COMPARATIVE EFFICACY OF THERAPEUTIC INTERVENTIONS FOR THE MANAGEMENT OF RECURRENT APHTHOUS ULCERS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

BACKGROUND: Recurrent aphthous ulceration (RAU) is an oral condition cavity affecting 2.5 billion people worldwide. We aimed to assess the comparative efficacy and safety of available interventions in the management of RAU. MATERIALS AND METHODS: An electronic search of 3 databases (Medline, CENTRAL, Scopus) was performed to identify randomized control trials evaluating the efficacy of RAU interventions published until December 2022. A network meta-analysis (NMA) was conducted on 4 outcomes: reduction in pain, duration of ulceration, the diameter of ulceration, and area of ulceration. The interventions are then arranged using the surface area under cumulative ranking (SUCRA). RESULTS: A total of 38 trials involving 2773 patients were included were included in quantitative synthesis by NMA. Our analysis showed that Diode laser [MD, -4.865 ± 1.951 (95%CI = (-8.690, -1.041)] was the most effective in reducing the pain score followed by Amlexanox [MD, -2.673 ± 1.075 (95%CI = -4.779, -0.566)]. Iralvex performed the best in reducing the duration of ulceration [MD, -6.481 ± 1.841 (95%CI = -10.090, -2.872)]. Diode laser, acacia nilotica with licorice formulation, and amlexanox were the most effective interventions for reduction of ulcer diameter. Majority of the trials reported absence of any adverse effects and those reported were mild. CONCLUSION: Our NMA has identified several interventions to be more effective than a placebo. Laser therapy may be an option for promoting pain management, however, most have only been tested in 1 or 2 trials. Further studies with rigorous methodology on larger samples are recommended to strengthen the current evidence.

Comparative effectiveness of interventions for the treatment of denture stomatitis: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Symptomatic denture stomatitis (DS) is a painful oral mucosal disorder that can impair quality of life in denture wearers. A complete cure of DS is difficult to achieve, and the most efficacious regimen to treat DS has not yet been conclusively established. PURPOSE: The purpose of this network meta-analysis was to assess the comparative efficacy of interventions used for the treatment of DS. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until February 2022 (PROSPERO Reg no: CRD42021271366). Network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of any form of intervention for the treatment of DS in denture wearers. Agents were ranked according to their effectiveness in the treatment of DS based on outcomes using surface under the cumulative ranking (SUCRA). RESULTS: A total of 25 articles were included in the quantitative analysis. Topical antifungal agents (risk ratio [RR]=4.37[95% confidence interval [CI]: 2.15,8.90), topical antimicrobial agents used along with systemic antifungal agents (RR=4.25[95% CI: 1.79,10.33]), systemic antifungal agents (RR=4.25[95% CI: 1.79,10.10]), photodynamic therapy (RR=4.25[95% CI: 1.75,8.98]), and topical plant products (RR=3.40[95% CI: 1.59,7.26]) were found to effectively improve DS. Microwave disinfection concurrently administered with topical antifungal agents (RR=7.38(95% CI: 2.75,19.81), microwave disinfection 7.38[95% CI: 2.75,19.81]), topical antifungal agents (RR=4.88[95% CI: 1.92,12.42]), topical plant products (RR=4.49[95% CI: 1.70,11.82]), systemic antifungal agents together with topical antimicrobial agents (RR=3.85[95% CI: 1.33,11.10]), topical antimicrobial agents (RR=3.39[95% CI: 1.17,9.81]), systemic antifungal agents (RR=3.37[95% CI: 1.21,9.34]), and photodynamic therapy or photochemotherapy (PDT) (RR=2.93[95% CI: 1.01,8.47]) were found to effectively resolve mycological DS. Topical antifungals ranked highest in the SUCRA ranking for clinical improvement, whereas microwave disinfection concurrently administered with topical antifungal agents ranked highest for mycological resolution. None of the agents demonstrated significant side effects except for topical antimicrobial agents which demonstrated altered taste and staining of oral structures. CONCLUSIONS: Available evidence suggests that topical antifungals, microwave, and systemic antifungals are effective in the treatment of DS, but confidence in these findings is low because of the limited number of studies and a high risk of bias. Additional clinical trials are needed on photodynamic therapy, topical plant products, and topical antimicrobials.

COMPARATIVE EFFICACY OF ANTIVIRAL AGENTS FOR PREVENTION AND MANAGEMENT OF HERPES LABIALIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

OBJECTIVE: To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials. METHODS: A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA). RESULTS: A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only. CONCLUSION: NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.

Integrating Real-World Evidence in Economic Evaluation of Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation in a Developing Country.

OBJECTIVE: This study aimed to estimate the cost effectiveness of non-vitamin K oral anticoagulants (NOACs) compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) in Thailand where suboptimal anticoagulation control is common. MATERIALS AND METHODS: A hypothetical cohort of 65-year-old patients with NVAF and their disease progression was simulated in the Markov model. The following anticoagulant agents were used: warfarin, dabigatran, rivaroxaban, and apixaban. Warfarin with high, intermediate, and low time in therapeutic ranges (TTR) was used as the three different reference treatments. Baseline clinical events were obtained from a recently published real-world study in Thailand. A lifetime horizon was utilized in this model, and all analyses were performed from societal and healthcare perspectives. The results were reported as incremental cost-effectiveness ratios (ICERs) in 2021 US dollars per quality-adjusted life-year (QALY) gained. The sensitivity analyses were performed to assess the influence of parameter uncertainty. RESULTS: Apixaban was a cost-effective intervention compared with warfarin with low and intermediate TTR groups. In the low TTR group, the ICERs were $779 and $816 per QALY gained from the societal and healthcare perspectives, respectively, and in the intermediate TTR group, the ICERs were $2038 and $3159 per QALY gained from the societal and healthcare perspectives, respectively. Both ICERs were below the accepted willingness-to-pay threshold ($4806) in the context of Thailand's healthcare. CONCLUSIONS: In a developing country where suboptimal anticoagulation control is common, apixaban was the cost-effective alternative to warfarin for patients with both low and intermediate TTR control.

Incremental net monetary benefit of biologic therapies in moderate to severe asthma: a systematic review and meta-analysis of economic evaluation studies.

OBJECTIVES: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using biologic therapies as an add-on treatment to standard therapy in patients with moderate to severe asthma. METHODS: We performed a comprehensive search in several databases published until April 2022. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year on any biologic therapies as an add-on treatment for moderate to severe asthma in patients of all ages. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were pooled across studies using a random-effects model, stratified by country income level (high-income countries (HICs) and low- and middle-income countries (LMICs)) and perspectives (health care or payer perspective (HCPP) and societal perspective (SP)) and age group (>12 years and 6-11 years). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 32 comparisons from 25 studies were included. Pooled INB indicated that the use of omalizumab as an add-on treatment to standard therapy in those aged >12 years was not cost-effective in HICs from the HCPP (n = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I2=86.18%) and SP (n = 5, -$14,000 (-$170,000 to $140,000), I2=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs (n = 2, -$45,000 (-$73,000 to $17,000), I2=00.00%). Subgroup analyses provided no explanations of the potential sources of heterogeneity. CONCLUSION: The use of biologic therapies in moderate to severe asthma is not cost-effective compared to standard treatment alone.

Pneumococcal Vaccination in Children: A Systematic Review and Meta-Analysis of Cost-Effectiveness Studies.

OBJECTIVES: Pneumococcal conjugate vaccines (PCVs) have significantly reduced disease burden caused by Streptococcus pneumoniae, a leading cause of childhood morbidity and mortality globally. This systematic review and meta-analysis aimed to assess the incremental net benefit (INB) of the 13-valent PCV (PCV13) and 10-valent PCV (PCV10) in children. METHODS: We performed a comprehensive search in several databases published before May 2022. Studies were included if they were cost-effectiveness or cost-utility analyses of PCV13 or PCV10 compared with no vaccination or with each other in children. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were calculated and then pooled across studies stratified by country income level, perspective, and consideration of herd effects, using a random-effect model. RESULTS: Seventy studies were included. When herd effects were considered, PCV13 was cost-effective compared with PCV10 from the payer perspective in both high-income countries (HICs) (INB, $103.94; 95% confidence interval, $75.28-$132.60) and low- and middle-income countries (LMICs) (INB, $53.49; 95% confidence interval, $30.42-$76.55) with statistical significance. These findings were robust across a series of sensitivity analyses. PCV13 was cost-effective compared with no vaccination across perspectives and consideration of herd effects in both HICs and LMICs, whereas findings were less consistent for PCV10. CONCLUSION: PCVs were generally cost-effective compared with no vaccination in HICs and LMICs. Our study found that PCV13 was cost-effective compared with PCV10 when herd effects were considered from the payer perspective in both HICs and LMICs. The results are sensitive to the consideration of herd effects.

Measurement and valuation of the attributes of innovation of healthcare technologies: a systematic review.

OBJECTIVE: Innovative technologies (e.g. treatments) play a pivotal role in improving patient's well-being and in consequence population health outcomes. However, there is lack of consensus and comprehensive summary what constitutes innovation. Additionally, valuing them using traditional cost-effectiveness analysis is unlikely to capture the full range of benefits of these innovative technologies. This review aims to understand how innovation attributes were measured and/or valued in healthcare. MATERIALS AND METHODS: We systemically searched four databases, PubMed, Embase, PsycINFO, and Econlit, from inception to April 2021. Studies were included if they measured and/or valued the attributes of innovation for healthcare identified in our previous systematic review. Any other potential recommended methods to measure and/or value the innovation attributes were also extracted. RESULTS: Of 546 articles, a total of 17 articles were finally included in this review. If attributes were measured and traded-off relative to costs, then it was considered as valuation of those attributes. Two specific attributes of innovation, i.e. substantial benefits and convenience and/or adherence were measured using adherence rate and life year or QALY gain. When innovation attribute was non-specific it was described as "overall innovation" and measured using overall innovativeness scale (e.g. point/binary scale). QALY-based cost-effectiveness analysis (CEA) was commonly used to assess and value substantial benefit attribute. Other valuation approaches were (i) rating, (ii) the economic value of life year gain, (iii) multiple criteria decision analysis (MCDA), (iv) incremental net health benefit (INHB), and (v) quality-adjusted cost of care (QACC). ICER threshold adjustment and multiple-criteria decision analysis (MCDA) are two common recommended approaches to capture the innovation comprehensively. We found that MCDA approaches often promoted and discussed but were sub-optimally used to incorporate different value attributes into decision-making. CONCLUSIONS: Existing methods used by payers to measure and value the innovation component of a new product do not reflect the full range of health and cost impacts. They generally do not consider the alternative perspectives of patients, providers, caregivers, and society. Key challenges remain to appropriately measure and value innovation attributes and incorporate them into HTA decision making.

Characterizing attributes of innovation of technologies for healthcare: a systematic review.

OBJECTIVES: Characterizing and evaluating the holistic value of innovative healthcare technologies (e.g. treatments, services) constitutes a crucial goal to maximize limited resources. However, the characteristics of innovation have not been well identified. This review aims to describe the characteristics of healthcare innovation. METHODS: We performed a comprehensive systematic search using PubMed, Embase, PsycINFO, and Econlit from inception to July 2022. Articles were included if they described innovation or the characteristics of innovation of the technologies in healthcare. Characteristics or definitions of innovation directly or indirectly described as innovation were extracted from the included articles. Two independent reviewers then conceptualized the identified characteristics of innovation to generate innovation attributes in healthcare. RESULTS: In total, 103 articles were included in this review. Eight attributes describing innovation, i.e. novelty, step change, substantial benefits, an improvement over existing technologies, convenience and/or adherence, added value, acceptable cost, and uncounted benefits, were conceptualized. Most of the identified innovation attributes were based on the researchers' perspective. CONCLUSIONS: This study conceptualized innovation attributes in healthcare based on the characteristics of healthcare innovation as defined in the literature. Further research is warranted to obtain a complete understanding of the perspectives of researchers and other stakeholders, including patients, healthcare providers, healthcare payers, and the pharmaceutical industry, on recognizing innovation in healthcare.KEY POINTSThis is the first systematic review to conceptualize attributes of healthcare innovation.We conceptualized eight attributes describing innovation, i.e. novelty, step change, substantial benefits, an improvement over existing technologies, convenience and/or adherence, added value, acceptable cost, and uncounted benefits based on the similar concept.In existing literature, patients' and caregivers' perspectives were less frequently found to describe the innovation attributes.Future research is needed to identify, measure, and value various stakeholders, including patients' and caregivers' perspectives on healthcare innovation.

Incremental net monetary benefit of direct oral anticoagulants for the prevention of venous thromboembolism after total knee or hip replacement: A systematic review and meta-analysis.

INTRODUCTION: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using direct oral anticoagulants (DOACs) for the prevention of venous thromboembolism (VTE) in patients undergoing total knee or hip replacements (TKR or THR). MATERIALS AND METHODS: We performed a comprehensive search in several databases published before June 2021. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year of DOACs compared to low molecular-weight heparins (LMWHs) or other anticoagulant agents for the prevention of VTE after TKR or THR. Risk of bias was also assessed using the biases in economic studies (ECOBIAS) checklist. Various monetary units were converted to purchasing power parity, adjusted to 2020 US dollars. The INBs were pooled across studies using a random-effects model, stratified by high-income countries (HICs) and low- and middle-income countries (LMICs). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 49 comparisons (TKR = 25 and THR = 24) from 16 studies was included. In HICs, DOACs were cost-effective compared to LMWHs from the health care system/payer perspective for the prevention of VTE after both TKR and THR with corresponding INBs (95 % CI; I2) of $231.91 ($178.71, $285.11; 0 %) and $254.99 ($159.20, $350.77; 27.79 %), respectively. In LMICs, DOACs were not cost-effective compared to LMWHs for both TKR and THR with the INBs of $94.13 (-$40.21, $228.47; 97.04 %) and $80.55 (-$157.37, $318.47; 99.78 %), respectively. No evidence of small-study effects was identified in any analyses. The cost-effectiveness of using DOACs for TKR and THR in HICs was robust across a series of sensitivity analyses. CONCLUSIONS: DOACs were cost-effective as compared to LMWHs for VTE prophylaxis following TKR and THR surgeries in HICs. Further studies from LMICs are warranted.

Does meta-analysis of economic evaluations have the potential to play a role in healthcare decision-making in the United States?

The current use of economic evidence in the decision-making process in the US is increasing. Meta-analysis of economic evaluations (MAEE) has gained recognition in recent years and can support decision-making at the global level or for countries with resource constraints. The focus of this article is to demonstrate how MAEE may contribute to the decision-making process in the US healthcare system. We demonstrated that MAEE can provide an efficient mechanism to quantitatively summarize cost-effectiveness findings based on all existing studies from the US answering the same question across different assumptions. This sort of evidence is important for US policymakers to support policy decision-making. MAEE methods can streamline the process of reviewing complex economic models and their findings, which has been previously reported by stakeholders as a barrier to the use of economic evidence in decision-making in the US. However, the currently proposed method may not fully address the issue of heterogeneity observed among MAEEs. There is a critical need to explore sources of heterogeneity and develop a standardized approach to handle it to improve the efficiency and acceptability of future MAEEs.