1,721,337 research outputs found
The daily diary and the questionnaire are not equivalent for the evaluation of bowel habits
Full text linkCOLLABORATOR ITALIAN CONSTIPATION STUDY GROUP:
Bellini M, Biagi S, Costa F, De Bortoli N, Gambaccini D, Mammini C, Mumolo MG, Ricchiuti A, Marchi S, Bove A, Balzano A, Sormani MP, Bruzzi P, Battaglia E, Niola P, Verna C, Grassini M, Bocchini R, Cimatti M, Fornasari L, Montaletti I, Pazzi P, Alduini P, Berni I, Ceccarelli G, Bassotti G, Corazzi N, Morozzi B, Viegas LB, Pucciani F, Giani I, Ringressi N
Incremental advance or seismic shift? The need to raise the bar of efficacy for drug approval
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MRI lesions as a surrogate for relapses in multiple sclerosis: a meta-analysis of randomised trials
No full textBackground A meta-analysis of randomised trials in relapsing-remitting multiple sclerosis published in 2009 showed
a quantitative relation between the treatment effects detected on MRI lesions and clinical relapses. We aimed to
validate that relation using data from a large and independent set of clinical trials in multiple sclerosis.
Methods We searched Medline for clinical trials that assessed disease-modifying drugs for relapsing-remitting
multiple sclerosis published from Sept 1, 2008, to Oct 31, 2012. We extracted data for the treatment effects on MRI
lesions and on relapses from each trial, and the correlation of log transformed relative measures of these treatment
effects was assessed with a weighted linear regression analysis. The R2 value was estimated to quantify the strength
of the correlation, and we used an interaction test to test for a difference in slope from the previously estimated
equation. We also ran several sensitivity analyses.
Findings We identified 31 eligible trials, which provided data for 18 901 patients with relapsing-remitting multiple
sclerosis. The regression equation derived using data from these studies showed a relation between the concurrent
treatment effects on MRI lesions and relapses (slope=0·52; R2=0·71), much the same as was previously estimated
(pinteraction=0·45). Analysis of trials that tested the same drugs in phase 2 and phase 3 studies showed that the effects on
MRI lesions over short follow-up periods (6–9 months) can also predict the effects on relapses over longer follow-up
periods (12–24 months), with reported effects on relapses that were within the 95% prediction intervals in eight of
nine trials.
Interpretation Our findings indicate that the effect of a treatment on relapses can be accurately predicted by the effect of
that therapy on MRI lesions, implying that the use of MRI markers as primary endpoints in future clinical trials of
treatments for multiple sclerosis can be considered, in specific situations, such as in trials testing generics or biosimilars
of drugs with a well known mechanism of action or in paediatric trials testing drugs already approved for adults
Evaluation and management of hyperlipidemia in children and adolescents.
No full textPurpose of review. To review the recent findings on evaluation and management of dyslipidemia in childhood and adolescence, giving a critical view on new therapeutic approaches.Recent findings. In 2008, the American Academy of Pediatric released an updated policy statement recommending more frequent screening to detect dyslipidemia in childhood and the first-line use of statins in children with dyslipidemia who did not respond to lifestyleintervention and who were more than 8 years of age. These recommendations have caused a lot of controversy within the medical community and media. This debate is also sharpened by the fact that only few trials have investigated the long-term efficacy of statins on prevention of adult cardiovascular disease, their application indyslipidemias other than familial hypercholesterolemia and the use of new pharmacological tools.The purpose of our paper could not be achieved clearly without a review of the physiology of cholesterol metabolism together with an analysis of causes of primary and secondary dyslipidemia affecting children. Moreover, recent knowledge on lipid lowering therapy is reviewed
Molecular epidemiology: New rules for new tools?
No full textMolecular epidemiology combines biological markers and epidemiological observations in the study of the environmental and genetic determinants of cancer and other diseases. The potential advantages associated with biomarkers are manifold and include: (a) increased sensitivity and specificity to carcinogenic exposures; (b) more precise evaluation of the interplay between genetic and environmental determinants of cancer; (c) earlier detection of carcinogenic effects of exposure; (d) characterization of disease subtypes-etiologies patterns; (e) evaluation of primary prevention measures. These, in turn, may translate into better tools for etiologic research, individual risk assessment, and, ultimately, primary and secondary prevention. An area that has not received sufficient attention concerns the validation of these biomarkers as surrogate endpoints for cancer risk. Validation of a candidate biomarker's surrogacy is the demonstration that it possesses the properties required for its use as a substitute for a true endpoint. The principles underlying the validation process underwent remarkable developments and discussion in therapeutic research. However, the challenges posed by the application of these principles to epidemiological research, where the basic tool for this validation (i.e., the randomized study) is seldom possible, have not been thoroughly explored. The validation process of surrogacy must be applied rigorously to intermediate biomarkers of cancer risk before using them as risk predictors at the individual as well as at the population level. © 2006 Elsevier B.V. All rights reserved
An approach to the design and implementation of clinical trials of empirical antibiotic therapy in febrile and neutropenic cancer patients
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Key drivers of innovativeness appraisal for medicines: The Italian experience after the adoption of the new ranking system
No full textObjective In 2017, the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) introduced a standardised process to appraise innovativeness of medicines. Innovative medicines are provided speeder market access and dedicated funds. Innovativeness criteria are: unmet therapeutic need, added therapeutic value and quality of the evidence (Grading of Recommendations Assessment, Development and Evaluation method). We investigated the role played by these three criteria on the final decision aimed to understand how the new Italian innovativeness appraisal framework was implemented. Design A desk research gathered AIFA's appraisal reports on innovativeness and data analyses were conducted. No patients were directly involved in this study. Setting and participants We scrutinised all 77 appraisal reports available on AIFA's website (2017-2020). Primary and secondary outcome measures The impact of the three domains on final decision was investigated through a series of univariate analyses. Results Among 77 appraisal reports on innovativeness available, 49 (64%) and 28 (36%) were for oncology and non-oncology medicines, respectively. The appraisals were equally distributed among 'fully innovative' (36%), 'conditionally innovative' (30%) and 'not innovative' (34%). Added therapeutic value was the most important driver on innovativeness decision, followed by quality of the evidence. Drugs for rare diseases and with paediatric/mixed indications were appraised 'innovative' by a larger proportion, but no statistical significance was found. Conclusions Despite some limitations, including the moderate number of appraisals, this paper provides an insight into the determinants of innovativeness appraisals for medicines in Italy and the accuracy of the appraisal process. This has important implications in terms of transparency and accountability in the prioritisation process applied to innovative medicines
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