The use of comparative effectiveness research to inform policy decisions on the inclusion of bevacizumab for the treatment of macular diseases in Thailand's pharmaceutical benefit package

Thunyarat Anothaisintawee,1,2 Pattara Leelahavarong,1 Tanapat Ratanapakorn,3 Yot Teerawattananon11Health Intervention and Technology Assessment Program, Ministry of Public Health, Nonthaburi, Thailand; 2Family Medicine Department and Section of Clinical Epidemiology and Biostatistics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Department of Ophthalmology, Khon Kaen Univerity, Khon Kaen, ThailandAbstract: There is increasing impetus to use pharmaceutical interventions, ie, ranibizumab or bevacizumab, for the treatment of particular macular diseases. This paper describes the evidence and decision-making of the National List of Essential Medicines Committee that recently announced the inclusion of bevacizumab for the treatment of macular diseases in its pharmaceutical benefit package. The findings of a systematic review and meta-analysis in this paper indicate that the intravitreal administration of bevacizumab is superior to nonpharmaceutical treatments for age-related macular degeneration (AMD) and diabetic macular edema (DME), but inconclusive for retinal vein occlusion, given the limited evidence. The study also failed to distinguish among the differences in terms of visual acuity improvement, reduction of central macular thickness, and response to treatment between AMD and DME patients treated with bevacizumab and those treated with ranibizumab. Although bevacizumab was not licensed for AMD and DME, the committee decided to include bevacizumab in the National List of Essential Medicines. It is expected that many patients who are in need of treatment but who are unable to afford the expensive alternative drug, ranibizumab, will be able to receive this effective treatment instead and be prevented from suffering irreversible loss of vision. At the same time, this policy will help generate evidence about the real-life effectiveness and safety profiles of the drug for future policy development in Thailand and other settings.Keywords: bevacizumab, macular degeneration, diabetic macular edema, retinal vein occlusion, comparative effectiveness researc

Efficacy of second generation direct-acting antiviral agents for treatment naïve hepatitis C genotype 1: A systematic review and network meta-analysis

10.1371/journal.pone.0145953PLoS ONE1012e014595

Prevalence of chronic kidney disease: a systematic review and meta-analysis

Many studies have estimated the prevalence of chronic kidney disease (CKD) but results have varied due partly to the type of equation used to estimate GFR, type of subjects, and ethnicity. This review aimed to estimate the prevalence of CKD Stage III, accounting for these factors. 403 studies were identified from Medline using the PubMed search engine, of which 34 studies were eligible. Data were independently extracted by two reviewers, and heterogeneity was assessed using metaregression. The pooled prevalence was estimated using a random effects model. In the general population, the prevalences of CKD Stage III using MDRD equation were 3.6% (95% CI: 2.5, 4.8), 10.7% (95% CI: 4.5 – 16.9%), and 16.3% (95% CI: 2.1 – 30.5%) for age groups ≤ 50, 50 – 60 and > 60 years. The prevalence was about double using the Cockcroft-Gault equations, i.e. 7.5% (95% CI: 6.9 – 8.2%) and 34.9 (95% CI: 25.9 – 44.8%) in age ≤ 50 and > 50 years, respectively. The prevalence was similar in Caucasians and Asians aged ≤ 60, i.e. 9.9 versus 9.3%. The prevalence was also higher in the diabetic population than in the general population, i.e. 18.2% versus 10.6%. The pooled prevalence of CKD in the general population varied according to age groups. The prevalence is similar in Caucasians and Asians within age 60 years or younger but other age groups need more studies in order to pool. Individual patient meta-analysis would be appropriate to resolve the causes of heterogeneity

Neoadjuvant Treatment with HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis

SIMPLE SUMMARY: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer causes more aggressive progression of disease and poorer outcomes for patients. HER2-targeted medicines used as neoadjuvant systemic therapy could improve clinical outcomes in early-stage or locally advanced breast cancer patients. The purpose of this systematic review and network meta-analysis was to identify the neoadjuvant anti-HER2 therapy with the best balance between efficacy and safety. We found that trastuzumab emtansine + pertuzumab + chemotherapy had a high pathologic complete response with a low risk of adverse events compared to other neoadjuvant anti-HER2 regimens, while the pertuzumab + trastuzumab + chemotherapy regimen showed the highest disease-free survival. However, further trial data on neoadjuvant regimens with trastuzumab emtansine are needed to confirm these findings. ABSTRACT: This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety. Methods: A network meta-analysis was applied to estimate the risk ratios along with 95% confidence intervals (CIs) for pathological complete response (pCR) and serious adverse events (SAE). A mixed-effect parametric survival analysis was conducted to assess the disease-free survival (DFS) between treatments. Results: Twenty-one RCTs with eleven regimens of neoadjuvant anti-HER2 therapy (i.e., trastuzumab + chemotherapy (TC), lapatinib + chemotherapy (LC), pertuzumab + chemotherapy (PC), pertuzumab + trastuzumab (PT), trastuzumab emtansine + pertuzumab (T-DM1P), pertuzumab + trastuzumab + chemotherapy (PTC), lapatinib + trastuzumab + chemotherapy (LTC), trastuzumab emtansine + lapatinib + chemotherapy (T-DM1LC), trastuzumab emtansine + pertuzumab + chemotherapy(T-DM1PC), PTC followed by T-DM1P (PTC_T-DM1P), and trastuzumab emtansine (T-DM1)) and chemotherapy alone were included. When compared to TC, only PTC had a significantly higher DFS with a hazard ratio (95% CI) of 0.54 (0.32–0.91). The surface under the cumulative ranking curve (SUCRA) suggested that T-DM1LC (91.9%) was ranked first in achieving pCR, followed by the PTC_T-DM1P (90.5%), PTC (74.8%), and T-DM1PC (73.5%) regimens. For SAEs, LTC, LC, and T-DM1LC presented with the highest risks (SUCRA = 10.7%, 16.8%, and 20.8%), while PT (99.2%), T-DM1P (88%), and T-DM1 (83.9%) were the safest regimens. The T-DM1PC (73.5% vs. 71.6%), T-DM1 (70.5% vs. 83.9%), and PTC_T-DM1P (90.5% vs. 47.3%) regimens offered the optimal balance between pCR and SAE. Conclusions: The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen. However, these results were based on a small number of studies, and additional RCTs assessing the efficacy of regimens with T-DM1 are still needed to confirm these findings