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Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.

ABSTRACT: Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing.Three electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-genetic informed prescribing, reported drug specific adverse drug events and clinical effectiveness outcomes. Two reviewers independently screened titles and abstracts, extracted data and assessed study quality. Meta-analyses of specific outcomes were conducted where data allowed.Fifteen studies, involving 5688 patients and 19 drugs, met the inclusion and exclusion criteria. Eight studies had statistically significant results for their primary outcome in favour of genotype-guided prescribing. Nine studies evaluated genotype-guided warfarin dosing. Analysis of percentage of time in therapeutic international normalized ratio range (1952 individuals) showed a statistically significant benefit in favour of genotype-guided warfarin dosing (mean difference = 6.67; 95% CI 1.34, 12.0, I(2) = 80%). There was a statistically significant reduction in numbers of warfarin-related minor bleeding, major bleeding and thromboembolisms associated with genotype guided warfarin dosing, relative risk 0.57 (95% CI 0.33, 0.99; I(2) = 60%). It was not possible to meta-analyze genotype-guided dosing for other drugs. Of the six non-warfarin genotype-guided trials, two demonstrated a statistically significant benefit for their primary outcome, odds ratio 0.03 (95% CI 0.00, 0.62, P < 0.001) for abacavir.There is evidence of improved clinical effectiveness associated with genotype-guided warfarin dosing.

SUBMITTER: Goulding R

PROVIDER: S-EPMC4594730 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.

Goulding Rebecca R Dawes Diana D Price Morgan M Wilkie Sabrina S Dawes Martin M

British journal of clinical pharmacology 20150722 4

<h4>Aim</h4>Adverse drug events lead to increased morbidity, mortality and health care costs. Pharmacogenetic testing that guides drug prescribing has the potential to reduced adverse drug events and increase drug effectiveness. Our aim was to quantify the clinical effectiveness of genotype-guided prescribing.<h4>Methods</h4>Three electronic databases were searched from January 1980 through December 2013. Studies were eligible if they were RCTs comparing genotype-guided prescribing with non-gene ...[more]

PMID: 25060532

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Project description:BackgroundTraditional angiography only displays two-dimensional images of the coronary arteries during stent implantation. However, intravascular imaging can show the structure of the vascular wall, plaque characteristics. This article aims to evaluate the efficacy of intravascular imaging-guided drug-eluting stent (DES) implantation.MethodWe conducted a systematic review and meta-analysis of randomized controlled trials of intravascular imaging-guided, including patients with DES implantation guided by intravascular ultrasound or optical coherence tomography and traditional angiography. The databases of PubMed, EMBASE, web of science, and Cochrane Library were searched. The primary outcome was target lesion revascularization (TLR). The secondary outcomes included the target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), cardiac death, all-cause death, and the major adverse cardiac events (MACE) during the 6-24 months follow-up. The fixed-effects model was used to calculate the relative risk (RR) and 95% confidence interval of the outcome event. Meanwhile, the trial sequence analysis was employed to evaluate the results.ResultThis meta-analysis included fourteen randomized controlled trials with 7307 patients. Compared with angiography-guided, intravascular imaging-guided DES implantation can significantly reduce the risk of TLR (RR 0.63, 0.49-0.82, P = 0.0004), TVR (RR 0.66, 0.52-0.85, P = 0.001), cardiac death (RR 0.58; 0.38-0.89; P = 0.01), MACE (RR 0.67, 0.57-0.79; P < 0.00001) and ST (RR 0.43, 0.24-0.78; P = 0.005). While there was no significant difference regarding MI (RR 0.77, 0.57-1.05, P = 0.10) and all-cause death (RR 0.87, 0.58-1.30, P = 0.50).ConclusionsCompared with angiography, intravascular imaging-guided DES implantation is associated with better clinical outcomes in patients with coronary artery disease, especially complex lesions (Registered by PROSPERO, CRD 42021289205).

Project description:Randomized clinical trials (RCTs) of lifestyle modification have reported beneficial effects of interventions, compared to control. Whether participation in the control group has benefits is unknown. To determine whether control group participants experience weight loss during the course of RCTs. After prospective registration (PROSPERO CRD42021233070), we conducted searches in Medline, Scopus, Web of Science, Cochrane library and Clinicaltrials.gov databases from inception to May 2021 without language restriction to capture RCTs on dietary advice or physical activity interventions in adults with overweight, obesity or metabolic syndrome. Data extraction and study quality assessment was performed by two independent reviewers. Weight loss in the control group, i.e., the difference between baseline and post-intervention, was pooled using random effects model generating mean difference and 95% confidence interval (CI). Heterogeneity was assessed using the I2 statistical test. Subgroup meta-analysis was performed stratifying by follow-up period, type of control group protocols and high-quality studies. Among the 22 included studies (4032 participants), the risk of bias was low in 9 (40%) studies. Overall, the controls groups experienced weight loss of - 0.41 kg (95% CI - 0.53 to - 0.28; I2 = 73.5% p < 0.001). To identify a result that is an outlier, we inspected the forest plot for spread of the point estimates and the confidence intervals. The magnitude of the benefit was related to the duration of follow-up (- 0.51 kg, 95% CI - 0.68, - 0.3, for 1-4 months follow-up; - 0.32 kg, 95% CI - 0.58, - 0.07, 5-12 months; - 0.20 kg, 95% CI - 0.49, 0.10, ≥ 12 months). In high-quality studies we found an overall weight loss mean difference of - 0.16 (95% CI - 0.39, 0.09) with a considerable heterogeneity (I2 = 74%; p < 0.000). Among studies including control group in waiting lists and combining standard care, advice and material, no heterogeneity was found (I2 = 0%, p = 0.589) and (I2 = 0%, p = 0.438); and the mean difference was - 0.84 kg (95% CI - 2.47, 0.80) and - 0.65 kg (95% CI - 1.03, - 0.27) respectively. Participation in control groups of RCTs of lifestyle interventions had a benefit in terms of weight loss in meta-analysis with heterogeneity. These results should be used to interpret the benefits observed with respect to intervention effect in trials. That control groups accrue benefits should be included in patient information sheets to encourage participation in future trials among patients with overweight and obesity.

Dataset Information

Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.

Publications

Genotype-guided drug prescribing: a systematic review and meta-analysis of randomized control trials.

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