In existing benefit‐risk assessment (BRA) methods, benefit and risk criteria are usually identified and defined separately based on aggregated clinical data and therefore ignore the individual‐level ...differences as well as the association among the criteria. We proposed a Bayesian multicriteria decision‐making method for BRA of drugs using individual‐level data. We used a multidimensional latent trait model to account for the heterogeneity of treatment effects with latent variables introducing the dependencies among outcomes. We then applied the stochastic multicriteria acceptability analysis approach for BRA incorporating imprecise and heterogeneous patient preference information. We adopted an efficient Markov chain Monte Carlo algorithm when implementing the proposed method. We applied our method to a case study to illustrate how individual‐level benefit‐risk profiles could inform decision‐making.
Chronic diseases often require continuing care, and early response to treatment can be an important predictor of long‐term efficacy. Often, an apparent lack of early efficacy may lead to ...discontinuation of treatment, with the decision made either by clinicians or by the patients themselves. Thus, it is important to determine whether or not a desired early outcome corresponds to a beneficial long‐term effect of continuing treatment, and conversely, whether or not the absence of such an outcome corresponds to a lack of long‐term benefit. However, primary clinical trials of such treatments are not commonly designed to answer such questions, for example by randomizing subjects to continue or discontinue treatment after observing early outcomes. We propose an approach to estimating the effect of continuing treatment after observing early outcomes using data from randomized controlled trials in which treatment discontinuation was not part of the design. Our approach estimates average causal effects of continuing treatment on long‐term outcomes in principal strata defined by the potential early outcomes under treatment. For illustration, we estimate the effects of continuing to take gaboxadol to treat insomnia conditional on early improvement in subjective sleep quality after two nights, based on a standard parallel‐arm randomized controlled trial.
To quantify the variation in primary open-angle glaucoma (OAG) prevalence with age, gender, race, year of publication, and survey methodology.
Medline, EMBASE, and PubMed were searched for studies of ...OAG prevalence. Studies with defined population samplings were sought. Forty-six published observational studies of OAG prevalence (103,567 participants with 2509 cases of OAG) were identified for inclusion in the systematic review and meta-analysis. Data on the number of people and the number of cases of OAG by age, race, and gender were sought for each study. Additional information was obtained regarding whether the definition of glaucoma relied on raised intraocular pressure (IOP) and whether visual field examination was performed routinely on all individuals. Bayesian meta-analysis was used to model the associations between the log odds of OAG and age, race, gender, year of publication, method of visual field testing, and effect of reliance on IOP in the definition of OAG.
Black populations had the highest OAG prevalence at all ages, but the proportional increase in prevalence of OAG with age was highest in white populations. The odds ratio per decade increase in age was 2.05 in white populations (95% credible interval, 1.91 to 2.18), 1.61 (95% credible interval, 1.53 to 1.70) in black populations, and 1.57 (95% credible interval, 1.46 to 1.68) in Asian populations. The average estimated prevalence in those older than 70 years of age was 6% in white populations, 16% in black populations, and 3% in Asian populations. After adjusting for age, race, year of publication, and survey methods, men were 1.37 (95% credible interval, 1.22 to 1.53) times more likely than women to have OAG. The prevalence of OAG was one third lower in studies in which routine visual fields were not assessed and that used an IOP criterion in the definition of glaucoma; this effect was reduced to the null after adjustment for age, racial group, and year of publication.
Although black populations had the highest prevalence of OAG at all ages, white populations showed the steepest increase in OAG prevalence with age. Men were more likely than women to have OAG.
The colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite ...regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.
To investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.
Propionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.
These data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.
NCT00750438.
Quantitative decision models such as multiple criteria decision analysis (MCDA) can be used in benefit‐risk assessment to formalize trade‐offs between benefits and risks, providing transparency to ...the assessment process. There is however no well‐established method for propagating uncertainty of treatment effects data through such models to provide a sense of the variability of the benefit‐risk balance. Here, we present a Bayesian statistical method that directly models the outcomes observed in randomized placebo‐controlled trials and uses this to infer indirect comparisons between competing active treatments. The resulting treatment effects estimates are suitable for use within the MCDA setting, and it is possible to derive the distribution of the overall benefit‐risk balance through Markov Chain Monte Carlo simulation. The method is illustrated using a case study of natalizumab for relapsing‐remitting multiple sclerosis.
Summary Background Little is known about the effectiveness of treatments for acute whiplash injury. We aimed to estimate whether training of staff in emergency departments to provide active ...management consultations was more effective than usual consultations (Step 1) and to estimate whether a physiotherapy package was more effective than one additional physiotherapy advice session in patients with persisting symptoms (Step 2). Methods Step 1 was a pragmatic, cluster randomised trial of 12 NHS Trust hospitals including 15 emergency departments who treated patients with acute whiplash associated disorder of grades I–III. The hospitals were randomised by clusters to either active management or usual care consultations. In Step 2, we used a nested individually randomised trial. Patients were randomly assigned to receive either a package of up to six physiotherapy sessions or a single advice session. Randomisation in Step 2 was stratified by centre. Investigator-masked outcomes were obtained at 4, 8, and 12 months. Masking of clinicians and patients was not possible in all steps of the trial. The primary outcome was the Neck Disability Index (NDI). Analysis was intention to treat, and included an economic evaluation. The study is registered ISRCTN33302125. Findings Recruitment ran from Dec 5, 2005 to Nov 30, 2007. Follow-up was completed on Dec 19, 2008. In Step 1, 12 NHS Trusts were randomised, and 3851 of 6952 eligible patients agreed to participate (1598 patients were assigned to usual care and 2253 patients were assigned to active management). 2704 (70%) of 3851 patients provided data at 12 months. NDI score did not differ between active management and usual care consultations (difference at 12 months 0·5, 95% CI −1·5 to 2·5). In Step 2, 599 patients were randomly assigned to receive either advice (299 patients) or a physiotherapy package (300 patients). 479 (80%) patients provided data at 12 months. The physiotherapy package at 4 months showed a modest benefit compared to advice (NDI difference −3·7, −6·1 to −1·3), but not at 8 or 12 months. Active management consultations and the physiotherapy package were more expensive than usual care and single advice session. No treatment-related serious adverse events or deaths were noted. Interpretation Provision of active management consultation did not show additional benefit. A package of physiotherapy gave a modest acceleration to early recovery of persisting symptoms but was not cost effective from a UK NHS perspective. Usual consultations in emergency departments and a single physiotherapy advice session for persistent symptoms are recommended. Funding NIHR Health Technology Assessment programme.
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