Dose-Levels and First Signs of Efficacy in Contemporary Oncology Phase 1 Clinical Trials

PURPOSE: Phase 1 trials play a crucial role in oncology by translating laboratory science into efficient therapies. Molecular targeted agents (MTA) differ from traditional cytotoxics in terms of both efficacy and toxicity profiles. Recent reports suggest that higher doses are not essential to produce the optimal anti-tumor effect. This study aimed to assess if MTA could achieve clinical benefit at much lower dose than traditional cytotoxics in dose seeking phase 1 trials. PATIENTS AND METHODS: We reviewed 317 recent phase 1 oncology trials reported in the literature between January 1997 and January 2009. First sign of efficacy, maximum tolerated dose (MTD) and their associated dose level were recorded in each trial. RESULTS: Trials investigating conventional cytotoxics alone, MTA alone and combination of both represented respectively 63.0% (201/317), 23.3% (74/317) and 13.7% (42/317) of all trials. The MTD was reached in 65.9% (209/317) of all trials and was mostly observed at the fifth dose level. First sign of efficacy was less frequently observed at the first three dose-levels for MTA as compared to conventional cytotoxics or combinations regimens (48.3% versus 63.2% and 61.3%). Sign of efficacy was observed in the same proportion whatever the treatment type (73-82%). MTD was less frequently established in trials investigating MTA alone (51.3%) or combinations (42.8%) as compared to conventional cytotoxic agents (75.6%). CONCLUSION: First sign of efficacy was less frequently reported at the early dose-levels and MTD was less frequently reached in trials investigating molecular targeted therapy alone. Similar proportion of trials reported clinical benefit

Autosoins et raisonnement informatisé : vers un nouvel usage des normes

La prise de décisions en médecine prend en compte de nombreux paramètres (symptômes, environnement, histoire de la maladie, données anatomiques, mesures biométriques et biologiques, etc.) relevés sur des individus ou des populations. Ces paramètres sont intégrés et traités pour servir une décision. La décision médicale peut procéder d’un raisonnement purement empirique, de l’utilisation d’une table statistique, ou s’appuyer sur un algorithme informatisé (système expert d’aide à la décision). ..

Un patrimoine scientifique exceptionnel : le fonds manuscrit Claude Bernard passe au numérique

Le fonds Claude Bernard, légué par voie testamentaire à Arsène d’Arsonval et transmis au Collège de France en 1949, rassemble près de 23 000 pages, désormais accessibles en ligne. Penser, classer, numériser D'un point de vue chronologique, le fonds comprend des notes prises au cours de l’hiver 1838-1939 (alors que Bernard était étudiant) et un cahier complété peu avant sa mort, en 1878. Toutefois cet ensemble ne possède ni « début », ni « fin » identifiés comme tels par son auteur, car Bernar..

Risques cardiovasculaires du tabagisme : reconnaissance tardive d’une épidémie non jugulée

Pierre CorvolProfesseur au Collège de France DR Nicolas Postel-VinayMédecin, unité d’hypertension artérielle, hôpital européen Georges Pompidou © P. Imbert, Collège de France Le tabac nuit gravement à la santé. Cette affirmation figurant sur les paquets de cigarettes s’impose comme une évidence. Mais il n’en a pas toujours été ainsi. Par le passé, les dangers liés à la consommation de tabac ont été longtemps ignorés voir coupablement minimisés. En 1997, Geoffrey Bible, Président de Philip Mo..

Observance et nouvelles technologies : nouveau regard sur une problématique ancienne

En médecine, l’un des intérêts des nouvelles techniques de l’information et de la communication réside dans l’efficacité et la sécurité des traitements, sans méconnaître le fait que tous les patients ne pourront pas bénéficier de ces techniques, faute de pouvoir les maîtriser

Intérêt et pratique de l'automesure tensionnelle dans la prise en charge des patients hypertendus en médecine générale (Enquêtes de pratique et d'évaluation de l'éducation auprès des patients, enquête d'opinion auprès des médecins généralistes d'Alsace, mise en place de moyens pour améliorer la pratique)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Home blood pressure measurement and digital health : communication technologies create a new context

Ambulatory blood pressure (BP) monitoring is encouraged by all international guidelines for the management of hypertension. Home BP monitoring is the preferred method of the patients. Automated BP devices with remote data transmission have been repeatedly shown to be useful in improving hypertension control in the frame of clinical trials on telemedicine. Recently, new technologies have created a new context. Despite the important number of smartphone apps devoted to BP developed these last 10 years, only two BP monitoring apps refer to the European Society of Hypertension (ESH) Guidelines and have been published in peer-reviewed journals: Hy-Result and ESH CARE. At present, the absence of close collaboration between start-up engineers and healthcare professionals is a risk for patient safety. Therefore, health professionals must become actors in the so-called digital health revolution

Automated interpretation of home blood pressure assessment (Hy-Result software) versus physician’s assessment : a validation study

OBJECTIVE: Hy-Result is the first software for self-interpretation of home blood pressure measurement results, taking into account both the recommended thresholds for normal values and patient characteristics. We compare the software-generated classification with the physician's evaluation. DESIGN METHOD: The primary assessment criterion was whether algorithm classification of the blood pressure (BP) status concurred with the physician's advice (blinded to the software's results) following a consultation (n=195 patients). Secondary assessment was the reliability of text messages. RESULTS: In the 58 untreated patients, the agreement between classification of the BP status generated by the software and the physician's classification was 87.9%. In the 137 treated patients, the agreement was 91.9%. The κ-test applied for all the patients was 0.81 (95% confidence interval: 0.73-0.89). After correction of errors identified in the algorithm during the study, agreement increased to 95.4% [κ=0.9 (95% confidence interval: 0.84-0.97)]. For 100% of the patients with comorbidities (n=46), specific text messages were generated, indicating that a physician might recommend a target BP lower than 135/85 mmHg. Specific text messages were also generated for 100% of the patients for whom global cardiovascular risks markedly exceeded norms. CONCLUSION: Classification by Hy-Result is at least as accurate as that of a specialist in current practice (http://www.hy-result.com)

Home blood pressure monitoring and e-Health: investigation of patients' experience with the Hy-Result system

International audienceBackground: Hy-Result is a validated system designed to help patients complying with the home blood pressure monitoring (HBPM) protocol and understanding their blood pressure (BP) readings. It is available as a standalone web application or within a wireless BP monitor app. Objective: The aim of the study was to explore patients' experience with Hy-Result. Methods: Online survey completed by 512 users of the Hy-Result web application or monitor app, and three focus groups with 24 hypertensive patients who monitor their BP at home and use the Hy-Result web application to record their data. We assessed the experience of patients with the functionalities and medical content of Hy-Result, their feelings and expectations, and the impact of Hy-Result on the physician-patient relationship. Results: (1) Functionalities: Over 90% of survey respondents and all focus group participants found Hy-Result easy to use. The main drawback of the web application is the need to manually enter all BP values at once. (2) Medical content: Hy-Result offers information on arterial hypertension and HBPM that most patients found useful. Users found that Hy-Result triggers appropriate reactions to BP readings, including adequately timed general practitioner visits. (3) Feelings and expectations: Over 90% of survey respondents trust Hy-Result and focus group participants understood that text messages are suggestions, not diagnoses. Hy-Result did not cause anxiety or excessive BP measurements. (4) Physician-patient relationship: Three-quarter of survey respondents agreed that Hy-Result may help when talking with their doctor about their BP values but only one-third of those have shown the report to their physician. For focus group participants, using Hy-Result should ideally be a physician prescription. They were aware that Hy-Result does not replace clinical judgment and that physicians still have a decisive role in BP management. Conclusion: Most of the users described Hy-Result as an easy-to-use and useful tool. Patients are willing to use it on physician request