C Cave

A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma

A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA Programme on behalf of NICE. The full report has been published elsewhere. This paper summarizes the results for the effectiveness of temozolomide in people with recurrent glioblastoma multiforme and anaplastic astrocytoma. The review was conducted using standard systematic review methodology involving a systematic literature search, quality assessment of included studies with systematic data extraction and data synthesis. One randomized controlled trial and four uncontrolled studies were identified for inclusion. The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from temozolomide may have been in those patients who had not received any prior chemotherapy regimens, however further randomized controlled trials are required to confirm this suggestion. Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life. Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed.

Clinical- and cost-effectiveness of pegylated interferon alfa in the treatment of chronic hepatitis C: A systematic review and economic evaluation

OBJECTIVES To assess the clinical-effectiveness and cost-effectiveness of pegylated interferon alfa (2a and 2b) combined with ribavirin in previously untreated patients with moderate to severe chronic hepatitis C, compared with the current standard treatment, which is nonpegylated interferon alfa combined with ribavirin. METHODS Systematic review and economic evaluation. A sensitive search strategy was applied to several electronic bibliographic databases. Relevant studies were critically appraised and meta-analyzed. A hypothetical cohort of 1,000 patients entered a Markov model and were followed up for a more than 30-year period to predict natural history, duration spent in each health state, and treatment costs. RESULTS Two fully published Phase III randomized controlled trials were included. Methodological quality was generally good. Dual therapy with pegylated interferon was significantly more effective than nonpegylated dual therapy with a pooled sustained virological response rate (SVR) of 55 percent (95 percent confidence interval [CI], 52-58 percent) compared with 46 percent (95 percent CI, 43-49 percent). The pooled relative risk of remaining infected was 0.83 (95 percent CI, 0.76-0.91 percent). Genotype was the strongest predictor of outcome, with SVRs in patients with the more responsive genotypes 2 and 3 reaching up to 80 percent. The incremental cost per quality-adjusted life year (QALY) for pegylated dual therapy compared with nonpegylated dual therapy was 12,123 pounds sterling. The cost per QALY remained under 30,000 pounds sterling for most patient subgroups and in sensitivity analyses. CONCLUSIONS Pegylated interferon is clinically effective, represents good value for the money, and is a significant advance in the treatment of this insidious disease.

The effects of study-task relevance on perceptual repetition priming

Repetition priming is easily elicited in many traditional paradigms, and the possibility that perceptual priming may be other than an automatic consequence of perception has received little consideration. This issue is explored in two experiments. In Experiment 1, participants named the target from a four-item category search study task more quickly than the nontarget study items at a later naming test. Experiment 2 extended this finding to conditions in which stimuli were individually presented at study. In three different study tasks, stimuli relevant to study-task completion elicited priming on a later test, but stimuli presented outside the context of a task did not. In both experiments, recognition was above chance for nonrelevant stimuli, suggesting that participants explicitly remembered stimuli that did not elicit priming. Results suggest that priming is sensitive to study-task demands and may reflect a more adaptive and flexible mechanism for modification of perceptual processing than previously appreciated.