quetiapine-fumarate and Neuralgia

We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials.. We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight.. Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information.. Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.

Topics: Bipolar Disorder; Data Accuracy; Drug-Related Side Effects and Adverse Reactions; Gabapentin; Humans; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials.. We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as "serious." We recorded whether AEs were grouped by anatomic or physiological system.. Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decision-making. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system.. Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

Topics: Bipolar Disorder; Data Accuracy; Drug-Related Side Effects and Adverse Reactions; Gabapentin; Humans; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

To identify variations in outcomes and results across reports of randomized clinical trials (RCTs).. Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic (e.g., clinical study reports) sources by 2015. We prespecified outcome domains. From each source, we collected "outcomes" (i.e., domain, measure, metric, method of aggregation, and time point); "treatment effect" (i.e., outcome plus the methods of analysis [e.g., how missing data were handled]); and results (i.e., numerical contrasts of treatment and comparison groups). We assessed whether results included sufficient information for meta-analysis.. We found 21 gabapentin (68 public, 6 nonpublic reports) and seven quetiapine RCTs (46 public, 4 nonpublic reports). For four (gabapentin) and seven (quetiapine) prespecified outcome domains, RCTs reported 214 and 81 outcomes by varying four elements. RCTs assessed 605 and 188 treatment effects by varying the analysis of those outcomes. RCTs reported 1,230 and 661 meta-analyzable results, 305 (25%) and 109 (16%) in public reports.. RCTs included hundreds of outcomes and results; a small proportion were in public reports. Trialists and meta-analysts may cherry-pick what they report from multiple sources of RCT information.

Topics: Amines; Analgesics; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Neuralgia; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs).. Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic sources (clinical study reports [CSRs] and individual participant data [IPD]).. We found 21 gabapentin RCTs (74 reports, 6 IPD) and 7 quetiapine RCTs (50 reports, 1 IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains "pain intensity" (gabapentin) and "depression" (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD] = -0.45; 95% confidence interval [CI]: -0.63 to -0.27) to ineffective (SMD = -0.06; 95% CI: -0.24 to 0.12). We could change the effect for depression from a medium effect (SMD = -0.55; 95% CI: -0.85 to -0.25) to a small effect (SMD = -0.26; 95% CI: -0.41 to -0.1).. Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.

Topics: Amines; Bias; Bipolar Disorder; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Meta-Analysis as Topic; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials or across sources for a single trial may produce inconsistent information about the adverse events associated with interventions.. We compared the methods authors use to decide which AEs to include in a particular source (i.e., "selection criteria"), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports (CSRs)) of trials for two drug-indications-gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting.. We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion "occurring in ≥2% of participants in any treatment group," while only 5/316 (2%) AEs met the criterion "occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.". Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might "cherry-pick" AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.

Topics: Adverse Drug Reaction Reporting Systems; Bipolar Disorder; Gabapentin; Humans; Information Dissemination; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

Data for individual trials included in systematic reviews may be available in multiple sources. For example, a single trial might be reported in 2 journal articles and 3 conference abstracts. Because of differences across sources, source selection can influence the results of systematic reviews. We used our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study, and evidence from previous studies, to develop practical guidance for using multiple data sources in systematic reviews. We recommend the following: (1) Specify which sources you will use. Before beginning a systematic review, consider which sources are likely to contain the most useful data. Try to identify all relevant reports and to extract information from the most reliable sources. (2) Link individual trials with multiple sources. Write to authors to determine which sources are likely related to the same trials. Use a modified Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart to document both the selection of trials and the selection of sources. (3) Follow a prespecified protocol for extracting trial characteristics from multiple sources. Identify differences among sources, and contact study authors to resolve differences if possible. (4) Prespecify outcomes and results to examine in the review and meta-analysis. In your protocol, describe how you will handle multiple outcomes within each domain of interest. Look for outcomes using all eligible sources. (5) Identify which data sources were included in the review. Consider whether the results might have been influenced by data sources used. (6) To reduce bias, and to reduce research waste, share the data used in your review.

Topics: Amines; Bipolar Disorder; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Data Collection; Gabapentin; gamma-Aminobutyric Acid; Humans; Information Storage and Retrieval; Meta-Analysis as Topic; Neuralgia; Quetiapine Fumarate; Research Report; Review Literature as Topic; Treatment Outcome

Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial.. We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., "clinical study reports") and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources.. CRD42015014037 , CRD42015014038.

Topics: Amines; Analgesics; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Data Interpretation, Statistical; Gabapentin; gamma-Aminobutyric Acid; Humans; Meta-Analysis as Topic; Neuralgia; Outcome Assessment, Health Care; Patient-Centered Care; Quetiapine Fumarate; Research Design; Selection Bias; Systematic Reviews as Topic