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

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.

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Risk factors for catheter-related thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2010.04126.x ◽

2011 ◽

Vol 9 (2) ◽

pp. 312-319 ◽

Cited By ~ 120

Author(s):

W. SABER ◽

T. MOUA ◽

E. C. WILLIAMS ◽

M. VERSO ◽

G. AGNELLI ◽

...

Keyword(s):

Risk Factors ◽

Clinical Trials ◽

Cancer Patients ◽

Prospective Studies ◽

Meta Analysis ◽

Patient Level Data ◽

Patient Level ◽

Level Data ◽

Catheter Related Thrombosis

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

Journal of SAFOG with DVD ◽

10.5005/jsafog-6-1-62 ◽

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.

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

British Journal Of Nutrition ◽

10.1017/s0007114513001050 ◽

2013 ◽

Vol 110 (8) ◽

pp. 1384-1393 ◽

Cited By ~ 49

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.

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