Pneumococcal Vaccination for Children in Asian Countries:A Systematic Review of Economic Evaluation Studies

Background: Evidence on costs and health benefits of pneumococcal conjugate vaccine (PCV) for children in Asian countries is limited but growing. As a region with a considerably high burden of pneumococcal disease, it is prominent to have a comprehensive overview on the cost-effectiveness of implementing and adopting a PCV vaccination program. Methods: We conducted a systematic review from Pubmed and Embase to identify economic evaluation studies of PCV for children in Asian countries up to May 2020. Data extraction included specific characteristics of the study, input parameters, cost elements, cost-effectiveness results, and key drivers of uncertainty. The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) statement was followed for this systematic review. The reporting quality of the included studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Results: After the screening process on both the title and abstract and full text of 518 records, a total of 25 studies fulfilled the inclusion criteria, and were included in the review. The majority of included studies demonstrates that PCV for children is cost-effective in most of the Asian region, and even cost-saving in some countries. Most of the included studies implemented cost utility analysis (CUA) using either quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Overall, the main drivers affecting the cost effectiveness were vaccine price, burden regarding pneumonia-related parameters, and the inclusion of herd effects. Conclusion: The children pneumococcal vaccination program appears to be a cost-effective intervention in Asia, and even cost-saving in certain conditions. Vaccine price, pneumonia-related disease burden, and the inclusion of the herd effect are observed as important key drivers in estimating cost-effectiveness in this region. Incorporating PCV in vaccination programs in this region was found to be highly favorable

Characteristics of drugs safety signals that predict safety related product information update

Purpose: Investigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016. Methods: A comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI. Results: Multivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug-event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs ≤5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05). Conclusions: This study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates

EFEK SAMPING OBAT PADA PENGOBATAN TUBERKULOSIS RESISTEN OBAT GANDA

Tuberkulosis (TB) merupakan permasalahan serius di dunia kesehatan. Sebanyak 10,6 juta dari populasi dunia menderita TB pada tahun 2021 dan 1,6 juta meninggal karena TB. Penyebab utama TB yaitu Mycobacterium tuberculosis yang sering menyerang paru-paru. Penggunaan Obat Anti-Tuberkulosis (OAT) merupakan andalan dalam pengobatan tuberkulosis. Tuberkulosis resisten obat ganda (TB ROG) merupakan penyakit yang resisten terhadap setidaknya dua obat yaitu (rifampisin dan isoniazid) serta membutuhkan pengobatan relatif lama dengan beberapa obat lini kedua. Obat tersebut dapat menimbulkan efek samping yang mengakibatkan kegagalan pengobatan. Tinjauan naratif ini menyajikan informasi ilmiah mengenai kejadian, jenis efek samping dan OAT yang menimbulkan efek samping pada TB ROG sehingga dapat bermanfaat dalam penatalaksanaan TB ROG. Studi review naratif ini  dikembangkan dari database elektronik PubMed pada perisode 2012-2022. Dari sumber informasi yang diperoleh, kami mengidentifikasi dua rejimen yang umum digunakan, yaitu rejimen jangka panjang/long term regimen (LTR) dan rejimen jangka pendek/short term regimen (STR). Analisis terhadap sumber informasi yang ada menunjukkan beragam kejadian efek samping obat (ESO) pada rejimen STR yaitu gangguan pendengaran karena aminoglikosida (63%), perpanjangan interval QTc karena clofazimine (33,3%), dan neuropati perifer karena bedaquiline (56,3%). Sedangkan, pada rejimen LTR, ESO berupa neuritis perifer (81%) dan gangguan saluran cerna (33,60%) karena linezolid, serta kerusakan hati (31,8%) dan perubahan warna kulit (22,7%) karena clofazimine. Beragam penanganan ESO dideskripsikan, antara lain melalui penurunan dosis rejimen, pergantian rejimen obat maupun penghentian obat. Tingginya kejadian ESO pada TB ROG mendorong perlunya manajemen ESO TB ROG yang adekuat untuk meningkatkan keberhasilan pengobatan pada pasien TB ROG

Prevalence of adverse drug reactions in the primary care setting: A systematic review and meta-analysis.

BackgroundAdverse drug reactions (ADRs) represent a major cause of iatrogenic morbidity and mortality in patient care. While a substantial body of work has been undertaken to characterise ADRs in the hospital setting, the overall burden of ADRs in the primary care remains unclear.ObjectivesTo investigate the prevalence of ADRs in the primary care setting and factors affecting the heterogeneity of the estimates.MethodsStudies were identified through searching of Medline, Embase, CINAHL and IPA databases. We included observational studies that reported information on the prevalence of ADRs in patients receiving primary care. Disease and treatment specific studies were excluded. Quality of the included studies were assessed using Smyth ADRs adapted scale. A random-effects model was used to calculate the pooled estimate. Potential source of heterogeneity, including age groups, ADRs definitions, ADRs detection methods, study setting, quality of the studies, and sample size, were investigated using sub-group analysis and meta-regression.ResultsThirty-three studies with a total study population of 1,568,164 individuals were included. The pooled prevalence of ADRs in the primary care setting was 8.32% (95% CI, 7.82, 8.83). The percentage of preventable ADRs ranged from 12.35-37.96%, with the pooled estimate of 22.96% (95% CI, 7.82, 38.09). Cardiovascular system drugs were the most commonly implicated medication class. Methods of ADRs detection, age group, setting, and sample size contributed significantly to the heterogeneity of the estimates.ConclusionADRs constitute a significant health problem in the primary care setting. Further research should focus on examining whether ADRs affect subsequent clinical outcomes, particularly in high-risk therapeutic areas. This information may better inform strategies to reduce the burden of ADRs in the primary care setting

Methods of defining the non-inferiority margin in randomized, double-blind controlled trials : a systematic review

BACKGROUND: There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its choice is often not reported. This study investigated how the non-inferiority margin is defined in the published literature, and whether its reporting has changed over time. METHODS: A systematic PubMed search was conducted for all published randomized, double-blind, non-inferiority trials from January 1, 1966, to February 6, 2015. The primary outcome was the number of margins that were defined by methods other than the historical evidence of the active comparator. This was evaluated for a time trend. We also assessed the under-reporting of the methods of defining the margin as a secondary outcome, and whether this changed over time. Both outcomes were analyzed using a Poisson log-linear model. Predictors for better reporting of the methods, and the use of the fixed-margin method (one of the historical evidence methods) were also analyzed using logistic regression. RESULTS: Two hundred seventy-three articles were included, which account for 273 non-inferiority margins. There was no statistically significant difference in the number of margins that were defined by other methods compared to those defined based on the historical evidence (ratio 2.17, 95% CI 0.86 to 5.82, p = 0.11), and this did not change over time. The number of margins for which methods were unreported was similar to those with reported methods (ratio 1.35, 95% CI 0.76 to 2.43, p = 0.31), with no change over time. The method of defining the margin was less often reported in journals with low-impact factors compared to journals with high-impact factors (OR 0.20; 95% CI 0.10 to 0.37, p < 0.0001). The publication of the FDA draft guidance in 2010 was associated with increased reporting of the fixed-margin method (after versus before 2010) (OR 3.54; 95% CI 1.12 to 13.35, p = 0.04). CONCLUSIONS: Non-inferiority margins are not commonly defined based on the historical evidence of the active comparator, and they are poorly reported. Authors, reviewers, and editors need to take notice of reporting this critical information to allow for better judgment of non-inferiority trials

Methods of defining the non-inferiority margin in randomized, double-blind controlled trials : a systematic review

Background There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its choice is often not reported. This study investigated how the non-inferiority margin is defined in the published literature, and whether its reporting has changed over time. Methods A systematic PubMed search was conducted for all published randomized, double-blind, non-inferiority trials from January 1, 1966, to February 6, 2015. The primary outcome was the number of margins that were defined by methods other than the historical evidence of the active comparator. This was evaluated for a time trend. We also assessed the under-reporting of the methods of defining the margin as a secondary outcome, and whether this changed over time. Both outcomes were analyzed using a Poisson log-linear model. Predictors for better reporting of the methods, and the use of the fixed-margin method (one of the historical evidence methods) were also analyzed using logistic regression. Results Two hundred seventy-three articles were included, which account for 273 non-inferiority margins. There was no statistically significant difference in the number of margins that were defined by other methods compared to those defined based on the historical evidence (ratio 2.17, 95% CI 0.86 to 5.82, p = 0.11), and this did not change over time. The number of margins for which methods were unreported was similar to those with reported methods (ratio 1.35, 95% CI 0.76 to 2.43, p = 0.31), with no change over time. The method of defining the margin was less often reported in journals with low-impact factors compared to journals with high-impact factors (OR 0.20; 95% CI 0.10 to 0.37, p < 0.0001). The publication of the FDA draft guidance in 2010 was associated with increased reporting of the fixed-margin method (after versus before 2010) (OR 3.54; 95% CI 1.12 to 13.35, p = 0.04). Conclusions Non-inferiority margins are not commonly defined based on the historical evidence of the active comparator, and they are poorly reported. Authors, reviewers, and editors need to take notice of reporting this critical information to allow for better judgment of non-inferiority trials

Impact of ACEIs and ARBs-related adverse drug reaction on patients’ clinical outcomes:a cohort study in UK primary care

Background: Adverse drug reaction (ADR) related to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may negatively affect patients’ treatment outcomes. Aim: To investigate the impact of ACEIs/ARBs-related ADR consultation on cardiovascular disease (CVD) events and all-cause mortality. Design and setting: Propensity score-matched cohort study of ACEIs/ ARBs between 2004 and 2019 using UK IQVIA medical research data. Method: ADR consultations were identified using standardised designated codes. Propensity scores were calculated based on comorbidities, concomitant medications, frailty, and polypharmacy. Cox’s proportional hazard regression model was used to compare the outcomes between patients in ADR and non-ADR groups. In the secondary analysis, treatment-pattern changes following the ADR were examined and the subsequent outcomes were compared. Results: Among 1 471 906 eligible users of ACEIs/ARBs, 13 652 (0.93%) patients had ACEIs/ARBs-related ADR consultation in primary care. Patients with ACEIs/ARBs-related ADR consultation had an increased risk of subsequent CVD events and all-cause mortality in both primary prevention (CVD events: adjusted hazard ratio [aHR] 1.22, 95% confidence interval [CI] = 1.05 to 1.43; all-cause mortality: aHR 1.14, 95% CI = 1.01 to 1.27) and secondary prevention cohorts (CVD events: aHR 1.13, 95% CI = 1.05 to 1.21; all-cause mortality: aHR 1.15, 95% CI = 1.09 to 1.21). Half (50.19%) of patients with ADR continued to use ACEIs/ARBs, and these patients had a reduced risk of mortality (aHR 0.88, 95% CI = 0.82 to 0.95) compared with those who discontinued using ACEIs/ARBs.Conclusion: This study provides information on the burden of ADR on patients and the health system. The findings call for additional monitoring and treatment strategies for patients affected by ADR to mitigate the risks of adverse clinical outcomes.</p

Methods of Defining the Noninferiority Margin : A Systematic Review

Background: Noninferiority trials are conducted to investigate whether the efficacy of the test drug is not worse than the active comparator based on a predefined noninferiority margin. There is no consensus on a preferred method for defining the noninferiority margin, and previous studies showed that the rationale for its choice is often not reported. Objectives: To investigate how the noninferiority margin is defined in the published literature, and whether its reporting has changed over time. Methods: A systematic PubMed search was conducted for all published randomized, double-blind, noninferiority trials from January 1, 1966, to February 6, 2015. The time trend of defining the margin since the first published noninferiority trial was analyzed using Poisson regression analysis. The impact of the 2010 US Food and Drug Administration (FDA) draft guidance for noninferiority clinical trials on the choice of the margin, and the impact of the extension of the Consolidated Standards of Reporting Trials (CONSORT) Statement on the reporting of noninferiority margins were analyzed using generalized estimating equations to account for the clustering of the margins within articles. Results: We included 275 articles, which account for 283 trials and 328 noninferiority margins. The rationale for the choice of the margin was not reported for 191 margins (58.2%). The under-reporting of the rationale for the choice of the margin has not improved neither since the first published noninferiority trial in this review in 2000 (P=0.86), nor since the publication of the extension of the CONSORT Statement in 2006 (P=0.96). The other 137 margins were mainly defined based on the historical evidence of the active comparator (n=56) or subjectively based on expert opinions (n=46). There was a 3.5-fold increase in the use of the fixed-margin method, the recommended method by the FDA to define the margin, after the publication of the FDA draft guidance (from 2.6% to 9%, P=0.04). Conclusions: Margins in noninferiority trials are poorly reported and this has not improved over recent years. Authors, reviewers, and editors need to take notice of reporting this critical information to allow for better judgment of noninferiority trials

Methods of defining the non-inferiority margin in randomized, double-blind controlled trials: a systematic review

BACKGROUND: There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its choice is often not reported. This study investigated how the non-inferiority margin is defined in the published literature, and whether its reporting has changed over time. METHODS: A systematic PubMed search was conducted for all published randomized, double-blind, non-inferiority trials from January 1, 1966, to February 6, 2015. The primary outcome was the number of margins that were defined by methods other than the historical evidence of the active comparator. This was evaluated for a time trend. We also assessed the under-reporting of the methods of defining the margin as a secondary outcome, and whether this changed over time. Both outcomes were analyzed using a Poisson log-linear model. Predictors for better reporting of the methods, and the use of the fixed-margin method (one of the historical evidence methods) were also analyzed using logistic regression. RESULTS: Two hundred seventy-three articles were included, which account for 273 non-inferiority margins. There was no statistically significant difference in the number of margins that were defined by other methods compared to those defined based on the historical evidence (ratio 2.17, 95% CI 0.86 to 5.82, p = 0.11), and this did not change over time. The number of margins for which methods were unreported was similar to those with reported methods (ratio 1.35, 95% CI 0.76 to 2.43, p = 0.31), with no change over time. The method of defining the margin was less often reported in journals with low-impact factors compared to journals with high-impact factors (OR 0.20; 95% CI 0.10 to 0.37, p < 0.0001). The publication of the FDA draft guidance in 2010 was associated with increased reporting of the fixed-margin method (after versus before 2010) (OR 3.54; 95% CI 1.12 to 13.35, p = 0.04). CONCLUSIONS: Non-inferiority margins are not commonly defined based on the historical evidence of the active comparator, and they are poorly reported. Authors, reviewers, and editors need to take notice of reporting this critical information to allow for better judgment of non-inferiority trials