BackgroundDengue is associated with significant economic expenditure and it is estimated that the Asia Pacific region accounts for >50% of the global cost. Indonesia has one of the world’s highest dengue burdens; Aedes aegypti and Aedes albopictus are the primary and secondary vectors. In the absence of local data on disease cost, this study estimated the annual economic burden during 2015 of both hospitalized and ambulatory dengue cases in Indonesia.MethodsTotal 2015 dengue costs were calculated using both prospective and retrospective methods using data from public and private hospitals and health centres in three provinces: Yogyakarta, Bali and Jakarta. Direct costs were extracted from billing systems and claims; a patient survey captured indirect and out-of-pocket costs at discharge and 2 weeks later. Adjustments across sites based on similar clinical practices and healthcare landscapes were performed to fill gaps in cost estimates. The national burden of dengue was extrapolated from provincial data using data from the three sites and applying an empirically-derived epidemiological expansion factor.ResultsTotal direct and indirect costs per dengue case assessed at Yogyakarta, Bali and Jakarta were US$791, US$1,241 and US$1,250, respectively. Total 2015 economic burden of dengue in Indonesia was estimated at US$381.15 million which comprised US$355.2 million for hospitalized and US$26.2 million for ambulatory care cases.ConclusionDengue imposes a substantial economic burden for Indonesian public payers and society. Complemented with an appropriate weighting method and by accounting for local specificities and practices, these data may support national level public health decision making for prevention/control of dengue in public health priority lists.

ObjectivesThis study aims to assess the value for money and budget impact of offering hemodialysis (HD) as a first-line treatment, or the HD-first policy, and the peritoneal dialysis (PD) first policy compared to a supportive care option in patients with end-stage renal disease (ESRD) in Indonesia.MethodsA Markov model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). Three policy options were compared, i.e., the PD-first policy, HD-first policy, and supportive care.ResultsThe PD-first policy for ESRD patients resulted in 5.93 life years, equal to the HD-first policy, with a slightly higher QALY gained (4.40 vs 4.34). The total lifetime cost for a patient under the PD-first policy is around 700 million IDR, which is lower than the cost under the HD-first policy, i.e. 735 million IDR per patient. Compared to supportive care, the incremental cost-effectiveness ratio of the PD-first policy is 193 million IDR per QALY, while the HD-first policy resulted in 207 million IDR per QALY. Budget impact analysis indicated that the required budget for the PD-first policy is 43 trillion IDR for 53% coverage and 75 trillion IDR for 100% coverage in five years, which is less than the HD-first policy, i.e. 88 trillion IDR and 166 trillion IDR.ConclusionsThe PD-first policy was found to be more cost-effective compared to the HD-first policy. Budget impact analysis provided evidence on the enormous financial burden for the country if the current practice, where HD dominates PD, continues for the next five years.

Drug-induced liver injury (DILI) is the most common adverse drug reaction in the treatment of tuberculosis (TB). Several studies showed that patients with TB and the slow-acetylator phenotype caused by NAT2 variants are highly susceptible to DILI caused by anti-TB drugs, hereafter designated AT-DILI. However, the role of NAT2 variants in AT-DILI has never been assessed for an Indonesian population. We recruited 50 patients with TB and AT-DILI and 191 patients with TB but without AT-DILI; we then used direct DNA sequencing to assess single-nucleotide polymorphisms in the coding region of NAT2. NAT2*6A was significantly associated with susceptibility to AT-DILI (P=7.7 × 10(-4), odds ratio (OR)=4.75 (1.8-12.55)). Moreover, patients with TB and the NAT2-associated slow-acetylator phenotype showed higher risk of AT-DILI than patients with the rapid- or intermediate-acetylator phenotypes (P=1.7 × 10(-4), OR=3.45 (1.79-6.67)). In conclusion, this study confirms the significance of the association between slow-acetylator NAT2 variants and susceptibility to AT-DILI in an Indonesian population.

Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia. Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and Sundanese controls were genotyped for HLA-B and their allele frequencies were compared. The HLA-B*15:02 allele was found in 66.7% of the patients with CBZ-induced SJS/TEN, but only in 29.4% of tolerant control (p = 0.029; odds ratio [OR]: 6.5; 95% CI: 1.2–33.57) and 22.9% of healthy controls (p = 0.0021; OR: 6.78; 95% CI: 1.96–23.38). These findings support the involvement of HLA-B*15:02 in CBZ-induced SJS/TEN reported in other Asian populations. Interestingly, we also observed the presence of the HLA-B*15:21 allele. HLA-B*15:02 and HLA-B*15:21 are members of the HLA-B75 serotype, for which a greater frequency was observed in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90–75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83–40]). Our findings suggest that screening for the HLA-B75 serotype can predict the risk of CBZ-induced SJS/TEN more accurately than screening for a specific allele.

BackgroundOff-patent pharmaceuticals (OPPs) hold vital importance in meeting public health objectives, especially in developing countries where resources are limited. OPPs are comprised of off-patent originals, branded generics and unbranded generics; nonetheless, these products are not identical and often there are differences in their equivalence, manufacturing quality standards and reliability of supply. This necessitates reconsideration of the lowest price policy objective in pharmaceutical decision making. The aim of this study was to develop a Multi-Criteria Decision Analysis (MCDA) framework through a pilot workshop to inform the national procurement of OPPs in Indonesia.MethodsAn initial list of potentially relevant criteria was identified based on previous work and a literature review. In a 2-day pilot policy workshop, twenty local experts representing different stakeholder groups and decision-making bodies selected the final criteria, approved the scoring function for each criterion, and assigned weights to each criterion.ResultsAn MCDA framework was proposed for OPP drug decision making in developing countries, which included price and 8 non-price criteria. Based on the pilot policy workshop 6 + 1 criteria were considered relevant for Indonesia: pharmaceutical price (40% weight), manufacturing quality (18.8%), equivalence with the reference product (12.2%), product stability and drug formulation (12.2%), reliability of drug supply (8.4%), real world clinical or economic outcomes, such as adherence or non-drug costs (4.2%) and pharmacovigilance (3.6%).ConclusionsAccording to the pilot policy workshop, other criteria apart from price need to be strengthened in the tendering process. The introduction of additional criteria for OPP procurement in an MCDA framework creates incentives for manufacturers to invest into improved manufacturing standards, equivalence proof, product quality, reliability of supply or even additional real-world data collection, which ultimately may result in more health gain for the society.