The Burden Associated with Intra-Operative Anastomotic Leaks in Colorectal Surgery

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Objectives: To assess the quality and identify different variables influencing quality of pharmacoeconomic studies published in Asia pacific (APAC), from 20062016.  Methods: A systematic literature search was performed on MEDLINE and Cochrane using different search terms for cost-effectiveness, cost-utility, and costbenefit analyses. Quality of Health Economic Studies (QHES) instrument was used for quality assessment. Descriptive statistics was applied to analyse the number of studies in QHES quality quartiles. Logistic regression was performed to evaluate the association of factors (funding, quality of journal, training of authors, per-capita healthcare expenditure, and out-of-pocket expense on health) with high quality (HQ, QHES ≥ 75) scores.  Results: Of 262 retrieved studies, 128 were found relevant and evaluated. The mean (SD) QHES score was 67.4 (1.35). Distribution of studies in each quality quartile was: High (n= 59 [46.09%]); Fair (n= 50 [39.06%]); Poor (n= 19 [14.83%]). Majority of studies (n= 80 [62.5%]) were conducted in Japan and Australia. A total of 19 (14.8%) HQ studies and 32 (25%) studies from other three quartiles either did not receive or disclose the funding. Only 11 (18.64%) HQ studies were published in speciality journals (specific to public health or healtheconomics) and 4 (6.78%) in Asian journals. Primary authors who had relevant training in public health, or healtheconomics were associated with higher number of HQ studies (n= 51, 86.44%). Training of primary authors was significantly associated with HQ studies (OR: 7.1; 95% CI: 2.9, 19.23). Impact factor of journal, per-capita expenditure on healthcare, and out-of-pocket expense on health did not show significant association with HQ scores.  Conclusions: High-quality pharmacoeconomic research is confined to only few countries of APAC; it can be improved by advance training of authors in public health or healtheconomics. Also, greater interest of various stakeholders in funding the pharmacoeconomic research and introduction of speciality journals in APAC are warranted. PRM3 Adapting Data Sources for Systematic Literature Review Retrieves Additional Data Relevant for Asian HTA O’Rourke JM1, Halfpenny NJ2, Quigley JM2, Scott DA1 Health Economics & Epidemiology, Abingdon, UK, 2ICON Clinical Research UK Ltd, Abingdon, UK 1ICON

Objectives: Systematic literature reviews (SLRs) are a prerequisite for many Health Technology Assessments (HTAs), with MEDLINE® and EMBASE® often stipulated as standard data sources. We investigated whether expanding these data sources to include Asian specific databases would retrieve additional literature relevant to HTA assessments in this region.  Methods: To test this hypothesis, we conducted an SLR of randomised controlled trials (RCTs) assessing selected treatments in adults with hepatitis C virus. Searches were performed in globally recommended electronic databases for peer-review publications (MEDLINE®, EMBASE®) and HCV specific conferences by AASLD and EASL and additionally in Asian specific sources (including APASL Conference, KoreaMed, KMbase, J-STAGE and CNKI). Endpoint specific data can also be found in EMA and FDA documents, thus we searched equivalent organisations in Asia for these data. Relevant abstracts from country/ regional specific sources were cross checked with data from standard databases to determine if additional, relevant studies were retrieved.  Results: Searching Asian data sources retrieved a large number of abstracts that were not identified through MEDLINE® or EMBASE®; from these, a small number of relevant abstracts were identified. For example, searches of APASL Conference uncovered trials across China, Korea, Japan, and Taiwan which were not retrieved from traditional data sources. The majority of abstracts retrieved from Asian specific electronic databases did not meet our eligibility criteria. This is attributed to the search tools in these databases which were often rudimental and therefore many non-RCT abstracts were retrieved which would be filtered out using advanced search tools in MEDLINE® and EMBASE®.  Conclusions: Searching Asian specific sources retrieves additional, relevant literature not identified by traditional data sources. This literature could affect evidence synthesis and ultimately impact decisions made by HTA bodies. Whilst there were challenges accessing these data, our work demonstrates the importance of adapting SLR protocols to capture additional data for HTA submissions in Asia.

PRM4 The Morphological Study of Human Brown Adipose Tissue During Fetal Development Ganlkhagva N, Dagdanbazar N, Sundui E, Jamsranjav O Mongolian National University Medical Scienses, Ulaanbaatar, Mongolia

Objectives: Main goal is to study the BAT (brown adipose tissue) during fetal development of Mongolians by morphometric indicator of structure.  Methods: Study implementation is followed by guideline was approved by the Statement of Ministry of Health in 16.08.2007 №223 Appendix №4 and study is also ruled by common methods of morphometric study such as measurement of Bunak.V.V, Avdantilov.G.G and histological method is used to study the examination of tissue and issue. Study involved 30 fetuses and morphometric measurement of period, length, width and thick are done and 60 units of BAT are assessed by micro preparation. BAT was got from the aborted infants when they are 12 weeks aborted by doctors’ instruction and those are measured and specialty of blood cell is done by inflowing, specialty of cell is done by general and particular method of tissue examination, locality is done by dissection.  Results: BAT is covered thin pellicle and fawn-coloured, when see it, it will different from common WAT and BAT is seen in the armpit, necks and between plate bones, ribs, back of sternums, aorta and top glands of kidney. Main part of BAT is in armpit, muscle serrates anterior and between muscle subscapular.  Conclusions: BAT are located through the ways of aorta and its major branches. However the main mass of the BAT are found between muscle serrates anterior and muscle subscapular. Our results reported that BAT were formed as morphological tissues at 15th weeks of fetal gestation period. Fetal body sizes and morphometric units of BAT are directly and strongly correlated with each other.

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PRM5 To Evaluate the Outcomes of Concomitant Chemoradiotherapy Followed by Extended Adjuvant Temozolomide in Patients with Newly Diagnosed Glioblastoma - A Retrospective Study Gupta S1, Gupta SK2, Mathur R2 Institute of Pharmaceutical Sciences and Research, NEW DELHI, India, 2Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi, India., Delhi, India 1Delhi

Objectives: The standard treatment in patients with newly diagnosed glioblastoma multiforme is radical surgical removal of the tumour, followed by radiotherapy given concurrently with temozolomide (TMZ) and then six cycles of adjuvant TMZ given monthly. It was a retrospective study including patients received more than six cycles of TMZ. This study evaluated outcomes and adverse effects of prescribing adjuvant TMZ for more than six cycles.  Methods: 117 patients were treated for Glioblastoma at Max Super Speciality Hospital, Saket between December 2009 and July 2014. Out of which 37 patients received more than six cycles of adjuvant TMZ. Primary Outcome of the study was median overall survival (OS) and secondary outcomes were median progression free survival (PFS) and patterns of recurrence by the extended use of adjuvant temozolomide therapy.  Results: The median age of 37 patients was 55 years. The standard therapy by Roger stupp et al concluded median OS as 14.6 months, whereas, the patients who received more than six cycles, a median of 24 months was achieved (P< 0.001) by wilcoxon signed rank test. Median PFS was 14 months in our study, in comparison, to the standard therapy by Roger Stupp et al; a median PFS was 6.9 months was achieved (P< 0.001) by wilcoxon signed rank test. Hematologic adverse effects were mild, 2.7% grade I toxicities occurred. 24.3% patients had no recurrence over a median follow-up period of 18 months. In rest 75.7% patients, most recurrence occurred infield. In multivariate analysis, adjuvant TMZ for more than six cycles was a significant prognostic factor for both progression free and overall survival.  Conclusions: Concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide (more than six cycles) had statistically significant survival benefit with minimum additional toxicity. Thus, extended adjuvant temozolomide (more than six cycles) should be considered in patients with newly diagnosed glioblastoma. PRM6 Cost-Effectiveness Analysis of Antihypertensive Drugs Usage by Combination of ACEI – CCB and ACEI – Diuretic in Outpatient Hypertension Therapy at Rsal Mintohardjo Jakarta (July-November 2015) Hasan D Faculty Of Medicine and Health Science, Islamic State University, Jakarta, Indonesia

Objectives: This study was to examine the cost-effectiveness and cost-efficiency of antihypertensive drug combination classes ACEI-CCB and ACEI-Diuretic in outpatients hypertension therapy at Mintohardjo Army Hospital (July-November 2015).  Methods: A cohort design was used to measure the effectiveness and cost-effectiveness analysis to measure the effeciency of antihypertensive drug combination ACEI-CCB and ACEI-Diuretic. The data for this study were collected prospectively from medical record of outpatient hypertension visit to Mintohardjo Army Hospital, Jakarta. The samples size in this study were 200 patients with hypertension who meet the inclusion and exclusion criteria and were divided into 2 groups. Group 1 were 100 hypertension patients using antihypertensive drugs combination ACEI_CCB and group 2 with the same amount of antihypertensive drug combination ACEI-Diuretic. Both groups of patients who get anti hypertension followed and observed for 3 months for each patient. The drug’s effectiveness is measured by counting the number of patients whose blood pressure is under control (< 140/90 mmHg) and 130/80 mmHg in patients with Diabetes mellitus. Cost efficiency is measured on the basis of the unit cost of each group and the value of the ratio of cost effectiveness.  Results: The results showed that the greatest effectiveness therapetic of drug found in the combination of ACEI-CCB that is marked with the patient’s blood pressure is controlled as much as 98%, whereas in the Group of ACEI-Diuretic patients blood pressure controlled only 91%. Efficiency found in the Group ACEI-Diuretic marked with unit cost (unit cost) the lowest Rp 1,073,848-., whereas in the Group of ACEI-CCB Rp 1.096.790,-.  Conclusions: ACEI-CCB is more effective than with ACEI-Diuretic in the treatment of hypertension patients in outpatient Mintohardjo Army Hospital period July – November 2015. ACEI- Diuretic is more effiicent than with ACEI-CCB in the treatment of hypertension patients in outpatient RSAL Mintohardjo period July – November 2015. PRM7 The Burden Associated with Intra-Operative Anastomotic Leaks in Colorectal Surgery Schiff A1, Roy S2, Pignot M3, Laschke K3, Stadler J3, Ghosh SK4, Yin C5, Fegelman E1 1Johnson & Johnson (Ethicon), Cincinnati, OH, USA, 2Johnson and Johnson Global Surgery, Somerville, NJ, USA, 3Kantar Health, Munich, Germany, 4Global Health Economics and Market Access, Ethicon, Inc., Cincinnati, OH, USA, 5JnJ Medical AP, Singapore, Singapore

Objectives: Anastomotic leaks following colorectal resections result in a significant clinical and economic burden. To complement published data on post-operative leaks, this study aimed to understand intra-operative approaches to managing positive anastomotic leak tests.  Methods: Electronic medical records of patients in China, Japan, and Korea with a positive leak test during colon resection were reviewed as part of a global retrospective, cross-sectional study. Surgeon information, patient demographics, comorbidities, surgical techniques, intraoperative interventions and post-operative outcomes were extracted. Statistics are reported as percentages and mean ± standard deviation.  Results: Data were reviewed for 165 patients with primary or metastatic colorectal cancer who presented a positive intra-operative leak test following resection procedure (36% anterior rectal resection, 26% laparoscopic sigmoidectomy, 14% laparoscopic left hemicolectomy, 14% open sigmoidectomy, and 10% open left hemicolectomy). Intraoperative anastomotic leak rates were estimated by participating surgeons to be at an average of 5%. Prior to

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leak testing, 42% patients’ anastomoses were over sewn, and over 2% were reinforced with a sealant. Following a positive test, about 90% of patients underwent over sewing of the staple line (median 4 suture strands used), sealant was applied in about 12% patients (median 2 sealant tubes used), a new anastomosis was created in about 6% patients (all with circular stapler), and about 7% had a colostomy. The average time required for these interventions was 19.4 ± 13.6 minutes. Despite addressing the intra-operative leak, a post-operative leak occurred in about 15% of patients.  Conclusions: Intraoperative anastomotic leaks are mostly managed by over sewing the staple line or by applying a surgical sealant, which can be time-, labor- and cost-intensive. Significant rates of post-operative leaks were observed despite addressing intra-operative leaks. Approaches towards standardizing anastomosis creation may help reduce the incidence of intraoperative leaks, the variability in management strategies, and the subsequent outcomes. PRM8 Empirical Calibration of Hepatitis C Virus (HCV) Natural History Model to the Chinese HCV-Infected Population

subtracted from the person’s follow-up time in the calculation of malaria disease incidence and the effectiveness of the interventions in terms of incidence rate ratio. We aimed to examine the implications of this common practice.  Methods: We examined the concepts of disease incidence and protective effect under different research purposes. We mathematically assess the relationship of the estimates of incidence rate and incidence rate ratio between assessments with and without the subtraction. We used published studies to illustrate.  Results: Conceptually, evaluation of disease prevention without the subtraction is analogous to intention-to-treat analysis in clinical trials, whereas the common practice of subtracting is analogous to per-protocol analysis. From a real world research point of view, the common practice leads to over-estimation of disease burden and intervention effectiveness. It does not indicate what will happen in real world when a preventive intervention is implemented. Case studies demonstrate that the over-estimation can be practically significant.  Conclusions: To subtract or not subtract a post-disease duration from follow-up time answer different practical questions, which need be clearly formulated. From a health policy and planning perspective, it is likely more appropriate not to subtract.

Lee K Goldhaber-Fiebert J,Stanford University, Stanford, CA, USA

Objectives: Hepatitis C Virus (HCV) infection represents a major public health challenge for China. About 10 million people in China are chronically HCV infected, accounting for 7% of the global burden. The current standard of HCV care in China relies on older, less-effective, interferon-based treatment regimens. There is, however, increasing demand for newer, highly effective but substantially more expensive treatments that include directly acting antivirals (DAAs). Model-based assessments of the comparative effectiveness and cost-effectiveness of alternative treatment strategies in China require representation of HCV’s natural history that faithfully reflects the epidemiology of HCV in China.  Methods: We construct a computerbased microsimulation model of the natural history of HCV infection to support future evaluations of alternative treatment strategies in China. The model includes risks of HCV infection, fibrosis progression, and transition to advanced liver disease states including decompensated cirrhosis and liver cancer. The model tracks whether each individual’s chronic HCV infection is currently detected or undetected, allowing for increased rates of detection through intervention. We reflect Chinese HCV epidemiology by calibrating our stratified infection and progression rates to multiple epidemiological targets that we identified through systematic review of China-specific studies.  Results: Empirical calibration identified model parameter values that are most consistent with observed data on HCV in China. The model output successfully produced fibrosis stage distribution close to the Chinese target data (f0-f4: 11,37,33,14,5%). We found that monthly risks of fibrosis progression among low risk groups were estimated close to the mean of prior distribution (0.01 and 0.008, respectively), whereas calibrated model had higher mortalities of advanced liver diseases than prior estimates.  Conclusions: We constructed and calibrated HCV natural history model that reflects the key features of HCV epidemiology in China. The model can be used to project the health and cost impact of future preventative and treatment intervention for HCV infection among the Chinese population. PRM9 Can Pharmaceutical Care Intervention Improve Lipid Profile in Type 2 Diabetes Patients; A Prospective Intervention Study in a Tertiary Hospital in Nigeria Ogbonna BO UNIVERSITY OF BENIN, BENIN CITY, EDO STATE, Nigeria

Objectives: Diabetes is the leading cause of emergency room visit and nontraumatic limb amputation globally, and many non-randomized studies indicated that pharmaceutical care (PC) is helpful at improving its management. This study analyzed the impact of pharmaceutical care on the lipid profiles of ambulatory type 2 diabetes patients to generate data and document information for effective management of the disease state.  Methods: The study was a single blinded randomized controlled prospective pre and post- test intervention study. The study at the medical outpatient unit lasted for 12 months; determine the effectiveness and net benefit of PC on lipid profile. The 124 eligible patients who gave their informed consent were randomly assigned into the intervention and control group. Patients in the intervention group received PC, which included point of care testing, medication reconciliation, drug therapy management, patient counseling on adherence and lifestyle modifications, and follow up, while those in the control group received the usual care. Data was analyzed for inferential statistics using students t-test at p< 0.05.  Results: the high-density lipoprotein (HDL) value dropped from a baseline of 0.6±0.79 mmol/l to 0.95±0.45 mmol/l (p= 0.0019). Very low-density lipoprotein (VLDL) dropped from 0.96±0.36 mmol/l to 0.60±0.35 mmol/l (p= 0.0053). The value of triglycerides (TG) changed 1.88±0.93 to 1.50±1.05 (p=  0.470) while that of total cholesterol (TC) dropped from 4.57±1.35 to 0.60± 2.23± 0.83 (p= 1.780) and low-density lipoproteins (LDL) from 1.88± 0.93 to 1.50± 57 (p= 5.760).  Conclusions: the study demonstrated that that PC intervention produced improvement on the lipid profile of type 2 diabetes patients. Study suggests that 12 months intervention can improve patients’ clinical outcome. The study implied that PC can lead to improved quality of life and reduction in emergency room visit since increase in HDL and reduction in VLDL, TG, TC, and LDL are positive indicators in diabetes management. PRM10 A Methodological Issue in Effectiveness Studies of Malaria Vaccines and Chemoprevention Cheung YB1, Xu Y1, Cairns M2, Milligan P2 1Duke-NUS Medical School, Singapore, Singapore, 2London School of Hygiene & Tropical Medicine, London, United Kingdom of Great Britain and Northern Ireland

Objectives: Studies of malaria vaccines and chemoprevention often classify a person who has suffered a malaria disease episode and received curative drug treatment as non-susceptible to new malaria infection for two to four weeks, depending on the pharmacokinetics of the curative drugs used. This duration is usually

RESEARCH ON METHODS – Cost Methods PRM11 A Systematic Review on Methodological Heterogeneity in Estimating Productivity Loss Associated with Colorectal Cancer Harsono K1, Soon S1, Chia JW2, Tan WS3, Chew MH3, Wee HL1 1National University of Singapore, Singapore, Singapore, 2National Cancer Centre Singapore, Singapore, Singapore, 3Singapore General Hospital, Singapore, Singapore

Objectives: Studies measuring productivity loss are inherently heterogeneous in their study designs and derivation methods. This systematic review aims to establish the extent of productivity loss in paid work associated with colorectal cancer (CRC) and examine the different measures of productivity loss by identifying sources of variation and drivers.  Methods: We searched PubMed and Web of Science for relevant studies published from January 2005 to August 2015 in the English language. Studies were included if they were (a) on economically-productive CRC patients and/ or caregivers, (b) reporting productivity loss of paid work associated with CRC, and (c) randomised controlled trials (RCTs), non-RCTs, cohort studies, case-control studies or cross-sectional studies. Information was abstracted by study design characteristics, patient/caregiver demographics, data sources, productivity loss components, calculation methods, and units of expression (in 2014 International dollars).  Results: 11 studies were included in this review (Europe (n= 5), the Americas (n= 3), Asia (n= 3)). All studies employed the human capital approach. At the national level (n= 2), productivity loss due to premature mortality ranged from $9.1mn–$1.27bn. Huge variations were found in estimates at the individual level (n= 9) depending on whether they were attributable to CRC, specific to defined interventions, or organised by phases of care or cancer spread. We identified five categories of sources of variation: study design, socio-demographics, clinical characteristics, care characteristics, and computation of productivity loss. Premature mortality or retirement was a key driver (43.6–66.5% of total productivity loss), with males affected more than females. Productivity loss was highest in the first year post-diagnosis for patients, and in the continuing phase for caregivers.  Conclusions: Clearly presenting information on clinico- and sociodemographics of study population, separate reporting of duration and derived productivity loss, units of expression, inclusion or exclusion of compensatory benefits, and applicable year and currency can facilitate appropriate use of productivity loss estimates. PRM12 How are Budget Impact Considerations Captured within Economic Evaluations? A Systematic Review of the Literature Focused on Rotavirus Vaccine Carvalho N University of Melbourne, Carlton, Australia

Background: In many low- and middle-income countries (LMICs), affordability is more important than cost-effectiveness as a gateway criterion for funding a new technology. Hence Budget Impact Analysis (BIA), in addition to cost-effectiveness analysis (CEA), is an essential decision-making component for policy-makers in the presence of limited resources. Despite this, BIAs remain less frequently conducted and less well researched than CEAs.  Objectives: To fill this gap by describing how budget impact considerations are captured within economic evaluations.  Methods: We develop and apply a quality assessment checklist based on the most recent recommendations from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force to examine the extent to which existing economic evaluations provide sufficient evidence about budget impact to enable decision-making. We use rotavirus vaccination as a case study because it represents a major investment that has been recommended by the World Health Organization and there exist many economic studies of it, yet it has seen only partial uptake in LMICs. A systematic review of the literature was conducted to identify economic evaluations of rotavirus vaccine conducted in LMICs. We critically appraised the quality of BIAs and assessed the extension of CEAs to provide useful budget impact information.  Results: Six BIAs and 56 CEAs were identified. All BIAs adhered to the majority of ISPOR recommendations. A small number of recommendations were not adhered to by most articles, including model validation, justification of program time horizon, and providing undiscounted financial streams. Most CEAs could not be extended to provide useful budget impact information. CEAs rarely presented annual costs undiscounted, or estimated financial streams of costs during the first few years of program scale-up.  Conclusions: By highlighting current gaps in standard practices, we propose a comprehensive vaccine-specific strategy for conducting transparent and valuable BIAs alone or alongside CEAs.