scholarly journals Calcium supplements and cancer risk: a meta-analysis of randomised controlled trials

2013 ◽  
Vol 110 (8) ◽  
pp. 1384-1393 ◽  
Author(s):  
Sarah M. Bristow ◽  
Mark J. Bolland ◽  
Graeme S. MacLennan ◽  
Alison Avenell ◽  
Andrew Grey ◽  
...  
Keyword(s):  
Vitamin D ◽  
Relative Risk ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Patient Level Data ◽  
Patient Level ◽  
Level Data ◽  
Total Cancer ◽  
Meta Analyses

Some evidence suggests that Ca and vitamin D supplements affect cancer risk; however, it is uncertain whether the effects are due to Ca, vitamin D or the combination. We investigated the effect of Ca supplements without co-administered vitamin D on cancer risk. Medline, Embase and the Cochrane Central Register of Controlled Trials, reference lists of meta-analyses and two clinical trial registries were searched for randomised, placebo-controlled trials of Ca supplements ( ≥ 500 mg/d), with ≥ 100 participants and duration >1 year. The lead authors of eligible trials supplied data on cancer outcomes. Trial-level data were analysed using random-effects meta-analyses and patient-level data using Cox proportional hazards models. A total of sixteen trials were eligible, six had no data available, ten provided trial-level data (n 10 496, mean duration 3·9 years), and of these, four provided patient-level data (n 7221, median duration 3·5 years). In the meta-analysis of trial-level data, allocation to Ca did not alter the risk of total cancer (relative risk 0·95, 95 % CI 0·76, 1·18, P= 0·63), colorectal cancer (relative risk 1·38, 95 % CI 0·89, 2·15, P= 0·15), breast cancer (relative risk 1·01, 95 % CI 0·64, 1·59, P= 0·97) or cancer-related mortality (relative risk 0·96, 95 % CI 0·74, 1·24, P= 0·75), but reduced the risk of prostate cancer (relative risk 0·54, 95 % CI 0·30, 0·96, P= 0·03), although there were few events. The meta-analysis of patient-level data showed similar results, with no effect of Ca on the risk of total cancer (hazard ratio 1·07, 95 % CI 0·89, 1·28, P= 0·50). Ca supplements without co-administered vitamin D did not alter total cancer risk over 4 years, although the meta-analysis lacked power to detect very small effects, or those with a longer latency.

scholarly journals Effect of Calcium Supplements on Risk of Myocardial Infarction and Cardiovascular Events: Meta-analysis

2014 ◽  
Vol 6 (1) ◽  
pp. 62-64
Author(s):  
MJ Bolland ◽  
A Avenell ◽  
JA Baron ◽  
A Grey ◽  
GS MacLennan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Confidence Interval ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Patient Level Data ◽  
Calcium Supplements ◽  
Patient Level ◽  
Level Data ◽  
Meta Analyses

ABSTRACT Objective To investigate whether calcium supplements increase the risk of cardiovascular events. Design Patient level and trial level meta-analyses. Data Sources Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010. Study Selection Eligible studies were randomized, placebo controlled trials of calcium supplements (. 500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than 1 year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self-reports, hospital admissions and death certificates. Results Fifteen trials were eligible for inclusion, five with patient level data (8,151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11,921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02-1.67, p = 0.035). Nonsignificant increases occurred in the incidence of stroke (1.20, 0.96-1.50, p = 0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, p = 0.057), and death (1.09, 0.96-1.23, p = 0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01-1.59, p = 0.038). Conclusion Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.

Abstract 17059: Re-Use of Clinical Trial Data From the NHLBI Data Repository (BioLINCC) for Patient-Level Meta-Analyses of Cardiovascular Outcomes: Challenges and Opportunities

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Helena Sviglin ◽  
Gauri Dandi ◽  
Eileen Navarro Almario ◽  
Tejas Patel ◽  
Colin O Wu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Cardiovascular Outcomes ◽  
Data Repository ◽  
Common Data Elements ◽  
Patient Level Data ◽  
Patient Level ◽  
Level Data ◽  
Data Elements ◽  
Meta Analyses

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.

scholarly journals Initial depression severity and response to antidepressants v. placebo: patient-level data analysis from 34 randomised controlled trials

2016 ◽  
Vol 209 (5) ◽  
pp. 427-428 ◽  
Author(s):  
Jonathan Rabinowitz ◽  
Nomi Werbeloff ◽  
Francine S. Mandel ◽  
François Menard ◽  
Lauren Marangell ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Severe Depression ◽  
Placebo Patient ◽  
Controlled Trials ◽  
Depression Severity ◽  
Patient Level Data ◽  
Patient Level ◽  
Level Data ◽  
Initial Depression ◽  
Randomised Controlled

SummarySeveral often-cited meta-analyses have reported that the efficacy of antidepressant medications depends on the severity of depression. They found that drug–placebo differences increased as a function of initial severity, which was attributed to decreased responsiveness to placebo among patients with severe depression rather than to increased responsiveness to medication. We retested this using patient-level data and also undertaking a meta-analysis of trial-level data from 34 randomised placebo controlled trials (n = 10 737) from the NEWMEDS registry. Although our trial-level data support prevous findings, patient-level data did not show any significant effect of initial depression severity on drug v. placebo difference.

scholarly journals Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost-effectiveness modelling

2015 ◽  
Vol 19 (100) ◽  
pp. 1-402 ◽  
Author(s):  
Rafael Perera ◽  
Emily McFadden ◽  
Julie McLellan ◽  
Tom Lung ◽  
Philip Clarke ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Primary Prevention ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Controlled Trials ◽  
Patient Level Data ◽  
Patient Level ◽  
Monitoring Strategies ◽  
Level Data ◽  
Meta Analyses

BackgroundVarious lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation.ObjectiveTo determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD.Data sourcesWe searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke’s Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature.MethodsIn two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year.ResultsA total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I2 = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention.LimitationHeterogeneity in meta-analyses.ConclusionsWhile acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence.Study registrationThis study is registered as PROSPERO CRD42013003727.FundingThe National Institute for Health Research Health Technology Assessment programme.

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