Natural products in non-alcoholic fatty liver disease (NAFLD): Novel lead discovery for drug development.

With changing lifestyles, non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. A substantial increase in the incidence, mortality, and associated burden of NAFLD-related advanced liver disease is expected. Currently, the initial diagnosis of NAFLD is still based on ultrasound and there is no approved treatment method. Lipid-lowering drugs, vitamin supplementation, and lifestyle improvement treatments are commonly used in clinical practice. However, most lipid-lowering drugs can produce poor patient compliance and specific adverse effects. Therefore, the exploration of bio-diagnostic markers and active lead compounds for the development of innovative drugs is urgently needed. More and more studies have reported the anti-NAFLD effects and mechanisms of natural products (NPs), which have become an important source for new drug development to treat NAFLD due to their high activity and low side effects. At present, berberine and silymarin have been approved by the US FDA to enter clinical phase IV studies, demonstrating the potential of NPs against NAFLD. Studies have found that the regulation of lipid metabolism, insulin resistance, oxidative stress, and inflammation-related pathways may play important roles in the process. With the continuous updating of technical means and scientific theories, in-depth research on the targets and mechanisms of NPs against NAFLD can provide new possibilities to find bio-diagnostic markers and innovative drugs. As we know, FXR agonists, PPARα agonists, and dual CCR2/5 inhibitors are gradually coming on stage for the treatment of NAFLD. Whether NPs can exert anti-NAFLD effects by regulating these targets or some unknown targets remains to be further studied. Therefore, the study reviewed the potential anti-NAFLD NPs and their targets. Some works on the discovery of new targets and the docking of active lead compounds were also discussed. It is hoped that this review can provide some reference values for the development of non-invasive diagnostic markers and new drugs against NAFLD in the clinic.

Regulatory assessment of nano-enabled health products in public health interest. Position of the scientific advisory board of the French National Agency for the Safety of Medicines and Health Products.

Nanomaterials are present in a wide variety of health products, drugs and medical devices and their use is constantly increasing, varying in terms of diversity and quantity. The topic is vast because it covers nanodrugs, but also excipients (that includes varying proportions of NMs) and medical devices (with intended or not-intended (by-products of wear) nanoparticles). Although researchers in the field of nanomedicines in clinical research and industry push for clearer definitions and relevant regulations, the endeavor is challenging due to the enormous diversity of NMs in use and their specific properties. In addition, regulatory hurdles and discrepancies are often cited as obstacles to the clinical development of these innovative products. The scientific council of the Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM) undertook a multidisciplinary analysis encompassing fundamental, environmental and societal dimensions with the aim of identifying topics of interest for regulatory assessment and surveillance. This analysis allowed for proposing some recommendations for approximation and harmonization of international regulatory practices for the assessment of the risk/benefit balance of these products, considering as well the public expectations as regards efficacy and safety of nanomaterials used in Health products, in terms of human and environmental health.

Evolution of drug regulations and regulatory innovation for anticancer drugs in China.

Over the past two decades, China has introduced significant changes to drug regulations through regulatory innovations to accelerate drug review and approvals, keeping in line with the rapidly growing scientific innovation in drug research and development (R&D). In this study, we outlined the revolution of drug regulation in China since the establishment of the State Drug Administration in 1998. More particularly, we performed a comprehensive analysis of newly approved anticancer drugs in China from the year 2005 to May 2021, as a powerful illustration of how the revolution has changed the drug R&D landscape. Innovative drug development in China has boomed, benefiting in particular from pro-innovation policies as well as expedited program designations by the authority. We found a significant increase in the number of both imported and domestic new anticancer drugs from 2005 to 2021, with the emergence of drugs with novel mechanisms of action, including immune checkpoint inhibitors and cell therapy products. Drug lag has also been dramatically shortened by more than 70% for imported drugs in years 2016-2020 compared to years 2006-2010. Furthermore, we provide an insight into the potential approaches to further optimize the science-based and clinical value-based regulatory and R&D drug ecosystem in China. This review provides evidence of significant impacts of regulations and policies on drug R&D and suggests that the constantly adapting regulatory ecosystem will speed up drug development in China and worldwide.

Modelo de negocios en la salud e investigación clínica: la cuestión de las patentes en la ciencia

Propósito/Contexto. En este artículo se exponen las tendencias y las características de un modelo de negocio que la industria farmacéutica ha venido imponiendo con la ayuda del desarrollo de nuevos medicamentos a los que se les cuestiona su "altura inventiva" y que, a pesar de ello, les son otorgadas las patentes de segunda generación, considerándose esta una práctica abusiva y que favorece el incremento de los precios de estas innovaciones en el mercado. Metodología/Enfoque. Mediante la presentación de un caso: "la declaración de interés público del medicamento imatinib en Colombia" se identifican las estrategias y las maniobras anticompetitivas que dejan pocas oportunidades a los Estados para distribuir de manera equitativa los beneficios de las invenciones de medicamentos. En el análisis bioético del caso se caracteriza el dilema como tipo práctico, esto es, aquel en el que persisten requerimientos morales en tensión con un interés privado, en esta ocasión, entre la salud pública, por un lado, y la propiedad intelectual como política internacional, por el otro. Resultados/Hallazgos. La tesis es que este es un problema transfronterizo sintomático de la falta de justicia global en razón a la suplantación del sentido de "bien común" que ha acallado los vínculos sociales, solidarios y colaborativos. Discusión/Conclusiones/Contribuciones. Se insta a un consenso sobre las bases sociales y el respeto de la dignidad de las personas, un mandato de solidaridad superior en beneficio del bien común y el "florecimiento de la humanidad".

Objetivo/Contexto. Este artigo expõe as tendências e características de um modelo de negócio que a indústria farmacêutica tem vindo a impor com a ajuda do desenvolvimento de novos medicamentos cujo nível de inventividade é questionado. Como resultado, é-lhes concedidas patentes de segunda geração, o que é considerado uma prática abusiva e favorece o aumento dos preços destes inovações no mercado. Metodologia/Abordagem. Através da apresentação de um caso "A Declaração de Interesse Público da droga Imatinib na Colômbia", são identificadas estratégias e manobras anticompetitivas, que deixam poucas oportunidades para os Estados distribuírem os benefícios das invenções de drogas de forma equitativa. Na análise bioética do caso, o dilema é especificado como sendo prático, ou seja, um dilema em que os requisitos morais persistem em tensão com um interesse privado, neste caso, entre a saúde pública, por um lado, e a propriedade intelectual como uma política internacional, por outro. Resultados/Descobertas. A tese é que se trata de um problema transfronteiriço sintomático de falta de justiça global devido à suplência de um senso o bem comum que silenciou os laços sociais de solidariedade e colaboração. Discussão/Conclusões/Contribuições. Apela a um consenso sobre os fundamentos sociais e o respeito pela dignidade das pessoas, um mandato de maior solidariedade em benefício do bem comum, o florescimento da humanidade.

Purpose/Background. This article exposes the tendencies and characteristics of a business model that the pharmaceutical industry has been imposing with the help of the development of new drugs whose degree of inventiveness is questioned. As a result, they are granted second generation patents, which is considered an abusive practice that favors the increase of the prices of these innovations in the market. Methodology/Approach. Through the presentation of a case "The Declaration of Public Interest of the Drug Imatinib in Colombia", anti-competitive stra-tegies and maneuvers are identified, which leave few opportunities for the States to distribute the benefits of drug inventions in an equitable manner. In the bioethical analysis of the case, the dilemma is specified as a practical one, that is, one in which moral requirements persist in tension with a private interest, in this case, between public health on the one hand, and intellectual property as an international policy, on the other. Results/Findings. The thesis is that this is a cross-border problem symptomatic of a lack of global justice due to the supplanting of the sense of the common good that has silenced social bonds of solidarity and collaboration. Discussion/Conclusions/Contributions. It calls for a consensus on social foundations and respect for the dignity of persons, a higher mandate of solidarity for the benefit of the common good, and the flourishing of humanity.

[Trace therapeutic substances of traditional Chinese medicine: great resources of innovative drugs derived from traditional Chinese medicine].

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.

Pharmaceutical net price transparency across european markets: Insights from a multi-agent simulation model.

With pharmaceutical health policy striving for fair and sustainable pricing under increasing budgetary pressures, public stakeholders are more and more willing to be involved in transparent access decision-making related to novel medicines, considered by them to be a societal good. Full net price transparency (NPT) is believed by many to promote price competition and to increase equity by making pharmaceutical products accessible to all. Using agent-based simulations, we find that a full NPT system implemented across EU countries would not be viable. This while, acting as rational economic agents, a group of middle- and lower-income countries would not be willing to give up their confidential agreements with the pharmaceutical industry. Even partial NPT would delay access predominantly in middle- to lower-income countries. Hence, we conclude that implementing net price transparency across Europe would be challenging to reach from a political perspective. Especially in lower-income countries there would remain a plea to be left free to negotiate confidential discounts with drug manufacturers. This while, counterintuitively, in those countries NPT will be seen to be unjust while violating Ramsey pricing and distributive justice principles.

Innovative medicine development.

BACKGROUND: In recent years the global landscape of pharmaceutical development has evolved drastically in order to adapt to innovative products such as immunotherapy, regenerative medicines and cell and gene therapy, all offering the hope to cure numerous untreated diseases. The global COVID-19 pandemic also led competent authorities in charge of approval of new medicines to implement adapted regulatory pathways allowing early access to innovative treatments and vaccines. New challenges are to be overcome, it is the short development time, or the small patient populations, or again drug product features requiring complete new production, testing and distribution strategies. OBJECTIVE: This paper provides a short overview of the different adaptations required to allow the development of such innovative medicines. METHOD: Several drug development strategies for products under clinical development or recently approved were assessed. RESULTS: Fully integrated strategies encompassing research, non-clinical, clinical and product manufacturing development along with adapted regulatory pathways, anticipation of market access and supported by risk based are important. In such fast pace, the development of relevant manufacturing processes and test methods assessing quality, safety and efficacy of new drugs falls on the critical path and requires particular attention, anticipation and detailed planning as early as possible in order to ensure successful filing and approval. CONCLUSION: Insights within innovative products approved recently reveal the importance of defining a solid chemistry manufacturing and control strategy early on as part of clinical development. Interactions with agencies at key milestones of development are also essential to reduce risks, prioritize development to support safety and allow early access to patients.

[Applications of chromatography in giant complex drug-organism system].

Chromatography is an important branch of analytical chemistry that focuses on the separation and analysis of complex structures. Following more than 100 years of development and improvement, chromatography theory and technology have gradually become sophisticated. It has become a coalition of science, technology, and art. Recently, chromatography has been successfully used in combination with mass spectrometry, nuclear magnetic resonance spectroscopy, and atomic emission spectroscopy. Chromatography and the combination with other techniques has significantly improved the analysis of complex systems, such as the environment, food, petrochemicals, biological specimens, and medicine. As one of the oldest healing systems, Traditional Chinese Medicine (TCM) has served to maintain the health of people in China and worldwide for thousands of years. Therefore, it has become a core representative of traditional Chinese culture. In the past two years, TCM has been widely used to treat COVID-19, especially in patients with mild symptoms. Recently, Chinese government emphasized the inheritance and innovation of TCM and stepped up efforts to promote its modernization. TCM includes herbal medicine, acupuncture, moxibustion, massage, food therapy, and physical exercise, such as Tai Chi. In most cases, the patients are administered a mixture of TCM formulas containing more than two herbal medicines, resulting in a highly complicated compound mixture. There is no doubt that long-term clinical practices have demonstrated the safety and therapeutic effect of TCM. However, the compound mixture must be simplified to identify the active compounds. This is mainly because of the existence of carcinogenic compounds, pesticides, and heavy metal residues introduced through plantation and production processes. Moreover, enzymes within the human system generate further new compounds in response to the entry of the TCM containing thousands of components. Consequently, the complex TCM and organism systems interact with each other, constituting a giant complex drug-organism system. The analysis of this giant complex system is acknowledged as a key aspect in the modernization process of TCM. In the last 20 years, many studies have been conducted to screen and identify effective compounds in TCM. These effective compounds can be either the original compounds or new metabolic components generated in vivo. All these efforts are aimed at simplifying the components of TCM and elucidating the therapeutic mechanism. It is well known that chromatography can provide technical support for complex systems owing to its unique advantage of outstanding separation and analysis capabilities. Therefore, chromatography and its combination with other technologies have become mainstream technologies for promoting the compilation of molecular structure, information, digitalization, and modernization of TCM. This paper reviews the research and application of chromatography and combination technologies in a giant complex TCM formula-organism system. Furthermore, the authors briefly introduce and summarize the understanding, research ideas, and activities of the authors' team on the modernization of TCM. "Liang Guanxi" and "He strategy" are proposed as novel strategies for studying the giant complex drug-organism system. A distinguished technology integrated with mathematical model of causal relation, combined receptor chromatography, identification of chemical molecular structure and evaluating of pharmacological activities was established. It was successfully employed to determine the core effector-response substances of "Liang Guanxi" herb pairs in a giant complex drug-organism system. Subsequently, utilizing the proposed technology of Combination of Traditional Chinese Medicine Molecular Chemistry, the author's team designed and developed four series of innovative drugs. Inspired by the hundred years of chromatography history and thousands of years of TCM culture, the future development of chromatographic technology is expected. Furthermore, the mechanisms of TCM in medical healthcare, prevention, and treatment of diseases are likely be explained through chromatography, leading to a new strategy to realize the molecularization and digitalization of TCM, which is beneficial to the development of original new drugs.

Chemotherapy resistance in epithelial ovarian cancer: Mechanisms and emerging treatments.

Ovarian cancer (OC) remains a fatal malignancy because most patients experience recurrent disease, which is resistant to chemotherapy. The outcomes for patients with platinum-resistant OC are poor, response rates to further chemotherapy are low and median survival is lower than 12 months. The complexity of platinum-resistant OC, which comprises a heterogeneous spectrum of diseases, is indeed far from being completely understood. Therefore, comprehending tumors' biological behaviour to identify reliable biomarkers, which may predict responses to therapies, is a demanding challenge to improve OC management. In the age of precision medicine, efforts to overcome platinum resistance in OC represent a dynamic and vast field in which innovative drugs and clinical trials rapidly develop. This review will present the exceptional biochemical environment implicated in OC and highlights mechanisms of chemoresistance. Furthermore, innovative molecules and new therapeutic opportunities are presented, along with currently available therapies and ongoing clinical trials.

Trends of Phase I Clinical Trials of New Drugs in Mainland China Over the Past 10 Years (2011-2020).

Background: In recent years, the number of clinical trials initiated in China has increased rapidly. The aim of this study was to overview the changing landscape of phase I clinical trials in mainland China from 2011 to 2020. Methods: We analyzed phase I clinical trials registered on 3 websites including the Chinese Clinical Trial Registry, ClinicalTrials.gov, and the China National Medical Products Administration Center for Drug Evaluation platform. Findings: A total of 2,842 phase I clinical trials were posted from January 1, 2011, to December 31, 2020. The overall number of clinical trials for innovative drugs was 1,497, accounting for half of all the phase I clinical trials (53%). Among these 1,486 innovative drug clinical trials, 924 were newly tested drugs with an average annual growth rate of 59%. Biological drug research increased significantly from 22.6% during 2011-2015 to 33.3% during 2016-2020. These principal investigators (PIs) of these clinical trials were mainly from Beijing (n = 871), followed by Shanghai (n = 496) and Jiangsu (n = 281). As for the therapeutic area of phase I clinical trials, cancer took up the most percentage of all the clinical trials (35%), followed by infectious disease (9%), nervous system disease (9%), etc. Most phase I clinical trials are conducted on healthy volunteers (n = 1,642, 57.8%), some cancer drugs are conducted in patients with cancer (n = 846, 29.8%), and only a few clinical trials were conducted in the elderly (n = 7). Among these clinical trials of the newly tested innovative drugs, the first in human (FIH) clinical trials accounted for 82% (744), and the First in Chinese (FIC) clinical trials only took up 18% (167). Only a small number of drugs could be made the transition to phase II (n = 207, 22%). In addition, despite the number of newly tested drugs during 2011-2015 (n = 163) was much less than that in 2016-2020 (n = 761), the percentage of drugs that could enter into phase II clinical trials in 2011-2015 (34%) was higher than that in 2016-2020 (20%). Conclusion: In the past 10 years, the development of phase I clinical trials has achieved great progress in mainland China due to the novel design and drug innovation policy. Nevertheless, future efforts are needed to make for improving the phase transition success rate of innovative drugs.

Emerging drugs for the treatment of attention-deficit hyperactivity disorder (ADHD).

INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities. AREAS COVERED: We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010-2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients. EXPERT OPINION: Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.

The current status of and prospects in research regarding gastrointestinal stromal tumors in China.

China still lacks statistical data regarding the incidence of gastrointestinal stromal tumors (GISTs). Data from 3 regions have demonstrated that the incidence of GISTs in China is similar to that in the United States. Furthermore, no significant differences between both nations with regard to epidemiological characteristics and genotyping of GISTs have been reported. Chinese physicians are demonstrating an increased interest in studies regarding GISTs. Currently, to the authors' knowledge, China publishes the most research articles regarding GIST annually worldwide. Despite the paucity of relevant research regarding the clinical practices for GISTs, a series of studies performed by Chinese physicians in the fields of recurrence risk classification, laparoscopic surgery, and adjuvant therapy have contributed to the diagnosis and treatment of GISTs. The lack of innovative drugs, slow approval of new drugs, and insufficient research funds have limited further advancements in GIST-related research in China. In recent years, increased investment in scientific research has allowed for these advancements to be made by creating conditions for Chinese physicians to conduct high-level clinical research. Chinese researchers hope to further shorten the gap between China and the rest of the world in the field of GIST research within a relatively short period. The purpose of the current review article was to present the most updated information regarding the diagnosis and treatment of GISTs in Chinese medical practice and to suggest prospective research in this field.

Percepción de usuarios de Cali-Colombia acerca de medicamentos genéricos / Perception of users of Cali-Colombia about generic medicines

RESUMEN En la población en general existe gran controversia alrededor del uso de medicamentos innovadores y de sus copias llamadas medicamentos genéricos. El objetivo de este estudio es cuantificar la aceptación de los pacientes, del Sistema General de Seguridad Social en Salud de Colombia (SGSSS) a la prescripción de medicamentos genéricos. Se realizó un estudio de tipo descriptivo con un diseño transversal en 63 hombres y 57 mujeres, todos adultos pacientes que asistieron a consulta externa de los sitios de práctica de una Facultad de Medicina de Cali-Colombia. Se concluye que si se usan medicamentos genéricos, se requiere que los médicos y los usuarios tengan confianza en él. Los resultados del presente estudio muestran que, aunque no en forma mayoritaria, todavía un porcentaje importante de los consumidores entrevistados dudan de la calidad y de los resultados terapéuticos de los genéricos. De manera preocupante, casi una cuarta parte de los participantes en el estudio piensa que los medicamentos genéricos son productos fraudulentos.

SUMMARY In the general population, there is a great controversy surrounding the use of innovative drugs and their copies called generic drugs. The objective of this study is to quantify the acceptance of patients from the General System of Social Security in Health of Colombia (SGSSS) to the prescription of generic drugs. A descriptive study was carried out with a transversal design. The universe was 63 men and 57 women, all adult patients who attended external consultation of the practice sites of the Faculty of Medicine of Cali-Colombia. It is concluded that if generic drugs are used, it is necessary that doctors and users have confidence in it, the results of the present study show that, although not in the majority, still a significant percentage of the consumers interviewed doubt the quality and the therapeutic results of generics. Worryingly, nearly a quarter of study participants think that generic drugs are fraudulent products.

Novel production method of innovative antiangiogenic and antitumor small peptides in Escherichia coli.

BACKGROUND: Developing innovative drugs with potent efficacy, specificity, and high safety remains an ongoing task in antitumor therapy development. In the last few years, peptide drugs have become attractive agents in cancer therapy. HM-3, mainly with antiangiogenic effect, and AP25, with an additional antiproliferative effect, are two peptides designed in our laboratory targeting αvß3 and α5ß1 integrins, respectively. The low molecular weight of the two peptides renders their recombinant expression very difficult, and the complicated structure of AP25 makes its chemical synthesis restricted, which presents a big challenge for its development. METHODS: Bifunctional peptides designed by the ligation of HM-3 and AP25, using linkers with different flexibility, were prepared using recombinant DNA technology in Escherichia coli. The fusion peptides were expressed in a modified auto-induction medium based on a mixture of glucose, glycerol, and lactose as carbon substrates and NH4+ as nitrogen source without any amino acid or other elements. Subsequently, the antiangiogenic, antiproliferative, and cell adhesion assays were conducted to evaluate the bioactivity of the two fusion peptides. RESULTS: The peptides were successfully expressed in a soluble form without any induction, which allows the culture to reach higher cell density before protein expression occurs. Human umbilical vein endothelial cell migration assay and chick embryo chorioallantoic membrane assay showed, at low doses, a significantly increased antiangiogenic effect (>75%) of the purified products compared with the single molecules. Meanwhile, MTT assay confirmed their enhanced antitumor activity against gastric cancer cell line MGC-803; however, no significant effect was observed on hepatoma HepG2 cells and no cytotoxicity on normal human lens epithelial cell SRA01/04 and human epithelial esophageal cells. CONCLUSION: Bifunctional molecules with antiangiogenic and antiproliferative effects were obtained by using this technique, which presents an alternative for small peptide production, instead of the conventional chemical method. The increased molecular weight facilitates the peptide expression with a simultaneous improvement in their stability and biological activity.

Registries supporting new drug applications.

PURPOSE: Knowledge of the benefits and risks of new drugs is incomplete at the time of marketing approval. Registries offer the possibility for additional, post-approval, data collection. For all new drugs, which were approved in the European Union between 2007 and 2010, we reviewed the frequency, the type, and the reason for requiring a registry. METHODS: The European Public Assessment Reports, published on the website of the European Medicine Agency, were reviewed for drugs approved by the Committee for Medicinal Products for Human Use. We searched for key characteristics of these drugs, including therapeutic area (ATC1 level), level of innovation (the score is an algorithm based on availability of treatment and therapeutic effect), and procedural characteristics. In addition, we identified if these registries were defined by disease (disease registry) or exposure to a single drug (drug registry). RESULTS: Out of 116 new drugs approved in the predefined period, for 43 (37%), 1 to 6 registry studies were identified, with a total of 73 registries. Of these 46 were disease registries and 27 (single) drug registries. For 9 drugs, the registry was a specific obligation imposed by the regulators. The level of innovation and the orphan status of the drugs were determinants positively predicting post-approval registries (OR 10.3 [95% CI 1.0-103.9] and OR 2.8 [95% CI 1.0-7.5], respectively). CONCLUSIONS: The majority of registries required by regulators are existing disease registries. Registries are an important and frequently used tool for post-approval data collection for orphan and innovative drugs.

A Decade of Data Protection for Innovative Drugs in Canada: Issues, Limitations, and Time for a Reassessment.

Drug regulators in Canada and in other nations require innovative pharmaceutical companies to submit undisclosed clinical or other data as a condition of approving the marketing of new pharmaceutical products-the origination of which involves considerable effort and investment. Data protection regulations were enacted in Canada in 2006, which-to some extent-closed a loophole in intellectual property law that had previously left innovative companies with no effective data protection for their clinical data. Although the regulations were intended to clarify and effectively implement Canada's international treaty obligations in the spirit of innovation, a review of Canada's first decade of effective data protection shows that Health Canada and Canadian courts have interpreted the scope of data protection for innovative drugs in a narrow manner that undermines and is inconsistent with the intent of the regulations. As the 10-year anniversary of data protection in Canada is this year (2016), this article demonstrates the need to advance Canada's data protection regime into one that consistently contributes to the promotion of investment in pharmaceutical research and development, to the mutual advantage of innovators and patients, in a manner conducive to the social and economic welfare of Canadians.

Estimating the potential annual welfare impact of innovative drugs in use in Switzerland.

Expenditures of health care systems are increasing from year to year. Therefore, this study aimed to estimate the difference in costs and benefits of innovative pharmaceuticals launched 2000 onward compared to standard treatment on the national economy of Switzerland in 2010. The approach and formula described in the pilot study by Tsiachristas et al. (1), which analyzed the situation of welfare effects in the Netherlands, served as a model for our own calculations. A literature search was performed to identify cost-utility or cost-effectiveness studies of drugs launched 2000 onward compared to standard treatment. All parameters required for the calculation of welfare effects were derived from these analyses. The base-case threshold value of a quality-adjusted life year was set to CHF 100,000. Overall, 31 drugs were included in the welfare calculations. The introduction of innovative pharmaceuticals since 2000 onward to the Swiss market led to a potential welfare gain of about CHF 781 million in the year 2010. Univariate sensitivity analysis showed that results were robust. Probably because of the higher benefits of new drugs on health and quality of life compared to standard treatment, these drugs are worth the higher costs. The literature search revealed that there is a lack of information about the effects of innovative pharmaceuticals on the overall economy of Switzerland. Our study showed that potential welfare gains in 2010 by introducing innovative pharmaceuticals to the Swiss market were substantial. Considering costs and benefits of new drugs is important.