PurposeDisruptions and shortages of drugs have become severe problems in recent years, which has triggered strong media and public interest in the topic. However, little is known about the factors ...that can be associated with the increased frequency of shortages. In this paper, the authors analyze the drivers of drug shortages using empirical data for Germany, the fourth largest pharmaceutical market.Design/methodology/approachThe authors use a dataset provided by the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte BfArM) with 425 reported shortages for drug substances (DSs) in the 24-month period between May 2017 and April 2019 and enrich the data with information from additional sources. Using logistic and negative binomial regression models, the authors analyze the impact of (1) market characteristics, (2) drug substance characteristics and (3) regulatory characteristics on the likelihood of a shortage.FindingsThe authors find that factors like market concentration, patent situation, manufacturing processes or dosage form are significantly associated with the odds of a shortage. The authors discuss the implications of these findings to reduce the frequency and severity of shortages.Originality/valueThe authors contribute to the empirical research on drug shortages by analyzing the impact of market characteristics, DS characteristics and regulatory characteristics on the reported shortages. The authors’ analysis provides a starting point for better prioritizing efforts to strengthen drug supply as it is currently intensely discussed healthcare authorities.
Since the cloning of the histamine H(3) receptor cDNA in 1999 by Lovenberg and co-workers, this histamine receptor has gained the interest of many pharmaceutical companies as a potential drug target ...for the treatment of various important disorders, including obesity, attention-deficit hyperactivity disorder, Alzheimer's disease, schizophrenia, as well as for myocardial ischaemia, migraine and inflammatory diseases. Here, we discuss relevant information on this target protein and describe the development of various H(3) receptor agonists and antagonists, and their effects in preclinical animal models.
In recent decades, significant advances in drug‐delivery systems have enabled more effective drug administration. To deliver drugs to specific organs, a range of organic systems (e.g., micelles, ...liposomes, and polymeric nanoparticles) have been designed. They suffer from limitations, including poor thermal and chemical stability, and rapid elimination by the immune system. In contrast, silica particles offer a biocompatible, stable, and “stealthy” alternative. Bioactive molecules can be easily encapsulated within silica particles by combining sol–gel polymerization with either spray‐drying or emulsion chemistry. Spray‐drying faces challenges, including low yield, surface segregation, and size limitations. In contrast, sol–gel emulsions enable the production of nanoparticles with homogeneous drug distribution, and permit ambient temperature processing, necessary for handling biologicals. Independent control of the size and release rate can be readily achieved. Preliminary in‐vivo experiments reveal enhanced blood stability of the nanoparticles, which, coupled with sustained release of anti‐tumor agents, show good potential for cancer treatment.
Silica particles present an interesting alternative to organic systems for drug delivery. Combining sol–gel synthesis with emulsion technology can produce particles (see Figure) with independently controlled size and release rates. The particle size is controlled by the emulsion chemistry, while the release rate is controlled by the particle microstructure. Preliminary in‐vivo experiments reveal enhanced blood stability of the nanoparticles, which, coupled with sustained release of anti‐tumor agents, show good potential for cancer treatment.
Proteins are in constant motion between different conformational states with similar energies. This has often been ignored in drug design. However, protein flexibility is fundamental to understanding ...the ways in which drugs exert biological effects, their binding-site location, binding orientation, binding kinetics, metabolism and transport. Protein flexibility allows increased affinity to be achieved between a drug and its target. This is crucial, because the lipophilicity and number of polar interactions allowed for an oral drug is limited by absorption, distribution, metabolism and toxicology considerations.
This paper examines how the recent transition of the opioid crisis from prescription opioids to more prevalent misuse of illicit opioids, such as heroin and fentanyl, altered labor supply behavior ...and disability insurance claiming rates. We exploit differential geographic exposure to the reformulation of OxyContin, the largest reduction in access to abusable prescription opioids to date, to study the effects of substitution to illicit markets. We observe meaningful reductions in labor supply measured in terms of employment-to-population ratios, hours worked, and earnings in states more exposed to reformulation relative to those less exposed. We also find evidence of increases in disability applications and beneficiaries.
Systems biology in drug discovery Butcher, Eugene C; Berg, Ellen L; Kunkel, Eric J
Nature biotechnology,
10/2004, Letnik:
22, Številka:
10
Journal Article
Recenzirano
The hope of the rapid translation of 'genes to drugs' has foundered on the reality that disease biology is complex, and that drug development must be driven by insights into biological responses. ...Systems biology aims to describe and to understand the operation of complex biological systems and ultimately to develop predictive models of human disease. Although meaningful molecular level models of human cell and tissue function are a distant goal, systems biology efforts are already influencing drug discovery. Large-scale gene, protein and metabolite measurements ('omics') dramatically accelerate hypothesis generation and testing in disease models. Computer simulations integrating knowledge of organ and system-level responses help prioritize targets and design clinical trials. Automation of complex primary human cell-based assay systems designed to capture emergent properties can now integrate a broad range of disease-relevant human biology into the drug discovery process, informing target and compound validation, lead optimization, and clinical indication selection. These systems biology approaches promise to improve decision making in pharmaceutical development.
Abstract
Although economic sociology emphasizes the role of social networks for shaping economic action, little research has examined how network governance structures affect prices in the ...unregulated and high-risk social context of online criminal trade. We consider how overembeddedness—a state of excessive interconnectedness among market actors—arises from endogenous trade relations to shape prices in illegal online markets with aggregate consequences for short-term gross illegal revenue. Drawing on transaction-level data on 16 847 illegal drug transactions over 14 months of trade in a ‘darknet’ drug market, we assess how repeated exchanges and closure in buyer–vendor trade networks nonlinearly influence prices and short-term gross revenue from illegal drug trade. Using a series of panel models, we find that increases in closure and repeated exchange raise prices until a threshold is reached upon which prices and gross monthly revenue begin to decline as networks become overembedded. Findings provide insight into the network determinants of prices and gross monthly revenue in illegal online drug trade and illustrate how network structure shapes prices in criminal markets, even in anonymous trade environments.
Biomarkers enable the characterization of patient populations and quantitation of the extent to which new drugs reach intended targets, alter proposed pathophysiological mechanisms and achieve ...clinical outcomes. In genomics, the biomarker challenge is to identify unique molecular signatures in complex biological mixtures that can be unambiguously correlated to biological events in order to validate novel drug targets and predict drug response. Biomarkers can stratify patient populations or quantify drug benefit in primary prevention or disease-modification studies in poorly served areas such as neurodegeneration and cancer. Clinically useful biomarkers are required to inform regulatory and therapeutic decision making regarding candidate drugs and their indications in order to help bring new medicines to the right patients faster than they are today.
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