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Haney EM, Huffman LH, Bougatsos C, et al. Screening for Lipid Disorders in Children and Adolescents [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007 Jul. (Evidence Syntheses, No. 47.)

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Screening for Lipid Disorders in Children and Adolescents [Internet].

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2Methods

Literature Search and Strategy

Relevant studies were identified from multiple searches of MEDLINE (1966 through September 2005) [Appendix 3]. Additional articles were obtained from recent systematic reviews, reference lists of related studies, reviews, editorials, websites and by consulting experts. Retrieved abstracts were entered into an electronic database (EndNote®).

Inclusion/Exclusion Criteria

Investigators reviewed all abstracts identified by the searches and determined eligibility by applying inclusion and exclusion criteria specific to each key question (Appendix 4). Full-text articles of included abstracts were then reviewed for relevance. Eligible studies were English-language, applicable to U.S. clinical practice, and provided primary data relevant to key questions. Studies of children and adolescents with previously diagnosed conditions known to cause dyslipidemia were not included. Animal studies were not included. Studies of risk factors were included only if they provided multivariate adjusted analyses.

For treatment studies, full text randomized controlled trials (RCTs), non-controlled clinical trials, and non-controlled prospective studies providing data on the treatment of children and adolescents with diet, drug therapy, exercise, or combinations of these were initially reviewed. Subsequently, only randomized controlled trials and meta-analyses of randomized controlled trials that reported serum lipid outcomes were included. For Key Question 10, outcomes included either adult lipid levels or adult CHD. Studies of other treatment modalities for dyslipidemia (surgery, apheresis) and studies of rare conditions such as homozygous FH were excluded. Information about adverse effects of treatment was obtained from RCTs and additional sources such as non-randomized controlled treatment trials and non-comparative studies of treatment.

Data Extraction and Synthesis

All eligible studies were reviewed and a “best evidence” approach was applied, in which studies with the highest quality and most rigorous design are emphasized. 47 Data were extracted from each study, entered directly into evidence tables, and summarized. Benefits and adverse effects of therapies were considered equally important and both types of outcomes were abstracted. Trials of therapy for children and adolescents with dyslipidemia were categorized by population and intervention.

Two reviewers independently rated the quality of randomized controlled trials using criteria specific to different study designs developed by the U.S. Preventive Services Task Force (Appendix 5). 48 The overall rating is a combination of internal and external validity scores. When reviewers disagreed, a final rating was reached through consensus.

Randomized controlled trials of similar treatments that met additional eligibility criteria were considered for meta-analysis. Meta-analyses were performed to provide estimates of the effectiveness of statins on improving lipid levels in children and adolescents with FH, and of the effectiveness of exercise on improving lipid levels in children and adolescents without FH who were normal or overweight. For each trial, the difference in mean percent change of lipid levels between treatment and control groups and its standard error were obtained and pooled using a random effects model. 49 When the percentage change and its standard error or 95% confidence interval were not reported, they were calculated from the mean and standard error of lipid levels from treatment and control groups at baseline and the endpoint (Appendix 6). A study was excluded when no information on dispersion was reported.

Effects of study level covariates, such as duration, mean age, percentage male/female, and dosage were checked by using random-effects meta regressions. 49 Specifically, drug dose for each statin study was analyzed using an equivalent dose of simvastatin according to published equivalency tables. 50

Size of Literature Reviewed

A total of 2,507 unique citations were identified by the literature searches (Appendix 4). Included were 160 papers about screening and testing for dyslipidemia (Key Question 2); 68 about interventions and tracking of lipid values over time (Key Questions 4–8 and 10); 8 about the adverse effects of screening (Key Question 3); and 81 about adverse effects of treatment (Key Question 9).Seven papers discussed the costs of screening, but none evaluated cost effectiveness in U.S. population (Key Question 11).

External Review Process

The USPSTF appointed liaisons to advise the Oregon Evidence-based Practice Center in formulating and reporting this systematic evidence review. An additional set of outside experts provided advice in the review formulation stage and commented on a draft version of the evidence synthesis.

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