4665) in 2018 (analysis of variance [ANOVA], P<.0001). Using first global patent filing dates, overall development time went from a mean of 4481 days (95% CI: 3053, 5908) in 2009 to 6298 days (95% CI: 4839, 7756) in 2018 (ANOVA, P=.0118). There was a statistically significant difference in the overall development mean time between small molecule drugs (3553, 95% CI: 3361, 3746) and biologics (3903, 95% CI: 3595, 4212), (t test, P=.0487) when using Canadian patent filing dates but not when first global patent filing dates were used. There was no statistically significant change in overall development time among drugs that were substantial, moderate or little to none additional therapeutic value compared to existing drugs. Out of 238 drugs, 218 (91.6%) would have been eligible for patent term extension with 195 (80.7%) eligible for the full 2 years. Patent term extension does not appear to be justified based on changes in overall development time, except possibly in the case of biologics. There are also trade offs in terms of increased expenditures that need to be considered if patent terms are lengthened.

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.

Staatshaftung getäuschter Hoheitsträger?

The scandal concerning rigged emissions tests to circumvent regulations is regularly not reflected through the lense of the German rules of State liabilty. This lack of attention follows from the fact that compensation for damage caused to individuals is regularly precluded under the German rules of State liability when the underlying regulation scheme is applied diligently by the competent public authority. In consequence, an unlawful market approval by manipulated but lawfully investigating public authorities appears to exclude liability. However, liability under the German rules of State liability is not limited to cases of misconduct by public authorities. Against this background the case is made for a liability of the manipulated State even though there is no evidence of misconduct on behalf of its authorities when applying approval procedures. The proposed special case for State liability rests on two pillars: the structural vulnerability of the relevant approval procedures for manipulation and a high degree of dependency of third party economic actors on the validity of the State’s approval mechanisms.

OP56 Are Therapeutic Positioning Reports Driving Pharmaceutical Reimbursement Outcomes In Spain?

IntroductionFollowing marketing authorization in Spain, new medicines are assessed by the Inter-Ministerial Pricing Commission for Pharmaceuticals (CIPM), which provides reimbursement recommendations with a maximum ex-factory price. However, there are 17 autonomous regions, which can make distinct reimbursement decisions. To drive consistency, the Spanish Agency for Medicines and Health Products has issued national Therapeutic Positioning Reports (TPRs) for new medicines since 2012. Since November 2017, CIPM recommendations have been published monthly, giving the opportunity to analyze the impact of TPRs on the speed and outcome of CIPM decisions, which this research evaluates.MethodsPublicly-available CIPM and TRP decisions were identified from www.msssi.gob.es and www.aemps.gob.es, respectively. Marketing authorization dates were identified from www.ema.europa.eu or www.aemps.gob.es (10 March 2007-11 February 2018). Pearson's chi-squared and Mann-Whitney U statistical tests were performed using R.ResultsOne hundred and ninety-three drug-indication pairings with an associated TPR were identified. The majority (62% [120/193]) were recommended as alternative treatment options with only 19 percent (36/193) deemed to be superior and 19 percent (37/193) not recommended. One hundred and eight CIPM recommendations were identified across seven monthly reports, issued a mean of 12.2 months after market approval, 59 percent (64/108) were positive and 41 percent (44/108) were negative recommendations. There were 34 drug-indication pairings with both CIPM and TPR recommendations available. Of these, 24 percent, 56 percent and 21 percent had TPR outcomes of ‘superior’, ‘alternative’ and ‘not recommended’, respectively and 71 percent and 29 percent had positive and negative CIPM outcomes. Drug-indication pairings with ‘negative’ TPRs were significantly more likely to have negative CIPMs than those with either ‘alternative’ or ‘superior’ TPRs (71% vs. 19%, respectively, χ2 = 5.16, p = 0.02) and were more likely to experience significantly longer delays to CIPM recommendation (23.9 vs. 13.5 months, respectively, U = 50, p = 0.03).ConclusionsDrug-indication pairings with ‘positive’ and ‘alterative’ TPR outcomes are associated with significantly better and faster CIPM recommendations than those with ‘not recommended’ TPR outcomes