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INTRODUCTION: Advanced gastric cancer (AGC) is one of the most common forms of cancer and remains difficult to cure. There is currently no recommended therapy for second-line AGC in the UK despite the availability of various interventions. This paper aims to compare different interventions for treatment of second-line AGC using more complex methods to estimate relative efficacy, fitting various parametric models and to compare results to those published adopting conventional methods of synthesis. METHODS: Seven studies were identified in an existing literature review evaluating seven comparators, which formed a connected network of evidence. Citations were limited to randomised controlled trials in previously-treated AGC patients. Evidence quality was assessed using the Cochrane Collaboration's tool. Studies were assessed for the availability of Kaplan-Meier curves for overall survival. Individual patient data (IPD) were recreated using digitisation software along with a published algorithm in R. The data were analysed using multi-dimensional network meta-analysis (NMA) methods. A series of parametric models were fitted to the pseudo-IPD. Both fixed and random-effects models were fitted to explore long-term survival prospects based on extrapolation methods and estimated mean survival. RESULTS: Relative efficacy estimates were compared to those previously reported, which utilised conventional NMA methods. Results presented were consistent within findings from other publications and identified ramucirumab plus paclitaxel as the best treatment; however, all the treatments assessed were associated with poor survival prospects with mean survival estimates ranging from 5.0 to 12.7 months. CONCLUSION: Whilst the approach adopted in this paper does not adjust for differences in trial patient populations and is particularly data-intensive, use of such sophisticated methods of evidence synthesis may be more informative for subsequent cost-effectiveness modelling and may have greater impact when considering an indication where observed data is particularly immature or survival prospects are more positive, which may then lead to more informative decision-making for drug reimbursement.
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INTRODUCTION: Early-onset schizophrenia (EOS) is a serious debilitating disorder with considerable morbidity and a reduced life expectancy; therefore, early diagnosis and effective treatments are particularly important. Negative symptoms are more prominent in adolescents and children (compared with adults), and are key predictors of worse functional and clinical outcomes in EOS. Therefore, this study aimed to explore the relative efficacy of antipsychotics used in the treatment of EOS, with a focus on studies reporting effectiveness using the Positive and Negative Syndrome scale (PANSS), a scale that includes an overall symptom measure, in addition to separate subscales for positive and, importantly, negative symptoms. METHODS: A systematic literature review was conducted using the MEDLINE and Cochrane Central Register of Controlled Trials databases to identify trials conducted in children and adolescents with schizophrenia, and symptom control was reported using the PANSS. A Bayesian random-effects network meta-analysis was performed, synthesising data for a number of outcomes, including mean change from baseline in PANSS scores, treatment discontinuation and weight gain. RESULTS: Eleven studies were included in the evidence synthesis, comprising 1714 patients across eight active interventions (aripiprazole, haloperidol, molindone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone) and placebo. All treatments showed a greater reduction in total PANSS scores vs placebo; however, only three interventions (molindone, olanzapine and risperidone) were associated with a statistically significant reduction in total PANSS scores at 6 weeks vs placebo. Haloperidol had the greatest reduction vs placebo; however, this result was not statistically significant [mean difference, -15.6, 95% credible interval (-35.4, 4.1)]. Haloperidol, olanzapine and risperidone showed a statistically significant reduction in positive PANSS scores vs placebo; however, whilst all interventions showed a trend of reduction in negative PANSS scores vs placebo, no comparisons were statistically significant. CONCLUSIONS: Many of the treatments are efficacious in controlling symptoms, and all showed a trend of superiority vs placebo for total, positive and negative PANSS scores, although only olanzapine and risperidone yielded statistically significant results vs placebo for both total and positive PANSS scores. Varying results for discontinuation and weight gain demonstrate a need to balance efficacy with side-effect profiles.
Subject(s)
Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Schizophrenia/drug therapy , Schizophrenic Psychology , Adolescent , Child , Humans , Psychiatric Status Rating Scales , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
INTRODUCTION: There is no consensus on how to investigate men with negative transrectal ultrasound guided prostate biopsy (TRUS-B) but ongoing suspicion of cancer. Three strategies used are transperineal (TP-B), transrectal saturation (TS-B) and MRI-guided biopsy (MRI-B). We compared cancer yields of these strategies. METHODS: Papers were identified by search of Pubmed, Embase and Ovid Medline. Included studies investigated biopsy diagnostic yield in men with at least one negative TRUS-B and ongoing suspicion of prostate cancer. Data including age, PSA, number of previous biopsy episodes, number of cores at re-biopsy, cancer yield, and Gleason score of detected cancers were extracted. Meta-regression analyses were used to analyse the data. RESULTS: Forty-six studies were included; 12 of TS-B, 14 of TP-B, and 20 of MRI-B, representing 4,657 patients. Mean patient age, PSA and number of previous biopsy episodes were similar between the strategies. The mean number of biopsy cores obtained by TP-B and TS-B were greater than MRI-B. Cancer detection rates were 30·0%, 36·8%, and 37·6% for TS-B, TP-B, and MRI-B respectively. Meta-regression analysis showed that MRI-B had significantly higher cancer detection than TS-B. There were no significant differences however between MRI-B and TP-B, or TP-B and TS-B. In a sensitivity analysis incorporating number of previous biopsy episodes (36 studies) the difference between MRI-B and TP-B was not maintained resulting in no significant difference in cancer detection between the groups. There were no significant differences in median Gleason scores detected comparing the three strategies. CONCLUSIONS: In the re-biopsy setting, it is unclear which strategy offers the highest cancer detection rate. MRI-B may potentially detect more prostate cancers than other modalities and can achieve this with fewer biopsy cores. However, well-designed prospective studies with standardised outcome measures are needed to accurately compare modalities and define an optimum re-biopsy approach.
