scholarly journals Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

2020 ◽  
Author(s):  
Noel Patson ◽  
Mavuto Mukaka ◽  
Kennedy N Otwombe ◽  
Lawrence Kazembe ◽  
Don P Mathanga ◽  
...  
Keyword(s):  
Systematic Review ◽  
Statistical Analysis ◽  
Missing Data ◽  
Drug Safety ◽  
Safety Data ◽  
Malaria Prevention ◽  
Controlled Trials ◽  
Safety Outcomes ◽  
In Pregnancy

Abstract Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of anti-malarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. Therefore, a systematic review was conducted to establish the current practice in statistical analysis for preventive antimalarial drug safety in pregnancy. Methods The search included five databased (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n=18, 100%) and mean/median (n=2, 11.1%). Results presentation included tabular (n=16, 88.9%) and text description (n=2, 11.1%). Univariate inferential methods were reported in most trials (n=16, 88.9%); including Chi-square/Fisher`s exact test (n=12, 66.7%), t-test (n=2, 11.1%) and Mann-Whitney/Wilcoxon test (n=1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n=4, 22.2%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n=7, 38.9%). Conclusion The review demonstrated that statistical analysis of safety data in anti-malarial drugs for malarial chemoprevention in pregnancy RCTs is inadequate. The analyses insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise anti-malarial drug safety evidence development, based on the available data.

scholarly journals Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

2019 ◽  
Author(s):  
Noel Patson ◽  
Mavuto Mukaka ◽  
Kennedy N Otwombe ◽  
Lawrence Kazembe ◽  
Don P Mathanga ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Missing Data ◽  
Drug Safety ◽  
Safety Data ◽  
Malaria Prevention ◽  
Antimalarial Drugs ◽  
Controlled Trials ◽  
Safety Outcomes ◽  
In Pregnancy

Abstract Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of antimalarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. We have therefore conducted a systematic review to establish the current practice in statistical analysis for antimalarial drug safety in pregnancy.Methods We searched PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials for original English articles reporting Phase III (randomized controlled trials) RCTs on antimalarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019.Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n=18, 100%) and mean/median (n=2, 11.1%). Results presentation included tabular (n=16, 88.9%) and text description (n=2, 11.1%). Univariate inferential methods were reported in most trials (n=16, 88.9%); including Chi-square/Fisher`s exact test (n=12, 66.7%), t-test (n=2, 11.1%) and Mann-Whitney/Wilcoxon test (n=1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n=4, 22.2%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n=7, 38.9%).Conclusion The review demonstrated that statistical analysis of safety data in antimalarial drugs for malarial chemoprevention in pregnancy RCTs are inadequate. The analysis insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise antimalarial drug safety evidence development, based on the available data.

scholarly journals Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials

2020 ◽  
Author(s):  
Noel Patson ◽  
Mavuto Mukaka ◽  
Kennedy N Otwombe ◽  
Lawrence Kazembe ◽  
Don P Mathanga ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Missing Data ◽  
Drug Safety ◽  
Safety Data ◽  
Malaria Prevention ◽  
Antimalarial Drugs ◽  
Controlled Trials ◽  
Safety Outcomes ◽  
In Pregnancy

Abstract Background Drug safety assessments in clinical trials present unique analytical challenges. Some of these include adjusting for individual follow-up time, repeated measurements of multiple outcomes and missing data among others. Furthermore, pre-specifying appropriate analysis becomes difficult as some safety endpoints are unexpected. Although existing guidelines such as CONSORT encourage thorough reporting of adverse events (AEs) in clinical trials, they provide limited details for safety data analysis. The limited guidelines may influence suboptimal analysis by failing to account for some analysis challenges above. A typical example where such challenges exist are trials of antimalarial drugs for malaria prevention during pregnancy. Lack of proper standardized evaluation of the safety of antimalarial drugs has limited the ability to draw conclusions about safety. We have therefore conducted a systematic review to establish the current practice in statistical analysis for antimalarial drug safety in pregnancy. Methods We searched PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials for original English articles reporting Phase III (randomized controlled trials) RCTs on antimalarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. Results Eighteen trials were included in this review that collected multiple longitudinal safety outcomes including AEs. Statistical analysis and reporting of the safety outcomes in all the trials used descriptive statistics; proportions/counts (n=18, 100%) and mean/median (n=2, 11.1%). Results presentation included tabular (n=16, 88.9%) and text description (n=2, 11.1%). Univariate inferential methods were reported in most trials (n=16, 88.9%); including Chi-square/Fisher`s exact test (n=12, 66.7%), t-test (n=2, 11.1%) and Mann-Whitney/Wilcoxon test (n=1, 5.6%). Multivariable methods, including Poisson and negative binomial were reported in few trials (n=4, 22.2%). Assessment of a potential link between missing efficacy data and safety outcomes was not reported in any of the trials that reported efficacy missing data (n=7, 38.9%). Conclusion The review demonstrated that statistical analysis of safety data in antimalarial drugs for malarial chemoprevention in pregnancy RCTs are inadequate. The analysis insufficiently account for multiple safety outcomes potential dependence, follow-up time and informative missing data which can compromise antimalarial drug safety evidence development, based on the available data.

scholarly journals Potential impact on estimated treatment effects of information lost to follow-up in randomised controlled trials (LOST-IT): systematic review

BMJ ◽  
2012 ◽  
Vol 344 (may18 1) ◽  
pp. e2809-e2809 ◽  
Author(s):  
E. A. Akl ◽  
M. Briel ◽  
J. J. You ◽  
X. Sun ◽  
B. C. Johnston ◽  
...  
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Treatment Effects ◽  
Controlled Trials ◽  
Potential Impact ◽  
Randomised Controlled ◽  
Lost To Follow Up

scholarly journals P074 PARASTOMAL AND INCISIONAL HERNIAS FOLLOWING EMERGENCY SURGERY FOR HINCHEY III-IV DIVERTICULITIS: A SYSTEMATIC REVIEW

2021 ◽  
Vol 108 (Supplement_8) ◽  
Author(s):  
Elisa Mäkäräinen ◽  
Tero Rautio ◽  
Filip Muysoms ◽  
Joonas Kauppila
Keyword(s):  
Systematic Review ◽  
Surgical Treatment ◽  
Incisional Hernia ◽  
Parastomal Hernia ◽  
Primary Anastomosis ◽  
Controlled Trials ◽  
Hartmann Procedure ◽  
Randomized Controlled ◽  
Hernia Incidence

Abstract Aim The aim of this systematic review was to report the risk of parastomal and incisional hernias after emergency surgery for Hinchey III–IV diverticulitis. Material and Methods The Cochrane Library, Embase, PubMed (MEDLINE), Web of Science and Scopus databases were systematically searched. All randomized controlled trials (RCTs) and cohort studies comparing HP with other surgical treatment options for perforated diverticulitis classified as purulent or faecal (Hinchey III–IV) were considered for inclusion. Exclusion criteria were case series and reports, letters, editorials, reviews and conference abstracts. The primary endpoint was parastomal hernia incidence. The secondary endpoint was incisional hernia incidence. Seven studies (six randomized controlled trials and one retrospective cohort) with a total of 831 patients were eligible for inclusion. Results The parastomal hernia incidence was 15.2–46.0% for Hartmann procedure, 0–85.2% for primary anastomosis, 4.3% for resection and 1.6 % for laparoscopic lavage. The incisional hernia incidences were 7.8–38.1% for Hartmann procedure, 4.5–27.2% for primary anastomosis, 3.2–25.5% for primary resection, 2.7–11.1% for laparoscopic lavage and 16.1–45.8% for secondary resection. Due to heterogeneity of follow-up methods, follow-up time and lack of both parastomal and incisional hernia as outcome, no meta-analysis was conducted. Conclusions The hernia incidences reported after surgical treatment for complicated diverticulitis may be biased and underestimated. For future RCTs, researchers are encouraged to pay attention to hernia diagnosis, symptoms and prevention.

scholarly journals The impact of inclusion, dose and duration of pyrazinamide (PZA) on efficacy and safety outcomes in tuberculosis: systematic review and meta-analysis protocol

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
James D. Millard ◽  
Elizabeth A. Mackay ◽  
Laura J. Bonnett ◽  
Geraint R. Davies
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Meta Analysis ◽  
World Health ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Safety Outcomes ◽  
Meta Regression ◽  
Indirect Comparisons

Abstract Background Pyrazinamide (PZA) is a key component of current and future regimens for tuberculosis (TB). Inclusion of PZA at higher doses and for longer durations may improve efficacy outcomes but must be balanced against the potential for worse safety outcomes. Methods We will search for randomised and quasi-randomised clinical trials in adult participants with and without the inclusion of PZA in TB treatment regimens in the Cochrane infectious diseases group’s trials register, Cochrane central register of controlled trials (CENTRAL), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) international clinical trials registry platform. One author will screen abstracts and remove ineligible studies (10% of which will be double-screened by a second author). Two authors will review full texts for inclusion. Safety and efficacy data will be extracted to pre-piloted forms by one author (10% of which will be double-extracted by a second author). The Cochrane risk of bias tool will be used to assess study quality. The study has three objectives: the association of (1) inclusion, (2) dose and (3) duration of PZA with efficacy and safety outcomes. Risk ratios as relative measures of effect for direct comparisons within trials (all objectives) and proportions as absolute measures of effect for indirect comparisons across trials (for objectives 2 and 3) will be calculated. If there is insufficient data for direct comparisons within trials for objective 1, indirect comparisons between trials will be performed. Measures of effect will be pooled, with corresponding 95% confidence intervals and p values. Meta-analysis will be performed using the generalised inverse variance method for fixed effects models (FEM) or the DerSimonian-Laird method for random effects models (REM). For indirect comparisons, meta-regression for absolute measures against dose and duration data will be performed. Heterogeneity will be quantified through the I2-statistic for direct comparisons and the τ2 statistic for indirect comparisons using meta-regression. Discussion The current use of PZA for TB is based on over 60 years of clinical trial data, but this has never been synthesised to guide rationale use in future regimens and clinical trials. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019138735

scholarly journals 4066 In Teenagers Who Smoke Cigarettes Are Nicotine Patches as Compared to Placebo Effective to Decrease the Number of Cigarettes Smoked? – A Systematic Review

2020 ◽  
Vol 4 (s1) ◽  
pp. 138-138
Author(s):  
Obumneke A Amadi
Keyword(s):  
Systematic Review ◽  
Smoking Cessation ◽  
Randomized Controlled Trials ◽  
Nicotine Patch ◽  
Controlled Trials ◽  
Smoking Abstinence ◽  
Randomized Controlled ◽  
Nicotine Patches ◽  
Continuous Abstinence

OBJECTIVES/GOALS: The aim was to examine whether nicotine patch was more effective in encouraging abstinence from cigarettes smoking compared to placebo. METHODS/STUDY POPULATION: Randomized controlled trials involving the general teenage age group smokers who were current smokers-“smoked less than 100 cigarettes over their lifetime and smoked at the time of the interview. Databases were searched for relevant studies reported in English that employed a randomized design published since 2000. Two authors extracted data and assessed quality. The primary outcomes and prioritization were continuous abstinence at 3, 6 and 12-month follow-up or more for the number of patients who responded to treatment, defined as a reduction/abstinence. Heterogeneity between studies did not preclude combined analyses of the data. RESULTS/ANTICIPATED RESULTS: 4 of 266 publications were included. Four studies reported positive effects on smoking cessation at end of treatment: (1) nicotine patches improved continuous abstinence at 6 weeks – 9 weeks months; (2) nicotine patch improved continuous abstinence at 3 to 6 months; (3) nicotine patches improved continuous abstinence 6 and 12 months; (4) nicotine patches improved continuous abstinence at 6 months – 12 and 24 months (5). All studies showed, continuous abstinence at follow up differed in percentage between groups both at 6 weeks through 24 months, with NRT (Nicotine patch) intervention groups achieving higher rates in most of the studies compared to placebo intervention group. Conclusions: NRT intervention methods seem to increase smoking abstinence in those treated for smoking cessation. Further and larger sample size studies are required to make stronger the base of evidence. DISCUSSION/SIGNIFICANCE OF IMPACT: Four randomized controlled trials investigating the effectiveness of smoking cessation interventions, for teenagers who smoke cigarettes were identified for inclusion in this review. Four of the studies reported significant effects on smoking cessation, providing evidence of effectiveness of NRT (nicotine patch), behavioral support and combinations of the two, although not all trials intervention treatments found an effect. The four studies reported important intervention effects at both the short and long follow-ups required: 6 weeks up to the 24 months, thereby, providing stronger evidence to support the effectiveness of NRT intervention on smoking cessation. All studies showed some evidence of improved smoking abstinence outcomes. The four studies had in common that the smoking cessation interventions provided a combination of intent to treat prevention, and of all the clinical trials none of them suggested a negative effect of smoking cessation treatment on substance use outcomes using NRT. However, the studies used reliable methods and reported their cases properly, but the small number of studies reviewed for the systematic review makes the conclusion about the effectiveness of these interventions uncertain. The papers visibly stated how the trials protected against bias, as indicated by the Yes (low risk). No (high risk) and U as “unclear risk.” All four studies conducted a random sequence generation of participants enrolled into the study sample.

scholarly journals The comparison between total hip arthroplasty and hemiarthroplasty in patients with femoral neck fractures: a systematic review and meta-analysis based on 25 randomized controlled trials

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Xiumei Tang ◽  
Duan Wang ◽  
Ying Liu ◽  
Jiali Chen ◽  
Zongke Zhou ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Total Hip Arthroplasty ◽  
Meta Analysis ◽  
Femoral Neck Fractures ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Acetabular Erosion

Abstract Background We performed an updated systematic review and meta-analysis which enrolled 25 prospective randomized controlled trials (RCTs) to compare the outcomes between total hip arthroplasty (THA) and hemiarthroplasty (HA) in patients with femoral neck fractures (FNFs). Methods We searched English databases which included PubMed, Embase (vis OvidSP), The Cochrane Library, and Web of Science, and Chinese databases Chinese National Knowledge Infrastructure (CNKI), VIP, Wang Fang, and China Biology Medicine Disc (CBM) in July 2020. The quality of each study was assessed according to the Cochrane Collaboration’s Risk of Bias. Risk ratios (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were pooled with random-effects models. Data regarding baseline characteristics, hospital and surgery outcomes, clinical outcomes, patients’ quality of life, common complications, prothesis-related complications, mortality, and costs were reported. Results A total of 25 RCTs involving 3223 patients (1568 THA and 1655 HA) were included. THA had longer hospital length (WMD = 0.721, P < 0.0001) and surgery time (WMD = 20.044, P < 0.0001), and more blood loss compared with HA (WMD = 69.109, P < 0.0001). THA showed better ratings in the Harris Hip Score during follow-up periods between 1 and 5 years while no differences within 6 months and after 9 years. THA was associated with higher quality-of-life EuroQol-5 Dimension (EQ-5D) scores after 2 years of surgery but no difference within 1 year. There was no difference in common complications. THA had significant higher rate of dislocation (WMD = 1.897, P = 0.002) and lower acetabular erosion (WMD = 0.030, P = 0.001). For mortality, there was no difference during all the follow-up periods except for slightly higher 2-year mortality after surgery. Conclusion This meta-analysis demonstrates that THA has better medium-term functional results and quality of life and lower acetabular erosion rate, while HA shows better in reducing hospital stay, surgery time, and blood loss and also has lower dislocation rate.

scholarly journals Synovial Sarcoma of the Nerve—Clinical and Pathological Features: Case Series and Systematic Review

Neurosurgery ◽  
2019 ◽  
Vol 85 (6) ◽  
pp. E975-E991 ◽  
Author(s):  
Stephen Shelby Burks ◽  
Ross C Puffer ◽  
Iahn Cajigas ◽  
David Valdivia ◽  
Andrew E Rosenberg ◽  
...  
Keyword(s):  
Systematic Review ◽  
Statistical Analysis ◽  
Synovial Sarcoma ◽  
Tumor Size ◽  
Clinical Course ◽  
Case Reports ◽  
Case Series ◽  
Pathological Features ◽  
Eligibility Criteria

Abstract BACKGROUND Synovial sarcoma of the nerve is a rare entity with several cases and case series reported in the literature. Despite an improved understanding of the biology, the clinical course is difficult to predict. OBJECTIVE To compile a series of patients with synovial sarcoma of the peripheral nerve (SSPN) and assess clinical and pathological factors and their contribution to survival and recurrence. METHODS Cases from 2 institutions collected in patients undergoing surgical intervention for SSPN. Systematic review including PubMed and Scopus databases were searched for related articles published from 1970 to December 2018. Eligibility criteria: (1) case reports or case series reporting on SSPN, (2) clinical course and/or pathological features of the tumor reported, and (3) articles published in English. RESULTS From patients treated at our institutions (13) the average follow-up period was 3.2 yr. Tumor recurrence was seen in 4 cases and death in 3. Systematic review of the literature yielded 44 additional cases with an average follow-up period of 3.6 yr. From pooled data, there were 10 recurrences and 7 deaths (20% and 14%, respectively). Adjuvant treatment used in 62.5% of cases. Immunohistochemical markers used in diagnosis varied widely; the most common are the following: Epithelial membrane antigen (EMA), cytokeratin, vimentin, cluster of differentiation (CD34), and transducin-like enhancer of split 1 (TLE1). Statistical analysis illustrated tumor size and use of chemotherapy to be negative predictors of survival. No other factors, clinically or from pathologist review, were correlated with recurrence or survival. CONCLUSION By combining cases from our institution with historical data and performing statistical analysis we show correlation between tumor size and death.

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