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Showing papers in "International Journal of Pharmaceutical Medicine in 2006"


Journal ArticleDOI
TL;DR: The impact of DTCA on public health should be viewed within the context of broader problems with underuse, overuse and inappropriate use of prescription drugs, and formal cost-benefit analyses need to be conducted to determine the net effects.
Abstract: The pharmaceutical industry spent over $US4 billion advertising prescription drugs directly to consumers in the US in 2004 The use of direct-to-consumer advertising (DTCA) has been a source of great controversy Supporters of DTCA argue that it provides an important source of health information for consumers, increases the treatment of under diagnosed conditions and improves medication adherence Critics argue that it misleads consumers, leads to overuse of medications, drives up prescription drug prices and costs, and harms the doctor-patient relationship The impact of DTCA on public health should be viewed within the context of broader problems with underuse, overuse and inappropriate use of prescription drugs A number of economic and marketing studies have examined the impact of DTCA on demand for prescription drugs These studies suggest that DTCA expands total market sales but does not have any appreciable effect on market share within the class In other words, DTCA increases the likelihood of an individual receiving drug treatment but does not have a significant impact on which drug is selected Much less is known about whether this expanded use addresses the problems with underuse of prescription drugs, or exacerbates problems with inappropriate use or overuse of prescription drugs The few studies that have been conducted on these issues suggest that DTCA probably leads to some appropriate use as well as some inappropriate use and overuse of medications Formal cost-benefit analyses need to be conducted to determine the net effects of DTCA on public health and to inform policy makers charged with protecting the public interest

23 citations


Journal ArticleDOI
TL;DR: RMPs were the topic of one of this year’s pre-conference training sessions at the 6th Annual Meeting of the International Society of Pharmacovigilance, and the objectives were to provide delegates with an overview of the drug-related risk management concept.
Abstract: In November 2005, the European Medicines Agency (EMEA) published its guideline on risk management plans (RMPs).1 Just under a year later, in order to aid consistency of the format and content of such plans, the EMEA released a template2 for companies to use when submitting what have become known as ‘EU-RMPs’. It was therefore timely that RMPs were the topic of one of this year’s pre-conference training sessions at the 6th Annual Meeting of the International Society of Pharmacovigilance (Liege, Belgium; 10–13 October 2006). The objectives of the training course, chaired by Dr Xavier Kurz, from the Department of Post-Authorisation Safety and Efficacy of Medicines at the EMEA, were: • to provide delegates with an overview of the drug-related risk management concept; • to guide participants in the preparation and assessment of RMPs; • to describe tools for pharmacovigilance plans and risk minimisation.

16 citations


Journal ArticleDOI
TL;DR: This paper is the first compressive review of the microdosing concept since the publication of the US Food and Drug Administration exploratory IND study guidance in January 2006, which covers the preclinical requirements to enable a microdose study in humans to take place.
Abstract: Microdosing, or human phase 0 clinical trials, is a technique whereby subpharmacological doses of prospective drug candidates are administered to human volunteers. A microdose study provides early pharmacokinetic data in humans and only requires minimal preclinical toxicology safety testing. A microdose is defined as 100th of the pharmacological dose (or predicted pharmacological dose) or a maximum of 100μg. Microdosing is a relatively recent innovation and there remains a degree of uncertainty as to whether such a small dose will adequately predict the pharmacokinetics of the therapeutically active dose. Notwithstanding this, in situations when traditional methods such as in vitro and laboratory animal models prove to be unreliable, microdosing can offer the supporting and alternative data on which to select suitable drug candidates for development, prior to commencing expensive full phase I clinical trials. The current published data on microdosing is somewhat sparse, although there have been a few papers in recent times. This paper is the first compressive review of the microdosing concept since the publication of the US Food and Drug Administration exploratory IND study guidance in January 2006, which covers the preclinical requirements to enable a microdose study in humans to take place.

14 citations


Journal ArticleDOI
TL;DR: Only a structured, methodological, science-driven process will develop translational medicine into an efficient tool to better project clinical outcomes of drug interventions from preclinical and early clinical data.
Abstract: Translational medicine has become a major tool for facilitating the transition of basic science results into clinical practice Its main remit is the facilitation of the transition of drugs or medical devices/diagnostics between preclinical research and human applications The major driver for development of this discipline in the pharmaceutical industry is the fact that the output of new drugs has been decreasing over past years, despite increased investment in research and development The predictive value of preclinical and early clinical results has become a key issue as many drug candidates face late attrition because of adverse safety or insufficient efficacy data It is likely this costly process would become more efficient if translation were properly addressed Biomarkers describing disease-related processes and drug effects need to be developed to achieve this, and their predictive values must be assessed A typical question is: ‘If we measure an effect of the drug candidate X on Y in rats, dogs or mice, what will happen to the same parameter in humans?’ Obviously, some biomarkers exist across all mammalian species (eg blood pressure) and are quite predictive, whereas others do not (eg rats, as opposed to humans, use corticosterone rather than cortisol as the main glucocorticoid) The important types of biomarkers are the serum-based markers (eg interleukin-6 for inflammatory processes) or imaging parameters, especially those obtained by magnetic resonance tomography The particular importance of safety biomarkers is acknowledged, yet concerted actions to find and establish more sensitive, specific and predictive markers are rare Early attempts to quantitatively assess the predictive value of biomarkers have been published and are under further development However, the impact of attempts to improve translation has not become obvious and it is tempting to assume that the approach is based more on an empty phrase than on robust scientific methodology This has to do with the fact that the standardisations and classifications of related processes, such as biomarker assessment or proof-of-principle study design are still lacking, and accompanying methodological research is as yet poor It is still an area of ‘gut feeling’ assessments and guesswork resulting in the reluctance of regulatory authorities to rely more on surrogates or biomarkers in general “Lost in translation” is a famous statement that describes an observation, but does not help to solve the problem Only a structured, methodological, science-driven process will develop translational medicine into an efficient tool to better project clinical outcomes of drug interventions from preclinical and early clinical data The direction is recognised, but there is still a long way to go

12 citations


Journal ArticleDOI
TL;DR: A survey of Chinese ADR alerts and findings regarding TCMs and other substances is included, providing an overview of the breadth and timeliness of the information available from China’s increasing pharmacovigilance.
Abstract: China’s National Center for Adverse Drug Reaction (ADR) Monitoring was established in 1989. In 1998, nearly a decade later, China joined the World Health Organization’s (WHO) Programme for International Drug Monitoring. During March 2004, China formally promulgated the final version of the Regulations on Adverse Drug Reaction Reporting and Monitoring. This modern system supplements an informal reporting system in scholarly publications that dates back to ancient times. Procedurally, the formal Chinese monitoring system requires pharmaceutical industry and healthcare professionals to report most ADR events quarterly. However, new, uncommon, serious or ‘group’ ADRs are required to be reported within a shorter time period. Reports will be made to local centres, which then analyse and transmit them to a national ADR centre operated by China’s State Food and Drug Administration (SFDA). The national authority is then empowered to authorise further studies, publish formal warning announcements or prohibit use of a product. Traditional Chinese medicine (TCM) products are also regulated as drugs in China. Because TCM product use is greatly increasing worldwide, Chinese ADR monitoring is particularly, if not uniquely, useful in its reporting of TCM-related ADRs. A survey of Chinese ADR alerts and findings regarding TCMs and other substances is included, providing an overview of the breadth and timeliness of the information available from China’s increasing pharmacovigilance. Overall, the system shows considerable progress and promise, especially if ADR reporting procedure awareness continues to grow among China’s healthcare professionals and public.

8 citations


Journal ArticleDOI
TL;DR: In this article, the authors focus on the nature of uncertainty in terms of risks and benefits, differences between trial care and prior care outside a trial, and the disclosure of any potential conflicts of interest and how these will be mediated.
Abstract: Phase I clinical trials in oncology are designed to study the toxicity of novel drugs and regimens in a small cohort of subjects and to establish a dose that can be used in future studies. Due to the toxicity of many antineoplastic therapies, these trials are typically conducted in subjects with advanced cancer and limited therapeutic options. Patients primarily enrol in phase I cancer trials with high expectations of personal medical benefit; however, the risks and benefits of these regimens are unknown and the benefit from enrolment in phase I cancer trials to date has been modest. The use of a vulnerable population with high expectations of benefit in a scientific experiment creates challenges for the protection of human research subjects. To ethically use one human being for the benefit of others in a phase I oncology trial requires that the research subject never be viewed merely as a means to an end, but that their interests as a person are always respected and safeguarded. This process begins with trial conception and continues even after completion of the trial. In trial design, particular attention should be given to the nature of the experimental agent or regimen and the most appropriate dose selection and escalation strategy and study endpoint. Older paradigms of inter-patient dose escalation and the establishment of maximally tolerated dose may not be appropriate for all studies. Once a well designed study has been established, the primary challenge is to ensure the voluntary informed consent of research participants. This process involves an explanation of the rationale for the study and details of what study participation actually involves in terms of schedules, drug administration, tests and procedures, and predicted toxicities. It also involves an explanation of the nature of phase I clinical trials with a focus on the nature of uncertainty in terms of risks and benefits, differences between trial care and prior care outside a trial, and the disclosure of any potential conflicts of interest and how these will be mediated. Phase I oncology trials are critically important in the advance of the care of future cancer patients, but such advances must be achieved on a foundation of respect for today’s patients. Trial design and enrolment must be conducted in a way that lets those who choose to participate do so in a way that also maximises their chance of medical benefit, minimises their risk of harm, and maintains the principle of respect for persons at all times.

7 citations


Journal ArticleDOI
TL;DR: Local submissions are a source of delayed start up in many centres participating in clinical trials; however, reasons for delay are not consistent across the applications and cannot be attributed to one specific part of the local approval process.
Abstract: Aim: This study aimed to evaluate the impact of local approval times on the schedule of a large multicentre study in the UK. Method" We reviewed the approval times of 178 applications that were made to the UK National Health Services Trusts (across 159 hospitals and 19 primary care trusts). Results: The mean time for approval was 82 days; more than half the submissions (94; 53%) took longer than 60 days for a decision. The reason for taking over 60 days varied but review of the trial documentation revealed that delays occurred in the Hospital R&D Office for 25 (14%) submissions, at the hospital or primary care trust level for 14 (8%) submissions, while the investigator was responsible for 23 (13%) applications taking longer than 60 days. Conclusion: Local submissions are a source of delayed start up in many centres participating in clinical trials; however, reasons for delay are not consistent across the applications and cannot be attributed to one specific part of the local approval process.

7 citations


Journal ArticleDOI
Luis M. Pereira1
TL;DR: Clinical trials simulation has the potential to greatly aid the setup and execution of actual confirmatory clinical trials so that they have a much smaller risk of failure, but caution is needed as something unknown cannot just be simply simulated from what is previously known.
Abstract: Despite current advances in clinical trial design and analysis, examples of drug failures after lengthy and expensive development processes can still be found. Clinical trials simulation (CTS) has been helpful in minimising the attrition factor of drug discovery and its capabilities continue to expand. In integrating different methodologies — pharmacokinetic and pharmacodynamic, statistical and computational — CTS has the potential to greatly aid the setup and execution of actual confirmatory clinical trials so that they have a much smaller risk of failure. However, caution is needed as something unknown cannot just be simply simulated from what is previously known. Much like an impossibility, akin to the idea of ‘bootstrapping’, the challenge is to look for answers to questions that nobody has posed before. Putting the focus on emulating real prospective patients, their full biological characteristics must be considered so that elusive adverse reactions that can stop drug development at a late clinical stage are avoided. The new generation of CTS may address some of the outstanding problems: experimental designs including hierarchical Bayesian approaches have been tried; Markov chain modelling and simulated annealing provide interesting features; machine learning classifiers, from genetic algorithms to artificial neural networks, may provide valuable insights; and game theory merged with CTS may produce significant advancements.

6 citations


Journal ArticleDOI
TL;DR: The eCTD has advantages over the CTD in terms of ease of use, archiving and for life-cycle management of registration information, and the technical requirements, the implementation by different countries and the practicalities are discussed.
Abstract: The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Common Technical Document (CTD) format has now become the obligatory format for the EU, Japan, Canada, Switzerland and Australia, and the recommended format in the US. Derivatives of the CTD are becoming widely adopted in other regions, including the ASEAN countries. An electronic CTD (eCTD) was developed in parallel with the CTD and the three ICH regions now accept eCTD filings. The purpose of this article is to survey the eCTD technical requirements, the implementation by different countries and to discuss some of the practicalities involved in writing, compiling and publishing eCTD applications. The eCTD has advantages over the CTD in terms of ease of use, archiving and for life-cycle management of registration information. The eCTD specification defines the folder structure, contents, XML backbone and the Study Tagging File for clinical and nonclinical studies. The design of the eCTD documentation needs to include considerations of document granularity, templates, shell documents and regional differences in filings; for example, the need for an Integrated Summary of Efficacy and Integrated Summary of Safety in the US. Regulatory agencies are moving to accept online filings, but these are currently commonly made using physical media such as CD, DVD or tape. The eCTD file needs to be ‘reviewer friendly’ by use of bookmarks, hyperlinking and tables of contents in individual documents. Prescriber and patient information can now be supplied electronically using the XML-based EU PIM Data Exchange Standard and the Structured Product Labelling in the US. Many commercial software tools are available for content management, assembly, compilation, publishing, labelling, electronic validation and review. eCTDs can be developed using leased or purchased software, specialist contract services, outsourcing from software vendors or using contract research organisations.

5 citations




Journal ArticleDOI
TL;DR: It is imperative that China develops a robust and reliable HSP system at the institutional level as drug studies are increasingly being undertaken in mainland China.
Abstract: With the increasing number of clinical trials being undertaken in China over the last few years, stakeholders in human subjects protections (HSP) are facing many new challenges; currently, these challenges in HSP are largely taken up by the ethical review committees and study investigators. This article identifies a number of issues with the present system and suggests ways to resolve these issues at the institutional level. Though the Chinese government has developed a basic regulatory framework for HSP, further work still needs to be done. It is imperative that China develops a robust and reliable HSP system at the institutional level as drug studies are increasingly being undertaken in mainland China.

Journal ArticleDOI
TL;DR: The development of paediatric indications for drugs primarily intended for the adult market has lagged until recent government initiatives comprising both mandatory and voluntary programmes have provided incentives for companies to incorporate the assessment of drugs for paediatric use into standard drug development.
Abstract: The development of paediatric indications for drugs primarily intended for the adult market has lagged until recent government initiatives comprising both mandatory and voluntary programmes have provided incentives for companies to incorporate the assessment of drugs for paediatric use into standard drug development. Although previously identified obstacles such as ethical concerns, the limitations of extrapolating adult data to children and a growing but still nascent research infrastructure still remain, over 100 drugs have had paediatric labelling added in the US programme alone in 8 years. The benefits for companies to add paediatric indications to their drugs include: compliance with regulations, extending periods of market protection, taking advantage of niche markets, addressing unmet public health needs and gaining competitive advantages among formulary and reimbursement decision-makers. The decision by companies to address paediatric use earlier rather than later in the development process is based on a number of considerations, such as recommendations by the regulatory authorities, the feasibility of extrapolating data from the adult experience and the need to account for extra time and costs that may be consequent to developing child-friendly formulations and conducting clinical studies in paediatric populations. CURRENT OPINION

Journal ArticleDOI
TL;DR: China is becoming an equal partner in global clinical development, a trend that is likely to grow significantly in the years to come.
Abstract: In the current context of China’s rapidly growing economy, multinational drug companies are investing significantly in research and development in China, a trend that has accelerated over the last 10 years. A robust regulatory framework, an abundance of highly equipped medical universities and large patient numbers in all therapy areas make China an increasingly attractive location to conduct clinical research. In addition, data from China are now accepted for inclusion in applications for market authorisation by regulatory agencies worldwide, including the Food and Drug Administration (FDA) in the US. Hence China is becoming an equal partner in global clinical development, a trend that is likely to grow significantly in the years to come.

Journal ArticleDOI
TL;DR: The new legislation strengthens the regulatory regime within the EU, provides better public health protection, greater transparency of the processes as well as faster access to new medicines, and delivers benefits for the industry as a whole.
Abstract: This article provides an overview of the European Union’s new medicines legislation, which came into force on 30 October 2005. It describes its scope, the areas of regulation affected by the legislation and explains how it impacts on procedures for obtaining and maintaining a marketing authorisation. Finally, it gives a view of the likely impact of the legislation on the pharmaceutical industry. We make it clear that the process by which European legislation is agreed is both complex and time consuming, with a number of stakeholders and institutions provided with the opportunity to engage in the exercise and influence the outcome. Therefore, the end product of the process is, perhaps inevitably, a compromise. Nevertheless, the new legislation strengthens the regulatory regime within the EU, provides better public health protection, greater transparency of the processes as well as faster access to new medicines. It delivers benefits for the industry as a whole in clarifying and streamlining procedures, providing appropriate rewards for innovation and balancing these with provisions that encourage earlier development of generic products, which bring significant savings in national healthcare budgets.

Journal ArticleDOI
TL;DR: Options are being sought by the industry and regulators to find better ways to uncover unexpected toxicities early in development and monitor evolving toxicity profiles during a product’s marketing phase to help mitigate the multitude of risks in pharmaceutical product development.
Abstract: The value of a pharmaceutical company may be defined as its pipeline or portfolio of products and their potential value in the marketplace. One strategy to help mitigate the multitude of risks in pharmaceutical product development is to balance a portfolio across therapeutic areas, levels of risk and potential for returns. Risks include unexpected toxicities, therapeutic failure and inappropriate risk-benefit for the patient, as well as technical, financial, regulatory, political or social failure. Strategic reviews of a company’s portfolio will help ensure its product line-up is balanced appropriately to meet corporate goals and that product risks have been considered. Following the withdrawal of VioxxTM from the marketplace, a higher level of scrutiny has been focused on the safety of new pharmaceutical products. There is preliminary evidence that the overall number of approvals for new molecular entities decreased in 2005 relative to 2004. Certainly, all approvals of new COX-2 inhibitors have been suspended, leaving lumiracoxib and etoricoxib with an uncertain fate. Accusations have been voiced that the VioxxTM withdrawal was a result of shortened regulatory review times in the US, promulgated by the Prescription Drug User Fee Act. However, analysis by the Tufts Center for the Study of Drug Development has shown drug withdrawals, pre- and post-Act, are the same — withdrawn drugs did not have shorter review times than drugs remaining on the market. Options are being sought by the industry and regulators to find better ways to uncover unexpected toxicities early in development and monitor evolving toxicity profiles during a product’s marketing phase. Most agree, it is undesirable to delay the approval of new products, as this would stifle innovation and leave patients without needed therapies.

Journal ArticleDOI
TL;DR: Background information is provided on the introduction of good clinical practice (GCP) along with information on the development and management methods currently employed in drug research in China to help improve the implementation of these regulations.
Abstract: If a medical institution in China wishes to carry out clinical studies on humans they must first gain accreditation from the relevant regulatory department of the State Council.

Journal ArticleDOI
TL;DR: The generation of neurons from ES cells is an innovative resource to elucidate mechanisms of neurotoxicity involved in neurodegeneration (Parkinson’s disease) or neurodevelopmental disorders (autism) and it is anticipated that this technology will significantly benefit the understanding of debilitating diseases and toxic effects associated with chemicals in humans.
Abstract: The predictive toxicity of chemicals to humans is largely based on scientific investigation in animal models. However, interspecies variability impacts the ability of certain animal models to emulate human response, which ultimately influences attrition rates in pharmaceutical development and safety assessment of new drugs. The availability of scalable human in vitro models for predictive toxicology may increase our confidence in risk assessment of chemicals in parallel to animal studies. Embryonic stem (ES) cells are pluripotent, not genetically modified cells isolated from preimplantation embryos. The establishment of human ES cells enables the production of large numbers of human cell types to evaluate the effects of chemicals on disease and toxic response. This review provides an overview of key opportunities for stem cell technology to produce in vitro models of disease and toxicity related to chemical exposure in humans. Specifically, the generation of neurons from ES cells is an innovative resource to elucidate mechanisms of neurotoxicity involved in neurodegeneration (Parkinson’s disease) or neurodevelopmental disorders (autism). This review reports the use of cardiomyocytes from ES cells as cellular substrates for preclinical safety assessment of compounds. QT prolongation may be evaluated in cardiomyocytes from ES cells on the basis of functional cardiac ion channels. The applications of ES cells in predictive toxicology may be as diverse as the cell types they generate, thus, we anticipate that this technology will significantly benefit our understanding of debilitating diseases and toxic effects associated with chemicals in humans.

Journal ArticleDOI
TL;DR: The mode and scale of collaboration for medical academic research in China is described, and the environment for collaboration has grown rapidly in recent years; however, there is still much potential for growth in the future.
Abstract: This paper describes the mode and scale of collaboration for medical academic research in China, and aims to provide a brief introduction to the current state of collaborative medical research in China today. By analysing the published literature between 1995 and 2004 and using statistics from the State Intellectual Property Office, we try to give a glimpse into how medical research has evolved over that period using information on research funding, patent applications and academic exchange. Through local governmental, international and institutional funding and communication, the environment for collaboration has grown rapidly in recent years; however, there is still much potential for growth in the future.

Journal ArticleDOI
TL;DR: With an understanding of the relationship between imaging biomarker changes and clinical outcomes, imaging can be used as a surrogate marker of response even for the later stages of drug development.
Abstract: There is currently increased focus on experimental medicine in drug development. Imaging methods potentially provide highly cost-effective, general approaches for the noninvasive characterisation of disease and pharmacokinetics, pharmacodynamics and drug effects directly in humans in ways that can enable this. The two methods most widely employed now are positron emission tomography (PET) and magnetic resonance imaging (MRI). PET allows the distribution of radiolabelled molecules to be mapped, enabling studies of molecule distribution and tissue metabolism. MRI was initially used primarily to define tissue structure, but a more recent range of functional MRI techniques promise the potential to define pharmacokinetic data over biologically meaningful timescales. With an understanding of the relationship between imaging biomarker changes and clinical outcomes, imaging can be used as a surrogate marker of response even for the later stages of drug development.

Journal ArticleDOI
TL;DR: Modified manufacturing conditions and newer pharmaceutical techniques or delivery systems can be used to enhance the stability and resistance of probiotics to gastric pH and to achieve targeted and sustained delivery.
Abstract: It is well established that alterations in gut flora are responsible for infectious diseases, especially in paediatric cases. An infant’s gut is sterile at the time of birth and the type of flora that develop depends on the type of feed provided to the newborn baby. Critical changes occur in the gut flora of an infant after birth and during weaning. Probiotics, the nutritional foods containing live microbes, effectively modulate gut flora and have been shown to have beneficial effects in a multitude of paediatric disorders. This review encompasses information regarding the development of intestinal flora in neonates, various paediatric disorders related to abnormal gut flora and application of probiotics in paediatric disorders and the mode of action of probiotics. We also outline a plethora of microbial strains and paediatric commercial patented preparations. The safety profile and tolerability of probiotics is also discussed at length. Future research will need to focus on mechanistic studies to explore molecular mechanisms of host-microbe interaction, use of genetic engineering, microarrays and proteomic technologies to produce advanced probiotic strains. Modified manufacturing conditions and newer pharmaceutical techniques or delivery systems can be used to enhance the stability and resistance of probiotics to gastric pH and to achieve targeted and sustained delivery.

Journal ArticleDOI
TL;DR: The international regulations for this purpose are described and an outline of major steps in the development of the bioequivalence two one-sided testing procedure is provided.
Abstract: Bioequivalence has been the topic of many publications since its development in the late twentieth century for the protection of public health when changing formulations of orally administered products. This review paper describes the international regulations for this purpose and provides an outline of major steps in the development of the bioequivalence two one-sided testing procedure. Study designs and analysis methods used in testing for bioequivalence are also described.

Journal ArticleDOI
TL;DR: Clinicians should be aware of the insights gained into ethnic differences in order to improve clinical management of certain diseases in ethnic groups through different forms of collaboration with regulatory authorities.
Abstract: In recent years, greater attention has been given to the detection of ethnic differences in drug response and the need to take these differences into account in drug development. Epidemiological studies have identified significant ethnic variations in the rate and pattern of certain diseases, such as cardiovascular diseases, and in the response to drug therapy. Racial or ethnic differences may be related to a number of factors, including social, environmental and genetic factors. Differences in genes or polymorphisms are common and represent major determinants of differences in the effects of medicines observed in various populations. Polymorphisms concern mainly drug metabolism enzymes, receptor proteins and hepatic metabolism. They may influence the pharmacokinetics and pharmacodynamics of a given compound. Although specific polymorphisms are not isolated to any particular ethnic group, polymorphism prevalence may vary between ethnic groups for various categories of medicines. Among drug classes that exhibit varying effects in ethnic groups, benzodiazepines, antidepressants, antipsychotics, analgesics, antihypertensives and antidiabetic agents have been studied. However, it remains unclear how to assess the impact of ethnic differences on drug development and registration. In the E5 guidance from the International Conference on Harmonisation, the aim is “to permit the clinical data collected in one region to be used in the registration or approval of a drug or biological product in another region, while allowing for the influence of ethnic factors”. As a rule, approval of a new pharmaceutical product requires the demonstration of efficacy and safety by controlled clinical trials and the selection of an appropriate and safe dosage. The extrapolation of the original data collected in one region to another region depends of the similarity in dose response, efficacy and safety of the drug in both regions with or without dose adjustment. It is the responsibility of the sponsor to decide whether or not the data can be extrapolated or if additional bridging studies are needed. The type of bridging studies depends on the critical properties of the compound, the ethnic differences between the new and original regions and the requirements of the regulatory authority in the new region. Advances have been made in recent years and clinicians should be aware of the insights gained into ethnic differences in order to improve clinical management of certain diseases in ethnic groups. Ethnic differences observed in clinical trials may justify the approval of a specific drug formulation for a specific ethnic group. Drug development plans should be adjusted according to these known differences and adjustments should be anticipated when possible through different forms of collaboration with regulatory authorities.

Journal ArticleDOI
Giancarlo Viberti1
TL;DR: A group of international experts met to discuss the problem of diabetic nephropathy and its prevention and treatment through the inhibition of the renin-angiotensin system (RAS), and the roles of the ROADMAP and ORIENT studies in assessing whether treatment with an ARB like olmesartan medoxomil can prevent or slow the incidence or progression of diabetic necropathy.
Abstract: Diabetic nephropathy is increasingly a global health problem and it appears to affect certain ethnic groups, such as Asians, more than others. At the 41st Annual Meeting of the European Association for the Study of Diabetes held in Athens, Greece (10–15 September 2005), a group of international experts met to discuss the problem of diabetic nephropathy and its prevention and treatment through the inhibition of the renin-angiotensin system (RAS). The experts’ meeting was attended by steering committee members 1 of two of the major clinical trials currently investigating the use of the angiotensin II receptor blocker (ARB) olmesartan medoxomil in patients with type 2 diabetes mellitus who are at risk of developing (ROADMAP 2 study) or already have (ORIENT 3 study) diabetic nephropathy. The ROADMAP study is being conducted in several European countries and the ORIENT study is taking place in Japan and Hong Kong. The meeting provided a forum for experts from the East and West to share knowledge and discuss issues relating to: the current understanding of diabetic nephropathy as a risk factor for renal and cardiovascular disease; the apparent differences in previous intervention trials in renal outcomes between Caucasian and Asian patients with diabetic nephropathy; and the roles of the ROADMAP and ORIENT studies in assessing whether treatment with an ARB like olmesartan medoxomil can prevent or slow the incidence or progression of diabetic nephropathy. 1. Diabetes, Hypertension and Renal Disease


Journal ArticleDOI
TL;DR: The unofficial theme for this year’s meeting was “safety pharmacology has arrived!” following the publication of regulatory documents such as International Conference on Harmonisation guidelines S7A and S7B.
Abstract: The 6th annual meeting of the Safety Pharmacology Society (SPS) took place in San Diego, California, and was the largest gathering to date for the society, with over 470 delegates in attendance. Indeed, the unofficial theme for this year’s meeting was “safety pharmacology has arrived!” following the publication of regulatory documents such as International Conference on Harmonisation (ICH) guidelines S7A[1] and S7B[2], the need for full safety reports for regulatory submission as opposed to summaries, and the safety pharmacology component of the new exploratory IND (investigational new drug) applications.

Journal ArticleDOI
TL;DR: The European League Against Rheumatism (EULAR) held the 7th Annual European Congress of Rheumatology in Amsterdam in June.
Abstract: The European League Against Rheumatism (EULAR) held the 7th Annual European Congress of Rheumatology (EULAR 2006) in Amsterdam in June. EULAR represents patient, health professional and scientific society interests in relation to rheumatology; EULAR aims to reduce the burden of rheumatic diseases on individuals and society, and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases.

Journal ArticleDOI
TL;DR: In this article, the authors developed the general structure and applied that framework to a stylised real-life example, and the overall market value of a pharmaceutical company can then be decomposed taking into account the firm's specific portfolio of "products" being at different stages of the drug development process.
Abstract: Traditional valuation tools such as discounted cash flow (DCF) models fail in valuing research and development (R&D)-intensive pharmaceutical firms adequately because most of the market value of the firm is embedded in unexercised real options whose future value is uncertain at this moment. From this basic insight, it follows that the (value of the) firm should optimally be characterised as a portfolio of real options, and also that compound option models should optimally be used to value the firm’s ‘products’ based on the typical development process of new drugs. The overall market value of a pharmaceutical company can then be decomposed taking into account the firm’s specific portfolio of ‘products’ being at different stages of the drug development process. In this paper, we develop the general structure and apply that framework to a stylised real-life example.

Journal ArticleDOI
TL;DR: The clinical trial is the societal node where all stakeholders in good clinical practice (GCP) meet and have common interests and the globalisation of clinical trials and the need to make the EU more attractive by acting at the political, scientific, industrial and patient level are described.
Abstract: The European Forum for Good Clinical Practice (EFGCP) is an international not-for profit association with a permanent secretariat in the European district of Brussels. It is the place ‘where science and ethics meet’. The EFGCP has a membership broadly representative of all stakeholders in clinical research, including patients. Its working parties, under the guidance of a Science and Ethics Council, are active in the fields of the strategy of educating professionals in the conduct of clinical trials, the principles of ethics review in drug research in humans, the incentives for the development of more and better medicines in children and the elderly, optimising the drug development process including its transparency via audits, etc. The 2006 EFGCP Annual Conference was held in Brussels on 31 January and 1 February in partnership with the European Association for Bio-Industries (EuropaBio), European Federation for Pharmaceutical Sciences (EUFEPS), European Clinical Research Infrastructures Network (ECRIN), European Platform for Patient Organisations, Science and Industry (EPPOSI), Belgian College for Pharmaceutical Medicine (BCPM), European Genetic Alliances’ Network (EGAN), Verband Forschender Arzneimittelhersteller (VFA; the German Association for Research-Based Pharmaceutical Companies), European AIDS Treatment Group (EATG) and the European Federation of Pharmaceutical Industry Associations (EFPIA). More than 80 participants representing the full spectrum of clinical research professionals from industry and contract research organisations (CROs), supervisory bodies in government, ethics committees, European Union (EU) agencies, investigator networks and patient associations had taken up the challenge of joining forces to debate the conditions for a revival of clinical R&D activities in Europe. Jean-Pierre Tassignon1, Chairman of the EFGCP, said in his introduction that the clinical trial is the societal node where all stakeholders in good clinical practice (GCP) meet and have common interests. A moral consensus between science and society is a prerequisite for the emergence of a European Research Area. The EFGCP adheres to the objective of helping this continent – ‘geographical Europe’, not just the EU – become the most competitive knowledge-based society. Clinical trials of the highest standard must be a core competency of such a knowledge-based society. Ingrid Klingmann2, EFGCP’s Conference Officer and coChair of the EFGCP Ethics Working Party, described the globalisation of clinical trials and the need – given competitive forces from emergent clinical regions – to make the EU more attractive by acting at the political, scientific, industrial and patient level. In the EU, 500 000 staff are employed within the pharmaceutical industry; most of these are highly skilled workers. The sector generates a trade surplus of 36 billion euro, 72 000 euro per employee. Additionally, investment in the European research base totals 24 billion euro per year, or 48 000 euro per employee. And the industry is the source of new medicines, with a high societal added value. How can this cornucopia last or, even better, become bigger?

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TL;DR: The San Antonio Breast Cancer Symposium (SABCS), held every December in San Antonio, Texas, USA, is an international scientific symposium at which basic scientists and clinicians interact and exchange information about breast cancer.
Abstract: The San Antonio Breast Cancer Symposium (SABCS), held every December in San Antonio, Texas, USA, is an international scientific symposium at which basic scientists and clinicians interact and exchange information about breast cancer. The 2005 symposium was thought to be attended by approximately 7000 delegates. The symposium involved five plenary sessions, four mini-symposia, 48 oral presentations and nearly 700 posters.