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The American Journal of Sports Medicine Nov 2014The role of evidence-based medicine in sports medicine and orthopaedic surgery is rapidly growing. Systematic reviews and meta-analyses are also proliferating in the... (Review)
Review
BACKGROUND
The role of evidence-based medicine in sports medicine and orthopaedic surgery is rapidly growing. Systematic reviews and meta-analyses are also proliferating in the medical literature.
PURPOSE
To provide the outline necessary for a practitioner to properly understand and/or conduct a systematic review for publication in a sports medicine journal.
STUDY DESIGN
Review.
METHODS
The steps of a successful systematic review include the following: identification of an unanswered answerable question; explicit definitions of the investigation's participant(s), intervention(s), comparison(s), and outcome(s); utilization of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines and PROSPERO registration; thorough systematic data extraction; and appropriate grading of the evidence and strength of the recommendations.
RESULTS
An outline to understand and conduct a systematic review is provided, and the difference between meta-analyses and systematic reviews is described. The steps necessary to perform a systematic review are fully explained, including the study purpose, search methodology, data extraction, reporting of results, identification of bias, and reporting of the study's main findings.
CONCLUSION
Systematic reviews or meta-analyses critically appraise and formally synthesize the best existing evidence to provide a statement of conclusion that answers specific clinical questions. Readers and reviewers, however, must recognize that the quality and strength of recommendations in a review are only as strong as the quality of studies that it analyzes. Thus, great care must be used in the interpretation of bias and extrapolation of the review's findings to translation to clinical practice. Without advanced education on the topic, the reader may follow the steps discussed herein to perform a systematic review.
Topics: Evidence-Based Medicine; Humans; Medical Writing; Meta-Analysis as Topic; Orthopedics; Publishing; Review Literature as Topic; Sports Medicine
PubMed: 23925575
DOI: 10.1177/0363546513497567 -
Journal of Periodontology Jan 2021The peri-implant soft tissue phenotype (PSP) encompasses the keratinized mucosa width (KMW), mucosal thickness (MT), and supracrestal tissue height (STH). Numerous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The peri-implant soft tissue phenotype (PSP) encompasses the keratinized mucosa width (KMW), mucosal thickness (MT), and supracrestal tissue height (STH). Numerous approaches to augment soft tissue volume around endosseous dental implants have been investigated. To what extent PSP modification is beneficial for peri-implant health has been subject of debate in the field of implant dentistry. The aim of this systematic review was to analyze the evidence regarding the efficacy of soft tissue augmentation procedures aimed at modifying the PSP and their impact on peri-implant health.
METHODS
A comprehensive search was performed to identify clinical studies that involved soft tissue augmentation around dental implants and reported findings on KMW, MT, and/or STH changes. The effect of the intervention on peri-implant health was also assessed. Selected articles were classified based on the general type of surgical approach to increase PSP, either bilaminar or an apically positioned flap (APF) technique. A network meta-analysis including only randomized-controlled trials (RCTs) reporting on PSP outcomes was conducted to assess and compare different techniques.
RESULTS
A total of 52 articles were included in the qualitative analysis, and 23 RCTs were included as part of the network meta-analysis. Sixteen RCTs reported the outcomes of PSP modification therapy with bilaminar techniques, whereas 7 involved the use of APF. The analysis showed that bilaminar techniques in combination with soft tissue grafts (connective tissue graft [CTG], collagen matrix [CM], and acellular dermal matrix [ADM]) resulted in a significant increase in MT compared to non-augmented sites. In particular, CTG and ADM were associated with higher MT gain as compared to CM and non-augmented sites. However, no significant differences in KMW were observed across different bilaminar techniques. PSP modification via a bilaminar approach utilizing either CTG or CM showed beneficial effects on marginal bone level stability. APF-based approaches in combination with free gingival graft (FGG), CTG, CM, or ADM showed a significant KMW gain compared to non-augmented sites. However, compared to APF alone, only FGG exhibited a significantly higher KMW gain. APF with any evaluated soft tissue graft was associated with with reduction of probing depth, soft tissue dehiscence and plaque index compared to non-augmented sites compared to non-augmented sites. The evidence regarding the effect of PSP modification via APF-based approaches on peri-implant marginal bone loss or preservation is inconclusive.
CONCLUSIONS
Bilaminar approach involving CTG or ADM obtained the highest amount of MT gain, whereas APF in combination with FGG was the most effective technique for increasing KMW. KMW augmentation via APF was associated with a significant reduction in probing depth, soft tissue dehiscence and plaque index, regardless of the soft tissue grafting material employed, whereas bilaminar techniques with CTG or CM showed beneficial effects on marginal bone level stability.
Topics: Connective Tissue; Dental Implants; Gingiva; Network Meta-Analysis; Phenotype
PubMed: 32710810
DOI: 10.1002/JPER.19-0716 -
Acta Obstetricia Et Gynecologica... Apr 2018A randomized controlled trial is a prospective, comparative, quantitative study/experiment performed under controlled conditions with random allocation of interventions... (Review)
Review
A randomized controlled trial is a prospective, comparative, quantitative study/experiment performed under controlled conditions with random allocation of interventions to comparison groups. The randomized controlled trial is the most rigorous and robust research method of determining whether a cause-effect relation exists between an intervention and an outcome. High-quality evidence can be generated by performing an randomized controlled trial when evaluating the effectiveness and safety of an intervention. Furthermore, randomized controlled trials yield themselves well to systematic review and meta-analysis providing a solid base for synthesizing evidence generated by such studies. Evidence-based clinical practice improves patient outcomes and safety, and is generally cost-effective. Therefore, randomized controlled trials are becoming increasingly popular in all areas of clinical medicine including perinatology. However, designing and conducting an randomized controlled trial, analyzing data, interpreting findings and disseminating results can be challenging as there are several practicalities to be considered. In this review, we provide simple descriptive guidance on planning, conducting, analyzing and reporting randomized controlled trials.
Topics: Gynecology; Humans; Obstetrics; Randomized Controlled Trials as Topic; Research Design
PubMed: 29377058
DOI: 10.1111/aogs.13309 -
Journal of Evidence-based Medicine Feb 2015To systematically review the methodological assessment tools for pre-clinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline. (Review)
Review
The methodological quality assessment tools for preclinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline: a systematic review.
OBJECTIVE
To systematically review the methodological assessment tools for pre-clinical and clinical studies, systematic review and meta-analysis, and clinical practice guideline.
METHODS
We searched PubMed, the Cochrane Handbook for Systematic Reviews of Interventions, Joanna Briggs Institute (JBI) Reviewers Manual, Centre for Reviews and Dissemination, Critical Appraisal Skills Programme (CASP), Scottish Intercollegiate Guidelines Network (SIGN), and the National Institute for Clinical Excellence (NICE) up to May 20th, 2014. Two authors selected studies and extracted data; quantitative analysis was performed to summarize the characteristics of included tools.
RESULTS
We included a total of 21 assessment tools for analysis. A number of tools were developed by academic organizations, and some were developed by only a small group of researchers. The JBI developed the highest number of methodological assessment tools, with CASP coming second. Tools for assessing the methodological quality of randomized controlled studies were most abundant. The Cochrane Collaboration's tool for assessing risk of bias is the best available tool for assessing RCTs. For cohort and case-control studies, we recommend the use of the Newcastle-Ottawa Scale. The Methodological Index for Non-Randomized Studies (MINORS) is an excellent tool for assessing non-randomized interventional studies, and the Agency for Healthcare Research and Quality (ARHQ) methodology checklist is applicable for cross-sectional studies. For diagnostic accuracy test studies, the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool is recommended; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool is available for assessing animal studies; Assessment of Multiple Systematic Reviews (AMSTAR) is a measurement tool for systematic reviews/meta-analyses; an 18-item tool has been developed for appraising case series studies, and the Appraisal of Guidelines, Research and Evaluation (AGREE)-II instrument is widely used to evaluate clinical practice guidelines.
CONCLUSIONS
We have successfully identified a variety of methodological assessment tools for different types of study design. However, further efforts in the development of critical appraisal tools are warranted since there is currently a lack of such tools for other fields, e.g. genetic studies, and some existing tools (nested case-control studies and case reports, for example) are in need of updating to be in line with current research practice and rigor. In addition, it is very important that all critical appraisal tools remain subjective and performance bias is effectively avoided.
Topics: Animals; Biomedical Research; Clinical Studies as Topic; Data Accuracy; Evidence-Based Medicine; Humans; Meta-Analysis as Topic; Practice Guidelines as Topic; Research Design; Review Literature as Topic
PubMed: 25594108
DOI: 10.1111/jebm.12141 -
Journal of Periodontology Nov 2020The periodontal phenotype consists of the bone morphotype, the keratinized tissue (KT), and gingival thickness (GT). The latter two components, overlying the bone,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The periodontal phenotype consists of the bone morphotype, the keratinized tissue (KT), and gingival thickness (GT). The latter two components, overlying the bone, constitute the gingival phenotype. Several techniques have been proposed for enhancing or augmenting KT or GT. However, how phenotype modification therapy (PMT) affects periodontal health and whether the obtained outcomes are maintained over time have not been elucidated. The aim of the present review was to summarize the available evidence in regard to the utilized approaches for gingival PMT and assess their comparative efficacy in augmenting KT, GT and in improving periodontal health using autogenous, allogenic, and xenogeneic grafting approaches.
METHODS
A detailed systematic search was performed to identify eligible randomized clinical trials (RCTs) reporting on the changes in GT and KT (primary outcomes). The selected articles were segregated into the type of approach based on having performed a root coverage, or non-root coverage procedure. A network meta-analysis (NMA) was conducted for each approach to assess and compare the outcomes among different treatment arms for the primary outcomes.
RESULTS
A total of 105 eligible RCTs were included. 95 pertaining to root coverage (3,539 treated gingival recessions [GRs]), and 10 for non-root coverage procedures (699 total treated sites). The analysis on root coverage procedures showed that all investigated techniques (the acellular dermal matrix [ADM], collagen matrix [CM], connective tissue graft [CTG]) are able to significantly increase the GT, compared with treatment with flap alone. However, KT was only significantly increased with the use of CTG or ADM. Early post-treatment GT was found to inversely predict future GR. For non-root coverage procedures, only the changes in KT could be analyzed; all investigated treatment groups (ADM, CM, free gingival graft [FGG], living cellular construct [LCC], in combination with an apically positioned flap [APF]), resulted in significantly more KT than treatment with APF alone. Additionally, the augmented GT was shown to be sustained, and KT displayed an incremental increase over time.
CONCLUSIONS
Within its limitations, it was observed that any graft material was able to significantly enhance GT, while KT in root coverage procedures was significantly enhanced with CTG and ADM, and in non-root coverage procedures, with ADM, CM, FGG, and LCC compared with APF alone. The autogenous soft tissue graft (CTG/FGG) proved to be superior in all comparisons for both outcomes of GT and KT.
Topics: Connective Tissue; Gingiva; Gingival Recession; Humans; Network Meta-Analysis; Phenotype; Tooth Root; Treatment Outcome
PubMed: 32392401
DOI: 10.1002/JPER.19-0715 -
Lancet (London, England) Feb 2019Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Generalised anxiety disorder is a disease that can be associated with substantial dysfunction. Pharmacological treatment is often the first choice for clinicians because of the cost and resource constraints of psychological alternatives, but there is a paucity of comparative information for the multiple available drug choices.
METHODS
A systematic review and network meta-analysis was performed on randomised trials in adult outpatients with generalised anxiety disorder identified from MEDLINE, Web of Science, Cochrane Library, ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), Wanfang data, Drugs@FDA and commercial pharmaceutical registries. Placebo and active control trials were included. Data were extracted from all manuscripts and reports. Primary outcomes were efficacy (mean difference [MD] in change in Hamilton Anxiety Scale Score) and acceptability (study discontinuations for any cause). We estimated summary mean treatment differences and odds ratios using network meta-analyses with random effects. This study is registered with PROSPERO, number CRD42018087106.
FINDINGS
Studies were published between Jan 1, 1994 and Aug 1, 2017, in which 1992 potential studies were screened for inclusion. This analysis is based on 89 trials, which included 25 441 patients randomly assigned to 22 different active drugs or placebo. Duloxetine (MD -3·13, 95% credible interval [CrI] -4·13 to -2·13), pregabalin (MD -2·79, 95% CrI -3·69 to -1·91), venlafaxine (MD -2·69, 95% CrI -3·50 to -1·89), and escitalopram (MD -2·45, 95% CrI -3·27 to -1·63) were more efficacious than placebo with relatively good acceptability. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also found to be efficacious and well tolerated but these findings were limited by small sample sizes. Quetiapine (MD -3·60 95% CrI -4·83 to -2·39) had the largest effect on HAM-A but it was poorly tolerated (odds ratio 1·44, 95% CrI 1·16-1·80) when compared with placebo. Likewise, paroxetine and benzodiazepines were effective but also poorly tolerated when compared with placebo. Risk of reporting bias was considered low, and when possible all completed studies were included to avoid publication bias.
INTERPRETATION
To our knowledge, this is the largest contemporary review of pharmacological agents for the treatment of generalised anxiety disorder by use of network analysis. There are several effective treatment choices for generalised anxiety disorder across classes of medication. The failure of initial pharmacological therapy might not be a reason to abandon a pharmacological treatment strategy.
FUNDING
No funding was received for this research.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 30712879
DOI: 10.1016/S0140-6736(18)31793-8 -
Journal of the American Medical... May 2022This study aimed to determine the comparative effectiveness of interventions in treatment of sarcopenia. The primary outcome was the measure of treatment effect on... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine the comparative effectiveness of interventions in treatment of sarcopenia. The primary outcome was the measure of treatment effect on muscle mass, and secondary outcomes were the treatment effect on muscle strength and physical performance.
DESIGN
Systematic review and network meta-analysis (NMA).
SETTING AND PARTICIPANTS
Participants with sarcopenia receiving interventions targeting sarcopenia in any setting.
METHODS
Data sources: Relevant RCTs were identified by a systematic search of several electronic databases, including CINAHL, Embase, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) from January 1995 to July 2019. Duplicate title and abstract and full-text screening, data extraction, and risk of bias assessment were performed.
DATA EXTRACTION
All RCTs examining sarcopenia interventions [mixed exercise (combined aerobic and resistance exercise), aerobic exercise, resistance exercise, balance exercise, physical activity and protein or nutrition supplementation, acupuncture, whole-body vibration, protein supplement or interventions to increase protein intake, any nutritional intervention other than protein, and pharmacotherapy] were included. Comparators were standard care, placebo, or another intervention.
DATA SYNTHESIS
We performed Bayesian NMA; continuous outcome data were pooled using the standardized mean difference effect size. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA) for each outcome.
RESULTS
A total of 59 RCTs were included after screening of 4315 citations and 313 full-text articles. Network meta-analysis of muscle mass outcome (including 46 RCTs, 3649 participants, 11 interventions) suggested that mixed exercise were the most effective intervention (SUCRA = 93.94%) to increase muscle mass. Physical activity and protein or nutrition supplementation, and aerobic exercise were the most effective interventions to improve muscle strength and physical performance, respectively. Overall, mixed exercise is the most effective intervention in increasing muscle mass and was one of the 3 most effective interventions in increasing muscle strength and physical performance.
CONCLUSIONS AND IMPLICATIONS
Mixed exercise and physical activity with nutritional supplementation are the most effective sarcopenia interventions. Most of the included studies have a high risk of bias. More robust RCTs are needed to increase the confidence of our NMA results and the quality of evidence.
Topics: Bayes Theorem; Humans; Muscle Strength; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sarcopenia
PubMed: 35183490
DOI: 10.1016/j.jamda.2022.01.057 -
Journal of Clinical Periodontology Nov 2020Aim of this systematic review (SR) of randomized controlled trials (RCTs) was to evaluate effect of different flap designs and graft materials for root coverage, in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Aim of this systematic review (SR) of randomized controlled trials (RCTs) was to evaluate effect of different flap designs and graft materials for root coverage, in terms of aesthetics, patient satisfaction and self-reported morbidity (post-operative pain/discomfort).
MATERIAL AND METHODS
A comprehensive literature search was performed. A mixed-modelling approach to network meta-analysis was utilized to formulate direct and indirect comparisons among treatments for Root Coverage Esthetic Score (RES), with its individual components, and for subjective patient-reported satisfaction and post-operative pain/discomfort (visual analogue scale (VAS) of 100).
RESULTS
Twenty-six RCTs with a total of 867 treated patients (1708 recessions) were included. Coronally Advanced Flap (CAF) + Connective Tissue Graft (CTG) (0.74 (95% CI [0.24, 1.26], p = .005)), Tunnel (TUN) + CTG (0.84 (95% CI [0.15, 1.53]), p = .01) and CAF + Graft substitutes (GS) (0.55 (95% CI [0.006, 1.094], p = .04)) were significantly associated with higher RES than CAF. No significant difference between CAF + CTG and TUN + CTG was detected (0.09 (95% CI [-0.54, 0.72], p = .77)). Addition of CTG resulted in less natural tissue texture (-0.21 (95% CI [-0.34, -0.08]), p = .003) and gingival colour (-0.06 (95% CI [-0.12, -0.03], p = .03)) than CAF. CTG techniques were associated with increased morbidity.
CONCLUSIONS
Connective tissue graft procedures showed highest overall aesthetic performance for root coverage, although graft integration might impair soft tissue colour and appearance. Additionally, CTG-based techniques were also correlated with a greater patient satisfaction and morbidity.
Topics: Connective Tissue; Esthetics, Dental; Gingiva; Gingival Recession; Humans; Network Meta-Analysis; Tooth Root; Treatment Outcome
PubMed: 32654220
DOI: 10.1111/jcpe.13346 -
Journal of Assisted Reproduction and... Aug 2021Wide controversy is still ongoing regarding efficiency of preimplantation genetic testing for aneuploidy (PGT-A). This systematic review and meta-analysis, aims to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Wide controversy is still ongoing regarding efficiency of preimplantation genetic testing for aneuploidy (PGT-A). This systematic review and meta-analysis, aims to identify the patient age group that benefits from PGT-A and the best day to biopsy.
METHODS
A systematic search of the literature was performed on MEDLINE/PubMed, Embase and Cochrane Central Library up to May 2020. Eleven randomized controlled trials employing PGT-A with comprehensive chromosomal screening (CCS) on Day-3 or Day-5 were eligible.
RESULTS
PGT-A did not improve live-birth rates (LBR) per patient in the general population (RR:1.11; 95%CI:0.87-1.42; n=1513; I=75%). However, PGT-A lowered miscarriage rate in the general population (RR:0.45; 95%CI:0.25-0.80; n=912; I=49%). Interestingly, the cumulative LBR per patient was improved by PGT-A (RR:1.36; 95%CI:1.13-1.64; n=580; I=12%). When performing an age-subgroup analysis PGT-A improved LBR in women over the age of 35 (RR:1.29; 95%CI:1.05-1.60; n=692; I=0%), whereas it appeared to be ineffective in younger women (RR:0.92; 95%CI:0.62-1.39; n=666; I=75%). Regarding optimal timing, only day-5 biopsy practice presented with improved LBR per ET (RR: 1.37; 95% CI: 1.03-1.82; I=72%).
CONCLUSION
PGT-A did not improve clinical outcomes for the general population, however PGT-A improved live-birth rates strictly when performed on blastocyst stage embryos of women over the 35-year-old mark.
Topics: Adult; Aneuploidy; Female; Fertilization in Vitro; Genetic Testing; Humans; Network Meta-Analysis; Pregnancy; Preimplantation Diagnosis; Randomized Controlled Trials as Topic
PubMed: 34036455
DOI: 10.1007/s10815-021-02227-9 -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Apr 2022This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, eventrate, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
For the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'. We performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting. Results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA. Network meta-analysis showed high-certainty evidence that for our primary outcome, 'time to treatment failure', for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: eventrate 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and eventrate was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs. For people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or eventrate in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), eventrate 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09). Network meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures. Network meta-analysis also showed high- to moderate-certainty evidence that, for 'time to first seizure,' in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, eventrate, zonisamide and lacosamide) for either seizure type. Generally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results. The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.
AUTHORS' CONCLUSIONS
High-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug eventrate, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and eventrate would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) is needed.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Humans; Network Meta-Analysis; Phenytoin
PubMed: 35363878
DOI: 10.1002/14651858.CD011412.pub4