Showing papers in "International Journal of Pharmaceutical Medicine in 2005"

European Respiratory Society

Abstract: The mission of the European Respiratory Society (ERS) is to advance respiratory medicine by stimulating and coordinating the actions of its members, in order to achieve the highest possible medical, paramedical and social standards in the treatment of respiratory disease in Europe. The society’s 2005 congress had approximately 16 000 registered participants from 100 countries and with over 110 scientific and clinical sessions, the congress was Europe’s largest annual scientific gathering in respiratory medicine.

American Thoracic Society 100 Years of Advances in the Treatment and Science of Respiratory Diseases; 20-25 May 2005; San Diego, California, USA

Abstract: This document is an update of the original 1993 statement on community-acquired pneumonia, incorporating new information about bacteriology, patient stratification, diagnostic evaluation, antibiotic therapy, and prevention. The statement includes a summary of the available literature, as well as evidence-based recommendations for patient management, developed by a multidisciplinary group composed of pulmonary, critical care, general internal medicine, and infectious disease specialists. The sections of this document are as follows: an overview of the purpose of our efforts and the methodology used to collect and grade the available data; a review of the likely etiologic pathogens causing community-acquired pneumonia (CAP), including a discussion of drug-resistant Streptococcus pneumoniae (DRSP); a proposed approach to patient stratification for the purpose of predicting the likely etiologic pathogens of different patient populations with CAP; a summary of available and recommended diagnostic studies; suggestions on how to define the need for hospitalization and admission to the intensive care unit (ICU) for patients with CAP; guidelines for antibiotic therapy of CAP, including principles of therapy and specific recommendations for each patient category; an approach to the nonresponding patient, as well as a discussion of when to switch to oral therapy and when to discharge an admitted patient with CAP who is responding to initial therapy; and recommendations for the use of pneumococcal and influenza vaccines.

Assessment of the AccuSwayPLUS System in Measuring the Effect of Lorazepam on Body Sway in Healthy Volunteers

Abstract: Aim: To assess the AccuSwayPLUS system, which aims to quantify deficiency in human balance, using the measurement of the effect of lorazepam on body sway in healthy volunteers.

An Anticounterfeiting Strategy Using Numeric Tokens

Abstract: The counterfeiting of pharmaceuticals continues to be a major worldwide problem with serious public health and economic consequences. In theory, anticounterfeiting tags could help to solve this problem. Unfortunately, there are currently no practical, effective tags that significantly resist counterfeiting. One possible solution is a relatively low-tech and low-cost approach called the ‘Call-in the Numeric Token’ (CNT) technique. It relies on participation by pharmaceutical customers (possibly including consumers). They check, via phone or the Internet, on the validity of the unique, random, unpredictable identity (ID) number assigned to each pharmaceutical container they possess. The numerical container ID is a virtual tag or token, rather than a physical one that is susceptible to counterfeiting. Counterfeiters are hampered by being unable to reliably guess valid IDs, by being unable to easily acquire large numbers of existing valid IDs, and by being detected when multiple customers report the same IDs. At least some counterfeit products can be detected even if only a small percentage of customers participate. The technique is particularly well suited for single-dose (‘unit of use’) packaging, but can otherwise be adapted and automated for resellers, wholesalers, repackagers, and other high-volume customers. While this technique will not completely eliminate counterfeiting, using the CNT technique can make pharmaceutical counterfeiting easier to detect and study.

The Pharmaceutical Year That Was: A View from San Diego, California, at the End of 2005

Abstract: Looking back over what has been important in pharmaceutical medicine during the past 12 months in the US, it has been another US Food and Drug Administration (FDA)-centric year. One’s retrospective vision is easily dazzled by the explosions surrounding two products and one person (Vioxx® 1, Plan B®, and Dr Lester Crawford). But those stories have been well-told elsewhere, and perhaps we should look at what else has been going on. Here is just one personal view. Approvals for new chemical entities in the US are down sharply this year. The most important factor contributing to this is probably the relatively dry R&D pipelines in large pharmaceutical companies over several recent years. At the time of writing, we await the customary end-of-year flurry of FDA approvals, but these will have to be record-breaking in order to offset the slow pace of approved New Drug Applications (NDAs). There is some evidence that review times are elongating again at the FDA (with Prescription Drug User Fee Act [PDUFA] date enforcement being essentially toothless), but it is doubtful that this is the major reason for fewer approvals this year. The agency has become increasingly concerned about product safety, thus requiring more and more clinical trials, and larger and larger databases; but no wonder when unbiased reports during 2005 demonstrated how few post-marketing research commitments agreed at the time of NDA/Biologics License Application (BLA) approval are fulfilled within a reasonable time period. It has also been a dry year for small pharmaceutical companies in terms of financing. There are some signs as the year draws towards its close that the financial window is opening a little. But the number of substantial financings is well down, as are valuations. The only bright spot has been interventions by Big Pharma, rather than by venture capitalists. Big Pharma has acquired products from Small Pharma for the dry pipelines mentioned above. Often this has been by ‘lock, stock and barrel’ acquisition of the smaller companies. While usually good for the investigational drug/biological projects themselves, creative scientists in small companies have often found themselves treated like skittles in a bowling alley.

Selective Reporting, Publication Bias and Clinical Trial Registry

Abstract: All information relevant to the care and safety of those who use marketed products should be published, and this is the responsibility of the organisations that carry out clinical research, and pharmaceutical companies in particular. Publication bias, or the selective reporting of results, threatens the validity of any evaluation of the medical literature, especially when findings are summarised quantitatively across multiple studies in a formal meta-analysis. Empirical studies have demonstrated that publication bias exists and can have a substantive effect on the conclusions drawn from published literature alone. Numerous statistical approaches to detecting and correcting for publication bias have been proposed, but all are based on unverifiable assumptions about the mechanism leading to selective publication. A preferred solution to the problem of publication bias is a preventive strategy, based on a central, publicly accessible registration of clinical trials at their inception, followed by full disclosure of their results. Progress toward that end has been made through guidance provided by medical journal editors, independent groups of researchers, and industry, but more work is needed before a consensus is reached on the scope and practical implementation of clinical trial registries.

Improving Pharmacovigilance Beyond Spontaneous Reporting

Abstract: About forty years ago pharmacovigilance started as a formal public health practice with the setting up of spontaneous reporting schemes. This can be recognised as the first generation of progress in this discipline. Since then, along with the consolidation of such programmes around the world, important new developments have taken place, reinforcing our ability to identify and characterise drug safety issues earlier and on more scientific grounds. The application of pharmacoepidemiological methods to drug safety evaluation has been crucial in this process, marking the second generation of progress. The conceptual evolution has been immense but there is still a lot of work to be done to transfer it into routine practice, in particular when the aim is to be proactive in anticipating and minimising drug safety issues. Patient risk management can be recognised as the third generation of progress and the new challenge for the first decades of the 21st century.

European Technology Platform on Innovative Medicines

Abstract: The European pharmaceutical industry is seriously lagging behind its competitors, mainly in the US, and seems to be particularly slow in harnessing the benefits of the revolution in biotechnology, as evidenced by the growing numbers of biotechnology corporations on the far side of the Atlantic as well as the movement of infrastructure and personnel from Europe across the Atlantic to better opportunities that are unavailable in Europe. The Technology Platform for Innovative Medicines for European citizens is proposed as an integral part of the European Commission proposals for the Seventh Framework Programme (2007–2013) and aims to redress this imbalance. It is aimed at enhancing and accelerating the development process of medicines, including those derived from biotechnology, so as to ensure the most rapid application of scientific breakthroughs into approved new medicines. This will be achieved by stimulating integrated forms of co-operation in research and development, in particular through reinforced public-private partnerships, with a view to providing the European population with early access to new, more targeted medicines, while at the same time, strengthening the European science base and fostering economic growth in the pharmaceutical and biotechnology industries.

Post-launch clinical investigator drug prescribing in the US : The behaviour of clinical trial investigators after participating in phase III trials

Abstract: Background: Clinical investigator physicians who take part in clinical trials influence how other doctors adopt new drugs; however, not much is known about the attributes of these investigators (usually with office-based practices and a smaller number working in hospitals or academic medical centres) who tend to prescribe more of the study drug once it gets to the market.

DNA vaccines : Focus on increasing potency and efficacy

Abstract: Compared with conventional approaches, DNA vaccine technology is a relatively new methodology for producing effective vaccines and has the major advantage of being simple and not requiring any special techniques for the purification and characterisation of recombinant proteins in the correct structure and conformation. The beauty of this approach lies in the ability of DNA vaccines to induce both cellular and humoral responses, thereby having special applications for making improved prophylactic vaccines against diseases for which traditional approaches have failed. Furthermore, the technology also provides an opportunity for developing therapeutic vaccines to treat chronic diseases such as HIV infection and viral hepatitis. These types of vaccines utilise advances in the fields of immunology and molecular biology to tailor more specifically the types of immune responses needed (cellular and/or humoral) against selected targets. In addition, DNA vaccines are potentially safer because, by delivering only the gene(s) encoding the particular immunogen(s) against which a protective or therapeutic immune response is desired, one can avoid the limitations and risks of certain other approaches such as live attenuated pathogens. So far, the efficacy of DNA vaccines has been low to modest in clinical trials, therefore significant efforts have been made to increase the potency of DNA vaccines by increasing the expression levels of the gene of interest, developing novel formulations and delivery technologies, and utilising biological adjuvants. Second-generation DNA vaccines are under development. This review will focus on the status of DNA vaccines against disease and the progress made in increasing the potency and efficacy of DNA vaccines.

The Qualified Person for Pharmacovigilance for Europe A Compliance and Quality Perspective

Abstract: A decade after the legal requirement for a qualified person (QP) for pharmacovigilance for Europe for each pharmaceutical company was promulgated, the exact obligations of the QP remain contentious This paper reviews the responsibilities of the QP, as set out in legislation and guidelines, pointing out ambiguities and uncertainties, and provides an interpretation of these The wide-ranging remit of the QP presents many challenges for the incumbent, not least of which is how one individual can take personal responsibility for multiple activities taking place across several countries The answer may lie in the institution of a number of inter-related capabilities: delegation of activities to trained individuals, while retaining responsibility; oversight of activities involving drug safety; awareness of what is happening in the company that could have an effect on benefit and risk; and personal involvement in certain key pharmacovigilance activities A robust quality assurance and control operation is vital, with the QP being central to this process

Clinical Trials in Russia: Growing Experience and Revision of Regulations.

Abstract: Clinical trials of pharmaceuticals have been running in Russia for more than ten years and while it is an attractive location for research, it remains a largely untapped resource as researchers look to expand patient recruitment outside the Western world.

The US Food and Drug Administration and Emergency Contraception

Abstract: High-dose progestins (progestagens) unquestionably reduce the probability of pregnancy when used within 72 hours of unprotected coitus. Two 0.75mg levonorgestrel tablets, taken 12 hours apart, is one such regimen. The tolerability and efficacy of this course of therapy is widely accepted, and its clinical experience comprises millions of doses in numerous countries. One such course of treatment, under the trade name Plan B® 1, has been approved as a prescription-only product by the US Food and Drug Administration (FDA) for several years. But getting a prescription requires an appointment with a doctor within the crucial time period required for efficacy. In contrast, US pharmacies require no appointment, are typically open seven days a week, and are more densely distributed than physicians in some rural areas. Thus, in the context of a huge tolerability database, it has been proposed that Plan B® should be available in pharmacies without prescription. Over-the-counter (OTC) sales of Plan B® are already allowed under individual states’ laws in Alaska, California, Hawaii, Maine, New Hampshire and New Mexico. A further five states have similar legislation pending: Massachusetts, New York, New Jersey, Oregon and Vermont. In three states, such legislation has either failed or was defeated: Illinois, Kentucky and Texas. Meanwhile, the manufacturer has been attempting to obtain FDA approval for the OTC switch for about 30 months. This single approval would grant OTC status nationwide. The New Drug Application supplement is evidently well supported with the relevant pharmacoepidemiological studies. The application was found to be approvable after the usual review, which included scrutiny by an outside advisory committee (who recommended approval by a large majority). It was therefore surprising when the then Acting Commissioner of the FDA, Mr Lester Crawford, issued a nonapprovable letter for this OTC switch in May 2004. According to one recently retired FDA Director, this was an event that is almost unique in administrative history. Normally, product approvals and permissions for labelling changes emanate from the scientific staff in the reviewing divisions and supervising offices, which are below the politically appointed commissioner by some three or four levels in the hierarchy. Mr Crawford is a civil servant without scientific or review-level regulatory experience. Mr Crawford’s initial justification for nonapproval was that the safety of the product had not been demonstrated in patients under 17 years of age, and that access to an OTC product by persons under that age could not be prevented. This had been considered during the scientific and clinical review and a riskmanagement plan had been agreed with the Sponsor. The Sponsor made further submissions to the FDA, addressing this theory during the rest of 2004, and on 1 January 2005, the review clock deadline passed without the FDA taking any action. This matter has gained in public visibility. In early 2005, Mr Crawford appeared for Senate confirmation hearings which ultimately promoted him to permanent FDA Commissioner from his hitherto acting status. During those hearings, he was asked about this issue by Senator Clinton, among others. He promised to reach a definitive decision by 1 September 2005, although he gave no promise as to whether he would approve or disapprove the OTC switch. Then, on 26 August 2005, Mr Crawford announced that he was deferring indefinitely his approval decision on the OTC switch for Plan B®. He decided to open a 60-day period for public comment, on a “legal complexity” that he thinks he has discovered with the practice of approval of products by FDA with age group restrictions. This latest event has led to an eruption of stereotypical outcry. Organisations that lobby for a ban on elective abortion are also generally opposed to Plan B®, believing either that women’s health will suffer (but nonspecifically) by approving the OTC switch, or making dire predictions of a massive increase in promiscuous behaviour among those underage. People who are opposed to contraception in general, of course, are opposed to

Staged Risk Management of Candidate Drug Efficacy: A Proposed Structure to Classify Levels of Proof Within a Clinical Development Programme

Abstract: There is a broad need within the drug development industry for a new approach to understanding the ‘levels-of-proof’ that operate within a drug development programme. This article outlines a proposed system to address this need. We suggest a hierarchy, which could be used as a general communication tool and riskassessment device when managing stages of clinical development and discussing the proofs, and possible profits, of ‘effect’. This structure starts with low levels of proof such as basic pharmacokinetics being proof of systemic exposure; higher levels of proof then include proof of compartmental exposure where appropriate. The hierarchy then graduates on to proof of pharmacological activity ascending from simple receptor activities through to more downstream pathway-related effects. The final tiers in the hierarchy represent proof of activity in diseaserelated pathways, disease-related surrogates, registrable endpoints and finally the highest level of proof is in health economic-related outcomes such as quality-adjusted life-years.

Clinical Trials and the Independence of Investigators

Abstract: Industry-funded research has long been criticised for its ability to allow bias through the manipulation of the reporting of results. This paper describes an approach that addresses some of these concerns by implementing a process for the conduct of clinical trials, especially trials conducted in private practice. The approach involves the use of a private practice clinician to act as chief investigator to design a study, recruit fellow investigators, employ a contract research organisation (CRO), organise insurance and to act as the designated sponsor of the project, thereby relegating ownership of the study data to the investigators, as sponsors, rather than the pharmaceutical company funding the trial. All parties involved must adhere to Good Clinical Practice (GCP) standards. In an ongoing trial using this model, the chief investigators adopted the role of sponsor but separated the management and finances of the trial from the other accounting procedures within the clinical practice by using the vehicle of a pre-existing, limited liability, registered private company which already undertook such activities with regards to clinical research conducted within the private practice setting. The study was a multicentre, placebo-controlled, double-blind, randomised, crossover design. Operating procedures were designed to overcome any potential areas of conflict of interest. A CRO was contracted to manage the day-to-day conduct of the trial. The sponsoring company, representing the investigators, was completely independent of the funding pharmaceutical company thereby ensuring unencumbered potential to publish findings, irrespective of their positive or negative results. The concept in which a pharmaceutical company funds, but does not sponsor, a trial ensures that the execution, ownership and reporting of the study findings remain the precinct of the sponsor, which is independent of commercial influences relevant to the pharmaceutical industry. Such autonomy, granted to the chief investigators, may provide a significant advance in the realisation of clinical drug trials, especially those conducted within community based private practice, and respects scientific integrity without sacrificing mandatory rigour.

Rare diseases and essential medicines : A global perspective

Abstract: This article addresses the question ‘to what extent medicines for rare diseases can be considered as essential’. Essential medicines are those that satisfy the priority healthcare needs of the population; they should be available at all times to all who need them. Rare diseases can be orphan diseases, which are universally rare, or neglected diseases, which are rare in industrialised countries but common in certain low- and middle-income countries. In both cases there is no profitable market for drug development.

Postmarketing surveillance: An overview from India

Abstract: The postmarketing monitoring and evaluation of the safety and effectiveness of all medicines is essential. The patterns of use, effectiveness and safety of a drug in general use may be substantially different to that in clinical trials due to differences in prescribing and patient groups; differences include the limited number of patients in studies, restrictions in patient populations (e.g. pregnancy and nursing mothers, children, the elderly and those predisposed to develop adverse events are frequently excluded), and the limited duration of drug use or period of evaluation in clinical trials. In addition, knowledge about effectiveness and safety in off-label use and interactions with concomitantly used drugs remains unknown. It is important to recognise that clinical trials and postmarketing surveillance address different issues. Postmarketing surveillance data provide new information that was unavailable in premarketing studies. Much larger observational studies can be done, at a lesser cost, to evaluate a drug in a customary use situation. Highest priority in a postmarketing surveillance system should be given to new chemical entities, populations in which drug effects are not well documented, certain important medical events (e.g. birth and death) and their relationship to drug use and pattern of prescription. Surveillance per se, or its results, will not and cannot be used to change the biological properties or effects of a drug, but can be used to minimise the harmful consequences and maximise the optimal use of a drug. LEADING ARTICLE

Transparency, accountability and cooperation in medicines development : Looking forward from 2005

Abstract: The development of pharmaceuticals, and health interventions in general, has taken on global dimensions regarding the science, politics and economics of medicines development and marketing. The fundamental reasons for these changes are much larger than pharmaceutical research itself. The reasons include political changes (in certain geographical regions and countries), growing economies with an increased potential to produce and deliver products locally, and the ever increasing reach of communications and science across national and cultural boundaries. Add to this a swell in basic pharmaceutical research (as well as in areas such as genetics and stem cell science), in places like India, China, Brazil and South Korea, alongside increased investment and capacity in manufacturing, and the development of pharmaceutical medicines takes on new proportions that could not have been foreseen in the 1990s. At the same time we see an increased public awareness and concern regarding ethics and transparency in clinical research around the world. In 2005 the Vioxx® 1 case in the US stirred public attention regarding responsibility and accountability in the development and marketing of medicines. This, combined with increased public scrutiny regarding the safety and oversight of medicines, has led to greater scrutiny by the media and consumer groups with regard to the processes of researching and delivering medicines. In addition, the increased amount of research being conducted in places such as Eastern Europe, Asia and Latin America has led to a growing call for improved ethical review and government oversight in all regions and countries where pharmaceutical research is conducted. The globalisation of, and increased scrutiny of, medicines development has brought with it demands for increased transparency. A major issue in 2005 was the implementation of procedures by different parties for the registration of clinical trials on pharmaceuticals. This came about as a direct result of the 9 September 2004 statement by the International Committee of Medical Journal Editors (ICMJE) requesting the public registration of clinical trials prior to their commencement. The ICMJE request was quickly followed by similar positions taken by the pharmaceutical industry, as well as by public and academic institutions and researchers. The pharmaceutical industry responded in a rapid and concerted manner, as represented in the position papers it put forward through the International Federation of Pharmaceutical Manufacturers Associations and its principal associations in the US, Europe and Japan. Not-for-profit and public-based research institutions, such as the European Clinical Research Infrastructures Network (ECRIN) and the Canadian Institutes of Health Research (CIHR), also took strong positions on the need for making available information on clinical trials to the research community as well as to patients’ groups. These actions are now being consolidated through the World Health Organization’s 2005 initiative establishing an International Clinical Trials Registry Platform. In 2005 we have also seen an increased interest in the promotion of good clinical practice (GCP) as a means toward developing public accountability – largely as a response to the growth and impact of medicines development. Within this expansion of GCP, both in terms of the areas of research within which GCP is applied (e.g. clinical trials registration, the responsibilities of the regulatory authority) as well as in geographic areas, we see a specific focus on improved ethical review and government oversight – both within and outside of the traditional International Conference on Harmonisation (ICH) regions. Countries such as South Korea, China, Thailand and Indonesia have taken major steps toward improving the quality of ethical review committees. Some

Prediction of Putative Adverse Drug Reaction-Related Proteins from Primary Sequence by Support Vector Machines

Abstract: Introduction: Adverse drug reactions (ADRs) are responsible for the failure of a significant portion of investigative drugs trials and the major reason for the withdrawal of drugs from clinical research. A number of ADRs are caused by the (undesired) interaction of drugs with key proteins involved in normal biological processes. Identification of these ADR-related proteins facilitates the design of drugs with fewer adverse effects by rationally avoiding unwanted interaction with these proteins. Method: This work explores the use of a statistical learning method, support vector machines (SVMs), for the identification of potential ADR-related proteins. A SVM classification system was trained and tested by using 759 ADR-related proteins of different species and 2280 non-ADR-related proteins. Results:93.9% of the ADR-related proteins and 98.2% of non-ADR-related proteins were correctly classified. Discussion: The SVM is potentially useful for facilitating the identification of ADR-related proteins. The development of methods to identify ADR indications of ADR-related proteins are progressing well, an example of which is the web-based ADR-related protein prediction tool SVMDART, which can be accessed at http://jing.cz3.nus.edu.sg/cgi-bin/dart.cgi.

Moving from Basic Research to New Therapies for Endocrine Disorders

Abstract: The 2005 annual meeting of the Endocrine Society (ENDO) attracted a wide range of attendees from basic research scientists through to clinical practitioners. The meeting took the theme ‘Pathways to Discovery and Practice’, and included in the programme were a number of theme-related symposia and events focusing on the translation of advances in basic endocrine research into new therapies for endocrine diseases. Some meeting highlights, particularly developments in drug therapy, are briefly reported here.

Guideline for Auditing Clinical Laboratories

Abstract: 1. Scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289 2. Audit of Clinical Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 2.1 Preparing a Laboratory Audit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 2.2 Conducting a Laboratory Audit: Review of Documentation Related to the Organisation . . . . . . . . . . . . . . . . . . . 290 2.2.1 Laboratory Management – Organisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 2.2.2 Personnel – Roles, Responsibilities and Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 2.3 Quality Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 2.3.1 Quality Assurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 2.4 Conducting a Laboratory Audit: Facilities and Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 2.4.1 Equipment and Reagents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 2.5 Kit Preparation and Investigator Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 2.6 Transportation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 2.7 Handling Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 2.7.1 Receipt and Processing of Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 2.8 Sample Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 2.9 Sample Retention/Destruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 2.10 Data Handling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 2.10.1 Data Handling and Release Process of Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 2.10.2 Reporting to Investigator and Transfer of Data to Sponsor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295 2.11 Computer Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 2.11.1 General Validation Documentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 2.11.2 System Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 2.11.3 Software Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 2.11.4 Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 2.11.5 Maintenance and Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 2.11.6 Security . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 2.11.7 Back-up and Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 2.11.8 Server Room . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 2.12 Archive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 3. Good Laboratory Practice (GLP) Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 GUIDELINES Int J Pharm Med 2005; 19 (5-6): 289-299 1364-9027/05/0005-0289/$34.95/0

Making Progress in the Acute Treatment of Stroke

Abstract: This review discusses the reasons for both the difficulty in making therapeutic progress in stroke studies, and the insights that neuroimaging, especially magnetic resonance imaging (MRI) and perfusion computed tomography (CT), are bringing to this difficult area of research. While many advances have been made in the treatment of coronary heart disease and acute coronary syndrome, acute cerebral neuroprotection has almost completely failed to have an impact on stroke (a major unmet clinical need), despite the introduction of tissue plasminogen activator (tPA). This paper discusses the reasons behind this lack of progress, including the problems posed by animal models of stroke. However, major scientific advances using neuroimaging, both in animals and humans, now permit the rational design of clinical trials and of patient selection to improve the chances of a positive therapeutic outcome. In the future, quantitative neuroimaging will provide surrogates that augment the existing, relatively insensitive, clinical endpoints, thereby reducing both patient numbers, and likely follow-up time, required to power a significant endpoint. An important therapeutic limitation is currently the difficulty of including MRI early after stroke onset because of the lack of clinics focused on acute cerebral injury. Recent developments in perfusion CT may help alleviate this important bottleneck.

European Clinical Research Infrastructures Network Meeting Report

Abstract: 1 CIC (Centres d’Investigation Clinique) INSERM-Hopitaux Network, France 2 KKS (Koordinierungszentren für Klinische Studien) Network, Germany 3 Danish Clinical Research Infrastructures Network (DCRIN), Denmark 4 Réseau Français des Unités d’Essais Cliniques (RFUEC), France 5 Consorzio Italiano per la Ricerca in Medicina (CIRM), Italy 6 Istituto di Ricerche Farmacologiche Mario Negri (IRFMN), Italy 7 Swedish Clinical Research Infrastructures Network (SweCRIN), Sweden 8 Spanish Clinical Research Network (SCReN), Spain 9 Fonds de Recherche en Santé du Québec-Gereq (FRSQ-GEREQ), Canada 10 European Forum for Good Clinical Practice (EFGCP) MEETING REPORT Int J Pharm Med 2005; 19 (1): 43-45 1364-9027/05/0001-0043/$34.95/0

American Society of Clinical Oncology: Advancing the Science of Clinical Oncology; 13???17 May 2005; Orlando, Florida, USA

Abstract: The annual meeting of the American Society of Clinical Oncology (ASCO) was an international 5-day event that attracted in excess of 29 000 delegates from the field of oncology. This year’s theme – ‘Advancing the Science of Clinical Oncology’ – was a reflection of the ground-breaking research that has been conducted in the field of oncology in the last few years and placed great emphasis on the importance of targeted therapies, molecular diagnostics, genomics and proteomics – specialties that are rapidly becoming an essential component in the daily practice of clinical oncologists. Great strides have also been made in the three most common cancers, breast, lung and colorectal, as well as promising data presented in cancers that have to date offered a poor prognosis to patients, such as prostate and pancreatic cancer. Such was the volume of first-class research covered at this year’s meeting that rather than the traditional single plenary session, delegates were invited to attend three such sessions, to cover presentations that the ASCO Scientific Program Committee considered to have practice-changing consequences.1 Generally hailed as the most exciting session at this year’s meeting was a late addition to the ASCO programme, added just two weeks before the event. The ‘Advances in Monoclonal Antibody Therapy for Breast Cancer’ session ended with a standing ovation from the audience in recognition of the exciting new developments and impressive results that were presented.

The Placebo Effect and the Pharmaceutical Industry

Abstract: The placebo effect has long been recognised in medical practice and numerous definitions of the placebo effect and its cause have been proposed. While having a significant impact on study design, it can also be of such a magnitude that pivotal trials demonstrating the superiority of a drug over placebo are difficult to achieve. This review discusses the factors contributing to the placebo response and why it is such an important consideration for the pharmaceutical industry when designing drug studies. The ethical use of placebos will also be considered, with particular reference to the Declaration of Helsinki and the rights of an individual against the rights of a study population as a whole.

Drug counterfeiting : The current situation and prevention strategies for the future

Abstract: Recent literature suggests that drug counterfeiting is not just a national but also an international concern, affecting health policy makers, drug manufacturers, wholesalers, drug enforcement agents, healthcare providers and patients across the globe. It is also clear that counterfeiting is not limited to the least developed nations but is increasingly prevalent in the largest pharmaceutical markets. Like the problem itself, the response to counterfeiting has gained credence at an international level, specifically with the World Health Organization's development of a global anticounterfeiting strategy. Governments too have begun to focus on the issue and industry leaders are now utilising new technologies against the counterfeiters. Specifically, the increasing use of radiofrequency identification tagging systems holds significant promise for the reduction of counterfeit drugs in the future.

The Influence of the Health Committee Report

Abstract: The UK House of Commons Health Committee’s report on The Influence of the Pharmaceutical Industry was published on 5 April 2005, the same day an election was called.[1] This wideranging report of 124 pages represents the first time that UK politicians have conducted an enquiry in the pharmaceutical arena since 1914. The previous report was published on the day Britain declared war (4 August) and the First World War thereby scuppered proposals for statutory drug regulation until the 1960s. Presumably the timing of the election will also have a detrimental effect on the influence of this work because the new government is unlikely to regard this area as a political priority. The most striking aspect of the report is the wide scope of its conclusions and recommendations. Here I will consider only regulation and postmarketing safety, on which the report has much to say. Conclusion/recommendation no. 13 states that “post-marketing surveillance in the UK is inadequate”. This is a surprising statement to find in a report so entitled. How and why did this group reach such a conclusion? The report’s summary criticises the UK regulatory authority, the Medicines and Healthcare Products Agency (MHRA), in general terms as being “too close to industry” but provides no coherent link from this to the Committee’s conclusion on postmarketing surveillance. The basis of the putative closeness revolves partly around the financial basis of the Agency (with funding entirely from fees charged to industry) and partly around behaviours which it seems odd to criticise, such as consultation. There is also specific mention of an interchange of staff, the absence of which would hamper the emerging discipline of pharmaceutical medicine. The Committee’s solution for the “failings of the MHRA” is a fundamental review of the organisation. They acknowledged a review by the National Audit Office in 2003[2] but regarded that as “expressly designed to assess public expenditure aspects of the work”. When considering postmarketing surveillance, the Committee focused on two recently highlighted important safety issues – COX-2 inhibitors and cardiovascular adverse events[3] (erroneously described as “heart failure”) and SSRIs and suicide.[4] Essentially, the Committee heard vocal critics of the regulators who were then put into a position of needing to defend themselves. At no stage did the Committee take a view of the regulatory performance of the MHRA in relation to other agencies around the world. They, therefore, did not recognise that any failings represent broader inadequacies in relation to systems of regulation and the underpinning science. Even more conspicuous was the absence of any detailed consideration of the European dimension to medicines regulation. In this respect the Committee only expressed concern in relation to the MHRA’s “need to compete with other European regulators for licence application business”. Apparently someone on the Committee took the trouble to visit Australia, but taking the Jubilee line to Canary Wharf to visit the European Medicines Agency would have been a much shorter and a more relevant journey. The yellow card system for spontaneous adverse drug reaction (ADR) reporting[5] comes in for particular criticism and is described as “worthless” and a “bit of a pup”. The report gives some recognition of the main purpose of the scheme (the detection of unrecognised hazards) but does not seem to take it properly into account. Again, a lack of consideration of international comparisons is conspicuous. The main solution proposed for the perceived problems with the scheme – patient reporting – may be politically expedient but no evidence in support of its value in detecting hazards is cited. Remarkably, the report states that “only 19 drugs have been withdrawn between 1993 and 2004” as though this was a measure of the ineffectiveness of the regulator. The Committee specifically suggested that MHRA should “investigate options for the development of more effective post-marketing surveillance systems” without recognising that the Agency has fairly recently done just that.[6] In this respect, their investigation contrasts with the National Audit Office whose report[2] they dismissed as being primarily financial. The Committee’s recommendations may be summarised as suggesting the need for more resources, more studies and greater separation of licensing and postmarketing activities. There are also hints that greater regulatory powers in this area might be needed. In summary, political consideration of a very broad issue (industry influence) has become substantially sidetracked into a largely unrelated but topical area (postmarketing safety regulation). Unfortunately this report fails to understand the real limitations of the existing system or appreciate the current international context. Rather it seems to have been driven by the hobby horses of critics. Paradoxically, in spite of their report’s conclusions often being incoherent, the Committee’s main recommendations in relation to postmarketing surveillance are reasonable.