30,239 research outputs found
Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation
Objectives:
To evaluate the clinical and costeffectiveness
of capecitabine and tegafur with uracil
(UFT/LV) as first-line treatments for patients with
metastatic colorectal cancer, as compared with 5-
fluorouracil/folinic acid (5-FU/FA) regimens.
Data sources: Electronic databases, reference lists of
relevant articles and sponsor submissions were also
consulted.
Review methods:
Systematic searches, selection
against criteria and quality assessment were performed
to obtain data from relevant studies. Costs were
estimated through resource-use data taken from the
published trials and the unpublished sponsor
submissions. Unit costs were taken from published
sources, where available. An economic evaluation was
undertaken to compare the cost-effectiveness of
capecitabine and UFT/LV with three intravenous 5-
FU/LV regimens widely used in the UK: the Mayo, the
modified de Gramont regimen and the inpatient de
Gramont regimens.
Results:
The evidence suggests that treatment with
capecitabine improves overall response rates and has
an improved adverse effect profile in comparison with
5-FU/LV treatment with the Mayo regimen, with the
exception of hand–foot syndrome. Time to disease
progression or death after treatment with UFT/LV in
one study appears to be shorter than after treatment
with 5-FU/LV with the Mayo regimen, although it also
had an improved adverse effect profile. Neither
capecitabine nor UFT/LV appeared to improve healthrelated
quality of life. Little information on patient
preference was available for UFT/LV, but there was
indicated a strong preference for this over 5-FU/LV.
The total cost of capecitabine and UFT/LV treatments
were estimated at £2111 and £3375, respectively,
compared with the total treatment cost for the Mayo
regimen of £3579. Cost estimates were also presented
for the modified de Gramont and inpatient de Gramont
regimens. These were £3684 and £6155, respectively.
No survival advantage was shown in the RCTs of the
oral drugs against the Mayo regimen. Cost savings of
capecitabine and UFT/LV over the Mayo regimen were
estimated to be £1461 and £209, respectively. Drug
acquisition costs were higher for the oral therapies
than for the Mayo regimen, but were offset by lower
administration costs. Adverse event treatment costs
were similar across the three regimens. It was inferred
that there was no survival difference between the oral
drugs and the de Gramont regimens. Cost savings of
capecitabine and UFT/LV over the modified de
Gramont regimen were estimated to be £1353 and
£101, respectively, and over the inpatient de Gramont
regimen were estimated to be £4123 and £2870,
respectively.
Conclusions:
The results show that there are cost
savings associated with the use of oral therapies. No
survival difference has been proven between the oral
drugs and the Mayo regimen. In addition, no evidence
of a survival difference between the Mayo regimen and
the de Gramont regimens has been identified.
However, improved progression-free survival and an
improved adverse event profile have been shown for
the de Gramont regimen over the Mayo regimen.
Further research is recommended into the following
areas: quality of life data should be included in trials of
colorectal cancer treatments; the place of effective oral
treatments in the treatment of colorectal cancer, the
safety mechanisms needed to ensure compliance and
the monitoring of adverse effects; the optimum
duration of treatment; the measurement of patient
preference; and a phase III comparative trial of
capecitabine and UFT/LV versus modified de Gramont
treatment to determine whether there was any survival
advantage and to collate the necessary economic data
Using transcriptomics to guide lead optimization in drug discovery projects : lessons learned from the QSTAR project
The pharmaceutical industry is faced with steadily declining R&D efficiency which results in fewer drugs reaching the market despite increased investment. A major cause for this low efficiency is the failure of drug candidates in late-stage development owing to safety issues or previously undiscovered side-effects. We analyzed to what extent gene expression data can help to de-risk drug development in early phases by detecting the biological effects of compounds across disease areas, targets and scaffolds. For eight drug discovery projects within a global pharmaceutical company, gene expression data were informative and able to support go/no-go decisions. Our studies show that gene expression profiling can detect adverse effects of compounds, and is a valuable tool in early-stage drug discovery decision making
Health technology assessment of pathogen reduction technologies applied to plasma for clinical use
Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains.Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed
Early Detection of Adverse Drug Reaction Signals by Association Rule Mining Using Large-Scale Administrative Claims Data
INTRODUCTION: Adverse drug reactions (ADRs) are a leading cause of mortality worldwide and should be detected promptly to reduce health risks to patients. A data-mining approach using large-scale medical records might be a useful method for the early detection of ADRs. Many studies have analyzed medical records to detect ADRs; however, most of them have focused on a narrow range of ADRs, limiting their usefulness. OBJECTIVE: This study aimed to identify methods for the early detection of a wide range of ADR signals. METHODS: First, to evaluate the performance in signal detection of ADRs by data-mining, we attempted to create a gold standard based on clinical evidence. Second, association rule mining (ARM) was applied to patient symptoms and medications registered in claims data, followed by evaluating ADR signal detection performance. RESULTS: We created a new gold standard consisting of 92 positive and 88 negative controls. In the assessment of ARM using claims data, the areas under the receiver-operating characteristic curve and the precision-recall curve were 0.80 and 0.83, respectively. If the detection criteria were defined as lift > 1, conviction > 1, and p-value < 0.05, ARM could identify 156 signals, of which 90 were true positive controls (sensitivity: 0.98, specificity: 0.25). Evaluation of the capability of ARM with short periods of data revealed that ARM could detect a greater number of positive controls than the conventional analysis method. CONCLUSIONS: ARM of claims data may be effective in the early detection of a wide range of ADR signals
Chapter Evolving Roles of Spontaneous Reporting Systems to Assess and Monitor Drug Safety
This chapter aims to describe current and emerging roles of spontaneous reporting systems (SRSs) for assessing and monitoring drug safety. Moreover, it offers a perspective on the near future, which entails the so-called era of Big Data, keeping in mind both regulator and researcher viewpoints. After a panorama on key data sources and analyses of post-marketing data of adverse drug reactions, a critical appraisal of methodological issues and debated future applications of SRSs will be presented, including the exploitation and challenges in evidence integration (i.e., merging and combining heterogeneous sources of data into a unique indicator of risk) and patient’s reporting via social media. Finally, a call for a responsible use of these studies is offered, with a proposal on a set of minimum requirements to assess the quality of disproportionality analysis in terms of study conception, performing and reporting
The cultural psychology of obesity: diffusion of pathological norms from Western to East Asian societies
We examine the accelerating worldwide obesity epidemic using a mathematical model relating a cognitive hypothalamic-pituitary-adrenal axis tuned by embedding cultural context to a signal of chronic, structured, psychosocial threat. The obesity epidemic emerges as a distorted physiological image of ratcheting social pathology involving massive, policy-driven, economic and social 'structural adjustment' causing increasing individual, family, and community insecurity. The resulting, broadly developmental, disorder, while stratified by expected divisions of class, ethnicity, and culture, is nonetheless relentlessly engulfing even affluent majority populations across the globe. The progression of analogous epidemics in affluent Western and East Asian socieities is particularly noteworthy since these enjoy markedly different cultural structures known to influence even such fundamental psychophysical phenomena as change blindness. Indeed, until recently population patterns of obesity were quite different for these cultures. We attribute the entrainment of East Asian societies into the obesity epidemic to the diffusion of Western socioeconomic practices whose imposed resource uncertainties and exacerbation of social and economic divisions constitute powerful threat signals. We find that individual-oriented 'therapeutic' interventions will be largely ineffective since the therapeutic process itself (e.g. relinace on drug treatments) embodies the very threats causing the epidemic
Evolving Roles of Spontaneous Reporting Systems to Assess and Monitor Drug Safety
This chapter aims to describe current and emerging roles of spontaneous reporting systems (SRSs) for assessing and monitoring drug safety. Moreover, it offers a perspective on the near future, which entails the so-called era of Big Data, keeping in mind both regulator and researcher viewpoints. After a panorama on key data sources and analyses of post-marketing data of adverse drug reactions, a critical appraisal of methodological issues and debated future applications of SRSs will be presented, including the exploitation and challenges in evidence integration (i.e., merging and combining heterogeneous sources of data into a unique indicator of risk) and patient’s reporting via social media. Finally, a call for a responsible use of these studies is offered, with a proposal on a set of minimum requirements to assess the quality of disproportionality analysis in terms of study conception, performing and reporting
- …