The Critical Intersect of Regulations, Health Technology Assessment, and Drug Safety Assessments.

Health technology assessment (HTA) is a multidisciplinary process that determines the value of health technology at different points in its lifecycle. Safety issues have become more important since regulatory authorities are increasingly adopting flexible standards, processes, and evidentiary requirements for drug approval. In this article, we compared the different role of regulatory authorities and HTA agencies. Additionally, the experience of regulatory-HTA collaboration for assessment and/or decision-making on safety issues in the lifecycle of a health technology is illustrated, including olmesartan (angiotensin II receptor antagonist) and the direct-acting hepatitis C virus (HCV) antiviral agents. Post-licensing data can be derived from various sources such as electronic health records, medical claims, drug and disease registries, post-authorization safety studies (PASS) or post-authorization safety efficacy studies (PAES), periodic benefit-risk assessment reports, as well as HTA reassessment reports, which incorporate utilization information from patients in a real-world setting and provide crucial evidence for various purposes. With the ongoing accumulation of safety and efficacy information during post-regulatory approval, a standardized process for continuous data collection and active reassessment of risk and benefit becomes crucial for managing the lifecycle of health technologies. In order to define evidence requirements clearly, reduce uncertainty, and minimize delays in HTA approval, early engagement and collaboration of HTA agencies in the regulatory review processes have become more common. However, there is currently limited interaction and collaboration between regulatory authorities and HTA agencies. This article aims to identify the challenges faced by regulators and HTA agencies today, emphasizing the significance of conducting regulatory reviews and health technology assessments throughout a technology's lifecycle, underlining the value of utilizing real-world data and evidence, and emphasizing the necessity of enhancing collaboration between regulatory authorities and HTA agencies, all within the overarching context of drug safety.

The Development of Health Technology Assessment in Taiwan: Perspectives and Analysis.

Efforts to advance health technology assessment (HTA) in Taiwan have aimed to optimize the allocation of National Health Insurance (NHI) resources. This study documents and analyzes the historical timeline of Taiwan's efforts in HTA, identifying areas to advance the HTA system, such as gaining broad stakeholder acceptance. We document ambitious plans to establish a larger, independent HTA center and how these plans did not materialize. The historical timeline also describes the primary focus of HTA shifting to serve the needs of decision-making authorities and committees. We argue that these changes resulted in growth of the HTA system, but also led to significant external criticism and potential compromise of its foundational principles. The inability to create a national HTA center can be attributed to several factors, including an immature ecosystem of HTA-Policy-Patient-Provider-Academic collaboration, a lack of a supportive culture, and challenging political and economic conditions. Nevertheless, if effectively managed, Taiwan's current HTA system could play a crucial role in rational decision-making, informed choices, and efficient NHI resource management. We argue that greater autonomy is crucial for enhancing financial sustainability and protecting against external influences to ensure objective and credible assessments. Additionally, we emphasize the importance of fostering a conducive learning environment to improve methodological expertise.

Taiwan accelerates its efforts to eliminate hepatitis C.

The estimated prevalence of anti-HCV was 3.3% (1.8-5.5%) in the general population in Taiwan with several regional disparities. The reactive anti-HCV in different regions may vary between 0% and 65%. The National Hepatitis C Program (NHCP) office estimated approximately 623,323 persons reactive with anti-HCV based on several extensive region- and cohort-wide studies. Taiwan has accelerated its efforts to eliminate hepatitis C since 2018 by committing to achieve World Health Organization (WHO)'s 2030 goal of treating 80% of eligible patients by 2025. Many aggressive measures by the Ministry of Health and Welfare (MOHW) have been ongoing including several key success factors such as political commitment by the MOHW to finance this national program and improve National Health Insurance (NHI) reimbursement restrictions for treatment. Meanwhile, the Taiwan Centers for Disease Control (CDC) instituted harm reduction programs and the Health Promotion Administration (HPA) started to improve awareness and perform national screening programs. The NHCP office instituted monitoring, evaluation, micro-elimination and funding to linkage to care programs. In addition to sustainable financing, it is imperative to scale-up screening coverage through a precision public health approach to fill the gap of under-diagnosis. Hopefully, we can achieve early elimination by announcing the treatment target of 250000 CHC patients by 2025.

The epidemiological profile of chronic hepatitis C with advanced hepatic fibrosis regarding virus genotype in Taiwan: A nationwide study.

BACKGROUND/PURPOSE: This study aims at investigating the epidemiological profile of chronic hepatitis C (CHC) regarding hepatitis C virus (HCV) genotype in Taiwan. METHODS: A total of 29,087 CHC patients with advanced fibrosis who received direct-acting antivirals (DAAs) therapy under Taiwan's National Health Insurance (NHI) during 2017-2018 were recruited. The HCV genotype distribution and its association with patients' demographic factors including age, gender, and geographical areas were examined. RESULTS: The most common genotypes were 1b (59.5%) and 2 (30.1%) with characteristics of older age (mean ± standard deviation (SD): 66.5 ± 10.7 years and 67.3 ± 10.9 years) and female gender predominant (57.1% and 59.4%), which were associated with iatrogenic infection decades ago. Most of patients with genotype 1a (5.9%) and 6 (3.7%) infection were relatively younger (59.2 ± 12.0 years and 60.0 ± 13.8 years) and male gender predominant (59.1% and 61.1%), except Liujia and Liuying districts in southern Taiwan. The youngest group (53.2 ± 11.8 years) and most male gender predominant (74.3%) was genotype 3 (0.37%). These genotypes with characteristics of being younger and male gender predominant were highly related to injection drug use in recent years. The number of genotype 4 patients were extremely rare (n = 25) and efficacy of genotype-4-specific-DAA was significantly poorer than non-genotype-4-specific DAA (P value = 0.0411). CONCLUSION: The significant differences in demographic characteristics among CHC patients with different HCV genotypes found in this study suggest HCV genotype was highly associated with transmission pattern and may be used as a reference for HCV control.

Brand name or generic? What are the health professionals prescribed for treating diabetes? A longitudinal analysis of the National Health Insurance reimbursement database.

OBJECTIVE: This study aimed to explore whether physicians prescribe more brand-name oral hypoglycemic agents (OHA) for diabetic patients with medical training background (MP) than for general patients (GP). RESEARCH DESIGN AND METHODS: A longitudinal analysis of 1,000,000 National Health Insurance cohorts of 1998-2008 was conducted. Univariate and multivariate models were performed to assess the associations of the outcome (the ratio of brand-name/generic odds in the MP group to that in the GP group) and the covariates, including patient medical training background, characteristics of patient, prescriber, and medical settings, and market competition. A generalized estimating equation method was used to control the dependency of longitudinal data. RESULTS: A total of 46,850 diabetic patients were prescribed with 2,703,149 OHA prescriptions during the study period. Compared with GP, MP had 1.37 times greater odds of being prescribed with brand-name instead of generic OHA, among whom pharmacists and physicians had the highest odds ratios of 2.78 (95%CI, 1.05-7.36) and 1.68 (95%CI, 0.99-2.85), respectively. Patients' diabetes severity, prescribers' level of experience, medical settings that were publicly owned, had a higher accreditation level, and were located in a higher urbanized area, lower market competition, and earlier dates of prescription were positively associated with brand-name prescription. Among all medical sub-specialties, cardiologists were more likely to prescribe brand-name OHA. CONCLUSIONS: This study is the first to demonstrate how a patients' medical training background, in addition to the characteristics of patients, prescribers, and medical settings, and market competition might influence physicians' prescribing choice of brand-name or generic OHA.

The impact of interscreening interval and age on prostate cancer screening with prostate-specific antigen.

BACKGROUND: Population-based screening for prostate cancer (PCa) has used serum prostate-specific antigen (PSA) since the early 1990s. However, the efficacy could be affected by screening interval, age ranges of screening, attendance, and contamination of the control group in randomised controlled trials. OBJECTIVE: Assess the impact of the above-mentioned factors on screening efficacy. DESIGN, SETTING, AND PARTICIPANTS: Parameters pertaining to the natural history of PCa and sensitivity were estimated using data from the Finnish quadrennial screening program starting at 55 yr of age and terminating at 71 yr of age and comprising 80 458 men (32 000 in the screening arm and 48 458 in the control arm). We performed Markov decision analyses for different screening policies with a simulated 25-yr follow-up. INTERVENTION: PSA screening. MEASUREMENTS: The impact of different interscreening intervals and target age ranges on advanced PCa (stage III or worse) and PCa mortality was assessed. RESULTS AND LIMITATIONS: With 65% attendance and 20% contamination, as in the Finnish trial, screening would result in an 11.1% (95% confidence interval [CI], 9.1-13.3%) reduction in advanced cancers and a 7.3% (95% CI, 5.3-9.7%) reduction in PCa death, with corresponding absolute risk difference of 2.6% (95% CI, 1.9-3.5%) and 1.8% (95% CI, 1.4-2.2%), respectively. Numbers needed to screen were 385 to prevent one case of advanced PCa and 556 to prevent one PCa death at 25 yr. Those figures remained similar from 12 yr onwards. Reduction in advanced PCa increased to 40% with annual screening and to 24% with biennial screening. When the age at screening initiation was increased by 5 yr, the benefit was reduced by 9% with annual screening and by 3% with biennial screening. CONCLUSIONS: We predicted the impact of basic screening characteristics on the benefit of the program. The screening interval (1-4 yr) had a greater impact on mortality reduction than did the age at start of screening (55-65 yr). CLINICAL TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN49127736.

A stochastic model for survival of early prostate cancer with adjustments for leadtime, length bias, and over-detection.

To compare the survival between screen-detected and clinically detected cancers, we applied a series of non-homogeneous stochastic processes to deal with leadtime, length bias, and over-detection by using full information on detection modes obtained from the Finnish randomized controlled trial for prostate cancer screening. The results show after 9-year follow-up the hazard ratio of prostate cancer death for screen-detected cases against clinically detected cases increased from 0.24 (95% CI: 0.16-0.35) without correction for these biases, to 0.76 after correction for leadtime and length biases, and finally to 1.03 (95% CI: 0.79-1.33) for a further adjustment for over-detection. Adjustment for leadtime and length bias but no over-detection led to a 24% reduction in prostate cancer death as a result of prostate-specific antigen test. The further calibration of over-detection indicates no gain in survival of screen-detected prostate cancers (excluding over-detected case as stayer considered in the mover-stayer model) as compared with the control group in the absence of screening that is considered as the mover. However, whether the model assumption on over-detection is robust should be validated with other data sets and longer follow-up.

Number of screens for overdetection as an indicator of absolute risk of overdiagnosis in prostate cancer screening.

As with wide-spread use of prostate cancer (Pca) screening with prostate-specific antigen testing, overdetection has increasingly gained attention. The authors aimed to estimate absolute risk of overdetection (RO) in Pca screening with various interscreening intervals and ages at start of screening. We estimated age-specific preclinical incidence rates (per 100,000 person-years) for progressive cancer (from 128 for age group 55-58 years to 774 for age group 67-71 years) and nonprogressive cancer (from 40 for age group 55-58 years to 66 for age group 67-71 years), the mean sojourn time (7.72 years) and the sensitivity (42.8% at first screen and 59.8% at the second screen) by using a multistep epidemiological model with data from the Finnish randomized controlled trial. The overall number of screens for overdetection (NSO) was 29 (95% confidence interval (CI): 18, 48) for screenees aged 55-67 years, equivalent to 3.4 (95% CI: 2.1, 5.7) overdetected Pcas per 100 screenees. The NSO decreased from 63 (95% CI: 37, 109) at the first screen to 29 (95% CI: 18, 48) at the third screen and from 43 (95% CI: 36, 52) for age 55 years to 25 (95% CI: 8, 75) at age 67 years at the first screen. In conclusion, around 3.4 cases for every 100 screened men would be overdetected during three screen rounds (~ 13 years of follow-up) in the Finnish randomized controlled trial. Elucidating the absolute RO under various scenarios makes contribution for evaluating the benefit and harm of Pca screening.

Impact of chewing betel-nut (Areca catechu) on liver cirrhosis and hepatocellular carcinoma: a population-based study from an area with a high prevalence of hepatitis B and C infections.

BACKGROUND: Chewing betel-nuts (Areca catechu) is carcinogenic but the risk for hepatocellular carcinoma (HCC) and liver cirrhosis (LC) is little considered. Worldwide 600 million people chew betel, including emigrants from palm-growing countries. OBJECTIVE: We aimed to assess the relationships and dose-response effects of betel chewing on LC and HCC risks, since habit cessation could reduce the increased risks of HCC and LC found in such communities. SUBJECTS: Screening 60 326 subjects aged 30-79 years in a population-based study in Taiwan identified LC in 588 and HCC in 131 subjects. Demographic features, hepatitis B/C infections, other risk factors and betel chewing were noted. Multiple Cox regression models were used to assess independent relationships, interactions and synergisms between age, betel chewing and hepatitis B/C. RESULTS: Betel chewing increased LC and HCC risk 4.25-fold (95 % CI 2.9, 6.2) in current chewers and 1.89-fold (95 % CI 1.13, 3.16) in ex-chewers v. never-chewers, with dose effects for quantity, duration and cumulative exposure in chewers. Subjects without hepatitis B/C infections had 5.0-fold (95 % CI 2.87, 9.03) increased risk of LC/HCC v. never-chewers, and betel chewing had an additive synergistic effect on hepatitis B/C-related risks. Risk reduction with betel habit cessation could exceed that expected from immunization programmes for hepatitis B and C. CONCLUSION: Increased risks of cirrhosis and hepatocellular cancer were found in betel chewers free of hepatitis B/C infection, and these risks were synergistically additive to those of hepatitis B/C infections. Estimated risk reduction from effective anti-betel chewing programmes would be sizeable.

Lack of compliance with basic infection control measures during cardiopulmonary resuscitation--are we ready for another epidemic?

OBJECTIVE: Healthcare workers in the emergency department are particularly vulnerable to communicable disease. This study aimed to evaluate compliance with standard precautions by analysis of the incidence and systems sources of such contaminations and by quantifying the use of personal protective equipment. METHOD: A prospective observational study from 1 November 2005 to 30 April 2006, using analysis of video segments. Videotapes were recorded in two rooms designed for cardiopulmonary resuscitation of out-of-hospital cardiac arrests, and compliance with basic infection control measures by all emergency department crews was monitored. RESULTS: A total of 44 consecutive performances of cardiopulmonary resuscitation were recorded for time-motion analysis. The percentages of staff wearing personal protective equipment were 90%, 50%, 20% and 75% for masks, eye protection, gowns and gloves, respectively. Compliance ranking scored doctors as high, trainees as moderate and nursing staff as low. Overall contamination rate was 16.9x10(-2) events/person-min. The two leading systems sources for contamination were lack of specific task assignments among rescuers (44%) and inadequate preparation for procedures (42%). CONCLUSIONS: Among healthcare workers in the emergency setting, the study disclosed suboptimal compliance with basic infection control measures, including use of personal protective equipment and avoiding contamination. By further time-motion analysis of resuscitation sessions, major systems sources and strategies for improvement could be identified.

Bacteremia in previously hospitalized patients: prolonged effect from previous hospitalization and risk factors for antimicrobial-resistant bacterial infections.

STUDY OBJECTIVE: Patients who came from the community but were recently discharged from the hospital have a higher risk of contracting antimicrobial-resistant bacterial infections. Our objectives are to determine the time from previous hospital discharge that affects subsequent antimicrobial susceptibility pattern and risk factors for antimicrobial-resistant infection in bacteremia in recently discharged patients. METHODS: Excluding patients of hospital-acquired, patients with regular health care-associated exposure, and patients whose previous hospitalization was not at our hospital, a total of 789 nonduplicated bacteremia episodes from community adult patients were enrolled in a 1-year study period. Antimicrobial-resistant bacteria, including multidrug-resistant gram-negative bacilli, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci causing bacteremia, were logistically analyzed according to different posthospitalization periods (3 to 90 days, 91 to 180 days, 181 to 360 days, and no hospitalization in the past 360 days) to identify the independent effect from previous hospitalization on subsequent antimicrobial-resistant bacteremia. RESULTS: Of the 789 bacteremia patients, the proportion of antimicrobial-resistant bacteremia is 14.6% (95% confidence interval [CI] 9.8% to 19.4%) for 3 to 90 days, 9.6% (95% CI 1.6% to 17.6%) for 91 to 180 days, and 6.4% (95% CI 0% to 13.4%) for 181 to 360 days since last hospitalization and 1.0% (95% CI 0.1% to 1.9%) for no hospitalization within the last 360 days. Risk of antimicrobial-resistant bacteremia decreased monthly after discharge by an odds ratio of 0.83 (95% CI 0.76 to 0.90) (P<.01). Previous carriage of antimicrobial-resistant bacteria in the past 360 days and previous stay at ICU in the past 180 days were independent risk factors for antimicrobial-resistant bacteremia in previously hospitalized patients. CONCLUSION: Previous hospitalization affects the antimicrobial susceptibility of subsequent bacteremia up to 360 days after hospital discharge. Presence of risk factors for antimicrobial-resistant bacteremia in previously hospitalized patients may help emergency physicians in selecting empirical antimicrobial agents and prompting infection control precautions.

Comparison of both clinical features and mortality risk associated with bacteremia due to community-acquired methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus.

BACKGROUND: The majority of research about community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection has focused on skin and soft-tissue infections. No literature has been published on the clinical features and outcomes of adult patients with CA-MRSA bacteremia in comparison with patients with community-acquired methicillin-susceptible S. aureus (CA-MSSA) bacteremia. METHODS: From 1 January 2001 through 31 December 2006, the demographic data and outcome of 215 consecutive adult patients admitted to a tertiary care center in Taiwan with S. aureus bacteremia (age, >16 years) who fulfilled the criteria for community-acquired S. aureus bacteremia were collected for analysis. RESULTS: The mean age (+/-SD) was 56.8+/-20.5 years. There were 30 patients (14%) with CA-MRSA bacteremia and 185 (86%) patients with CA-MSSA bacteremia. Cutaneous abscess (odds ratio, 5.46; 95% confidence interval, 1.66-17.94) and necrotizing pneumonia (odds ratio, 24.81; 95% confidence interval, 2.63-234.03) were the independent predictors of CA-MRSA bacteremia; endovascular infection was the only independent predictor of CA-MSSA bacteremia. After Cox regression analysis, the independent significant risk factors for 30-day mortality included increased age, shock, and thrombocytopenia (<100,000 cells/microL). After adjustment, the day 30 mortality of patients with CA-MRSA bacteremia was not significantly higher than that of patients with CA-MSSA bacteremia (adjusted hazard ratio, 1.01; 95% confidence interval, 0.30-3.39; P = .986). Most (92%) of 25 available CA-MRSA isolates were multilocus sequence typing 59. CONCLUSIONS: The number of adult patients with CA-MRSA bacteremia increased with time, and the disease was associated with more necrotizing pneumonia and cutaneous abscess but less endovascular infection than was CA-MSSA bacteremia. Patients with CA-MRSA bacteremia did not have higher mortality than did patients with CA-MSSA, even though most of the patients with CA-MRSA bacteremia did not receive empirical glycopeptide therapy.

Multiple detection modalities and disease natural history of breast cancer.

Multiple detection modalities have increasingly gained attention in population-based screening. However, the disease natural history and its efficacy have been barely addressed. We reviewed a series of articles addressing multiple detection modalities including mammography, ultrasound and magnetic resonance image between 1995 and 2005. A stochastic model was developed to estimate transition parameters pertaining to the disease natural history defined by multiple detection modalities. The effectiveness of the combination of ultrasound or magnetic resonance image (MRI) with mammography was projected using a series of computer simulation models. The results indicated that multiple detection modalities may lead to reduced mortality. However, the benefit and the selection of detection modalities are affected by biological factors including age, breast tissue type and histological type. In addition, other social factors may also affect the utilization of multiple detection modalities.

A community-based epidemiological study of periodontal disease in Keelung, Taiwan: a model from Keelung community-based integrated screening programme (KCIS No. 18).

AIMS: To estimate the prevalence and severity of periodontal disease (PD) in the Taiwanese population aged 35-44 years and to investigate the association between demographic factors and PD. MATERIALS AND METHODS: Between 2003 and 2005, residents of Keelung of the appropriate age were invited to screening. The community periodontal index (CPI) and loss of attachment (LA) index were used to measure the periodontal status at subject (prevalence) and sextant levels (severity). Basic demographic information was also collected by a questionnaire. RESULTS: Of 8462 enrollees, 94.8% had some signs of PD, of whom 29.7% had periodontal pockets >3 mm and 35% LA >3 mm. Calculus was the most common problem in terms of both prevalence (49.6%) and severity (affecting an average of 3.0 sextants per person). Risk factors for poor periodontal status (as measured by CPI) were older age (odds ratio, OR: 1.44), male gender (OR: 2.70), low education level (OR: 1.40), and being a manual worker (OR: 1.51). Similar findings were observed for LA. CONCLUSION: The prevalence of PD in 35-44-year-olds was found to be high in this large community-based study of screening for PD with CPI and LA. Poorer periodontal health was observed in males, the less educated, and manual workers.

Predictive model of antimicrobial-resistant gram-negative bacteremia at the ED.

BACKGROUND: Despite numerous studies identifying the risk factors related to gram-negative antimicrobial resistance, an epidemiological model to reliably predict antimicrobial gram-negative resistance in clinics, before the bacterial culture result is available, has not yet been developed. OBJECTIVES: The aim of this study was to develop a predictive model to assist physicians in selecting appropriate antimicrobial agents before the details of the microbiology and drug susceptibility are known. MATERIALS AND METHODS: A prospective study was conducted between June 1, 2001, and May 31, 2002, at the emergency department (ED) of National Taiwan University Hospital. Enrollees were patients with gram-negative bacteremia (GNB) at ED. Other information collected included demographic characteristics, underlying comorbidities, hospital exposure and health care-associated factors, and details of initial presentation. Two primary outcomes were defined, including cefazolin-resistant (CZ-RES) GNB and ceftriaxone-resistant (CTX-RES) GNB. Two thirds of the data was randomly allocated to a derivation data set (for developing predictive models), and the rest, to a validation data set (for testing model validity). Simplified models, using a coefficient-based scoring method, were also developed for clinical applications. RESULTS: Based on 695 episodes of GNB, predictors of CZ-RES GNB were time since last hospitalization (increased risk for durations <1 month), prior infection with a CTX-RES strain, post-transplantation immunosuppressant use, residence in a nursing home or history of stroke with repeated choking, and poor oxygen saturation (<95%) at admission to ED. Cirrhosis showed a protective effect by reducing the odds of antimicrobial-resistant GNB. The area under receiver operating characteristic (ROC) curve for the CZ-RES model was 0.76 (95% confidence interval, 0.71-0.81). The CTX-RES model included all the variables that were in the CZ-RES model plus abnormal leukocyte count (<1000 or >15,000 /mm3) at entry to ED. In this case, however, previous hospitalization within the last 2 weeks was a key factor. The area under this ROC curve was 0.82 (95% confidence interval, 0.76-0.88). There was lacking of difference in the area under the ROC curve between the 2 final (simplified) models either based on the derivation or validation data sets. CONCLUSION: We have developed 2 models for predicting risk of antimicrobial gram-negative infection by identifying and quantifying associated risk factors. These models could be used by physicians to determine the most appropriate choice of antibiotic for first-line therapy, particularly in situations where the culture result is not yet known.

Correlates of family, school, and peer variables with adolescent substance use in Taiwan.

This study examines adolescent substance use in relation to family, peer and school factors in the context of Taiwan. Information on family characteristics, satisfaction with performance at school, and peer influence was collected using a case-control study in which a two-stage method was applied to ascertain substance use. A set of hypotheses on interrelationships of substance use (tobacco, alcohol, betel, illicit drugs) and influences were tested with a structural equation model. There was a strong negative relation between family factors and peer relationships (p=0.005). Family variables played an important role in motivation and effort to study (p=0.004). High motivation and effort to study (p=0.0012) and good school adjustment (p=0.078) led to higher satisfaction with performance at school. A significant positive association between peer relationships and deviant peer behaviour was observed (p<0.001). Satisfaction with performance at school was negatively related to deviant peer behaviour (p=0.052). The direct effect of deviant peer behaviour was marginally statistically significant (p=0.011) and an indirect effect of family factors on substance use was statistically significant (p=0.041). In conclusion, the study found that a strong family-peer relationship and family influence has a significant effect on substance use.

Cost-effectiveness analysis of colorectal cancer screening with stool DNA testing in intermediate-incidence countries.

BACKGROUND: The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all. METHODS: We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of dollar 13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective. RESULTS: Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were dollar 9,794, dollar 9,335, and dollar 7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters. CONCLUSION: In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.

Evolution of breast cancer screening in countries with intermediate and increasing incidence of breast cancer.

BACKGROUND: Few studies have been published regarding the practice of breast cancer screening in Asian countries. AIMS: The present study illustrates how the health policy for breast cancer screening has evolved in Taiwan from selective mammographic screening within a high-risk group, firstly to a programme of physical examination by public health nurses, and finally to a two-stage breast cancer screening programme, with a risk assessment followed by mammography for those at moderate to high risk. DATA SOURCES: Breast cancer screening has evolved from 1995 to 2004 in Taiwan in three stages: (1) selective screening for breast cancer with mammography, ultrasound and physical examination only in first-degree relatives of breast cancer cases (1995-1998); (2) a programme of mass screening (1999-2001) with physical examination by public health nurses; and (3) two-stage breast cancer screening with a risk factor questionnaire and mammography for those deemed at moderate-to-high risk (2002-2004). The questionnaire was based on significant risk factors in a previous epidemiological study, in conjunction with the physical examination programme, a risk score was constructed from the logistic regression coefficients from the previous study, and women with a score above the median in the previous epidemiological study were assigned to mammography. RESULTS: Two-stage mammography screening had the most favourable results compared with the two previous screening regimes. It had a positive predictive value of recall after mammography of 14%, compared with 8% for selective screening and 2% for physical examination. Of screen-detected cancers in the two-stage programme, 71% were either ductal carcinoma in situ or stage T1, compared with 61% for selective screening and 60% for physical examination. The area under the receiver operating characteristic curve was 71% for the two-stage programme. CONCLUSIONS: For a low- to medium-risk country such as Taiwan, two-stage screening has acceptable parameters of recall and cancer detection, and compares well with other screening strategies.