Integrated Real-World Data Warehouses across Seven Evolving Asian Healthcare Systems: A Scoping Review.

BACKGROUND: Asia consists of diverse nations with extremely variable healthcare systems and socio-economic intricacies. Integrated real-world data (RWD) research warehouses provide vast interconnected datasets that uphold statistical rigor. However, their intricate details remain underexplored, restricting their broader application in healthcare research, policies and partnerships. OBJECTIVE: Building on our prior research that analyzed integrated RWD warehouses in India, Thailand and Taiwan, this study is an extension to seven distinct Asian healthcare systems: Hong Kong, Indonesia, Malaysia, Pakistan, the Philippines, Singapore, and Vietnam. We aimed to map the evolving landscape of RWD use, elucidate the current state of real-world evidence (RWE) generation from integrated databases, and understand evolving preferences for RWD methodologies and database(s) use. METHODS: : A systematic scoping review methodology was employed, centering on contemporary English literature search on PubMed (search date: May 9, 2023). Rigorous screening followed defined eligibility criteria to pinpoint studies utilizing integrated RWD from multiple healthcare facilities in at least one of the seven target Asian nations. No statistical hypotheses were established for the description of the results. Point estimates and their associated errors were determined for the data collected from eligible studies. RESULTS: Out of the 1483 RWE research titles identified on May 9, 2023, 369 (24.9%) fulfilled the requirements for data extraction and subsequent analysis. Singapore, Hong Kong, and Malaysia contributed to ≥100 publications, each marked by a higher proportion of SCS at 51% (80/157), 66.2% (86/130), and 50% (50/100), respectively, and were classified as Solo Scholars. Indonesia, Pakistan, Vietnam and the Philippines had fewer publications and a higher proportion of CCCS at 78.8% (26/33), 58.1% (18/31), 74.1% (20/27), and 86.4% (19/22), respectively and were classified as Global Collaborators. Collaboration with the countries outside the seven target nations appeared in 84.2%-97.7% of the CCCS of each nation. Among target nations, Singapore and Malaysia emerged as preferred research partners for other nations. From 2018 to 2023, most nations displayed an increasing trend in study numbers, with Vietnam (24.5%) and Pakistan (21.2%) leading the growth; the only exception was the Philippines, which declined by -14.5%. Clinical registry databases were predominant across all CCCS from every target nation. For SCS, Indonesia, Malaysia, and the Philippines favored clinical registries; Singapore had a balanced usage of clinical registries and EMR/EHR, while Hong Kong, Pakistan, and Vietnam leaned towards EMR/EHR. Over 90% of the studies took more than 2 years from completion to publication. CONCLUSIONS: The observed variations in contemporary RWD publications across the 7 nations in Asia exemplify distinct research landscapes across nations that are partially explained by their diverse economic, clinical, and research settings. Nevertheless, recognizing these variations is pivotal for fostering tailored, synergistic strategies that amplify RWD's potential in guiding future healthcare research and policy decisions.

Real-world evidence of lorlatinib therapy in Taiwanese patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

BACKGROUND: Lorlatinib is a brain-penetrant, third-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-positive metastatic non-small cell lung cancer (NSCLC). In a global phase II study, patients who experience disease progression despite prior treatment with ALK tyrosine kinase inhibitors (TKIs) was assessed. Herein, we report real-world clinical outcomes of lorlatinib-treated patients with ALK-positive advanced NSCLC who were heavily pretreated and progressed on first- and second-generation ALK-TKIs, in a Taiwanese population under the lorlatinib expanded access program (EAP). METHODS: This multicenter observational study examined the effectiveness and safety of ALK-positive advanced NSCLC patients that progressed from previous second-generation ALK-TKI therapy and received lorlatinib treatment subsequently. Patients who received lorlatinib treatment under EAP between Jul 2017 and Sep 2019 were eligible. Patients were followed for at least one year from the first lorlatinib treatment until study completion. RESULTS: Sixty-three patients were eligible for safety analysis (male: 46.0 %; median age: 52.8 [27.5-78.3] years; brain metastases: 81.0 %). Fifty-four patients with more than one-month lorlatinib treatment were included in the effectiveness analysis. Prior to lorlatinib treatment, 10 patients (18.5 %) received one ALK-TKI, 27 (50.0 %) received two ALK-TKIs, and 17 (31.5 %) received three or more ALK-TKIs. The overall median rwPFS was 9.2 months (95 % confidence interval: 5.3-21.1). The best overall response rate (n = 51) was 13.7 %, with a disease control rate of 80.4 %. CONCLUSION: Lorlatinib exhibits substantial activity and tolerability when used clinically in a later-line setting in a Taiwanese population with ALK-positive advanced NSCLC.

Integrated Real-World Study Databases in 3 Diverse Asian Health Care Systems in Taiwan, India, and Thailand: Scoping Review.

BACKGROUND: The use of real-world data (RWD) warehouses for research in Asia is on the rise, but current trends remain largely unexplored. Given the varied economic and health care landscapes in different Asian countries, understanding these trends can offer valuable insights. OBJECTIVE: We sought to discern the contemporary landscape of linked RWD warehouses and explore their trends and patterns in 3 Asian countries with contrasting economies and health care systems: Taiwan, India, and Thailand. METHODS: Using a systematic scoping review methodology, we conducted an exhaustive literature search on PubMed with filters for the English language and the past 5 years. The search combined Medical Subject Heading terms and specific keywords. Studies were screened against strict eligibility criteria to identify eligible studies using RWD databases from more than one health care facility in at least 1 of the 3 target countries. RESULTS: Our search yielded 2277 studies, of which 833 (36.6%) met our criteria. Overall, single-country studies (SCS) dominated at 89.4% (n=745), with cross-country collaboration studies (CCCS) being at 10.6% (n=88). However, the country-wise breakdown showed that of all the SCS, 623 (83.6%) were from Taiwan, 81 (10.9%) from India, and 41 (5.5%) from Thailand. Among the total studies conducted in each country, India at 39.1% (n=133) and Thailand at 43.1% (n=72) had a significantly higher percentage of CCCS compared to Taiwan at 7.6% (n=51). Over a 5-year span from 2017 to 2022, India and Thailand experienced an annual increase in RWD studies by approximately 18.2% and 13.8%, respectively, while Taiwan's contributions remained consistent. Comparative effectiveness research (CER) was predominant in Taiwan (n=410, or 65.8% of SCS) but less common in India (n=12, or 14.8% of SCS) and Thailand (n=11, or 26.8% of SCS). CER percentages in CCCS were similar across the 3 countries, ranging from 19.2% (n=10) to 29% (n=9). The type of RWD source also varied significantly across countries, with India demonstrating a high reliance on electronic medical records or electronic health records at 55.6% (n=45) of SCS and Taiwan showing an increasing trend in their use over the period. Registries were used in 26 (83.9%) CCCS and 31 (75.6%) SCS from Thailand but in <50% of SCS from Taiwan and India. Health insurance/administrative claims data were used in most of the SCS from Taiwan (n=458, 73.5%). There was a consistent predominant focus on cardiology/metabolic disorders in all studies, with a noticeable increase in oncology and infectious disease research from 2017 to 2022. CONCLUSIONS: This review provides a comprehensive understanding of the evolving landscape of RWD research in Taiwan, India, and Thailand. The observed differences and trends emphasize the unique economic, clinical, and research settings in each country, advocating for tailored strategies for leveraging RWD for future health care research and decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/43741.

Generating fit-for-purpose real-world evidence in Asia: How far are we from closing the gaps?

Evidence generated by randomized controlled trials (RCTs) does not often represent the patient journey and clinical outcomes in the real world due to limited external validity or generalizability. Studies based on real-world data are intended to generalize results to the broader population; however, if the influence of external factors or confounders is not effectively managed, the cause-and-effect relationship and internal validity may be challenged, resulting in flawed results. The collection of quality real-world evidence (RWE) is crucial in Asia as there is often an underrepresentation of Asian populations in RCTs. In addition, few countries in Asia are catching up with the Western world in issuing practical foundational principles and guidance for conducting and adopting evidence for regulatory and reimbursement decisions. However, privacy and data protection laws are generally lagging behind technological developments in electronic medical records. While leveraging RWE in clinical and regulatory decision-making holds excellent potential, collective efforts across industry, governments, and research institutions are required for generating standardized practices and building capabilities for developing fit-for-purpose RWE in Asia.

Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT. METHODS: We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed. RESULTS: Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT. CONCLUSIONS: Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes.

Risk of cognitive impairment in men with advanced prostate cancer treated with NHAs: A systematic review and network meta-analysis.

Novel hormonal agents (NHAs) have significantly improved outcomes in men with advanced prostate cancer. However, it remains unclear whether NHAs are associated with subsequent cognitive impairment. Thus, we sought to perform a network meta-analysis to compare the risk of cognitive impairment across NHA types. Databases (PubMed, Embase, Scopus, and Web of Science), trial registries (Clinicaltrial.gov), the European Medicines Agency, and the US Food and Drug Administration drug safety reports were searched from inception through July 30, 2021. Eligible studies were clinical trials evaluating the risk of cognitive impairment between NHAs and placebo/standard care. Two independent investigators extracted the data and performed quality assessments using the Cochrane Risk of Bias Tool and ROBINS-I. We estimated the risk ratios by the frequentist approach and calculated the ranking probabilities of all treatments with the surface under the cumulative ranking probabilities. The primary outcome and secondary outcome were odds ratio (OR) and incidence rate ratio of cognitive impairment, respectively. We identified 15 trials with 14,723 participants comparing HNAs with placebo/standard care. Treatments associated with cognitive impairment, from the most to the least, were enzalutamide (OR, 3.66; 95% confidence interval [CI], 2.84-4.73), apalutamide (OR, 1.76; 95% CI, 1.08-2.87), abiraterone acetate (OR, 1.64; 95% CI, 1.01-2.45), and darolutamide (OR, 1.11 95% CI, 0.51-2.39). After adjustment of treatment time duration, enzalutamide still had the highest risk of cognitive impairment with an incidence rate ratio of 2.17 (95% CI, 1.65-2.78). These findings suggest that NHAs, especially enzalutamide, may increase the risk of cognitive impairment compared with placebo/standard care.

Contemporary Databases in Real-world Studies Regarding the Diverse Health Care Systems of India, Thailand, and Taiwan: Protocol for a Scoping Review.

BACKGROUND: Real-world data (RWD) related to patient health status or health care delivery can be broadly defined as data collected outside of conventional clinical trials, including those from databases, treatment and disease registries, electronic medical records, insurance claims, and information directly contributed by health care professionals or patients. RWD are used to generate real-world evidence (RWE), which is increasingly relevant to policy makers in Asia, who use RWE to support decision-making in several areas, including public health policy, regulatory health technology assessment, and reimbursement; set priorities; or inform clinical practice. OBJECTIVE: To support the achievement of the benefits of RWE in Asian health care strategies and policies, we sought to identify the linked contemporary databases used in real-world studies from three representative countries-India, Thailand, and Taiwan-and explore variations in results based on these countries' economies and health care reimbursement systems by performing a systematic scoping review. Herein, we describe the protocol and preliminary findings of our scoping review. METHODS: The PubMed search strategy covered 3 concepts. Concept 1 was designed to identify potential RWE and RWD studies by applying various Medical Subject Headings (MeSH) terms ("Treatment Outcome," "Evidence-Based Medicine," "Retrospective Studies," and "Time Factors") and related keywords (eg, "real-world," "actual life," and "actual practice"). Concept 2 introduced the three countries-India, Taiwan, and Thailand. Concept 3 focused on data types, using a combination of MeSH terms ("Electronic Health Records," "Insurance, Health," "Registries," "Databases, Pharmaceutical," and "Pharmaceutical Services") and related keywords (eg, "electronic medical record," "electronic healthcare record," "EMR," "EHR," "administrative database," and "registry"). These searches were conducted with filters for language (English) and publication date (publications in the last 5 years before the search). The retrieved articles will undergo 2 screening phases (phase 1: review of titles and abstracts; phase 2: review of full texts) to identify relevant and eligible articles for data extraction. The data to be extracted from eligible studies will include the characteristics of databases, the regions covered, and the patient populations. RESULTS: The literature search was conducted on September 27, 2022. We retrieved 3,172,434, 1,094,125, and 672,794 articles for concepts 1, 2, and 3, respectively. After applying all 3 concepts and the language and publication date filters, 2277 articles were identified. These will be further screened to identify eligible studies. Based on phase 1 screening and our progress to date, approximately 44% (1003/2277) of articles have undergone phase 2 screening to judge their eligibility. Around 800 studies will be used for data extraction. CONCLUSIONS: Our research will be crucial for nurturing advancement in RWD generation within Asia by identifying linked clinical RWD databases and new avenues for public-private partnerships and multiple collaborations for expanding the scope and spectrum of high-quality, robust RWE generation in Asia. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43741.

Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70-100 mg/dL in Taiwan.

BACKGROUND: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70-100 mg/dL in Taiwan could be cost-effective. METHODS: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. RESULTS: Moderate-intensity statin use, a treatment regimen expected to achieve LDL <70 mg/dL in the base case, resulted in a net gain of 562 QALYs but with an additional expenditure of $11.4 million per 10,000 patients over ten years. The ICER was $20,288 per QALY gained. The probabilities of being cost-effective at willingness-to-pay thresholds of one and three gross domestic product per capita ($24,329 in 2017) per QALY were 51.1% and 94.2%, respectively. Annual drug cost was the most influential factor on the ICER. CONCLUSION: Lowering the target LDL-C level from 100 to 70 mg/dL among treatment-naïve CAD patients could be cost-effective given the health benefits of preventing cardiovascular events and deaths.

Statin adherence and persistence on secondary prevention of cardiovascular disease in Taiwan.

BACKGROUND: Evidence and treatment guidelines support the use of statins in patients with established atherosclerotic cardiovascular disease (ASCVD) for secondary prevention of subsequent cardiovascular (CV) event. However, treatment adherence and persistence are still a concern. METHODS: We constructed a retrospective population-based cohort of patients, who initiated statin treatment within 90 days after discharge from hospital for ASCVD using the claims database of Taiwan National Health Insurance. Proportion of days covered (PDC) was used to measure statin adherence, and PDC ≥80% was defined as good adherence. The study outcomes were subsequent rehospitalisation or in-hospital death due to composite ASCVD, myocardial infarction or ischaemic stroke. Their associations with statin prescription adherence or persistence were analysed using time-dependent Cox proportional hazards model. RESULTS: The study cohort included 185 252 postdischarge statin initiators. There were 50 015 subsequent ASCVD rehospitalisations including 2858 in-hospital death during 7 years of study period. Good adherence was significantly associated with lower risk of ASCVD rehospitalisation (adjusted HR (aHR) 0.90; 95% CI 0.87 to 0.92) and significantly lower risk of in-hospital death (aHR 0.59; 95% CI 0.53 to 0.65). Compared with constant use of statin, patients in the three less persistent states (recent stop, non-persistence and intermittent use) were associated with higher risk of subsequent ASCVD rehospitalisation, aHRs were 1.16, 1.13 and 1.26, respectively (all p<0.05). The increased risks were consistent with specific outcome of acute myocardial infarction and ischaemic stroke. Also, patients in the recent stop period had significantly higher risk for fatal CV event. CONCLUSIONS: Good adherence and persistence to statin therapy are significantly associated with lower risk of secondary ASCVD rehospitalisation and in-hospital death.

The net clinical benefits of febuxostat versus allopurinol in patients with gout or asymptomatic hyperuricemia - A systematic review and meta-analysis.

BACKGROUND AND AIMS: Systemic reviews and meta-analyses suggest hyperuricemia is a cardiovascular risk factor. The effects of xanthine oxidase inhibitors on cardiac outcomes remain unclear. We assessed the effects of febuxostat and allopurinol on mortality and adverse reactions in adult patients with hyperuricemia. METHODS AND RESULTS: PubMed and EMBASE were searched to retrieve randomized controlled trials of febuxostat and allopurinol from January 2005 to July 2018. The meta-analysis consisted of 13 randomized controlled trials with a combined sample size of 13,539 patients. Febuxostat vs. allopurinol was not associated with an increased risk of cardiac-related mortality in the overall population (OR: 0.72, 95% CI: 0.24-2.13, P = 0.55). Regarding adverse skin reactions, the patients receiving febuxostat had significantly fewer adverse skin reactions than those receiving allopurinol treatment (OR: 0.50, 95% CI: 0.30-085, P = 0.01). Compared with allopurinol, febuxostat was associated with an improved safety outcome of cardiac-related mortality and adverse skin reactions (OR: 0.72, 95% CI: 0.55-0.96, P = 0.02). The net clinical outcome, composite of incident gout and the safety outcome, was not different significantly in the patients receiving febuxostat or allopurinol (OR: 1.04, 95% CI: 0.76-0.1.42, P = 0.79). In sensitivity analyses, a borderline significance was found in the patients randomized to febuxostat vs. allopurinol regarding cardiac-related mortality (OR: 1.29, 95% CI: 1.00-1.67, P = 0.05) after the CARES study was included. CONCLUSION: Febuxostat vs. allopurinol was associated with the improved safety outcome and have comparable mortality and net clinical outcome in patients with hyperuricemia. REGISTRATION NUMBER: PROSPERO(CRD42018091657).

Long-term statin adherence in patients after hospital discharge for new onset of atherosclerotic cardiovascular disease: a population-based study of real world prescriptions in Taiwan.

BACKGROUND: Despite the recommendations of statins treatment for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), treatment adherence and persistence are still a concern. This study examined the real world practice of long-term adherence and persistence to statins treatment initiated after hospital discharge for ASCVD, and their associated factors in a nationwide cohort. METHODS: Post discharge statin prescriptions between 2006 and 2012 were extracted from the Taiwan National Health Insurance claims database. Good adherence, defined as proportion of days covered (PDC) ≥0.8 and mean medication possession ratio (MPR), was measured every 180-day period. Non-persistence was defined on the date patients failed to refill statin for 90 days after the end of the last prescription. Their associations with influential factors were analyzed using a generalized estimating equation and Cox's proportional hazard model. RESULTS: There was a total of 185,252 post-discharge statin initiations (from 169,624 patients) and followed for 467,398 patient-years in the study cohort. Percentage of good adherence (mean MPR) was 71% (0.87) at 6-months; declined to 54% (0.68), 47% (0.59), and 42% (0.50) at end of year 1, 2, and 7, respectively. Persistence in statin treatment was 86, 67, 50, and 25% at 6-month, 1-, 2-, and 7-year, respectively. Comparing the statin-cohort initiated from year 2006 to 2012, 1-year persistence increased from 58 to 73%, and 1-year good adherence improved from 45 to 61%. Factors associated with sub-optimal adherence and non-persistence included: prescription by primary care clinics or non-cardiology specialties; patients' age > 75 years; no history of previous statin use; ASCVD events with ischemic stroke diagnosis; comorbidities of renal disease, liver disease, depression, and chronic obstructive pulmonary disease. CONCLUSIONS: Despite the improving trends, long-term adherence and persistence of statin treatment were suboptimal in Taiwan. Strategies to maintain statin treatment adherence and persistence need to be implemented to further enhance the positive trend.

Cost-effectiveness of amlodipine compared with valsartan in preventing stroke and myocardial infarction among hypertensive patients in Taiwan.

Hypertension is a major risk factor for strokes and myocardial infarction (MI). Given its effectiveness and safety profile, the calcium channel blocker amlodipine is among the most frequently prescribed antihypertensive drugs. This analysis was conducted to determine the costs and quality-adjusted life years (QALYs) associated with the use of amlodipine and valsartan, an angiotensin II receptor blocker, in preventing stroke and MI in Taiwanese hypertensive patients. A state transition (Markov) model was developed to compare the 5-year costs and QALYs for amlodipine and valsartan. Effectiveness data were based on the NAGOYA HEART Study, local studies, and a published meta-analysis. Utility data and costs of MI and stroke were retrieved from the published literature. Medical costs were based on the literature and inflated to 2011 prices; drug costs were based on National Health Insurance prices in 2014. A 3% discount rate was used for costs and QALYs and a third-party payer perspective adopted. One-way sensitivity and scenario analyses were conducted. Compared with valsartan, amlodipine was associated with cost savings of New Taiwan Dollars (NTD) 2,251 per patient per year: costs were NTD 4,296 and NTD 6,547 per patient per year for amlodipine and valsartan users, respectively. Fewer cardiovascular events were reported in patients receiving amlodipine versus valsartan (342 vs 413 per 10,000 patients over 5 years, respectively). Amlodipine had a net gain of 58 QALYs versus valsartan per 10,000 patients over 5 years. Sensitivity analyses showed that the discount rate and cohort age had a larger effect on total cost and cost difference than on QALYs. However, amlodipine results were more favorable than valsartan irrespective of discount rate or cohort age. When administered to Taiwanese patients for hypertension control, amlodipine was associated with lower cost and more QALYs compared with valsartan due to a lower risk of stroke and MI events.

Therapeutic inertia and intensified treatment in diabetes mellitus prescription patterns: A nationwide population-based study in Taiwan.

Objective To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan. Methods Using reimbursement claims from Taiwan's National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006-2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem. Results The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group. Conclusion In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.

The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia.

BACKGROUND: Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC. PATIENTS AND METHODS: We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I-IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality. RESULTS: A total of 2,946 patients had primary stage I-IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55). CONCLUSION: In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments. IMPLICATIONS FOR PRACTICE: Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.

Treatment efficacy differences of sorafenib for advanced hepatocellular carcinoma: a meta-analysis of randomized clinical trials.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a heterogeneous disease. We explored whether any specific subgroups of patients may gain more survival benefits from sorafenib as the first-line therapy for advanced HCC. METHODS: PubMed and the Cochrane library were searched for phase III clinical trials that compared sorafenib with other treatments as first-line therapy for advanced HCC. We retrieved data from the published articles and then calculated synthesized hazard ratios (HRs) of overall mortality for patients of different subgroups, using patients who received other treatments as the reference. RESULTS: Four phase III clinical trials comparing sorafenib with other treatments were included in this study. The HRs were not significantly different between patients from various geographic regions (p = 0.183), patients with different Eastern Cooperative Oncology Group performance statuses (p = 0.699), or patients with different tumor involvement (p = 0.221). By contrast, the synthesized HR for hepatitis C virus (HCV)+ patients was 0.65 [95% confidence interval (CI) 0.53-0.80], which was significantly lower than that for HCV- patients (0.87, 95% CI 0.79-0.96, p = 0.013). CONCLUSIONS: As the first-line therapy for advanced HCC, sorafenib might provide more survival benefits to HCV+ patients than to HCV- patients.

Comparative effectiveness of first-line platinum-based chemotherapy regimens for advanced lung squamous cell carcinoma.

BACKGROUND: Platinum-based chemotherapy is the standard first-line therapy for patients with advanced lung squamous cell carcinoma (SCC). We compared the effectiveness of first-line chemotherapy regimens. METHODS: We searched the database of the Taiwan Cancer Registry for patients with newly diagnosed advanced lung SCC from 2004 to 2007. Medication prescription data were retrieved from the database of National Health Insurance, Taiwan. We identified patients who received standard first-line platinum-based chemotherapy, which was defined as chemotherapy with a platinum (P) compound (cisplatin or carboplatin) in addition to 1 of the 4 chemotherapy agents, including gemcitabine (G), docetaxel (D), paclitaxel (T), and vinorelbine (V). Deaths were identified by searching the National Death Registry. Overall survival (OS) was compared between patients who underwent different therapies. RESULTS: In total, 2790 patients were identified; 983 patients (35.2%) received standard first-line chemotherapy with P and G (58.1%), D (14.5%), T (11.6%), or V (15.8%). Older patients (age ≥ 70 years) were less likely to receive P + D than P + G, P + T, or P + V (P = .018). Patients who received P + G, P + D, P + T, or P + V had similar OS (median, 8.9, 7.9, 9.5, and 8.2 months; P = .816). In multivariate analyses adjusting for age, sex, and stage, the first-line chemotherapy regimen was not a predictor for OS. With P + G as the reference group, the adjusted hazard ratios of P + D, P + T, and P + V were 1.03, 0.90, and 1.02, respectively (P = .710). CONCLUSIONS: In patients with advanced lung SCC, various regimens did not have a significant effect on survival outcomes.

A model measuring therapeutic inertia and the associated factors among diabetes patients: A nationwide population-based study in Taiwan.

This article presents an analysis conducted on the patterns related to therapeutic inertia with the aim of uncovering how variables at the patient level and the healthcare provider level influence the intensification of therapy when it is clinically indicated. A cohort study was conducted on 899,135 HbA1c results from 168,876 adult diabetes patients with poorly controlled HbA1c levels. HbA1c results were used to identify variations in the prescription of hypoglycemic drugs. Logistic regression and hierarchical linear models (HLMs) were used to determine how differences among healthcare providers and patient characteristics influence therapeutic inertia. We estimated that 38.5% of the patients in this study were subject to therapeutic inertia. The odds ratio of cardiologists choosing to intensify therapy was 0.708 times that of endocrinologists. Furthermore, patients in medical centers were shown to be 1.077 times more likely to be prescribed intensified treatment than patients in primary clinics. The HLMs presented results similar to those of the logistic model. Overall, we determined that 88.92% of the variation in the application of intensified treatment was at the within-physician level. Reducing therapeutic inertia will likely require educational initiatives aimed at ensuring adherence to clinical practice guidelines in the care of diabetes patients.

Long-acting insulin analogues and diabetic retinopathy: a retrospective cohort study.

PURPOSE: Long-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of sight-threatening diabetic retinopathy (STDR) associated with treatment using long-acting insulin analogues compared with intermediate-acting insulin in patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective cohort consisting of patients with T2DM aged 20 years of age and older with newly initiated treatment with long-acting insulin analogues (glargine and detemir) and intermediate-acting human insulin was identified from the National Health Insurance database between January 2004 and December 2006 and was subdivided into different cohorts. The risk of the development of STDR was determined by Cox regression models and compared between different cohorts. FINDINGS: Of the 46,739 eligible patients, initiators of insulin glargine, insulin detemir, and neutral protamine Hagedorn (NPH) insulin were identified for comparison using propensity-score matching methods. Long-acting insulin analogues were not associated with changed risk for STDR by intention-to-treat and time-varying use approaches between either matched or unmatched cohorts. IMPLICATIONS: The strategies that aim at preventing diabetic retinopathy by treating T2DM patients with long-acting insulin analogues remain further prospective studies with longer follow-up period to validate our observations within an appropriate dosage range and to further evaluate the safety of long-acting insulin analogues on reducing the progression of diabetic retinopathy.

Association of adjuvant antiviral therapy with risk of cancer progression and deaths in patients with hepatitis-B-virus-related hepatocellular carcinoma following curative treatment: a nationwide cohort study.

BACKGROUND: Limited information about tumor status and the time at which antiviral therapy was initiated may have influenced effect estimation in previous research. The aim of this study was to investigate the effect of antiviral therapies on HBV-related HCC progression and deaths in patients receiving curative treatment based on clear clinical-pathological cancer status and the association of start time of adjuvant antiviral therapy initiation and outcomes. METHODOLOGY: A nationwide inception cohort study of newly diagnosed HCC patients who suffered from viral hepatitis B and received curative HCC therapy as the first course of treatment were identified from the Taiwan Cancer Registry between January 1, 2004, and December 31, 2009. Matched Cox proportional hazards models based on propensity score matching and incorporated time-varying exposure were used to estimate adjusted hazard ratios and 95% confidence intervals (CIs). FINDINGS: Among 3,855 HCC patients with HBV, antiviral therapy was administered to 490 (12.7%) following curative treatment. Antiviral-treated patients had a higher percentage of young age, early stage, and smaller tumor size of HCC compared with untreated patients. After propensity score matching, treated patients demonstrated a higher risk of HCC progression (hazard ratio, 1.42; 95%CI, 1.20-1.69) and death from all causes (1.45; 1.15-1.82) than untreated patients. Similar results were also obtained in sub-cohort of patients who were alive with cancer-free status at least one year after receiving curative treatment and the sub-cohort of patients with liver resection. The interval length between initiation of antiviral therapy and first-line curative treatment did not show a significant association with all-cause mortality. CONCLUSIONS: This study found that adjuvant antiviral therapy did not reduce the risk of HCC progression or mortality in HBV-related HCC patients after cancer status adjusting.

Type 2 diabetes mellitus is associated with increased mortality in Chinese patients receiving curative surgery for colon cancer.

BACKGROUND: We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery. METHODS: From three national databases of patients in Taiwan, we selected a cohort of colon cancer patients who had been newly diagnosed with stage I or stage II colon cancer between January 1, 2004 and December 31, 2008 and had undergone curative surgery. We collected information regarding DM (type 2 DM only), the use of antidiabetic medications, other comorbidities, and survival outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS) were compared between patients with and without DM. RESULTS: We selected 6,937 colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients with DM were older and less likely to receive adjuvant chemotherapy but had a similar tumor stage and grade, compared with colon cancer patients without DM. Compared with colon cancer patients without DM, patients with DM had significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7% vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and comorbidities in our multivariate analysis, DM remained an independent prognostic factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence interval: 1.18-1.49), but not for cancer-specific mortality. Among the colon cancer patients who had received antidiabetic drug therapy, patients who had used insulin had significantly shorter CSS and OS than patients who had not. CONCLUSION: Among patients who receive curative surgery for early colon cancer, DM is a predictor of increased overall mortality.