Biomedical subjects

Giens XVII

Publications and source records attributed to Giens XVII.

6 recordsLinked to original sources

PubMedDate not supplied

[Methodology and long-term follow-up of drug induced side effects in children (cancer, leukemia, AIDS, growth hormone)].

Long-term follow up for medicines used in children is necessary in some therapeutic areas. Long-term effects (e.g. in cancer) may be detected many years after the treatment period. Growth, development and maturation specific to children can make these effects particularly harmful. The development plan of a paediatric drug should include, long term follow up on the basis of pharmacological-toxicological and safety data. These aspects should be taken into account when modifying the protocol (lower dosage, withdrawal of some associations etc). The follow up period may be very long, as in cancer (e.g. second tumour after treatment for cancer). A cohort is the best choice for this follow up, but other alternatives may be useful, including a specific follow-up Unit. Long-term follow-up is nevertheless difficult and expensive, manpower-dependent and the risk of failure is great especially in the teenage years.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

[Identification, during development, of a methodology targeted at determining the positioning of new drugs for therapeutic strategies: examples of rheumatoid arthritis and cardiac insufficiency].

The Marketing Authorization (MA) granted to a new molecular entity does not allow for proper anticipation of its future positioning within the therapeutic strategy. A specific methodology should be devised as early as during the pre-MA development phase that could result in an initial positioning that should be subjected to further reappraisal with regard to scientific advances, the arrival of new treatments and further developments with this molecule. A methodology is thus proposed, based on early optimisation of the development plan, the granting of subsequent MAs, and reappraisal of the positioning within the strategy, based on analysis of all available data. It should be possible to take into account the economic context, within an agreed system with pre-defined medico-economic criteria. This may in turn raise the issue of the role of the various parties involved in this assessment, as well as how to understand the respective opinions of stakeholders: authorities, sponsors, prescribers and patients, each of whom has a specific view of the definition of the strategic objective that should apply to the disease concerned.

Arthritis, Rheumatoid↗

PubMedDate not supplied

[Good clinical practice in clinical trials: training clinicians,incentives to apply good clinical practice and assessment of compliance].

Fourteen years after the concept was created, it seemed important to assess how well investigators actually apply Good Clinical Practice. Various sources of information have revealed a general deficiency in their application: "investigation by the working group, Afssaps (French Agency for the Safety of Health-Care Products) inspections, industrial data". The deficiencies identified stem from different factors: lack of professionalization, lack of training, lack of motivation, the large numbers of poorly conducted studies. The working group drew up proposals intended to improve the training of investigators, to dissuade investigators from pursuing inadequate procedure and to verify the level of compliance. However in this respect, the investigator is not the only one at fault. Improved practice unavoidably requires better assistance on the part of the sponsors, more consistent supervision of monitoring, and greater vigilence by the authorities involved in the control and use of trials.

Clinical Trials as Topic↗

PubMedDate not supplied

[Role of pharmacokinetic-pharmacodynamic relationships in drug development].

An important part of drug development relies on the analysis of the relationships between drug doses and therapeutic and/or side effects. This analysis implies an in-depth understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of the drug and of the relationship which links them (PK-PD relationship). The aim of this round table was to define the place of the study of PK-PD relationships in drug development. After reviewing the definitions of PK models, PD models, and of integrated PK-PD models, the article highlights the importance of studying the PK-PD relationship during the successive phases of drug development (pre-clinical, phase I/II, phase III) and in specific populations (children, elderly people). A number of examples taken from pharmaceutical development or international literature are given. They show the methodology used and the type of information which can be drawn at each step of drug development. The article also presents the difficulties which prevent a more systematic application of this kind of approach during drug development. Scientific limits, problems in relation with the misunderstanding of the approach both in academic institutions and in pharmaceutical companies, and difficulties related to the lack of specific guidelines are discussed. The conclusion emphasizes the importance of using PK-PD modeling all along drug development and presents a number of actions which could further broaden its use.

Clinical Trials as Topic↗

PubMedDate not supplied

[Clinical trials in oncology: specific methodology problems].

Clinical benefit in oncology patients can only be derived from coordinated and successive experimental trials. The following consensus thus emerged from the working party: The assessment of tolerance during clinical trials requires the actuarial rate of acute adverse events (AE) to be registered and the development of epidemiological structures involved in long-term assessment of AE. Experimental trials have to be assessed according to descriptive epidemiological data (generated in France and Europe) and completed with observational studies on post-marketing medical practice. The principle of an a priori authorization given by the Afssaps for gene and cell therapy trials was legalised in October 2001. The working group spoke strongly in favour of authorizing early trials only validating the process, and for reasonable objectives in terms of viral security assessment of annex therapeutic products. With regard to the development of new antiproliferative agents, the active dose (or optimal biological dose) replaces the maximal tolerable dose. Early efficacy criteria could be biological and specific. With cumulative subacute rather than acute toxicity, these agents can not be properly evaluated with a short term benefit/risk ratio as is done for cytotoxic drugs. Elderly people constitute a fragile, heterogeneous and increasing population, in whom adequate assessment of anticancer agents is mandatory. It is important to promote controlled clinical trials in children and to systematically monitor them over a very long period of time. Only rare tumours may be considered as orphan situations. Finally, a list of all clinical trials conducted in oncology should be made by the Afssaps, with the help of the FNLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) who have already begun this work.

Antineoplastic Agents↗

PubMedDate not supplied

[Compliance, efficacy and quality of life].

Compliance is the appropriateness of patient behaviour to therapeutic prescriptions. Good compliance increases treatment efficacy although its constraints may harm quality of life. Factors affecting compliance are related to the patient, the disease, health-care workers, family and treatment itself. Psycho-sociologic theories have attempted to explain patient behaviour. In clinical trials, compliance has to be optimized, i.e. in the protocol, during the study and the statistical analysis. In real life, compliance concerns all those involved in health-care, particularly for education, training and motivation of the patients and their immediate environment. Observational surveys relating to compliance are needed to determine prioriites and to develop a "compliance approach" based on improving information and the use of tools for better therapeutic adherence. Evaluation of the quality of life and patient satisfaction aspects is necessary to validate this approach.

Drug Therapy↗