Economic Evaluations of Digital Health Interventions for Patients With Heart Failure: Systematic Review.

BACKGROUND: Digital health interventions (DHIs) have shown promising results in enhancing the management of heart failure (HF). Although health care interventions are increasingly being delivered digitally, with growing evidence on the potential cost-effectiveness of adopting them, there has been little effort to collate and synthesize the findings. OBJECTIVE: This study's objective was to systematically review the economic evaluations that assess the adoption of DHIs in the management and treatment of HF. METHODS: A systematic review was conducted using 3 electronic databases: PubMed, EBSCOhost, and Scopus. Articles reporting full economic evaluations of DHIs for patients with HF published up to July 2023 were eligible for inclusion. Study characteristics, design (both trial based and model based), input parameters, and main results were extracted from full-text articles. Data synthesis was conducted based on the technologies used for delivering DHIs in the management of patients with HF, and the findings were analyzed narratively. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for this systematic review. The reporting quality of the included studies was evaluated using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. RESULTS: Overall, 27 economic evaluations were included in the review. The economic evaluations were based on models (13/27, 48%), trials (13/27, 48%), or a combination approach (1/27, 4%). The devices evaluated included noninvasive remote monitoring devices (eg, home telemonitoring using digital tablets or specific medical devices that enable transmission of physiological data), telephone support, mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems. Most of the studies (24/27, 89%) used cost-utility analysis. The majority of the studies (25/27, 93%) were conducted in high-income countries, particularly European countries (16/27, 59%) such as the United Kingdom and the Netherlands. Mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems yielded cost-effective results or even emerged as dominant strategies. However, conflicting results were observed, particularly in noninvasive remote monitoring devices and telephone support. In 15% (4/27) of the studies, these DHIs were found to be less costly and more effective than the comparators (ie, dominant), while 33% (9/27) reported them to be more costly but more effective with incremental cost-effectiveness ratios below the respective willingness-to-pay thresholds (ie, cost-effective). Furthermore, in 11% (3/27) of the studies, noninvasive remote monitoring devices and telephone support were either above the willingness-to-pay thresholds or more costly than, yet as effective as, the comparators (ie, not cost-effective). In terms of reporting quality, the studies were classified as good (20/27, 74%), moderate (6/27, 22%), or excellent (1/27, 4%). CONCLUSIONS: Despite the conflicting results, the main findings indicated that, overall, DHIs were more cost-effective than non-DHI alternatives. TRIAL REGISTRATION: PROSPERO CRD42023388241; https://tinyurl.com/2p9axpmc.

Evaluation of usability and user feedback to guide telepharmacy application development in Indonesia: a mixed-methods study.

BACKGROUND: In Indonesia, the adoption of telepharmacy was propelled by the COVID-19 pandemic, prompting the need for a user-friendly application to support both the general population and pharmacists in accessing healthcare services. Therefore, this study aimed to evaluate usability and user feedback of a pioneering telepharmacy application known as Tanya Obat (translating to "Ask about Medications") in Indonesia, from the perspectives of the general population and pharmacists. METHODS: A mixed-methods sequential study was conducted with the early-stage Tanya Obat application in Bandung City. Participants, including the general population and pharmacists, were instructed to use the application for a week. Questionnaires for the general population and pharmacists were distributed from March to May and February to June 2023, respectively. The System Usability Scale questionnaire was adopted to describe usability of the developed application. Further exploration of the quantitative results required collecting open-ended feedback to assess the impressions of the participants, difficulties encountered, and desired features for enhanced user-friendliness. The collected statements were summarized and clustered using thematic analysis. Subsequently, the association between the characteristics of participants and perceived usability was determined with the Chi-square test. RESULT: A total of 176 participants, comprising 100 individuals from the general population and 76 pharmacists, engaged in this study. In terms of usability, the questionnaire showed that Tanya Obat application was on the borderline of acceptability, with mean scores of 63.4 and 64.1 from the general population and pharmacists, respectively. Additionally, open-ended feedback targeted at achieving a more compelling user experience was categorized into two themes, including concerns regarding the functionality of certain features and recommendations for improved visual aesthetics and bug fixes. No significant associations were observed between the characteristics of participants and perceived usability (p-value > 0.05). CONCLUSION: The results showed that the perceived usability of Tanya Obat developed for telepharmacy was below average. Therefore, feature optimizations should be performed to facilitate usability of this application in Indonesia.

Antidepressant use during pregnancy and the risk of developing gestational hypertension: a retrospective cohort study.

BACKGROUND: Prior studies reported that exposure to antidepressants during pregnancy may be associated with gestational hypertension. The aim of this study is to assess the association between the use of antidepressants during pregnancy and the risk of developing gestational hypertension. METHODS: A retrospective cohort study using the prescription database IADB.nl was conducted among nulliparous women with singleton pregnancies between 1994 and 2015 in the Netherlands. Logistic regression analysis was used to estimate odds ratios (OR), adjusted OR (aOR) and their corresponding 95% confidence intervals (95% CI). Gestational hypertension as main outcome measure was defined as at least one dispensed record of an antihypertensive drug (methyldopa, nifedipine, labetalol, ketanserin, nicardipine) after 20 weeks of gestation until 14 days after delivery. Sub-analyses were conducted for class of antidepressant, duration and amount of use of antidepressant (≤30, ≥30 Defined Daily Doses or DDDs), and maternal age. Sensitivity analyses to assess uncertainties were conducted. RESULTS: Twenty-eight thousand twenty women were included, of which 539 (1.92%) used antidepressants. The risk of gestational hypertension was doubled for women using antidepressant (aOR 2.00 95% CI 1.28-3.13). Significant associations were also found for the subgroup selective serotonin reuptake inhibitors (SSRIs) (aOR 2.07 95% CI 1.25-3.44), ≥30 DDDs (aOR 2.50 95% CI 1.55-3.99) and maternal age of 30-34 years (aOR 2.59 95% CI 1.35-4.98). Varying the theoretical gestational age showed comparable results. CONCLUSION: Prolonged use of antidepressants during the first 20 weeks of gestation appeared to be associated with an increased risk of developing gestational hypertension. When balancing the benefits and risks of using these drugs during pregnancy, this should be taken into account.

Exploratory Approach to Incorporating Carbon Footprint in Health Technology Assessment (HTA) Modelling: Cost-Effectiveness Analysis of Health Interventions in the United Kingdom.

BACKGROUND: Health interventions contribute to the production of greenhouse gas emissions. Thus, reducing carbon footprint is essential in supporting the UK National Health Service (NHS) pathway to net zero. This study explores the approach in which carbon footprint can be included when applying Health Technology Assessment (HTA) modelling using obesity intervention in the United Kingdom (UK) as a case study. METHODS: Using decision analytic modelling, we conducted an HTA incorporating the impacts of obesity-related treatment decisions on UK carbon emissions. A cohort Markov model was used to track the emissions of the UK population after receiving one of two obesity treatments: semaglutide and bariatric surgery. RESULTS: This study introduced two new carbon measurement tools that may be useful for future policymaking, incremental carbon footprint effectiveness ratio (ICFER) and incremental carbon footprint cost ratio (ICFCR), which made it possible to assess the emission impacts of proposed health policies. Using the obesity intervention case study, we found that both treatments have an incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-years (QALYs) gained. This is below the UK threshold, indicating that these are cost-effective treatments for obesity, but could increase the NHS carbon footprint. However, it could reduce the overall UK societal carbon footprint by reducing the number of people with obesity. The ICFCR shows a reduction of 1.13-4.51 kgCO2e (kilogram of carbon dioxide equivalent) for every pound spent on obesity treatment. CONCLUSION: This study illustrates a case study for estimating the effect of health policies on carbon emissions and provides a quantitative measure for obesity-related treatment decisions.

The Cost-Effectiveness of Dolutegravir in Combination with Tenofovir and Lamivudine for HIV Therapy: A Systematic Review.

The World Health Organization (WHO) recommends dolutegravir (DTG), a human immunodeficiency virus (HIV) medicine, as the first- and second-line treatment for all populations because, when compared to an efavirenz (EFV) regimen, plus two nucleoside reverse transcriptase inhibitors (NRTIs) has demonstrated significant effectiveness in HIV suppression in persons. This study aims to review evidence of the cost-effectiveness of DTG in combination with tenofovir and lamivudine compared with the standard of care for HIV therapy. The systematic review involved searching electronic databases for articles published between January 2018 and May 2022. Electronic database sources include PubMed, ScienceDirect, and EBSCO for articles on DTG in combination with tenofovir and lamivudine as subjects with cost-effectiveness outcomes. The inclusion criteria in this systematic review were studies about the cost-effectiveness analysis (CEA) of DTG in combination with tenofovir and lamivudine, written in English. A total of 145 articles were identified from three databases. After removing nine duplicates, 142 articles were screened by title and abstract, excluding 123 articles. After a full-text screening of 19 articles, five articles were selected for further analysis. Five articles reviewed in sub-Saharan Africa, India, and China implemented different modelling methods for CEA but produced similar results. The results of these studies demonstrate that it is more cost-effective than standard care for HIV treatment. The study conducted in sub-Saharan Africa from 2018 to 2020 showed a cost-effective result with disability-adjusted life years averted (DALY averted) by 83%; in India, it resulted in incremental cost-effectiveness ratio (ICER) $130 per year of live-saved (YLS); and a study in China found that dolutegravir plus tenofovir and lamivudine led to 0.006 incremental quality-adjusted life years (QALYs) with cost savings of $64. The DTG regimen is cost-effective and recommended for HIV therapy in all studies that provide results.

Assessment of childhood immunization services at private healthcare facilities in Indonesia: a case study in a highly-populated city.

Introduction: The need to enhance the utilization of the private sector for immunization programs in Indonesia while maintaining the high quality of services provided is evident. This study aimed to rapidly assess immunization services at private healthcare facilities in Indonesia by using Bandung, the most densely populated city, as the reference case. Methods: Initially, a situation analysis was conducted by collecting data from selected healthcare facilities (n = 9). Furthermore, a qualitative study was taken into account by developing framework approaches and conducting interviews with different layers, such as mid-level managers at healthcare facilities (n = 9), professional organizations (n = 4), and public stakeholders (n = 7). Results: The situation analysis showed that private healthcare facilities had provided sufficient time for essential childhood immunization services with adequate staff. Nevertheless, the number of limited staff the Ministry of Health (MoH) has trained remains a programmatic problem. Furthermore, private healthcare facilities have used the MoH guidelines and additional internal guidelines for immunization services as the primary reference, including in the efforts to provide complete and reliable equipment. Vaccine availability at private healthcare facilities is manageable with an acceptable out-of-stock level. The results of our interviews highlighted three key findings: the lack of coordination across public and private sectors, the need for immunization service delivery improvement at private healthcare facilities, and the urgency to strengthen institutional capacity for advocacy and immunization systems support. Conclusion: Even though private healthcare facilities have been shown to make a modest contribution to childhood immunization services in Indonesia, efforts should be made to expand the role of private healthcare facilities in improving the performance of routine immunization programs.

Hepatic Safety of Febuxostat and Allopurinol for Gout Patients: A Systematic Review of Randomized Controlled Trial.

Purpose: This study aims to systematically review the hepatic safety of febuxostat and allopurinol in adult gout patients. Methods: We searched for information using the following databases: PubMed, Cochrane Library, and Scopus. The inclusion criteria were to review all randomized controlled trials (RCT) that compared allopurinol and febuxostat for adult gout patients that had an assessment of liver function outcomes. Non-English studies on case reports, case series, reviews, and abstracts only were excluded. We extracted information from the studies to answer the research question, ie, study design, publication year, population, sample size, patient characterization, duration, Jadad score, and liver function outcomes. Results: We screened 512 publications from the databases and identified 11 studies that met the inclusion criteria. Ten out of 11 included studies were double-blind RCTs. In the majority of the included studies, no statistically significant differences were observed in terms of hepatic safety data between febuxostat and allopurinol. However, in studies where allopurinol titration was used, it posed a challenge to maintain blinding. Notably, consistent adverse events related to liver function findings were observed across all reviewed RCTs. These abnormal liver function test results sometimes led to study withdrawal based on the investigators' assessment. Nevertheless, the investigators classified most liver function test elevations as mild to moderate in severity. Conclusion: Our analysis concluded that adult gout patients enrolled in the included RCTs exhibited similar hepatic safety profiles for both febuxostat and allopurinol treatment. Liver function abnormalities were identified in all RCTs included in this systematic review. Consequently, it is important for the product labeling information of both allopurinol and febuxostat to present and describe the current safety data to guide healthcare practitioners when prescribing these medications to patients. Pharmacovigilance and post-marketing pharmacoepidemiology data are essential in establishing the comprehensive safety profile.

Evaluation of Global Post-Outbreak COVID-19 Treatment Interventions: A Systematic Review and Bibliometric Analysis of Randomized Controlled Trials.

Purpose: The outbreak of COVID-19 has led to a global pandemic with millions of cases and deaths. Many randomized controlled trials (RCTs) were conducted to establish effective therapies. However, the methodological quality of these trials is paramount, as it directly impacts the reliability of results. This systematic review and bibliometric analysis aim to assess the methodological approach, execution diversity, global trends, and distribution of COVID-19 treatment RCTs post-outbreak, covering the period from the second wave and onward up to the present. Methods: We utilize articles from three electronic databases published from September 1, 2020, to April 1, 2023. Inclusion and exclusion criteria were applied to identify relevant RCTs. Data extraction involved the collection of various study details. Risk of Bias (RoB) 2 tool assessed methodological quality, while implementation variability was evaluated against registration information. Bibliometric analysis, including keyword co-occurrence and country distribution, used VOSviewer and Tableau software. Results: Initially, 501 studies were identified, but only 22 met the inclusion criteria, of which 19 had registration information. The methodological quality assessment revealed deficiencies in five main domains: randomization process (36%), deviations from intended interventions (9%), missing outcome data (4%), measurement of the outcome (18%), and selection of reported results (4%). An analysis of alignment between research protocols and registration data revealed common deviations in eight critical aspects. Bibliometric findings showcased global collaboration in COVID-19 treatment RCTs, with Iran and Brazil prominently contributing, while keyword co-occurrence analysis illuminated prominent research trends and terms in study titles and abstracts. Conclusion: This study offers valuable insights into the evaluation of COVID-19 treatment RCTs. The scarcity of high-quality RCTs highlights the importance of enhancing trial rigor and transparency in global health emergencies.

The Potential of Single Nucleotide Polymorphisms (SNPs) as Biomarkers and Their Association with the Increased Risk of Coronary Heart Disease: A Systematic Review.

Human genetic analyses and epidemiological studies showed a potential association between several types of gene polymorphism and the development of coronary heart disease (CHD). Many studies on this pertinent topic need to be investigated further to reach an evidence-based conclusion. Therefore, in this current review, we describe several types of gene polymorphisms that are potentially linked to CHD. A systematic review using the databases EBSCO, PubMed, and ScienceDirect databases was searched until October of 2022 to find relevant studies on the topic of gene polymorphisms on risk factors for CHD, especially for the factors associated with single nucleotide polymorphisms (SNPs). The risk of bias and quality assessment was evaluated by Joanna Briggs Institute (JBI) guidelines. From keyword search results, a total of 6243 articles were identified, which were subsequently narrowed to 14 articles using prespecified inclusion criteria. The results suggested that there were 33 single nucleotide polymorphisms (SNPs) that can potentially increase the risk factors and clinical symptoms of CHD. This study also indicated that gene polymorphisms had a potential role in increasing CHD risk factors that were causally associated with atherosclerosis, increased homocysteine, immune/inflammatory response, Low-Density Lipoprotein (LDL), arterial lesions, and reduction of therapeutic effectiveness. In conclusion, the findings of this study indicate that SNPs may increase risk factors for CHD and SNPs show different effects between individuals. This demonstrates that knowledge of SNPs on CHD risk factors can be used to develop biomarkers for diagnostics and therapeutic response prediction to decide successful therapy and become the basis for defining personalized medicine in future.

Economic evaluation of COVID-19 vaccination: A systematic review.

Background: Safe and effective vaccination is considered to be the most critical strategy to fight coronavirus disease 2019 (COVID-19), leading to individual and herd immunity protection. We aimed to systematically review the economic evaluation of COVID-19 vaccination globally. Methods: We performed a systematic search to identify relevant studies in two major databases (MEDLINE/PubMed and EBSCO) published until September 8, 2022. After deduplication, two researchers independently screened the study titles and abstracts according to pre-determined inclusion and exclusion criteria. The remaining full-text studies were assessed for eligibility. We assessed their quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and summarized and narratively presented the results. Results: We identified 25 studies that assessed the economic evaluation of COVID-19 vaccination worldwide by considering several input parameters, including vaccine cost, vaccine efficacy, utility value, and the size of the targeted population. All studies suggested that COVID-19 vaccination was a cost-effective or cost-saving intervention for mitigating coronavirus transmission and its effect in many countries within certain conditions. Most studies reported vaccine efficacy values ranging from 65% to 75%. Conclusions: Given the favorable cost-effectiveness profile of COVID-19 vaccines and disparities in affordability across countries, considering prioritization has become paramount. This review provides comprehensive insights into the economic evaluation of COVID-19 vaccination that will be useful to policymakers, particularly in highlighting preventive measures and preparedness plans for the next possible pandemic.

Determinants of Cardiovascular Diseases in the Elderly Population in Indonesia: Evidence from Population-Based Indonesian Family Life Survey (IFLS).

Introduction: Cardiovascular disease (CVD) is the leading cause of death worldwide and is the number one mortality cause in Indonesia. The highest percentage of its prevalence occurs in the elderly population. This research aims to assess the determinants of CVDs in the elderly population in Indonesia based on the Indonesian Family Life Survey 5 (IFLS-5), a sub-nationally representative survey data, in 2014-2015. Methods: A national cross-sectional population-based survey was conducted using multicenter data from approximately 13 provinces in Indonesia in 2014-2015. We included elderly subjects aged 60 years old and above with complete data on sociodemographic, smoking habits, obesity, dietary pattern, and physical activity and diagnosis data on hypertension, diabetes mellitus (DM), and hypercholesterolemia. Multivariate logistic regression was performed to estimate odds ratio (OR) and corresponding 95% confidence interval (95% CI) and p-value. Results: We included complete data from 2873 respondents. The determinants associated with CVDs in the elderly population in Indonesia included college background (OR 6.26 [95% CI 2.690-14.613], p < 0.001), unemployment (OR 1.88 [95% CI 1.294-2.75], p = 0.001), urban population (OR 2.11 [95% CI 1.427-3.114], p < 0.001), obesity (OR 1.59 [95% CI 0.842-3.02], p = 0.152), low and medium physical activities (OR 2.34 [95% CI 1.335-4.121], p = 0.003 and OR 2.54 [95% CI 1.449-4.486], p = 0.001, respectively), hypertension (OR 4.25 [95% CI 2.945-6.137], p < 0.001), DM (OR 2.77 [95% CI 1.683-4.591], p < 0.001), and hypercholesterolemia (OR 2.99 [95% CI 1.860-4.812], p < 0.001). Conclusion: The determinants of CVDs in the elderly population in Indonesia based on Indonesian Family Life Survey (IFLS)-5 data are hypertension, hypercholesterolemia, DM, lower physical activity, higher educational background, urban population, unemployment, and obesity. The findings of this current study highlight that more appropriate control measures such as tailored intervention by policymakers and healthcare providers for those at high risk should be initiated and implemented.

Antihypertensive Medications for Severe Hypertension in Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertension in pregnancy causes significant maternal and fetal mortality and morbidity. A comprehensive assessment of the effectiveness of antihypertensive drugs for severe hypertension during pregnancy is needed to make informed decisions in clinical practice. This systematic review aimed to assess the efficacy and safety of antihypertensive drugs in severe hypertension during pregnancy. METHODS: A systematic review using the electronic databases MEDLINE (PubMed) and Cochrane Library was performed until August 2021. The risk-of-bias 2 tool was used to assess the risk-of-bias in each study included. Meta-analysis was conducted to assess heterogeneity and to estimate the pooled effects size. RESULTS: Seventeen studies fulfilled the inclusion criteria and 11 were included in the meta-analysis. Nifedipine was estimated to have a low risk in persistent hypertension compared to hydralazine (RR 0.40, 95% CI 0.23-0.71) and labetalol (RR 0.71, 95% CI 0.52-0.97). Dihydralazine was associated with a lower risk of persistent hypertension than ketanserin (RR 5.26, 95% CI 2.01-13.76). No difference was found in the risk of maternal hypotension, maternal and fetal outcomes, and adverse effects between antihypertensive drugs, except for dihydralazine, which was associated with more adverse effects than ketanserin. CONCLUSIONS: Several drugs can be used to treat severe hypertension in pregnancy, including oral/sublingual nifedipine, IV/oral labetalol, oral methyldopa, IV hydralazine, IV dihydralazine, IV ketanserin, IV nicardipine, IV urapidil, and IV diazoxide. In addition, nifedipine may be preferred as the first-line agent. There was no difference in the risk of maternal hypotension, maternal and fetal outcomes, and adverse effects between the drugs, except for adverse effects in IV dihydralazine and IV ketanserin.

Early cost-effectiveness analysis of screening for preeclampsia in nulliparous women: A modelling approach in European high-income settings.

BACKGROUND: Preeclampsia causes substantial maternal and perinatal morbidity and mortality and significant societal economic impact. Effective screening would facilitate timely and appropriate prevention and management of preeclampsia. OBJECTIVES: To develop an early cost-effectiveness analysis to assess both costs and health outcomes of a new screening test for preeclampsia from a healthcare payer perspective, in the United Kingdom (UK), Ireland, the Netherlands and Sweden. METHODS: A decision tree over a 9-month time horizon was developed to explore the cost-effectiveness of the new screening test for preeclampsia compared to the current screening strategy. The new test strategy is being developed so that it can stratify healthy low risk nulliparous women early in pregnancy to either a high-risk group with a risk of 1 in 6 or more of developing preeclampsia, or a low-risk group with a risk of 1 in 100 or less. The model simulated 25 plausible scenarios in a hypothetical cohort of 100,000 pregnant women, in which the sensitivity and specificity of the new test were varied to set a benchmark for the minimum test performance that is needed for the test to become cost-effective. The input parameters and costs were mainly derived from published literature. The main outcome was incremental costs per preeclampsia case averted, expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Base case results showed that the new test strategy would be more effective and less costly compared to the current situation in the UK. In the Netherlands, the majority of scenarios would be cost-effective from a threshold of €50,000 per preeclampsia case averted, while in Ireland and Sweden, the vast majority of scenarios would be considered cost-effective only when a threshold of €100,000 was used. In the best case analyses, ICERs were more favourable in all four participating countries. Aspirin effectiveness, prevalence of preeclampsia, accuracy of the new screening test and cost of regular antenatal care were identified as driving factors for the cost-effectiveness of screening for preeclampsia. CONCLUSION: The results indicate that the new screening test for preeclampsia has potential to be cost-effective. Further studies based on proven accuracy of the test will confirm whether the new screening test is a cost-effective additional option to the current situation.

Cost-Effectiveness of Contraceptive Use in Indonesia after the Implementation of the National Health Insurance System.

Since 2014, Indonesia has initiated to implement a national health insurance system, which included both of short- (SARC) and long-acting reversible contraceptive (LARC) into the benefit package. The aim of this study was to analyze the cost-effectiveness of contraceptive use in Indonesia after the implementation of the national health insurance in 2014-2017. A decision tree model was developed to analyze the cost-effectiveness of contraceptive use in Indonesia in 2014-2017 by comparing two strategies of pregnancy prevention: contraceptive and non-contraceptive. For contraceptive strategy, we took into account SARC and LARC. In a comparison with non-contraceptive, we calculated that the incremental cost-effectiveness ratio (ICER) of SARC would be $5.18, $4.80 and $3.76 per pregnancy averted for injection, condom, and pill, respectively. For LARC, we calculated that the ICER would be $1.67 and $0.84 for implant and intrauterine device (IUD), respectively, compared with non-contraceptive. In general, the cost-effectiveness value of LARC ($1.25) was much better than SARC ($4.58). The cost of contraceptive was considered to be the most influential parameter affecting both the ICER of SARC and LARC. In conclusion, the use of LARC in Indonesia was considered to be more cost-effective than SARC since the implementation of national health insurance system. In particular, IUD yielded the greatest cost-effectiveness value, compared with other methods.

Cost-Effectiveness Analysis of Sacubitril/Valsartan Compared to Enalapril for Heart Failure Patients in Indonesia.

OBJECTIVE: Sacubitril/valsartan is a relatively new medication that is more effective than the usual enalapril for heart failure patients with reduced ejection fraction. Therefore, this study aims to determine the cost-effectiveness of sacubitril/valsartan compared to enalapril in Indonesia's healthcare system. METHODS: In this study, a Markov decision-analytic model was developed to estimate the total cost, health outcomes, and cost-effectiveness of sacubitril/valsartan compared to enalapril from Indonesia's healthcare perspective. The input parameters for the cost-effectiveness were predominantly from the PARADIGM-HF trial. Subsequently, the country-specific data were synthesized for medication and hospitalization costs, cardiovascular and non-cardiovascular death, as well as re-hospitalization rate. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) gained was estimated to determine the cost-effectiveness. Deterministic and probabilistic sensitivity analyses were conducted to assess the impact of parameter uncertainty. RESULTS AND DISCUSSION: In the base case, sacubitril/valsartan was more costly and effective than enalapril with a total cost of IDR 91,783,325,865 (USD 6,487,522) vs IDR 68,101,971,241 (USD 4,813,653) and a total QALYs of 19,680 vs 18,795, resulting in an ICER of IDR 26,742,098 (USD 1890). Based on the willingness to pay threshold GDP per capita in Indonesia, it can be considered cost-effective. The most influential drivers of cost-effectiveness in deterministic sensitivity analysis were risk of mortality outside hospitalization, hospital admission rate, and cost of sacubitril/valsartan. The vast majority of simulation results from probabilistic analysis suggested that sacubitril/valsartan was likely resulted in higher cost and improved QALYs compared with enalapril, indicating the robustness of the model. CONCLUSION: Based on the current price in Indonesia, sacubitril/valsartan can be considered a cost-effective option, although this depends heavily on the willingness to pay threshold. Further studies that incorporate real-world evidence with sacubitril/valsartan are needed to inform the decision-making process.

Effectiveness of Remdesivir, Lopinavir/Ritonavir, and Favipiravir for COVID-19 Treatment: A Systematic Review.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel strain that causes acute respiratory illnesses known as coronavirus disease 2019 (COVID-19). Currently, there is limited information regarding the therapeutic management for this disease. Several studies have stated that antivirals drugs such as remdesivir, favipiravir, and lopinavir/ritonavir may potentially inhibit the virus from spreading to the host. OBJECTIVE: The aim of this systematic review was to summarize the clinical effectiveness and safety of remdesivir, favipiravir, and lopinavir/ritonavir on COVID-19. METHODS: The PubMed and Cochrane Library databases were searched up to July 2021 to identify eligible experimental randomized controlled trials on remdesivir, favipiravir, and lopinavir/ritonavir for COVID-19 patients. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. RESULTS: From 158 references, 15 studies were included in the review. The results showed that remdesivir has some potential benefits for hospitalized COVID-19 patients, as seen from clinical improvements such as faster recovery time, less duration of hospitalization, and fewer respiratory side effects among COVID-19 patients. However, the impact of remdesivir in reducing mortality remains uncertain. Treatment with favipiravir has shown promising improvement in the clinical status of COVID-19 patients, although the results suggested no significant differences in some clinical parameters such as length of hospitalizations and clinical recovery. A combination of favipiravir with other supportive therapy showed more favorable outcomes for COVID-19 patients. Furthermore, the use of lopinavir/ritonavir in COVID-19 patients reported no significant clinical improvement compared to standard care with notable adverse effect reactions. CONCLUSION: This study provides an overview of the evidence-based role of remdesivir, favipiravir, and lopinavir/ritonavir in the management of COVID-19. A thorough assessment of the benefit-risk profile in COVID-19 patients is urgently needed. The current review was based on very limited available data; therefore, further well-designed clinical trials are required.

Multi-criteria decision analysis to prioritize the introduction of new vaccines in Indonesia by using the framework of the strategic multi-attribute ranking tool for vaccines (SMART vaccines).

Background: Decision-making processes regarding new vaccine prioritizations are complex. The objective of this study was to prioritize the introduction of new vaccines in Indonesia.Methods: A multi-criteria decision analysis (MCDA) was applied in this study. A preliminary data collection form was developed to collect country-specific data in relation to 30 pre-defined attributes. In particular, an open-ended questionnaire was conducted among targeted respondents from global level, national level and vaccine manufacturers, which were involved in the financial flows of new vaccine procurement in Indonesia. For setting new vaccines priorities, targeted respondents were asked to assign weight on 10 selected criteria.Results: Top 3 attributes with the highest weight from respondents were premature deaths averted per year, incident cases prevented per year, and cost-effectiveness. Applying criteria scores and weight assessment, the result showed that PCV, rotavirus, HPV, and JE would be on the 1st, 2nd, 3rd, and 4th rank for setting new vaccine priority in Indonesia. There was a significant difference score (p value <0.05) between all these vaccines.Conclusions: PCV, rotavirus and HPV vaccines should be more prioritized than JE vaccine. This ranking is in line with the WHO's priority list, which potentially illustrates the validity and usefulness of our MCDA-approach.

Cost-Effectiveness and Budget Impact Analyses of Pneumococcal Vaccination in Indonesia.

As a country with the high number of deaths due to pneumococcal disease, Indonesia has not yet included pneumococcal vaccination into the routine program. This study aimed to analyse the cost-effectiveness and the budget impact of pneumococcal vaccination in Indonesia by developing an age-structured cohort model. In a comparison with no vaccination, the use of two vaccines (PCV10 and PCV13) within two pricing scenarios (UNICEF and government contract price) was taken into account. To estimate the cost-effectiveness value, a 5-year time horizon was applied by extrapolating the outcome of the individual in the modelled cohort until 5 years of age with a 1-month analytical cycle. To estimate the affordability value, a 6-year period (2019-2024) was applied by considering the government's strategic plan on pneumococcal vaccination. In a comparison with no vaccination, the results showed that vaccination would reduce pneumococcal disease by 1,702,548 and 2,268,411 cases when using PCV10 and PCV13, respectively. Vaccination could potentially reduce the highest treatment cost from the payer perspective at $53.6 million and $71.4 million for PCV10 and PCV13, respectively. Applying the UNICEF price, the incremental cost-effectiveness ratio (ICER) from the healthcare perspective would be $218 and $162 per QALY-gained for PCV10 and PCV13, respectively. Applying the government contract price, the ICER would be $987 and $747 per QALY-gained for PCV10 and PCV13, respectively. The result confirmed that PCV13 was more cost-effective than PCV10 with both prices. In particular, introduction cost per child was estimated to be $0.91 and vaccination cost of PCV13 per child (3 doses) was estimated to be $16.61 and $59.54 with UNICEF and government contract prices, respectively. Implementation of nationwide vaccination would require approximately $73.3-$75.0 million (13-14% of routine immunization budget) and $257.4-$263.5 million (45-50% of routine immunization budget) with UNICEF and government contract prices, respectively. Sensitivity analysis showed that vaccine efficacy, mortality rate, and vaccine price were the most influential parameters affecting the ICER. In conclusion, pneumococcal vaccination would be a highly cost-effective intervention to be implemented in Indonesia. Yet, applying PCV13 with UNICEF price would give the best cost-effectiveness and affordability values on the routine immunization budget.

Effectiveness and Safety Profile of Alternative Tobacco and Nicotine Products for Smoking Reduction and Cessation: A Systematic Review.

BACKGROUND: Alternative tobacco and nicotine products such as electronic cigarettes (EC), smokeless tobacco, and nicotine replacement therapy (NRT) are currently being assessed as options in tobacco harm reduction due to their potential role in smoking reduction and smoking cessation. OBJECTIVE: To provide the current evidence on the effectiveness and safety of various alternative tobacco and nicotine products for smoking reduction and cessation. METHODS: A systematic review using databases from MEDLINE (PubMed), EMBASE, and The Cochrane Library was conducted up to December 2020 to identify eligible experimental and observational studies assessing the use of alternative tobacco and nicotine products on smoking reduction and smoking cessation and the safety of these products. The Cochrane Risk of Bias 2 (RoB 2) and ROBINS-I tools were used to assess the risk of bias of the included studies. Results were described through a narrative synthesis of the evidence. RESULTS: From 1955 retrieved references, 44 studies (31 randomized controlled trials/RCTs and 13 prospective cohort studies) met the inclusion criteria and were included in the review. Twenty-nine studies were assessing EC, one study evaluated heat-not-burn (HNB) product, five studies were focused on snus, and nine studies assessed NRT in the form of nicotine patch, gum, etc. The overall results suggested that alternative tobacco and nicotine products in the form of EC, snus, and NRT can moderately reduce daily cigarette consumption and has potential to assist smoking cessation attempts, with fewer adverse events. CONCLUSION: The findings suggested that alternative tobacco and nicotine products have a potential role in assisting smoking reduction and cessation, highlighting their role in the tobacco harm reduction approach. Further studies should focus on investigating long-term outcomes, safety, and effectiveness of alternative tobacco and nicotine products to better inform smoking reduction/cessation policy. PROSPERO REGISTRATION NUMBER: CRD42020205830.

Impact of Switch Options on the Economics of Pneumococcal Conjugate Vaccine (PCV) Introduction in Indonesia.

As one of Gavi, the Vaccine Alliance (previously the Global Alliance for Vaccines and Immunization), graduating countries, Indonesia is still eligible to access Gavi price for PCV13, PCV10 A and B. This study aims to estimate the economic impact of switch from the existing product/presentation of PCV (single-dose of PCV13) to the new product/presentation of PCV (multi-dose of PCV13, PCV10 A and B) since PCV is one of the most expensive vaccines in the Expanded Program on Immunization (EPI) schedule. Assuming that Gavi-Advance Market Commitment (AMC) price for all PCVs can be accessed in 2021, the use of multi-dose PCV13, PCV10 A and PCV10 B with Gavi-AMC price in 2021-2024 were considered as respective scenarios. The result showed that the scenario assuming the use of single-dose of PCV13 with contract price in 2019-2020 that would be switched into multi-dose of PCV10 B with Gavi-AMC price in 2021-2024 resulted in the highest potential saving, compared with other scenarios. Our analysis suggests an economic advantage to switch from single-dose into a multi-dose presentation. Vaccination coverage, vaccine price, vaccine wastage and additional Gavi-AMC vaccine costs were considered to be the most influential parameter affecting the savings in all scenarios. Applying the effectiveness of PCV13 and PCV10 A on reducing the risk for invasive pneumococcal disease (IPD), potential averted incidence of IPD in children under one year of age during 2019-2024 would be 246,164 and 105,587 in both scenarios. Despite the result confirmed that PCV13 may provide an additional benefit, a more comprehensive economic evaluation study is required to investigate further the comparison of cost-effectiveness values among all PCVs in Indonesia.