RESUMEN
Chronic myelogenous leukaemia (CML) results from the Bcr-Abl oncoprotein, which has a constitutively activated Abl tyrosine kinase domain. Although most chronic phase CML patients treated with imatinib as first-line therapy maintain excellent durable responses, patients who have progressed to advanced-stage CML frequently fail to respond or lose their response to therapy owing to the emergence of drug-resistant mutants of the protein. More than 40 such point mutations have been observed in imatinib-resistant patients. The crystal structures of wild-type and mutant Abl kinase in complex with imatinib and other small-molecule Abl inhibitors were determined, with the aim of understanding the molecular basis of resistance and to aid in the design and optimization of inhibitors active against the resistance mutants. These results are presented in a way which illustrates the approaches used to generate multiple structures, the type of information that can be gained and the way that this information is used to support drug discovery.
Asunto(s)
Antineoplásicos/farmacología , Química Farmacéutica/métodos , Diseño de Fármacos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Animales , Sitios de Unión , Cristalización , Cristalografía por Rayos X , Industria Farmacéutica/métodos , Humanos , Modelos Químicos , Modelos Genéticos , Modelos Moleculares , Conformación Molecular , Mutación PuntualRESUMEN
OBJECTIVES: Since 1997, members of the International Network of Agencies for Health Technology Assessment (INAHTA) have collaborated on a Joint Project to track the diffusion, evaluation, and clinical policy of positron emission tomography (PET). Part 2 of this updated Joint Project report summarizes HTA-based strategies for directing the clinical use of PET and a discussion on the value of HTA in managing the diffusion of high cost diagnostic technologies, which were presented at an INAHTA-sponsored workshop at the Health Technology Assessment International Annual Meeting in 2004 on strategies for managing high cost diagnostic technologies. METHODS: A summary of the workshop proceedings is presented. CONCLUSIONS: Sharing assessment work, universal agreement in assessment conclusions, stakeholder input, and modeling techniques help manage the uncertainty in the evidence base while targeting clinical use of PET toward the most promising indications. Emphasis on HTA findings, linkage between financing of clinical PET and outcome evaluation, and targeted dissemination of scientific findings empower providers to reduce unnecessary utilization and contain costs within a quality improvement framework. Above all, a trustworthy source of HTA information and a process that is conducive to using scientific evidence as the basis for decision making are essential for managing the diffusion of complex and costly diagnostic technologies in patient care.
Asunto(s)
Difusión de Innovaciones , Tomografía de Emisión de Positrones/instrumentación , Evaluación de la Tecnología Biomédica/organización & administración , Financiación del Capital/organización & administración , Política de Salud , Humanos , Cooperación Internacional , Tomografía de Emisión de Positrones/economíaRESUMEN
The German Betäubungsmittelverschreibungsverordnung BtmVV (prescription regulation of narcotics), 5 part 2, 01 July 2001 commissioned the German Medical Association to establish guidelines on methadone maintenance therapy according to the medical-scientific state of the art. A joint commission of the German Medical Association and the National Association of Statutory Health Insurance Physicians developed guidelines for substitution therapy of opiate dependence which were adopted by the board of the German Medical Association in March 2002 and were published in the Deutsche Arzteblatt in May 24, 2002. The present study is a systematic review of the scientific literature on successful treatment in general, as well as on particular aspects of methadone substitution therapy considered by the German Medical Association's guidelines. The literature was updated until January 2004. Older randomised controlled trials and more recent quasi-experimental studies provide evidence that methadone maintenance therapy is an effective strategy to reduce illicit drug use, to improve the health situation of drug users, to diminish criminal behaviour, and to promote rehabilitation of opiate-dependent individuals. The evaluation of international studies clearly shows that access criteria to substitution therapy beyond the diagnosis of opiate dependence, e.g. the presence of a life-threatening co-morbidity, is not a prerequisite for substitution in other countries, and therefore is not discussed in the international literature. Study evidence shows that the German Medical Association's guidelines for substitution therapy of opiate dependence reflect the best evidence available from scientific studies and apply it to the conditions of the German healthcare system.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Metadona/uso terapéutico , Pacientes Ambulatorios , Trastornos Relacionados con Sustancias/rehabilitación , Alemania , Humanos , Sociedades MédicasRESUMEN
Positron Emission Tomography (PET) has been regarded as a breakthrough technology that helps diagnoses various conditions. PET was developed in the United States during the 1960s, and has since diffused rather slowly into most modern health care systems. Germany is an exception, as here the diffusion of PET has been rapid, and more than 70 PET scanners have been installed. At present, PET scans are not included in the health care basket though they are often used and members of the statutory sickness fund frequently seek reimbursement for this technology. The Standing Committee therefore conducted a formal inquiry into the value of PET scanning in publicly funded (statutory) ambulatory health care. The Committee's decisions were based on a technology assessment of PET. This report found that PET has been approved by the German Federal Institute for Drugs and Medical Devices (BfArM) for five indications. The evidence for these five indications was compared to that for other diagnostic methods such as magnetic resonance imaging. The assessment found no convincing evidence to support the introduction of PET into statutory ambulatory health care in Germany. In April 2002 the Standing Committee consequently denied approval for the reimbursement of PET as a publicly funded diagnostic procedure.
Asunto(s)
Atención Ambulatoria , Pruebas Diagnósticas de Rutina , Tomografía Computarizada de Emisión , Alemania , Humanos , Programas Nacionales de SaludRESUMEN
The "Bundesausschuss der Aerzte und Krankenkassen" (hereafter referred to as the "Bundesausschuss") is one of Germany's self-governing bodies in ambulatory health care. This Federal Standing Committee of Physicians and Sickness Funds has the mandate, among others, to issue directives for the ambulatory health care provided by 110,000 physicians to the approximately 70 million citizens of Germany. The Bundesausschuss' directives are legally binding and must be followed by both the physicians who provide ambulatory medical services and the sickness funds who insure these services. Although elements of evidence-based medicine were first introduced in 1990, health technology assessment (HTA) was not systematically integrated into the decision making process of the working group for medical and surgical procedures until 1998. The HTA reports of the Bundesausschuss take account of the status of the technology in other health care systems (public systems in particular) and of statements by the scientific community and interested parties, such as patient groups, and review the evidence currently available (in primary studies, systematic reviews, other assessments, etc.). These reports are prepared by representatives of the physicians and the sickness funds, in close collaboration, whenever possible, with academic experts in health technology assessment. The reports serve as a basis for the decisions made by the Bundesausschuss, which ensures their impact, and are published on the Internet at http://www.kbv.de/hta. The Bundesausschuss reports also reflect the deliberation process for each technology, in the context of the legal environment. They also explain how a decision was reached. The shortcomings of HTA process are the time and financial resources required to conduct these assessment. The advantages include the increased transparency of the decision-making process, for both the German "social" court system and for the insured. Further developments will be directed by the future framing of the legal environment by the ministry of health. A similar decision-making body has recently been installed for the hospital sector and both committees will be co-ordinated by a board, which will organize the deliberation process. It will be important to further encourage and integrate the use of evidence in the decision-making processes of these statutory bodies.