Cost-effectiveness of emicizumab prophylaxis for haemophilia A with inhibitors: an adaptive health technology assessment for the Indian setting.

OBJECTIVE: To assess the cost-effectiveness of emicizumab prophylaxis for patients having haemophilia A with inhibitors in the Indian context using an adaptive health technology assessment (aHTA) methodology. DESIGN: Economic evaluation using multiple approaches aimed at adjusting previously generated cost-effectiveness results based on (1) price differences only ('simple') and (2) differences in cost and expected treatment duration ('moderate') and differences in cost, inflation and life expectancy ('complex'). SETTING: Typical haemophilia care in India. PARTICIPANTS: Patients with haemophilia A and inhibitors. INTERVENTION: Emicizumab prophylaxis using two vial strengths (30 or 150 mg/mL) in comparison to no prophylaxis. MAIN OUTCOME MEASURES: Adjusted incremental cost-effectiveness ratio (ICERa), incremental costs and incremental quality-adjusted life years associated with emicizumab prophylaxis from both the health system and societal perspectives. RESULTS: Using the simple ICER adjustment method, emicizumab prophylaxis resulted in potential cost savings from the payers' perspective for both vial strengths in patients aged ≥12 and <12 years. However, from a societal perspective, emicizumab prophylaxis was not cost-effective. Using the moderate adjustment method, emicizumab prophylaxis showed potential cost saving from the health system perspective. The complex adjustment method also revealed cost savings for emicizumab prophylaxis from the health system and societal perspectives across different age groups. CONCLUSION: We found that implementing emicizumab prophylaxis for patients with haemophilia A and inhibitors in India has the potential to result in cost savings. This study highlights the feasibility of using the expanded aHTA methodology for rapid evidence generation in the Indian context. However, it is crucial to address certain research gaps, including data limitations, challenges in translating international evidence to Indian context and associated uncertainties. Additionally, conducting a comprehensive budget impact analysis is necessary. These findings hold significant implications for decision-making regarding the potential provision of emicizumab prophylaxis through federal or/and state government-funded programmes and institutions in India.

Comprehensive league table of cost-utility ratios: A systematic review of cost-effectiveness evidence for health policy decisions in India.

Background and objectives: Although a relatively recent concept for developing countries, the developed world has been using League Tables as a policy guiding tool for a comprehensive assessment of health expenditures; country-specific "League tables" can be a very useful tool for national healthcare planning and budgeting. Presented herewith is a comprehensive league table of cost per Quality Adjusted Life Years (QALY) or Disability Adjusted Life Years (DALY) ratios derived from Health Technology Assessment (HTA) or economic evaluation studies reported from India through a systematic review. Methods: Economic evaluations and HTAs published from January 2003 to October 2019 were searched from various databases. We only included the studies reporting common outcomes (QALY/DALY) and methodology to increase the generalizability of league table findings. To opt for a uniform criterion, a reference case approach developed by Health Technology Assessment in India (HTAIn) was used for the reporting of the incremental cost-effectiveness ratio. However, as, most of the articles expressed the outcome as DALY, both (QALY and DALY) were used as outcome indicators for this review. Results: After the initial screening of 9,823 articles, 79 articles meeting the inclusion criteria were selected for the League table preparation. The spectrum of intervention was dominated by innovations for infectious diseases (33%), closely followed by maternal and child health (29%), and non-communicable diseases (20%). The remaining 18% of the interventions were on other groups of health issues, such as injuries, snake bites, and epilepsy. Most of the interventions (70%) reported DALY as an outcome indicator, and the rest (30%) reported QALY. Outcome and cost were discounted at the rate of 3 by 73% of the studies, at 5 by 4% of the studies, whereas 23% of the studies did not discount it. Budget impact and sensitivity analysis were reported by 18 and 73% of the studies, respectively. Interpretation and conclusions: The present review offers a reasonably coherent league table that reflects ICER values of a range of health conditions in India. It presents an update for decision-makers for making decisions about resource allocation.

An economic evaluation of implementing a decentralized dengue screening intervention under the National Vector Borne Disease Control Programme in Tamil Nadu, South India.

BACKGROUND: Lack of effective early screening is a major obstacle for reducing the fatality rate and disease burden of dengue. In light of this, the government of Tamil Nadu has adopted a decentralized dengue screening strategy at the primary healthcare (PHC) facilities using blood platelet count. Our objective was to determine the cost-effectiveness of a decentralized screening strategy for dengue at PHC facilities compared with the current strategy at the tertiary health facility (THC) level. METHODS: Decision tree analysis followed a hypothetical cohort of 1000 suspected dengue cases entering the model. The cost-effectiveness analysis was performed at a 3% discount rate for the proposed and current strategy. The outcomes are expressed in incremental cost-effectiveness ratios (ICERs) per quality-adjusted life years gained. One-way sensitivity analysis and probabilistic sensitivity analysis were done to check the uncertainty in the outcome. RESULTS: The proposed strategy was found to be cost-saving and ICER was estimated to be -41 197. PSA showed that the proposed strategy had a 0.84 probability of being an economically dominant strategy. CONCLUSIONS: The proposed strategy is cost-saving, however, it is recommended to consider optimal population coverage, costs to economic human resources and collateral benefits of equipment.

Cost-Effectiveness of Portable Electrocardiogram for Screening Cardiovascular Diseases at a Primary Health Center in Ahmedabad District, India.

Background: District Health Authority in Ahmedabad, Gujarat has introduced Project Lifeline, 12-lead portable ECG devices across all primary health centers (PHC) in the district to screen cardiac abnormalities among high-risk and symptomatic adults for providing primary management and proper timely referral. The prime purpose of the study was to assess the cost-effectiveness of portable ECG for the screening of cardiovascular diseases (CVD) among high-risk and symptomatic adults at the PHC in Ahmedabad, Gujarat. Methods: Cost-effective analysis was conducted using a societal perspective. An incremental costing approach was adapted, and cost-effectiveness analysis was done using a decision-analytic model. We surveyed 73 patients who screened positive for cardiac abnormality, documented the type of ECG abnormalities, and diagnosed CVD. The program cost was obtained from the implementers. Transition probabilities were derived from primary data supported by expert opinion for the intervention arm, while a systematic search of the literature was undertaken to derive transition probabilities for the control arm. Results: The ECG screening at PHC saves 2.90 life years at an incremental cost of 89.97 USD (6657.47 INR), yielding a cost-effectiveness ratio of 31.07 USD (2,299.06 INR) per life-year saved, which is below the willingness to pay threshold. The budget impact analysis was also performed. Results are sensitive to the relative risk reduction associated with the non-participation and the cost of initial screening. Conclusion: Cost-effectiveness analysis clearly shows that the facility to screen cardiac abnormality at the PHC level is highly recommended for high-risk adults and symptomatic cases.

Economic evaluation of implementing a decentralised Hepatitis B virus diagnostic intervention under National Viral Hepatitis Control Programme in Tamil Nadu, South India.

OBJECTIVE: To assess the cost-effectiveness of decentralised diagnostic programme for hepatitis B virus (HBV) implemented in Tamil Nadu, South India with specific focus on a selected key population at increased risk of HBV. METHODS: A combination of decision tree and Markov model was developed to compare cost-effectiveness of the new and standard strategy. Cost and health outcomes were calculated based on the proportion of cohort in each respective health state. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) of the intervention and comparator strategies were calculated. The model parameter uncertainties were evaluated by sensitivity analysis. RESULTS: Considering decentralised HBV diagnosis followed by early treatment and vaccination for negatives for a cohort of 1000 population resulted in 505 QALYs gained and incremental cost-saving of 180749 ($2620). The decentralised diagnostic strategy could avert 294 deaths, gain 293 life years and reduce out-of-pocket expenditure of 3274 ($47) per person for HBV management. CONCLUSION: Decentralised HBV diagnosis followed by early treatment and vaccination for negatives in Tamil Nadu can save lives and reduce out-of-pocket expenditures compared to standard strategy.

OBJECTIF: Evaluer le rapport coût-efficacité du programme de diagnostic décentralisé du virus de l'hépatite B (VHB) mis en œuvre au Tamil Nadu, dans le sud de l'Inde, avec un accent particulier sur une population clé sélectionnée à risque accru du VHB. MÉTHODES: Une combinaison d'arbre de décision et de modèle de Markov a été développée pour comparer la rentabilité de la stratégie nouvelle et standard. Les coûts et les résultats pour la santé ont été calculés sur base de la proportion de la cohorte dans chaque état de santé respectif. Les coûts totaux, les années de vie corrigées de la qualité (QALY), le rapport coût-efficacité supplémentaire de l'intervention et les stratégies de comparaison ont été calculés. Les incertitudes des paramètres du modèle ont été évaluées par analyse de sensibilité. RÉSULTATS: La prise en compte d'un diagnostic décentralisé du VHB suivi d'un traitement précoce et d'une vaccination des cas négatifs pour une cohorte de 1000 habitants a permis de gagner 505 QALY et d'économiser des coûts supplémentaires de ₹180.749 (2.620 USD). La stratégie de diagnostic décentralisée pourrait éviter 294 décès, gagner 293 années de vie et réduire les dépenses personnelles de ₹3274 (47 USD) par personne pour la prise en charge du VHB. CONCLUSION: Le diagnostic décentralisé du VHB suivi d'un traitement précoce et de la vaccination des cas négatifs au Tamil Nadu peut sauver des vies et réduire les dépenses personnelles par rapport à la stratégie standard.

Evaluation of variation of interfraction doses to organs at risk during brachytherapy of cervical cancer.

BACKGROUND: Two-dimensional treatment planning using radiographs or simulator films was the standard in planning brachytherapy for patients with cervical cancer. Three-dimensional (3D) treatment planning has improved treatment efficacy. This retrospective study compares conventional and 3D treatment planning of brachytherapy in patients with cervical cancer and interfraction dose variation to bladder and rectum (D2cc). METHODS: The mean doses to bladder and rectum (D2cc) were computed by computed tomography (CT)-based planning during 100 sessions of intracavitary brachytherapy for carcinoma cervix with the same source configuration as generated for conventional planning, and these estimates were compared with the doses at International Commission on Radiation Units and measurements (ICRU) rectal, bladder points and point A. Interfraction variation of doses to bladder and rectum during various sessions was also analysed. RESULT: The mean ICRU bladder dose and D2cc of the bladder for all patients was 3.7 Gy and 7.4 Gy, respectively (p < 0.001). The mean ICRU rectal dose from conventional plan was 4.3Gy and with CT planning, 4.45 Gy (p = 0.04). Interfraction dose variations for D2cc of the bladder were min -5.3 Gy and max 4.8 Gy and those of the rectum were min -1.8 Gy and max 1.72Gy. CONCLUSION: Dosimetric evaluation of conventional and 3D CT-based treatment planning for the same brachytherapy sessions demonstrated underestimation of ICRU bladder dose points (p < 0.001) and the rectal ICRU point dose and D2cc (p=0.04). The doses to organs at risk did not show a statistically significant variation between the fractions. However, large variation was noted between the interfractional maximum and minimum doses to bladder and rectum.

Evaluation of antimicrobial property of modified acrylic resin-containing cetylpyridinium chloride.

OBJECTIVE: To evaluate the antimicrobial property of cetylpyridinium chloride (CPC) when polymerized with cold cure acrylic and to assess the duration of its release from modified acrylic. MATERIALS AND METHODS: CPC was added in different concentrations (0%, 2.5%, 5%, and 10%) to cold cure acrylic resin and 180 acrylic discs were prepared. These were divided into four groups of 45 each depending on the concentration of CPC. The antimicrobial property of the modified acrylic for Streptococcus mutans was tested using disc diffusion assay in agar. The duration of release of CPC from self-cure acrylic was tested with optical density reading of solutions by ultraviolet spectrophotometer. The effect of addition of CPC on diametral tensile strength (DTS) of acrylic was tested using UTM (Instron) and the effect of water aging on modified acrylic was compared with unaged specimens. RESULTS AND CONCLUSION: The normality of the data was checked by Shapiro-Wilktest, and as the data failed to show normal distribution, inferential statistics were performed using nonparametric tests of significance. Antimicrobial activity of modified acrylic increased with increase in CPC concentration. Greatest CPC release was observed on the seventh day with a decrease in release from 7 to 180 days. There was a decrease in the diametral strength of the modified resin and water aging had a significant effect on the DTS of the modified resin.

Dosimetric and isocentric variations due to patient setup errors in CT-based treatment planning for breast cancer by electronic portal imaging.

BACKGROUND: Inaccuracies in treatment setup during radiation therapy for breast cancers may increase risks to surrounding normal tissue toxicities, i.e. organs at risks (OARs), and compromise disease control. This study was planned to evaluate the dosimetric and isocentric variations and determine setup reproducibility and errors using an online electronic portal imaging (EPI) protocol. METHODS: A total of 360 EPIs in 60 patients receiving breast/chest wall irradiation were evaluated. Cumulative dose-volume histograms (DVHs) were analyzed for mean doses to lung (V20) and heart (V30), setup source to surface distance (SSD) and central lung distance (CLD), and shifts in anterior-posterior (AP), superior-inferior (SI), and medial lateral (ML) directions. RESULTS: Random errors ranged from 2 to 3 mm for the breast/chest wall (medial and lateral) tangential treatments and 2-2.5 mm for the anterior supraclavicular nodal field. Systematic errors ranged from 3 to 5 mm in the AP direction for the tangential fields and from 2.5 to 5 mm in the SI and ML direction for the anterior supraclavicular nodal field. For right-sided patients, V20 was 0.69-3.96 Gy, maximum lung dose was 40.5 Gy, V30 was 1.4-3 Gy, and maximum heart dose was 50.5 Gy. Similarly, for left-sided patients, the CLD (treatment planning system) was 25 mm-30 mm, CLD (EPIs) was 30-40 mm, V20 was 0.9-5.9 Gy, maximum lung dose was 45 Gy, V30 was 2.4-4.1 Gy, and maximum heart dose was 55 Gy. CONCLUSION: Online assessment of patient position with matching of EPIs with digitally reconstructed radiographs (DRRs) is a useful method in evaluation of interfraction reproducibility in breast irradiation.

Single nucleotide polymorphisms of microRNA in cardiovascular diseases.

Despite the advances in medicine and in science of diagnosis, cardiovascular diseases (CVD) remain the number one cause of morbidity and mortality worldwide. Apart from the modifiable risk factors, genetic factors are believed to also influence the outcome of this umbrella of diseases. Under the genetic factors, miRNA polymorphisms, namely miR-146a (rs2910164), miR-196 (rs11614913) and miR-499 (rs3746444), have become an important tool to study the mechanism that underlie the pathogenesis of this disease. In this review, we analyze the advances made through various research studies and the evidence provided by them in the area of miRNA polymorphisms by comparing the allelic frequencies and genotyping patterns. Interestingly, these studies have contradicting results even those conducted in same set of population. We also highlight the gap in literature search as majority of these studies have been conducted in Chinese population and data gaps are evident in Caucasian population, along with developing countries like, India, where no such data is available. This makes the daunting task of presenting a global picture and of the extent these polymorphisms play a role in CVD progression, even more difficult. Therefore, we suggest that more work needs to be done by taking various geographical domains in to consideration. Also, larger sample size calculated through statistical tools is the key to progress in establishing the genetic co-relation of miRNA polymorphisms and CVDs.

Non isocentric film-based intracavitary brachytherapy planning in cervical cancer: a retrospective dosimetric analysis with CT planning.

PURPOSE: To compare intracavitary brachytherapy dose estimation for organs at risk (bladder and rectum) based on semi-orthogonal reconstruction of radiographs on non-isocentric X-ray unit and Computed Tomography (CT) - based volumetric planning in cervical cancer. MATERIAL AND METHODS: Bladder and rectal points as per International Commission on Radiation Units and Measurements (ICRU) report 38, were retrospectively evaluated on 15 high dose rate intracavitary brachytherapy applications for cervical cancer cases. With the same source configuration as obtained during planning on radiographs performed on a non-isocentric X-ray unit, the mean doses to 2cc of most irradiated part of bladder and rectum were computed by CT planning and these estimates were compared with the doses at ICRU bladder and rectal points. RESULTS: The mean ICRU point dose for bladder was 3.08 Gy (1.9-5.9 Gy) and mean dose to 2 cc (D2cc) bladder was 6.91 Gy (2.9-12.2 Gy). ICRU rectal dose was 3.8 Gy (2.4-4.45 Gy) and was comparable with D2cc rectum dose 4.2 Gy (2.8-5.9 Gy). Comparison of mean total dose (ICRU point vs. D2cc) for each patient was found to be significantly different for bladder (p = 0.000), but not for rectum (p = 0.08). CONCLUSIONS: On comparison of ICRU point based planning with volumetric planning on CT, it was found that bladder doses were underestimated by the film based method. However, the rectal doses were found to be similar to the D2cc doses. The results with non isocentric film based treatment planning were similar to the existing literature on orthogonal film based simulator planning.