Les phases précoces du développement clinique d'un médicament. / [Early clinical drug development].

The first administrations of a molecule to humans, so-called phase I studies of drug development, follow experimental animal studies which allow to have a first assessment of the pharmacological effects and toxicity of the molecule under development. Typically, these studies are performed in "healthy" subjects or in relapsing patients with cancer. Participants' safety is a priority. Trained professionals administer single doses, followed by repeated doses, in authorized medical centres. They allow to study the pharmacokinetic and pharmacodynamic profile of tested molecules in humans and to explore some sources of variability of these parameters. These studies are highly regulated and their methodology is fairly standardized.

Higher Drug Prices from Anticompetitive Conduct: Three Case Studies.

U.S. consumers pay high drug prices. Brand-name drug companies claim that these prices are justified by pathbreaking research and development. But, sometimes the prices result from anticompetitive conduct. This article offers three case studies of how such behavior can increase price based on wakefulness drug Provigil, the allergic-reaction-treating EpiPen, and infection-treating Daraprim. The article contends that behavior that makes no sense other than by harming a competitor, that undercuts a regulatory regime, or that involves collusive conduct should not be protected. In targeting this behavior, antitrust scrutiny promises to lower drug prices.

Nonobviousness of pharmaceutical inventions: implications for patent prosecution and litigation.

Nonobviousness is the most critical patentability criterion. Patents covering new molecular entities and second-generation molecules in the pharmaceutical industry are often challenged for prima facie obviousness during prosecution and/or litigation. In such situations, the patentee has to either reject or rebut the same by clear and convincing evidence or demonstrate unexpected results, to establish nonobviousness. This paper tries to show how the lead compound requirement is consistent with 35 U.S.C. § 103; the prima facie obviousness challenge can be overcome; the two-prong approach is consistent with the Supreme Court's KSR v. Teleflex, 2007 (KSR) decision. The showing is illustrated with the analysis of new molecular entities in the proton-pump inhibitor family.

Fixed-dose combinations banned in India: is it the right decision? An eye-opening review.

Introduction: Fixed-dose combination (FDC) medicines contain more than one approved active pharmaceutical ingredient (API), are manufactured as a fixed-dose and packed in a single dosage form. FDCs have been drawing attention from the pharmaceutical industries because of the government's ban on 328 irrational FDCs in September 2018. The Drug Technical Advisory Board (DTAB) recommended that 'there is no therapeutic justification' for the active ingredients in the banned FDCs and accordingly these combinations 'may involve a risk to human beings'. Areas covered: The review illustrates the present status of FDCs, its regulatory framework, approvals in India and discusses the substantive cause behind the ban on FDCs in India. Expert opinion: The expert stress to establish a robust regulatory system for the approval of FDCs in India. The pharmaceutical industries should not perceive the ban against irrational FDCs as an impediment; rather, they should view as an opportunity to establish a stronger healthcare system. The current review is an eye-opener for the section of people who consider that the ban on FDCs is irrational. However, the ban on 328 FDCs may prove a landmark decision for the development of stronger healthcare policy in India.

Drug prices and trends before and after requesting compulsory licenses: the Ecuadorian experience.

Introduction: The Ecuadorian Institute of Intellectual Property (IEPI) granted several compulsory licenses between 2011 and 2017. In 2009, the President of Ecuador signed a decree that was intended to facilitate the request of compulsory licenses (CL) in the country, not only for Enfarma EP but for any privately owned local company in order to produce more accessible medicines. Areas covered: The national and international regulatory framework of pharmaceutical patents and the local applicability of CL in Ecuador. The authors also analyzed the results of requesting unplanned and epidemiologically unnecessary CL at a national level. Finally, the authors reviewed the effects of requesting, granting or denying CL on price per unit in the last 7 years of available data. Expert opinion: The authors think that compulsory licenses are useful tools when negotiating drug prices or when the demand cannot be satisfied due to economic constrain within the local health system. However, the authors' experience suggests that Ecuador did not have an established and reliable production system neither an adequate plan before requesting CL, therefore the positive effects of this measure were not clearly established.

Public health-oriented intellectual property and trade policies in Africa and the regional mechanism under Trade-Related Aspects of Intellectual Property Rights amendment.

OBJECTIVE: The short communication is prompted by the debate relating to the effect of pharmaceutical patents on access to affordable medicines, particularly in Africa. A recent amendment made to the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement creates a policy space for the regional alliance of low-income countries for the collective procurement and local production of drugs under compulsory licensing. This article examines the extent to which the regional mechanism can deliver access to pharmaceuticals. The article examines the regional mechanism in the light of the recent regional trade agreements and pharmaceutical plans of some regional economic blocs in Africa as well as the newly signed African Continental Free Trade Agreement (AfCFTA). STUDY DESIGN: This short communication adopts a descriptive approach in linking the regional mechanism in the TRIPS amendment to the regional trade agreements of African countries at the subregional and continental levels. METHODS: To ascertain the extent to which TRIPS Agreements regional model can deliver access to medicines in Africa, the article adopts a desk review approach by examining the relevant provisions of TRIPS Agreement, particularly the newly added Article 31bis, and the provisions of the relevant regional and continental free trade agreements in Africa. RESULTS: The article finds that although the regional model has great prospects in supporting the wider effort to deliver access to medicine, the limitations to its operative utilization may weaken its potency in addressing the urgent public health needs of the continent. CONCLUSION: The article concludes by stressing the inevitability of Africa's integration in tackling the deficiency of access to generic medicines in Africa. It was noted that even though there could be some potential challenges, the regional mechanism is indeed the way to go for low-income countries.

Confidentiality agreements: a challenge in market regulation.

BACKGROUND: Sustainability and the ability to maintain the right to health, with the guarantee of access to quality medicines and health services, have been a great challenge for countries with universal health systems. The great technological advances bring with it an expressive increase in the expenditures of the health systems, especially those directed towards the acquisition of high-cost drugs, which are still under patent protection, have a high cost and, in some cases, present uncertainties about their effectiveness and safety. As a way of maintaining the proper functioning of the systems and guaranteeing access to these medicines, some countries started to negotiate discounts with manufacturing companies. Pricing agreements have been adopted by developed countries with the objective of reducing their spending on high-cost medicines and, although they represent an opportunity for better negotiation with the industries, they violate the principle of transparency that regulates the world market. However, the existence of confidentiality agreements has meant that the declared prices are not the actual prices, unfairly harming the countries that use these price lists as beacons in their systems. METHODS: Representatives of health, judicial, legislative, patient organizations and academics from eight countries in Latin America and South Korea participated in a meeting in September 2017 in Chile to discuss price confidentiality agreements and the impact on public health policies. During the meeting, participants were presented with a hypothetical case to subsidize the discussion on the topic. Divided into groups, participants should propose recommendations for the problem by pointing out the pros and cons if each proposed recommendation was adopted. The groups were then confronted by a simulated jury and finally issued a single and final recommendation for the problem. RESULTS: The topic was widely discussed and recommendations were raised by the participants. Among them, it is worth noting the elaboration of norms that regulate the negotiations of prices between the countries bringing transparency and harmony in the adopted conducts. In addition, the possible consequences and potential impacts of confidentiality on drug prices and inputs, such as information asymmetry and inequity of access between countries, were pointed out. CONCLUSION: Despite there are efforts to make price negotiations more transparent, there is still no well-established standardization that promotes a well-functioning market. Confidentiality agreements hamper the fairness of access to essential health products.

Can direct-to-consumer advertising of prescription drugs be effectively regulated?

The government of New Zealand is currently considering a new Therapeutic Products Regulatory Scheme that includes how direct-to-consumer advertising (DTCA) of prescription drugs should be regulated. This article reviews three different types of possible regulation of DTCA: government regulation, industry self-regulation and a mixture of the two. Recent studies demonstrate that DTC ads in the US continue to be misleading and contain minimal if any educational value, despite governmental regulatory efforts by the Food and Drug Administration. Other regulatory models are equally unsuccessful at controlling DTCA. Available evidence suggests that DTC ads are commonly misinterpreted as trusted public health messages and are more likely to affect vulnerable subgroups of New Zealanders. Taken together with the international evidence that regulation has consistently failed to prevent the inappropriate promotion of prescription medicines, these findings suggest that DTCA is more likely to cause harm than benefit and should be banned.

Incentives and disincentives to drug innovation: evidence from recent literature.

Aim: Drug innovation is strongly driven by economic incentives. How these incentives work in determining or changing the level of activity of innovators and the direction of their innovation remains understudied. We seek to address these issues in reviewing recent literature on drug innovation, which offers one major unifying theme of pharmacoeconomic scholarship presented at the 2019 AEA-ASSA annual convention. Methods: Drawn from three AEA-ASSA convention panel sessions, papers were reviewed for newly charted research terrains and new research trajectories, and their theoretical and practical implications on efficiency, effectiveness, and value in the production and utilization of pharmaceutical products. Results: While high and continuously rising drug prices are typically claimed as the price of scientific innovation, the reviewed literature finds that this link only partially accounts for the problem. High risk aversion owing to information asymmetries and vastly intractable uncertainties is prevalent among innovating firms. Predatory business models abound. Reverse predatory strategies also exist to maintain product exclusivity without much added clinical benefits, and to constrain generic competition. CEO compensation practices contribute to rising drug prices. Finally, the US government's hands-off policy on drug list prices leave the forces of supply and demand to allocate them and reward innovation (at times perversely), even as the government extensively regulates or over-regulates practically every other aspect of innovation. Conclusions: Price-elasticity of demand is critical in drug innovation. The drug value chain is price-sensitive to the balance of incentives and disincentives to innovation. American health policy should consider charting a middle course that introduces some form of regulatory price control, while stimulating and sustaining the benefits of market competition. That should incentivize stakeholders to take into account both resources and value for money in making decisions based on best-quality, clinical-economic evidence.