Health-related risk behaviors among U.S. childhood cancer survivors: a nationwide estimate.

BACKGROUND: Childhood cancer survivors (CCS) are subject to a substantial burden of treatment-related morbidity. Engaging in health protective behaviors and eliminating risk behaviors are critical to preventing chronic diseases and premature deaths. This study is aimed to provide updated information on currently smoking, physical inactivity, binge drinking patterns and associated factors among CCS using a nationwide dataset. METHODS: We constructed a sample of CCS (cancer diagnosis at ages < 21y) and healthy controls (matched on age, sex, residency, race/ethnicity) using 2020 Behavioral Risk Factor Surveillance System. We used Chi-square tests and Wilcoxon rank-sum test to examine differences in sociodemographics and clinical characteristics between two groups. Logistic, ordinal regression and multivariable models (conditional models for matching) were used to determine factors associated with risk behaviors. RESULTS: The final sample (18-80y) included 372 CCS and 1107 controls. Compared to controls, CCS had a similar proportion of binge drinking (~ 18%) but higher prevalence of currently smoking (26.6% vs. 14.4%, p < 0.001), physical inactivity (23.7% vs. 17.7%, p = 0.012), and of having 2-or-3 risk behaviors (17.2% vs. 8.1%, p < 0.001). Younger age, lower educational attainment, and having multiple chronic health conditions were associated with engaging in more risk behaviors among CCS. Females, compared to male counterparts, had lower odds of binge drinking (adjusted odds ratio (aOR) = 0.30, 95% confidence interval (CI): 0.16-0.57) among CCS but not in all sample. Having multiple chronic health conditions increased odds of both currently smoking (aOR = 3.52 95%CI: 1.76-7.02) and binge drinking (aOR = 2.13 95%CI: 1.11-4.08) among CCS while it only increased odds of currently smoking in all sample. DISCUSSION: Our study provided risk behavior information for wide age-range CCS, which is currently lacking. Every one in four CCS was currently smoking. Interventions targeting risk behavior reduction should focus on CCS with multiple chronic health conditions.

Short- and Long-Term Survival of Metastatic Biliary Tract Cancer in the United States From 2000 to 2018.

INTRODUCTION: Information about survival outcomes in metastatic biliary tract cancer (BTC) is sparse, and the numbers often quoted are based on reports of clinical trials data that may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of a standardized combination chemotherapy regimen since 2010 on survival is unclear. METHODS: We performed an analysis of the Surveillance, Epidemiology, and End Results database to determine the real-world overall survival trends in a cohort of patients with metastatic BTC diagnosed between the years 2000 and 2017 with follow-up until 2018. We analyzed data for the entire cohort, evaluated short-term and long-term survival rates, and compared survival outcomes in the pre-2010 and post-2010 periods. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to evaluate factors associated with survival. RESULTS: Among 13, 287 patients, the median age was 68 years. There was a preponderance of female (57%) and white (77%) patients. Forty-one percent died within 3 months of diagnosis (short-term survivors) and 20% were long-term survivors (12 months or longer). The median overall survival (OS) for the entire cohort was 4.5 months. Median OS improved post-2010 (4.5 months) compared to pre-2010 (3.5 months) (P < .0001). On multivariate analysis, age <55 years, intrahepatic cholangiocarcinoma, surgical resection, and diagnosis post-2010 were associated with lower hazard of death. CONCLUSION: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials because a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.

Healthcare utilization and cost barriers among U.S. childhood cancer survivors.

BACKGROUND: To evaluate healthcare utilization and cost barrier patterns among childhood cancer survivors (CCS) compared with noncancer controls. PROCEDURE: Using the 2014-2019 Behavioral Risk Factor Surveillance System, we identified CCS < 50 years and matched controls. We used chi-squared tests to compare characteristics between the two groups. Logistic regression analyses were used to assess the likelihood of having a checkup, receiving influenza vaccine, and experiencing healthcare cost barriers (being unable to see the doctor due to cost) during the past 12 months. Conditional models accounted for the matching. RESULTS: We included 231 CCS and 692 controls. CCS had lower household income (p < 0.001), lower educational attainment (p = 0.021), more chronic health conditions (p < 0.001), and a higher proportion of being current smokers (p = 0.005) than controls. Both groups had similar rates of having a checkup and influenza vaccine; however, a quarter of CCS experienced healthcare cost barriers compared with 13.9% in controls (p = 0.001; regression findings: adjusted odds ratio (aOR) = 1.72, 95% confidence interval (CI): 1.11-2.65). Compared with the youngest CCS group (18-24 years), CCS ages 25-29 years were five times more likely to experience healthcare cost barriers (aOR = 4.79; 95% CI, 1.39-16.54). Among CCS, current smokers were less likely to have a checkup (aOR = 0.46; 95% CI, 0.23-0.94). Uninsured CCS were less likely to have a checkup (aOR = 0.33; 95% CI, 0.14-0.75) and ∼8 times more likely to experience healthcare cost barriers (aOR = 8.28; 95% CI, 3.45-19.88). CONCLUSION: CCS being 25-29 years, uninsured, or current smokers encounter inferior outcomes in healthcare utilization and cost barriers. We suggest emphasis on programs on care transition and smoking cessation for CCS.

Economic Evaluations in National Cancer Institute-Sponsored Network Cancer Clinical Trials.

OBJECTIVES: Amid a rapid increase in cancer care costs, we examined the extent to which economic evaluations (EEs) were conducted for new treatments evaluated in clinical trials at SWOG, a large National Cancer Institute-sponsored cancer research network. METHODS: We investigated phase III cancer treatment clinical trials activated from 1980 onward with primary articles reporting the protocol-designated endpoints published in scientific journals by 2017. Using PubMed, Web of Science, and EconLit, we searched for EEs using trial name, cancer type, information on the comparison arms, and refined keywords for EE designs. We reported the overall proportion of trials with associated EEs and trends of this proportion over time. We synthesized and analyzed information on funding sources, health outcomes, and sources of quality-of-life and cost data from the EEs. RESULTS: Among 182 examined trials, 15 EEs were associated with 13 (7.1%) trials. Among the EEs, almost half (7 of 15) were either unfunded or did not report funding information, whereas nearly half (7 of 15) were funded by pharmaceutical companies and 2 (2 of 15, 13.3%) were supported by federal funding. All EEs reported a healthcare payer perspective. The proportion of trials with an associated EE increased from 1980 to 1989 and 2000 to 2009, but never exceeded 11%. Sources for cost and quality-of-life data for the EEs primarily came from outside the clinical trials. CONCLUSIONS: Few economic studies of treatments evaluated in National Cancer Institute-sponsored clinical trials have been conducted. Policymakers, payers, and patients lack economic evidence to consider newly evaluated cancer treatments, despite an urgent need to control healthcare costs.

Prevalence and correlates of HIV infection among men who inject drugs in a remote area of Vietnam.

BACKGROUND: Lack of information on the HIV epidemic among men who inject drugs (MWID) in northwestern Vietnam, a remote area, may hamper national efforts to control the disease. We examined HIV prevalence, needle-syringe sharing behaviors, and associated factors among MWID in three areas of northwestern Vietnam. METHODS: We used descriptive analysis to report the characteristics, frequency of risk behaviors, and of access to healthcare services among the MWID. Univariable logistic regression was used to assess the associations between the HIV infection, needle-syringe sharing behaviors, and their independent variables. We further explored these associations in multivariable analyses where we included independent variables based on a priori knowledge and their associations with the dependent variables determined in univariable analyses (p <  0.25). RESULTS: The HIV prevalence was 37.9, 16.9, and 18.5% for Tuan Giao, Bat Xat, and Lao Cai City, respectively, and 25.4% overall. MWID of Thai minority ethnicity were more likely to be HIV-positive (adjusted odds ratio (AOR) 3.55; 95% confidence interval (CI) 1.84-6.87). The rate of needle-syringe sharing in the previous 6 months was approximately 9% among the MWID in Tuan Giao and Lao Cai City, and 27.8% in Bat Xat. Two thirds of the participants never underwent HIV testing before this study. Ever having been tested for HIV before this study was not associated with any needle-syringe sharing behaviors. Among the HIV-positive MWID, those who received free clean needles and syringes were less likely to give used needles and syringes to peers (AOR 0.21; 95% CI 0.06-0.79). Going to a "hotspot" in the previous week was associated with increased odds of needle-syringe sharing in multiple subgroups. CONCLUSION: Our findings on HIV prevalence and testing participation among a subset of MWID in the northwestern Vietnam were corroborated with trend analysis results from the most recent HIV/STI Integrated Biological and Behavioral Surveillance report (data last collected in 2013.) We provided important insights into these MWID's risky injection behaviors. We suggest heightened emphasis on HIV testing and needle and syringe provision for this population. Also, policymakers and program implementers should target hotspots as a main venue to tackle HIV epidemics.

Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT): Baseline Results.

PURPOSE: To describe baseline results of the Alabama Screening and Intervention for Glaucoma and Eye Health through Telemedicine (AL-SIGHT) for patients at federally qualified health centers (FQHCs). Candidates were persons at risk for glaucoma-associated diseases (GAD) based on age, race/ethnicity, current diagnosis of GAD, family history, and diabetes. DESIGN: Baseline screening visit followed by remote diagnosis and referral for follow-up examinations. METHODS: Patients presenting to FQHCs who were at least 18 years of age were enrolled and underwent screening for acuity, autorefraction, intraocular pressure, visual field testing, and fundus imaging. Results were transmitted to an ophthalmologist at University of Alabama at Birmingham for diagnosis who made referrals for follow-up; follow-up attendance was noted. Questionnaires assessed participants' perspectives on screening. Primary outcomes were rates of disease detection, referral for follow-up, follow-up attendance, and participant satisfaction. RESULTS: Of the 500 participants enrolled (mean age 58 years), 45.6% were African American and 51.6% White. Remote diagnostic evaluation of ocular screening by ophthalmologist revealed 30% GAD, 6.8% diabetic retinopathy, 37.6% cataract, 68.4% refractive error, 9.2% other eye conditions. In all, 47.2% of the participants were referred for follow-up examination and for acuity 20/40 or worse or IOP ≥23 mm Hg in one or both eyes. Follow-up examination attendance was 76.7% for those referred. Participants reported being very satisfied with screening (85.8%) and with the convenience of screening in their primary care clinic (92.2%). CONCLUSIONS: The high percentage of patients diagnosed with treatable eye conditions at telemedicine screening suggest these programs in FQHCs can be effective and scalable nationwide. Attendance when referred for follow-up examination was high. Participants welcomed screenings in their communities.

Telehealth use among pediatric Alabama Medicaid enrollees, March-December 2020: Variations by race/ethnicity & place of residence.

During the early days and months of the COVID-19 pandemic, healthcare facilities experienced a slump in non-COVID-related visits, and there was an increasing interest in telehealth to deliver healthcare services for adult and pediatric patients. The study investigated telehealth use variation by race/ethnicity and place of residence for the pediatric enrollees of the Alabama Medicaid program. This retrospective observational study examined Alabama Medicaid claims data from March to December 2020 for enrollees less than 19 years. There were 637,792 pediatric enrollees in the Alabama Medicaid program during the study period, and 16.9% of them had used telehealth to meet healthcare needs. This study employed a multivariate Poisson mixed-effects model with robust error variance to obtain differences in telehealth utilization and found that Non-Hispanic Black children were 80% as likely, Hispanic children were 55% as likely, and Asian Children were 46% as likely to have used telehealth compared to Non-Hispanic White children. Pediatric enrollees in large rural areas and isolated areas were significantly less likely (IRR: 0.90 for both, p<0.05) to use telehealth than those in urban areas. This study's findings suggest that attention needs to be paid to addressing race/ethnicity disparities in accessing telehealth services.

Cost of Home-Based Couples Human Immunodeficiency Virus Counseling and Testing and Human Immunodeficiency Virus Self-Testing During Pregnancy and Postpartum in Southwestern Kenya.

OBJECTIVE: Home-based couples HIV testing and counseling and HIV self-testing (HIVST) for pregnant women can promote HIV status disclosure and male partner testing; however, cost data are lacking. We examined a home-based couples intervention (HBCI) and HIVST intervention costs per couple (unit cost) during pregnancy and postpartum in Kenya. METHODS: This randomized controlled trial is comparing HBCI and HIVST for couples among pregnant women attending antenatal care clinics in two counties in southwestern Kenya. We used micro-costing to estimate the unit cost per couple receiving the intervention as the total of direct and indirect costs for each study arm in 2019 US$. We used a one-month window to conduct a time and motion study to determine personnel effort and resources. We then compared the unit cost by arm, identified key cost drivers, and conducted sensitivity analyses for cost uncertainties. RESULTS: At base-case, the unit cost was $129.01 and $41.99, respectively, for HBCI and HIVST. Personnel comprised half of the unit cost for both arms. Staff spent more time on activities related to participant engagement in HBCI (accounting for 6.4% of the unit cost) than in HIVST (2.3%). Staff training was another key cost driver in HBCI (20.1% of the unit cost compared to 12.5% in HIVST). Sensitivity analyses revealed that the unit cost ranges were $104.64-$154.54 for HBCI and $30.49-$56.59 for HIVST. CONCLUSIONS: Our findings may guide spending decisions for future HIV prevention and treatment programs for pregnant couples in resource-limited settings such as Kenya.

Telemedicine for unhealthy alcohol use in adults living with HIV in Alabama using common elements treatment approach: A hybrid clinical efficacy-implementation trial protocol.

Background: Unhealthy alcohol use is an unaddressed barrier to achieving and maintaining control of the human immunodeficiency virus (HIV) epidemic. Integrated screening, treatment of common behavioral and mental health comorbidities, and telemedicine can improve alcohol treatment and HIV clinical and quality of life outcomes for rural and underserved populations. Objective: In a randomized controlled clinical trial, we will evaluate the effectiveness and implementation of telephone-delivered Common Elements Treatment Approach (T-CETA), a transdiagnostic cognitive behavioral therapy protocol, on unhealthy alcohol use, HIV, other substance use and mental health outcomes among predominantly rural adults with HIV receiving care at community clinics in Alabama. Methods: Adults with HIV receiving care at four selected community clinics in Alabama will receive a telephone-delivered alcohol brief intervention (BI), and then be assigned at random (stratified by clinic and sex) to no further intervention or T-CETA. Participants will be recruited after screening positively for unhealthy alcohol use or when referred by a provider. The target sample size is 308. The primary outcome will be change in the Alcohol Use Disorder Identification Test (AUDIT) at six- and 12-months post-enrollment. Additional outcomes include HIV (retention in care and viral suppression), patient-reported mental health (anxiety, depression, posttraumatic stress), and quality of life. A range of implementation measures be evaluated including T-CETA provider and client acceptability, feasibility, cost and cost-effectiveness. Conclusions: This trial will inform alcohol treatment within HIV care programs, including the need to consider comorbidities, and the potential impact of alcohol interventions on HIV and quality of life outcomes.

Monitoring the effects of urbanization and flood hazards on sandy ecosystem services.

Urbanization, storms, and floods have compromised the benefits derived from various types of sand dune landscapes, particularly in developing countries located in humid monsoon tropical regions. One pertinent question is which driving forces have had a dominant impact on the contributions of sand dune ecosystems to human well-being. Has the decline in sand dune ecosystem services (ES) been primarily due to urbanization or flooding hazards? This study aims to address these issues by developing a Bayesian Belief Network (BBN) to analyze six different sand dune landscapes worldwide. The study uses various data types, including multi-temporal and -sensor remote sensing (SAR and optical data), expert knowledge, statistics, and GIS to analyze the trends in sand dune ecosystems. A support tool based on probabilistic approaches was developed to assess changes in ES over time due to the effects of urbanization and flooding. The developed BBN has the potential to assess the ES values of sand dunes during both rainy and dry seasons. The study calculated and tested the ES values in detail over six years (from 2016 to 2021) in Quang Nam province, Vietnam. The results showed that urbanization has led to an increase in the total ES values since 2016, while floods only had a minimal impact on dune ES values during the rainy season. The fluctuations of ES values were found to be more significant due to urbanization than floods. The study's approach can be useful in future research on coastal ecosystems.

Alcohol-focused and transdiagnostic treatments for unhealthy alcohol use among adults with HIV in Zambia: A 3-arm randomized controlled trial.

BACKGROUND: Clinical and quality of life outcomes in people living with human immunodeficiency virus (PLWH) are undermined by unhealthy alcohol use (UAU), which is highly prevalent in this population and is often complicated by mental health (MH) or other substance use (SU) comorbidity. In sub-Saharan Africa, evidence-based and implementable treatment options for people with HIV and UAU are needed. METHODS: We are conducting a hybrid clinical effectiveness-implementation trial at three public-sector HIV clinics in Lusaka, Zambia. Adults with HIV, who report UAU, and have suboptimal HIV clinical outcomes, will be randomized to one of three arms: an alcohol-focused brief intervention (BI), the BI with additional referral to a transdiagnostic cognitive behavioral therapy (Common Elements Treatment Approach [CETA]), or standard of care. The BI and CETA will be provided by HIV peer counselors, a common cadre of lay health worker in Zambia. Clinical outcomes will include HIV viral suppression, alcohol use, assessed by audio computer-assisted self-interview (ACASI) and direct alcohol biomarkers, Phophatidylethanol and Ethyl glucuronide, and comorbid MH and other SU. A range of implementation outcomes including cost effectiveness will also be analyzed. CONCLUSION: Hybrid and 3-arm trial design features facilitate the integrated evaluation of both brief, highly implementable, and more intensive, less implementable, treatment options for UAU among PLWH in sub-Saharan Africa. Use of ACASI and alcohol biomarkers will strengthen understanding of treatment effects.

Community-Level Social Determinants of Health and Well-Child Visits Among Alabama Medicaid Enrollees.

Well-child visits focus on health promotion and disease detection and are critical to the appropriate provision of care. Evidence has shown that participation in well-child visits is associated with various patient-level factors; however, there has been an increasing focus on the influence of community-level social determinants of health (SDoH). This study explored associations between well-child visits and community-level SDoH at the census tract level among children enrolled in Alabama Medicaid. Through this analysis, it is possible to understand the distribution of care among this underserved population in different geographic settings, thus identifying potential disparities and areas for targeted intervention. Using administrative data from 2015 to 2017 enrollees in Alabama Medicaid that have been geographically linked to information on urbanicity and poverty, logistic regressions (both in total and stratified by age group) were estimated with separate community-level urbanicity, poverty variables, and individual characteristics. The regressions were repeated using a combined urbanicity/poverty variable. Looking at urbanicity and poverty together, with the exception of the least urban areas, it was those living in census tracts where there was discordance in urbanicity and poverty that had the highest likelihood of receiving well-child visits compared with those in census tracts classified as medium poverty (all urbanicity levels). There is a positive effect for Medicaid enrollees in the middle tertile of urbanicity in areas of low and high poverty and in wealthier more urban areas. If poverty and urbanicity were explored separately, some of the nuances would not have been apparent.

Alabama Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (AL-SIGHT): Study Design and Methodology.

PRCIS: This paper presents the methods and protocol of a community-based telemedicine program to identify glaucoma and other eye diseases. PURPOSE: To describe the study rationale and design of the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine project. METHODS: The study will implement and evaluate a telemedicine-based detection strategy for glaucoma, diabetic retinopathy, and other eye diseases in at-risk patients seen at federally qualified health centers located in rural Alabama. The study will compare the effectiveness of the remote use of structural and functional ocular imaging devices to an in-person examination. Study participants will receive a remote ocular assessment consisting of visual acuity, intraocular pressure, visual field testing, and imaging of the retina and optic nerve with spectral-domain optical coherence tomography, and the data will be reviewed by an ophthalmologist and optometrist. It will also compare the effectiveness of financial incentives along with a validated patient education program versus a validated patient education program alone in improving follow-up adherence. Finally, cost and cost-effectiveness analyses will be performed on the telemedicine program compared with standard in-person care using effectiveness measured in numbers of detected eye disease cases. CONCLUSIONS: The study aims to develop a model eye health system using telemedicine to prevent vision loss and address eye health among underserved and at-risk populations.

Testing strategies for couple engagement in prevention of mother-to-child transmission of HIV and family health in Kenya: study protocol for a randomized controlled trial.

BACKGROUND: HIV-related maternal deaths and HIV infection among infants remain unacceptably high across sub-Saharan Africa despite increased antenatal care attendance and provision of antiretroviral therapy to pregnant women. In the Jamii Bora ("Better Family" in Swahili) Study, we seek to test the efficacy of an interdependence theory-based couple intervention. The intervention reaches pregnant women and male partners through home visits by male-female pairs of lay health workers. The aim is to increase access to home-based couples' HIV testing and counseling services to improve family health. METHODS: This is a three-arm randomized control trial among 1080 pregnant women 15 years of age or older, living with their male partners, and who have not undergone couples' HIV testing and counseling in Kisumu and Migori Counties in Kenya. Couples will be randomized into three groups: home-based couple visits, HIV self-testing kits for couple use, or standard care (male partner clinic invitation letters). Participants will be followed up to 18 months postpartum. The study has three aims: in aim 1, we will determine the effects of the intervention on our primary outcome of couple HIV testing, compared to HIV self-testing kits and standard care; in aim 2, we will examine the intervention impact on HIV prevention behaviors, facility delivery, and postnatal healthcare utilization, as well as secondary health outcomes of maternal viral suppression and HIV-free child survival up to 18 months for couples living with HIV; and in aim 3, we will compare the cost-effectiveness of the home-based couple intervention to the less resource-intensive strategies used in the other two study arms. Assessments with couples are conducted at baseline, late pregnancy, and at months 3, 6, 12, and 18 after birth. DISCUSSION: The results from this study will inform decision-makers about the cost-effective strategies to engage pregnant couples in the prevention of mother-to-child transmission and family health, with important downstream benefits for maternal, paternal, and infant health. TRIAL REGISTRATION: ClinicalTrials.gov NCT03547739 . Registered on May 9, 2018.

Preliminary study on HIV status disclosure to perinatal infected children: retrospective analysis of administrative records from a pediatric HIV clinic in the southern United States.

OBJECTIVE: The World Health Organization recommends disclosing HIV-status between 6 and 12 years; American Academy of Pediatrics recommends that children are informed at "school age." Neither suggests an optimal age when children should learn of their status to improve viral load suppression. Considering that virally suppressed people do not transmit HIV and that interrupting the transmission cycle is critical to ending the HIV epidemic, our objective is to examine the relationship between age of disclosure and viral load suppression by evaluating data from a pediatric HIV clinic in the southern United States. Records from perinatal infected patients seen between 2008 and 2018 were analyzed (N = 61). RESULTS: Longitudinal suppression was low across all groups when benchmarked against the UNAIDS 90% global target; black patients were less likely to achieve suppression compared to white patients (41% vs. 75%, p = 0.04). Adopted children were more likely to achieve suppression than children living with biological family (71% vs. 44%, p < 0.05). Children who learned of their status between 10 and 12 had the highest rate of suppression (65%) compared to peers who learned of their status younger (56%) or older (38%). Our preliminary study is designed to spark research on refining the current recommendations on HIV-status disclosure to perinatal infected children.

Association of National Cancer Institute-Sponsored Clinical Trial Network Group Studies With Guideline Care and New Drug Indications.

Importance: National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying effective new antineoplastic regimens. However, the downstream clinical effect of their trials has not been systematically examined. Objective: To examine the association of NCTN trials with guideline care and new drug indications. Design, Setting, and Participants: This retrospective cohort study evaluated phase 3 SWOG Cancer Research Network clinical trials from January 1, 1980, through June 30, 2017. Only completed trials with published results were included. To be considered practice influential (PI), a trial must have been associated with guideline care through its inclusion in National Comprehensive Cancer Network (NCCN) clinical guidelines or US Food and Drug Administration (FDA) new drug approvals in favor of a recommended treatment. Data were analyzed from June 15, 2018, through March 29, 2019. Main Outcomes and Measures: Estimated overall rate of PI trials, as well as trends over time. The total federal investment supporting the set of trials was also determined. Results: In total, 182 trials consisting of 148 028 patients were studied. Eighty-two studies (45.1%; 95% CI, 37.7%-52.6%) were PI, of which 70 (38.5%) influenced NCCN guidelines, 6 (3.3%) influenced FDA new drug approvals, and 6 (3.3%) influenced both. The number of PI trials was 47 of 65 (72.3%) among those with positive findings and 35 of 117 (29.9%) among those with negative findings. Thus, 35 of 82 PI trials (42.7%) were based on studies with negative findings, with nearly half of these studies (17 of 35 [48.6%]) reaffirming standard of care compared with experimental therapy. The total federal investment spent in conducting the trials was $1.36 billion (2017 US dollars), a rate of $7.5 million per study or $16.6 million per PI trial. Conclusions and Relevance: Nearly half of all phase 3 trials by one of the NCTN's largest groups were associated with guideline care or new drug indications, including those with positive and negative findings. Compared with the costs of a new drug approval in pharmaceutical companies, typically estimated at more than $1 billion, the amount of federal funds invested to provide this valuable evidence was modest. These results suggest that the NCTN program contributes clinically meaningful, cost-efficient evidence to guide patient care.

Cost-Effectiveness of Herpes Zoster Vaccination: A Systematic Review.

BACKGROUND: Herpes zoster (HZ) is one of the most common diseases among adults. Its reactivation is characterized by a severe and painful complication. In addition to the existing herpes zoster vaccine (ZVL), the FDA approved a new adjuvanted subunit zoster vaccine (RZV) in 2017 for use in adults aged 50 years and older. Several studies have assessed the cost-effectiveness of ZVL, many of which were conducted before the long-term vaccine  efficacy data was available in 2014. OBJECTIVE: Our objectives were to (i) summarize and compare the cost-effectiveness analyses (CEAs) of ZVL conducted before and after 2014, (ii) summarize the CEAs of RZV, and (iii) critically assess the cost-effectiveness models and identify key parameters to consider for future CEAs of RZV. METHODS: We searched PubMed and two other databases from inception to March 2018 for original cost-effectiveness, cost-utility, or cost-benefit analyses of HZ vaccines. Three investigators independently reviewed and assessed full-text articles after screening the titles and abstracts to determine eligibility. For all included studies, we assessed study quality using the Drummond and Jefferson's checklist and extracted study characteristics, model structure, vaccine characteristics, incidence of HZ and complications, incremental cost-effectiveness ratio, and sensitivity analyses. We summarized data by type of vaccine, year of publication, and funding sources. RESULTS: Twenty-seven studies met eligibility criteria. All studies were from high-income countries and were of moderate-to-high or high quality. Twenty studies repeatedly used four cost-effectiveness models. The assumption on long-term efficacy of ZVL was not based on clinical trial data in > 50% of studies. Fifteen out of 25 studies concluded that ZVL was cost-effective compared with no vaccine at a vaccine price ranging between US$93 and US$236 per dose (2018 US$), 40% of which were published after 2014. All industry-funded studies favored the use of ZVL. The single study assessing RZV found it to be more effective and less costly than ZVL, and cost-effective compared with no vaccination. More studies conducted after 2014 included various efficacy endpoints for ZVL, adverse reactions, and productivity loss compared with those conducted before 2014. CONCLUSIONS: A majority of studies of ZVL found it to be cost-effective compared with no vaccine using the authors' chosen willingness-to-pay thresholds. RZV was dominant in the single study comparing the two vaccines, but the finding needs to be confirmed with further studies in different settings. Future studies should assume vaccine efficacy in line with clinical data, account for more efficacy endpoints for ZVL, and include other HZ long-term complications, vaccine adverse reactions, and productivity loss.

Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review.

BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.

The scientific impact and value of large, NCI-sponsored randomized phase III cancer chemoprevention trials.

BACKGROUND: The cancer research groups of the National Cancer Institute's National Clinical Trials Network have a history of successful conduct of large randomized phase III trials of chemoprevention for cancer. An important question for funding agencies is whether the conduct of large chemoprevention trials provides strong scientific return on investment. METHODS: We evaluated the scientific impact of four large chemoprevention trials - two for breast cancer and two for prostate cancer - using citation analysis, a bibliometric technique. The results were compared to the scientific impact of a series of treatment trials conducted over the same 20-year time period (1991-2010, inclusive). Average annual citation counts were compared using t-tests. Scientific impact was also assessed relative to trial costs. RESULTS: Twenty-seven treatment trials with 17,208 patients and four chemoprevention trials with 87,550 patients were examined. The mean annual citation rate for primary articles was higher for chemoprevention trials compared to treatment trials (188.1 vs. 40.4, p = .001). For both primary and secondary article publications, mean annual citations for articles associated with chemoprevention trials were also higher (483.9 vs. 69.0, p = .0003). Large chemoprevention trials were estimated to provide 50% more total citations from primary and secondary articles on a cost-adjusted basis. CONCLUSION: Based on these criteria, the scientific impact of large phase III cancer chemoprevention trials was very high in absolute terms, and as good as or better than that of treatment trials after accounting for expenditure. For appropriate scientific questions, large chemoprevention trials provide a good scientific return on investment for federal funding agencies.