Maguire, Melissa J., Hemming, Karla, Hutton, Jane and Marson, Anthony G. (2008) Overwhelming heterogeneity in systematic reviews of observational anti-epileptic studies. Epilepsy Research, Volume 80 (Number 2-3). pp. 201-212. doi:10.1016/j.eplepsyres.2008.03.024 ISSN 0920-1211.
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Abstract
Purpose: Observational studies may provide important information on the long-term effects of treatments for epilepsy, but systematic reviews of observational studies may be more prone to heterogeneity and biases. These issues were investigated in a systematic review of non-randomised add-on anti-epileptic drug studies.
Methods: Searches of MEDLINE (1966-2006), EMBASE (1974-2006), CINAHL (1982-2006), the Cochrane database of systematic reviews, the Cochrane Controlled Trials register, the DARE database and hand-searching congress proceedings were conducted. Randomised controlled trials, follow-on randomised controlled trials and prospective and retrospective cohort studies of gabapentin, topiramate, or levetiracetam as add-on therapy in adults (>12 years aid) were identified. Outcomes were 50% responders and proportion seizure free.
Results: Thirty-eight non-randomised gabapentin studies, 82 topiramate and 84 levetiracetam studies were identified. There was marked heterogeneity of effect estimates from observational studies which prohibited the pooling of estimates in random effects models. Median effect estimates were larger and more varied for observational studies than randomised placebo-controlled trials (RCTs). For example, the median value (10(th) and 90(th) percentile) for 50% responders for gabapentin was 36% (15 and 71%) compared to 23% (19 and 38%) for gabapentin RCTs. Patient and study covariates in meta-regression models could not explain the vast heterogeneity. Publication bias was evident and a sensitivity analysis, allowing for the effects of publication bias, showed that effect estimates could increase by up to 6% for seizure freedom rates.
Discussion: Reports of observational anti-epileptic studies give limited information on patient selection and characteristics. Systematic reviews of observational studies are prone to significant heterogeneity and bias which cannot adequately be explained by reported study characteristics. Reporting standards for observational studies of anti-epileptic drugs could be improved by following guidelines for reporting non-randomised studies of interventions. (C) 2008 Elsevier B.V. All rights reserved.
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics |
| Library of Congress Subject Headings (LCSH): | Systematic reviews (Medical research), Meta-analysis, Epilepsy -- Treatment -- Research, Anticonvulsants |
| Journal or Publication Title: | Epilepsy Research |
| Publisher: | Elsevier BV |
| ISSN: | 0920-1211 |
| Official Date: | August 2008 |
| Dates: | Date Event August 2008 Published |
| Volume: | Volume 80 |
| Number: | Number 2-3 |
| Number of Pages: | 12 |
| Page Range: | pp. 201-212 |
| DOI: | 10.1016/j.eplepsyres.2008.03.024 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| Funder: | Medical Research Council (Great Britain) (MRC) |
| Grant number: | G0400642 (MRC) |
| URI: | https://wrap.warwick.ac.uk/29472/ |
Data sourced from Thomson Reuters' Web of Knowledge
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