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HighlightsWe illustrate the steps involved in carrying out cost-effectiveness analysis using net benefit regressions with possibly censored demo data by providing step-by-step guidance and code applied to a data set.We demonstrate the importance of these new methods by illustrating how naïve methods for handling censoring can lead to biased cost-effectiveness results.

ObjectivesPatient-Centered Communication (PCC) is an essential element of patient-centered cancer care. Thus, this study aimed to examine the prevalence of and factors associated with optimal PCC among cancer survivors during COVID-19, which has been less studied.MethodsWe used national survey (Health Information National Trends Survey) among cancer survivors (n = 2579) to calculate the prevalence (%) of optimal PCC in all 6 PCC domains and overall (mean) by time (before COVID-19, 2017-19 vs. COVID-19, 2020). Multivariable logistic regressions were performed to explore the associations of sociodemographic (age, birth gender, race/ethnicity, income, education, usual source of care), and health status (general health, depression/anxiety symptoms, time since diagnosis, cancer type) factors with optimal PCC.ResultsThe prevalence of optimal PCC decreased during COVID-19 overall, with the greatest decrease in managing uncertainty (7.3%). Those with no usual source of care (odd ratios, ORs =1.53-2.29), poor general health (ORs=1.40-1.66), depression/anxiety symptoms (ORs=1.73-2.17) were less likely to have optimal PCC in most domains and overall PCC.ConclusionsWe observed that the decreased prevalence of optimal PCC, and identified those with suboptimal PCC during COVID-19.Practice implicationsMore efforts to raise awareness and improve PCC are suggested, including education and guidelines, given the decreased prevalence during this public health emergency.

Poor mental health has been found to be more prevalent among those with cancer and is considered a public health crisis since COVID-19. This study assessed the impact of COVID-19 and cancer survivorship on mental health and investigated factors, including online patient-provider communications (OPPC; email/internet/tablet/smartphone), associated with poor mental health prior to and during the early COVID-19. Nationally representative Health Information National Trends Survey data during 2017-2020 (n = 15,871) was used. While the prevalence of poor mental health was high (40-42%), Difference-In-Difference analyses revealed that cancer survivorship and COVID-19 were not associated with poor mental health. However, individuals that used OPPC had 40% higher odds of poor mental health. Low socioeconomic status (low education/income), younger age (18-64 years), and female birth gender were also associated with poor mental health. Findings highlight the persistence of long-standing mental health inequities and identify that OPPC users might be those who need mental health support.

Neurological surgery is a historically challengingspecialty to match into, with match rates of 65%. With the USMLE Step 1 exam now graded on a pass/fail basis, there is piqued interest in whether Step 2 will become the “new” Step 1 as a factor to assess candidates for competitive specialties such asneurosurgery. To date, there is no literature that describes the differences in Step 2 scores between matched and unmatched allopathic seniors and how these differences have changed through time.

To evaluate the consistency of contraceptionplan identified at delivery hospitalization withreported contraception use over 6 monthspostpartum.

Cost-effectiveness analyses of new cancer treatments in real-world settings (e.g., post-clinical trials) inform healthcare decision makers about their healthcare investments for patient populations. The results of these analyses are often, though not always, presented with statistical uncertainty. This paper identifies five ways to characterize statistical uncertainty: (1) a 95% confidence interval (CI) for the incremental cost-effectiveness ratio (ICER); (2) a 95% CI for the incremental net benefit (INB); (3) an INB by willingness-to-pay (WTP) plot; (4) a cost-effectiveness acceptability curve (CEAC); and (5) a cost-effectiveness scatterplot. It also explores their usage in 22 articles previously identified by a rapid review of real-world cost effectiveness of novel cancer treatments. Seventy-seven percent of these articles presented uncertainty results. The majority those papers (59%) used administrative data to inform their analyses while the remaining were conducted using models. Cost-effectiveness scatterplots were the most commonly used method (34.3%), with 40% indicating high levels of statistical uncertainty, suggesting the possibility of a qualitatively different result from the estimate given. Understanding the necessity for and the meaning of uncertainty in real-world cost-effectiveness analysis will strengthen knowledge translation efforts to improve patient outcomes in an efficient manner.

Appropriate support in the home may not be readily available for people living in the community with mental illness and physical comorbidities. This mixed-method study evaluated a smart home technology intervention for individuals within this population as well as providing health care providers with health monitoring capabilities. The study recruited 13 participants who were offered a smartphone, a touchscreen monitor, and health devices, including smartwatches, weigh scales, and automated medication dispensers. Healthcare providers were able to track health device data, which were synchronized with the Lawson Integrated DataBase. Participants completed interviews at baseline as well as at 6-month and 12-month follow-ups. Focus groups with participants and care providers were conducted separately at 6-month and 12-month time points. As the sample size was too small for meaningful statistical inference, only descriptive statistics were presented. However, the qualitative analyses revealed improvements in physical and mental health, as well as enhanced communication with care providers and friends/family. Technical difficulties and considerations are addressed. Ethics analyses revealed advancement in equity and fairness, while policy analyses revealed plentiful opportunities for informing policymakers. The economic costs are also discussed. Further studies and technological interventions are recommended to explore and expand upon in-home technologies that can be easily implemented into the living environment.

ObjectiveTo estimate traumatic brain injuries (TBIs) and acute care costs due to sports activities.MethodsA planned secondary analysis of 7799 children from 5 years old to

BackgroundThe current standard of care in the treatment of children with physical trauma presenting to non-designated pediatric trauma centers is consultation with a pediatric trauma center by telephone. This includes contacting a pediatric trauma specialist and transferring any child with a potentially serious injury to a regionalized level I pediatric trauma center. This approach to care frequently results in medically unnecessary transfers and may place undue burdens on families. A newer model of care, the "Virtual Pediatric Trauma Center" (VPTC), uses telemedicine to make the expertise of a level I pediatric trauma center virtually available to any hospital. While the use of the VPTC model of care is increasing, there have been no studies comparing the VPTC to standard care of injured children at non-designated trauma centers with respect to patient- and family-centered outcomes. The goal of this study is to compare the current standard of care to the VPTC with respect to family-centered outcomes developed by parents and community advisory boards.MethodsWe will use a stepped-wedge trial design to enroll children with physical trauma presenting to ten hospitals, including level II, level III, and non-designated trauma centers. The primary outcome measures are parent/family experience of care and distress 3 days following injury. Secondary aims include 30-day healthcare utilization, parent/family out-of-pocket costs at 3 days and 30 days after injury, transfer rates, and parent/family distress 30 days following injury. We expect at least 380 parents/families of children will be eligible for the study following an emergency department physician's request for a level I pediatric trauma center consultation. We will evaluate parent/family experience of care and distress using previously validated instruments, healthcare utilization by family recollection and medical record abstraction, and out-of-pocket costs using standard economic analyses.DiscussionWe expect that the findings from this study will inform other level I pediatric trauma centers and non-pediatric trauma centers on how to improve their systems of care for injured children. The results will help to optimize communication, confidence, and shared decision-making between parents/families and clinical staff from both the transferring and receiving hospitals.Trial registrationClinicalTrials.gov Identifier: NCT04469036. Registered July 13, 2020 before start of inclusion.

Cost-effectiveness analysis is an essential part of the evaluation of new medical interventions. While in many studies both costs and effectiveness (eg, survival time) are censored, standard survival analysis techniques are often invalid due to the induced dependent censoring problem. We propose methods for censored cost-effectiveness data using the net-benefit regression framework, which allow covariate-adjustment and subgroup identification when comparing two intervention groups. The methods provide a straightforward way to construct cost-effectiveness acceptability curves with censored data. We also propose a more efficient doubly robust estimator of average causal incremental net benefit, which increases the likelihood that the results will represent a valid inference in observational studies. Lastly, we conduct extensive numerical studies to examine the finite-sample performance of the proposed methods, and illustrate the proposed methods with a real data example using both survival time and quality-adjusted survival time as the measures of effectiveness.

Cost-effectiveness analysis (CE Analysis) provides evidence about the incremental gains in patient outcomes costs from new treatments and interventions in cancer care. The utilization of "real-world" data allows these analyses to better reflect differences in costs and effects for actual patient populations with comorbidities and a range of ages as opposed to randomized controlled trials, which use a restricted population. This rapid review was done through PubMed and Google Scholar in July 2022. Relevant articles were summarized and data extracted to summarize changes in costs (in 2022 CAD) and effectiveness in cancer care once funded by the Canadian government payer system. We conducted statistical analyses to examine the differences between means and medians of costs, effects, and incremental cost effectiveness ratios (ICERs). Twenty-two studies were selected for review. Of those, the majority performed a CE Analysis on cancer drugs. Real-world cancer drug studies had significantly higher costs and effects than non-drug therapies. Studies that utilized a model to project longer time-horizons saw significantly smaller ICER values for the treatments they examined. Further, differences in drug costs increased over time. This review highlights the importance of performing real-world CE Analysis on cancer treatments to better understand their costs and impacts on a general patient population.

Cost-effectiveness analysis, the most common type of economic evaluation, estimates a new option's additional outcome in relation to its extra costs. This is crucial to study within the clinical setting because funding for new treatments and interventions is often linked to whether there is evidence showing they are a good use of resources. This article describes how to analyze a cost-effectiveness dataset using the framework of a net benefit regression. The process of creating estimates and characterizing uncertainty is demonstrated using a hypothetical dataset. The results are explained and illustrated using graphs commonly employed in cost-effectiveness analyses. We conclude with a call to action for researchers to do more person-level cost-effectiveness analysis to produce evidence of the value of new treatments and interventions. Researchers can utilize cost-effectiveness analysis to compare new and existing treatment mechanisms.

ObjectiveThe objective was to (i) assess the long-term cost-effectiveness of acceptance and commitment therapy (ACT), a workplace dialog intervention (WDI), and ACT+WDI compared to treatment as usual (TAU) for common mental disorders and (ii) investigate any differences in cost-effectiveness between diagnostic groups.MethodsAn economic evaluation from the healthcare and limited welfare perspectives was conducted alongside a randomized clinical trial with a two-year follow-up period. Persons with common mental disorders receiving sickness benefits were invited to the trial. We used registry data for cost analysis alongside participant data collected during the trial and the reduction in sickness absence days as treatment effect. A total of 264 participants with a diagnosis of depression, anxiety, or stress-induced exhaustion disorder participated in a two-year follow-up of a four-arm trial: ACT (N=74), WDI (N=60), ACT+WDI (N=70), and TAU (N=60).ResultsFor all patients in general, there were no statistically significant differences between interventions in terms of costs or effect. The subgroup analyses suggested that from a healthcare perspective, ACT was a cost-effective option for depression or anxiety disorders and ACT+WDI for stress-induced exhaustion disorder. With a two-year time horizon, the probability of WDI to be cost-saving in terms of sickness benefits costs was 80% compared with TAU.ConclusionsACT had a high probability of cost-effectiveness from a healthcare perspective for employees on sick leave due to depression or anxiety disorders. For participants with stress-induced exhaustion disorder, adding WDI to ACT seems to reduce healthcare costs, while WDI as a stand-alone intervention seems to reduce welfare costs.

BackgroundSmoking among patients diagnosed with cancer poses important health and financial challenges including reduced effectiveness of expensive cancer therapies. This study explores the value of smoking cessation programs (SCPs) for patients already diagnosed with cancer. It also identifies conditions under which SPCs may be wise investments.MethodsUsing a simplified decision analytic model combined with insights from a literature review, we explored the cost-effectiveness of SCPs.ResultsThe findings provide insights about the potential impact of cessation probabilities among cancer patients in SCPs and the potential impact of SCPs on cancer patients' lives.ConclusionThe evidence suggests that there is good reason to believe that SCPs are an economically attractive way to improve outcomes for cancer patients when SCPs are offered in conjunction with standard cancer care.

Crohn's disease (CD) is an inflammatory bowel disease with increasing incidence and prevalence worldwide. Perianal fistulas are seen in up to 26% of CD patients and are often refractory to medical therapy. Current treatments for CD perianal fistulas (pCD) include antibiotics, biologics, and for refractory cases, fecal diversion (FD) with ileostomy or colostomy. Mesenchymal stem/stromal cell therapy (MSCs) is a new modality that have shown efficacy in treating pCD. MSCs locally injected into pCD can lead to healing, and a phase III clinical trial (ADMIRE-CD) showed 66% clinical response, leading to approval of MSCs (Alofisel, Takeda) in the European Union. It is unclear if MSCs would be more cost-effective than the current standard of FD. We therefore developed a decision tree model to determine the cost-effectiveness of MSCs compared to FD for pCD. Our study showed that both autologous and allogeneic MSCs are more cost-effective than FD in an academic medical center and even in a worst-case scenario with 100% chance of all complications for MSCs treatment and 0% chance of complications for FD, both allogeneic and autologous MSCs are still cost saving compared to FD.

BackgroundParenting programs can be economically attractive interventions for improving the mental health of both parents and their children. Few attempts have been made to analyse the value of children's and parent's outcomes simultaneously, to provide a qualified support for decision making.MethodsA within trial cost-effectiveness evaluation was conducted, comparing Ladnaan, a culturally tailored parenting program for Somali-born parents, with a waitlist control. Quality-adjusted life years (QALY) for parents were estimated by mapping the General Health Questionnaire-12 to Euroqol's EQ-5D-3L to retrieve utilities. Behavioural problems in children were measured using the Child Behaviour Checklist (CBCL). Intervention costs were estimated for the trial. A net benefit regression framework was employed to study the cost-effectiveness of the intervention, dealing with multiple effects in the same analysis to estimate different combinations of willingness-to pay (WTP) thresholds.ResultsFor a WTP of roughly €300 for a one point improvement in total problems on the CBCL scale (children), Ladnaan is cost-effective. In contrast, the WTP would have to be roughly €580,000 per QALY (parents) for it to be cost-effective. Various combinations of WTP values for the two outcomes (i.e., CBCL and QALY) may be used to describe other scenarios where Ladnaan is cost-effective.ConclusionsDecision-makers interested in multiple effects must take into account combinations of effects in relation to budget, in order to obtain cost-effective results. A culturally adapted parenting program may be cost-effective, depending on the primary outcome, or multiple outcomes of interest. Trial registration clinicaltrials.gov, NCT02114593. Registered 15 April 2014-prospectively registered, https://www.clinicaltrials.gov/ct2/results?recrs=&cond=&term=NCT02114593&cntry=&state=&city=&dist=.

BackgroundWeight telemonitoring may be an effective way to improve patients' ability to manage heart failure and prevent unnecessary utilization of health services. However, the effectiveness of such interventions is dependent upon patient adherence.ObjectiveThe purpose of this study was to determine how adherence to weight telemonitoring changes in response to 2 types of events: hospital readmissions and emergency department visits.MethodsThe Better Effectiveness After Transition-Heart Failure trial examined the effectiveness of a remote telemonitoring intervention compared with usual care for patients discharged to home after hospitalization for decompensated heart failure. Participants were followed for 180 days and were instructed to transmit weight readings daily. We used Poisson regression to determine the within-person effects of events on subsequent adherence.ResultsA total of 625 events took place during the study period. Most of these events were rehospitalizations (78.7%). After controlling for the number of previous events and discharge to a skilled nursing facility, the rate for adherence decreased by nearly 20% in the 2 weeks after a hospitalization compared with the 2 weeks before (adjusted rate ratio, 0.81; 95% confidence interval: 0.77-0.86; P < .001).ConclusionsExperiencing a rehospitalization had the effect of diminishing adherence to daily weighing. Providers using telemonitoring to monitor decompensation and manage medications should take advantage of the potential "teachable moment" during hospitalization to reinforce the importance of adherence.

BackgroundVolume of operative cases may be an important factor associated with improved survival for early-stage pancreatic cancer. Most high-volume pancreatic centers are also academic institutions, which have been associated with additional healthcare costs. We hypothesized that at high-volume centers, the value of the extra survival outweighs the extra cost.Study designThis retrospective cohort study used data from the California Cancer Registry linked to the Office of Statewide Health Planning and Development database from January 1, 2004 through December 31, 2012. Stage I-II pancreatic cancer patients who underwent resection were included. Multivariable analyses estimated overall survival and 30-day costs at low- vs high-volume pancreatic surgery centers. The incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) were estimated, and statistical uncertainty was characterized using net benefit regression.ResultsOf 2,786 patients, 46.5% were treated at high-volume centers and 53.5% at low-volume centers. There was a 0.45-year (5.4 months) survival benefit (95% CI 0.21-0.69) and a $7,884 extra cost associated with receiving surgery at high-volume centers (95% CI $4,074-$11,694). The ICER was $17,529 for an additional year of survival (95% CI $7,997-$40,616). For decision-makers willing to pay more than $20,000 for an additional year of life, high-volume centers appear cost-effective.ConclusionsAlthough healthcare costs were greater at high-volume centers, patients undergoing pancreatic surgery at high-volume centers experienced a survival benefit (5.4 months). The extra cost of $17,529 per additional year is quite modest for improved survival and is economically attractive by many oncology standards.

BackgroundParents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits.MethodsIn this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge.ResultsWe enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups.ConclusionsAlberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings.Trial registrationClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016.

PurposeWe previously demonstrated lower early mortality for young adults (YAs) with acute lymphoblastic leukemia (ALL) who received induction treatment at specialized cancer centers (SCCs) versus community hospitals. The aim of this study is to determine the impact of inpatient location of treatment throughout therapy on long-term survival, complications, and cost-associations that have not yet been evaluated at the population level.MethodsUsing the California Cancer Registry linked to a hospitalization database, we identified patients, 0-39 years of age, diagnosed with first primary ALL who received inpatient treatment between 1991 and 2014. Patients were classified as receiving all or part or none of their inpatient treatment at an SCC within 3 years of diagnosis. Inverse probability-weighted, multivariable Cox regression models estimated the associations between location of treatment and sociodemographic and clinical factors with survival. We compared 3-year inpatient costs overall and per day by age group and location of care.ResultsEighty-four percent (0-18 years; n = 4,549) of children and 36% of YAs (19-39 years; n = 683) received all treatment at SCCs. Receiving all treatment at an SCC was associated with superior leukemia-specific (hazard ratio [HR], 0.76; 95% CI, 0.67 to 0.88) and overall survival (HR, 0.87; 95% CI, 0.77 to 0.97) in children and in YAs (HR, 0.71; 95% CI, 0.61 to 0.83; HR, 0.70; 95% CI, 0.62 to 0.80) even after controlling for complications. The cost of inpatient care during the full course of therapy was higher in patients receiving all of their care at SCCs.ConclusionOur results demonstrate that inpatient treatment at an SCC throughout therapy is associated with superior survival; therefore, strong consideration should be given to referring these patients to SCCs.

BackgroundModern therapy for type 1 diabetes (T1D) increasingly utilizes technology such as insulin pumps and continuous glucose monitors (CGMs). Prior analyses suggest that T1D costs are driven by preventable hospitalizations, but recent escalations in insulin prices and use of technology may have changed the cost landscape.MethodsWe conducted a retrospective analysis of T1D medical costs from 2012 to 2016 using the OptumLabs Data Warehouse, a comprehensive database of deidentified administrative claims for commercial insurance enrollees. Our study population included 9445 individuals aged ≤18 years with T1D and ≥13 months of continuous enrollment. Costs were categorized into ambulatory care, hospital care, insulin, diabetes technology, and diabetes supplies. Mean costs for each category in each year were adjusted for inflation, as well as patient-level covariates including age, sex, race, census region, and mental health comorbidity.ResultsMean annual cost of T1D care increased from $11 178 in 2012 to $17 060 in 2016, driven primarily by growth in the cost of insulin ($3285 to $6255) and cost of diabetes technology ($1747 to $4581).ConclusionsOur findings suggest that the cost of T1D care is now driven by mounting insulin prices and growing utilization and cost of diabetes technology. Given the positive effects of pumps and CGMs on T1D health outcomes, it is possible that short-term costs are offset by future savings. Long-term cost-effectiveness analyses should be undertaken to inform providers, payers, and policy-makers about how to support optimal T1D care in an era of increasing reliance on therapeutic technology.

PurposeEnd-of-life (EOL) cancer care is costly, with challenges regarding intensity and place of care. We described EOL care and costs for patients with colorectal cancer (CRC) in the United States and the province of Ontario, Canada, to inform better care delivery.MethodsPatients diagnosed with CRC from 2007 to 2013, who died of any cancer from 2007 to 2013 at age ≥ 66 years, were selected from the US SEER cancer registries linked to Medicare claims (n = 16,565) and the Ontario Cancer Registry linked to administrative health data (n = 6,587). We estimated total and resource-specific costs (2015 US dollars) from public payer perspectives over the last 360 days of life by 30-day periods, by stage at diagnosis (0-II, III, IV).ResultsIn all months, especially 30 days before death, higher percentages of SEER-Medicare than Ontario patients received chemotherapy (15.7% v 8.0%), and imaging tests (39.4% v 31.1%). A higher percentage of Ontario patients were hospitalized (62.5% v 51.0%), but 43.2% of hospitalized SEER-Medicare patients had intensive care unit (ICU) admissions versus 17.9% of hospitalized Ontario patients. Cost differences between cohorts were greater for patients with stage IV disease. In the last 30 days, mean total costs for patients with stage IV disease were $15,881 (SEER-Medicare) and $12,034 (Ontario) versus $19,354 and $17,312 for stage 0-II. Hospitalization costs were higher for SEER-Medicare patients ($11,180 v $9,434), with lower daily hospital costs in Ontario ($1,067 v $2,004).ConclusionThese findings suggest opportunities for reducing chemotherapy and ICU use in the United States and hospitalizations in Ontario.

IntroductionThree pivotal trials have considered the addition of docetaxel (D) chemotherapy to conventional androgen-deprivation therapy (ADT) for the treatment of metastatic hormone- sensitive prostate cancer (HSPC). While an initial small trial was inconclusive, two larger trials demonstrated significant clinical benefit, including pronounced survival benefits (added 17 months) among patients with high-volume metastatic disease. Given the evolving clinical evidence, the cost-effectiveness of this approach warrants exploration.MethodsThe cost-effectiveness of six cycles of ADT+D compared to ADT alone to treat patients with high-volume metastatic HSPC was assessed from a Canadian public payer perspective. We included three health states: HSPC, metastatic castration-resistant prostate cancer (CRPC), and death. Survival data were obtained from the CHAARTED trial, which reported outcomes specifically for high-volume disease. We used Ontario costs data and utilities from the literature.ResultsIn the base case analysis, ADT+D cost an additional $25 757 and produced an extra 1.06 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of $24 226/QALY gained. Results from one-way sensitivity analysis across wide ranges of estimates and a range of scenarios, including an alternate model structure, produced ICERs below $35 000/QALY gained in all cases.ConclusionsThe use of D with ADT in high-volume metastatic HSPC appears to be an economically attractive treatment approach. The findings were consistent with other studies and robust in sensitivity analysis across a variety of scenarios.

BackgroundHigh orphan drug prices have gained the attention of payers and policy makers. These prices may reflect the need to recoup the cost of drug development from a small patient pool. However, estimates of the cost of orphan drug development are sparse.MethodsUsing publicly available data, we estimated the differences in trial characteristics and clinical development costs with 100 orphan and 100 non-orphan drugs.ResultsWe found that the out-of-pocket clinical costs per approved orphan drug to be $166 million and $291 million (2013 USD) per non-orphan drug. The capitalized clinical costs per approved orphan drug and non-orphan drug were estimated to be $291 million and $412 million respectively. When focusing on new molecular entities only, we found that the capitalized clinical cost per approved orphan drug was half that of a non-orphan drug.ConclusionsMore discussion is needed to better align on which cost components should be included in research and development costs for pharmaceuticals.

BackgroundTo determine whether telemedicine improves access to outpatient neurology care for underserved patients, we compared appointment completion between urban, in-person clinics and telemedicine clinics held in rural and underserved communities where neurology consultations are provided remotely.MethodsIn this retrospective study, we identified patients scheduled for outpatient care from UCDH pediatric neurologists between January 1, 2009, and July 31, 2017, in person and by telemedicine. Demographic and clinical variables were abstracted from electronic medical records. We evaluated the association between consultation modality and visit completion in overall and matched samples using hierarchical multivariable logistic regression.ResultsWe analyzed 13,311 in-person appointments by 3,831 patients and 1,158 telemedicine appointments by 381 patients. The average travel time to the site of care was 45.8 ± 52.1 minutes for the in-person cohort and 22.3 ± 22.7 minutes for the telemedicine cohort. Telemedicine sites were located at an average travel time of 217.1 ± 114.8 minutes from UCDH. Telemedicine patients were more likely to have nonprivate insurance, lower education, and lower household income. They had different diagnoses and fewer complex chronic conditions. Telemedicine visits were more likely to be completed than either "cancelled" or missed ("no show") compared with in-person visits (OR 1.57, 95% CI: 1.34-1.83; OR 1.66, 95% CI: 1.31-2.10 matched on travel time to the site of care; OR 2.22, 95% CI: 1.66-2.98 matched on travel time to UCDH).ConclusionsThe use of telemedicine for outpatient pediatric neurology visits has high odds of completion and can serve as an equal adjunct to in-person clinic visits.

BackgroundSurgical guidelines for soft tissue sarcoma (STS) emphasize pretreatment evaluation and reports of the perils of unplanned excision exist. Given the paucity of population-based data on this topic, our objective was to analyze clinical outcomes and costs of planned versus unplanned STS excisions in the Medicare population.MethodsWe analyzed 3913 surgical patients with STS ≥66 y old from 1992 to 2011 using the Surveillance, Epidemiology, and End Results-Medicare datafiles. Planned excisions were classified based on preoperative MRI and/or biopsy, whereas unplanned excisions were classified by excision as the first procedure. Inverse probability of treatment weighting with propensity scores was used to adjust for clinicopathologic differences. Re-excisions, complications, and Medicare payments were compared with multivariate models. Overall survival and disease-specific survival were analyzed using Cox proportional hazards and competing risk models.ResultsBefore the first excision, 24.3% had an MRI and biopsy, 27.3% had an MRI, 11.4% had a biopsy, and 36.9% were unplanned. Re-excision rates were highest for unplanned excisions: 46.3% compared to 18.1%, 36.4%, and 29.7% for other groups (P  0.05). Planned excisions were associated with increased Medicare costs (P

BackgroundEconomic evaluations commonly accompany trials of new treatments or interventions; however, regression methods and their corresponding advantages for the analysis of cost-effectiveness data are not widely appreciated.MethodsTo illustrate regression-based economic evaluation, we review a cost-effectiveness analysis conducted by the Canadian Cancer Trials Group's Committee on Economic Analysis and implement net benefit regression.ResultsNet benefit regression offers a simple option for cost-effectiveness analyses of person-level data. By placing economic evaluation in a regression framework, regression-based techniques can facilitate the analysis and provide simple solutions to commonly encountered challenges (e.g., the need to adjust for potential confounders, identify key patient subgroups, and/or summarize "challenging" findings, like when a more effective regimen has the potential to be cost-saving).ConclusionsEconomic evaluations of patient-level data (e.g., from a clinical trial) can use net benefit regression to facilitate analysis and enhance results.

BackgroundVariations in adjusted costs have been observed among trauma centres in the United States but patient outcomes were not better in centres with higher costs. Attempts to improve injury care efficiency are hampered by insufficient patient-level information on resource use and on the drivers of resource use intensity.ObjectivesTo estimate patient-level resource use for injury admissions, identify determinants of resource use intensity, and evaluate inter-hospital variations in resource use.MethodsWe conducted a retrospective cohort study including ≥16-year-olds admitted to adult trauma centres in a mature, inclusive Canadian trauma system between 2014 and 2016. We extracted data from the trauma registry and hospital financial reports. We estimated resource use with activity-based costs, identified determinants of resource use intensity using a multilevel linear model and assessed the relative importance of each determinant with Cohen's f2. We evaluated inter-provider variations with intraclass correlation coefficients (ICC) and 95% confidence intervals.ResultsWe included 32,411 patients. Median costs per admission were $4857 (Quartiles 1 and 3 2961-8448). The most important contributors to total resource use were the medical ward (57%), followed by the operating room (OR; 23%) and the intensive care unit (13%). The strongest determinant of resource use intensity was discharge destination (Cohen's f2 = 7%). The most resource intense patient group was spinal cord injuries with $11,193 (7115-17,606) per admission. While resource use increased with increasing age for the medical ward, it decreased with increasing age for the OR. Resource use was 18% higher in level I centres compared to level IV centres and we observed significant variations in resource use across centres (ICC = 5% [4-6]), particularly for the OR (28% [20-40]).ConclusionsResource use for acute injury care in Quebec is not solely due to the clinical status of patients. We identified determinants of resource use that can be used to establish evidence-based resource allocations and improve injury care efficiency. The method we developed for estimating patient-level, in-hospital resource use for injury admissions and identifying related determinants could be reproduced using local trauma registry data and our unit costs or unit costs specific to each setting.

DisclosuresFunding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP, Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Mickle, Dreitlein, and Pearson are ICER employees. Lasser, Cipriano, and Hoch have nothing to disclose.

ObjectiveHeterogeneity of depression experiences has led to suggestions that interventions focus on depression symptom combinations rather than depression severity alone. Our analyses explore the question, "What is the relationship between different combinations of depression symptoms and work productivity losses?"MethodsThese analyses use a population-based sample of 2219 working adults. Using the PHQ-8 items, cluster analysis methods were used to identify depression symptom clusters. The Work Limitations Questionnaire's four work productivity loss dimensions were regressed on the identified depression symptoms clusters.ResultsThe symptoms clusters of workers with mild to moderate depression had significant but similar work productivity losses. However, the symptom combinations within these clusters of workers varied.ConclusionTo create effective work accommodations, attention should focus on the combinations of depression symptoms and specific job characteristics rather than severity alone.

BackgroundOutcomes for pancreatic resection have been studied extensively due to the high morbidity and mortality rates, with high-volume centers achieving superior outcomes. Ongoing investigations include healthcare costs, given the national focus on reducing expenditures. Therefore, we sought to evaluate the relationships between pancreatic surgery costs with perioperative outcomes and volume status.MethodsWe performed a retrospective analysis of 27,653 patients who underwent elective pancreatic resections from October 2013 to June 2017 using the Vizient database. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation. Generalized linear modeling adjusting for demographic, clinical, and operation characteristics was performed to assess the relationships between cost and length of stay, complications, in-hospital mortality, readmissions, and hospital volume. High-volume centers were defined as hospitals performing ≥ 19 operations annually.ResultsThe unadjusted mean cost for pancreatic resection and corresponding hospitalization was $20,352. There were no differences in mean costs for pancreatectomies performed at high- and low-volume centers [- $1175, 95% confidence interval (CI) - $3254 to $904, p = 0.27]. In subgroup analysis comparing adjusted mean costs at high- and low-volume centers, there was no difference among patients without an adverse outcome (- $99, 95% CI - $1612 to 1414, p = 0.90), one or more adverse outcomes (- $1586, 95% CI - $4771 to 1599, p = 0.33), or one or more complications (- $2835, 95% CI - $7588 to 1919, p = 0.24).ConclusionsWhile high-volume hospitals have fewer adverse outcomes, there is no relationship between surgical volume and costs, which suggests that, in itself, surgical volume is not an indicator of improved healthcare efficiency reflected by lower costs. Patient referral to high-volume centers may not reduce overall healthcare expenditures for pancreatic operations.

BackgroundAlthough Dialectical Behaviour Therapy (DBT) is an evidence-based psychosocial treatment for borderline personality disorder (BPD), the demand for it exceeds available resources. The commonly researched 12-month version of DBT is lengthy; this can pose a barrier to its adoption in many health care settings. Further, there are no data on the optimal length of psychotherapy for BPD. The aim of this study is to examine the clinical and cost-effectiveness of 6 versus 12 months of DBT for chronically suicidal individuals with BPD. A second aim of this study is to determine which patients are as likely to benefit from shorter treatment as from longer treatment.Methods/designPowered for non-inferiority testing, this two-site single-blind trial involves the random assignment of 240 patients diagnosed with BPD to 6 or 12 months of standard DBT. The primary outcome is the frequency of suicidal or non-suicidal self-injurious episodes. Secondary outcomes include healthcare utilization, psychiatric and emotional symptoms, general and social functioning, and health status. Cost-effectiveness outcomes will include the cost of providing each treatment as well as health care and societal costs (e.g., missed work days and lost productivity). Assessments are scheduled at pretreatment and at 3-month intervals until 24 months.DiscussionThis is the first study to directly examine the dose-effect of psychotherapy for chronically suicidal individuals diagnosed with BPD. Examining both clinical and cost effectiveness in 6 versus 12 months of DBT will produce answers to the question of how much treatment is good enough. Information from this study will help to guide decisions about the allocation of scarce treatment resources and recommendations about the benefits of briefer treatment.Trial registrationNCT02387736 . Registered February 20, 2015.

A key component of the current framework for economic evaluation is the measurement and valuation of health outcomes using generic preference-based health-related quality-of-life (HRQoL) instruments. In 2015, a research synthesis reported the absence of conceptual and empirical research regarding the appropriateness of current preference-based instruments for people with aphasia-a disorder affecting the use and understanding of language-and suggested the development and validation of an accessible, pictorial variant could be an appropriate direction for further research. This paper describes the respective rationale and development process for each of three preliminary studies that have been undertaken to develop pictorial variants of two widely used preference-based HRQoL instruments (EQ-5D-3L and EQ-5D-5L). The paper also proposes next steps for this program of research, drawing on the lessons learned from the preliminary work and the demand for a pictorial preference-based instrument in the research community. Guidance for the use of the preliminary, pictorial instruments is also provided.

Quitting smoking after a diagnosis of cancer results in greater response to treatment and decreased risk of disease recurrence and second primary cancers. The objective of this study was to evaluate the potential cost-effectiveness of two smoking cessation approaches: the current basic smoking cessation program consisting of screening for tobacco use, advice, and referral; and a best practice smoking cessation program that includes the current basic program with the addition of pharmacological therapy, counseling, and follow-up. A Markov model was constructed that followed 65-year-old smokers with cancer over a lifetime horizon. Transition probabilities and mortality estimates were obtained from the published literature. Costs were obtained from standard costing sources in Ontario and reports. Probabilistic and deterministic sensitivity analyses were conducted to address parameter uncertainties. For smokers with cancer, the best practice smoking cessation program was more effective and more costly than the basic smoking cessation program. The incremental cost-effectiveness ratio of the best practice smoking cessation program compared to the basic smoking cessation program was $3367 per QALY gained and $5050 per LY gained for males, and $2050 per QALY gained and $4100 per LY gained for females. Results were most sensitive to the hazard ratio of mortality for former and current smokers, the probability of quitting smoking through participation in the program and smoking-attributable costs. The study results suggested that a best practice smoking cessation program could be a cost-effective option. These findings can support and guide implementation of smoking cessation programs.

PurposeSeveral genomic tests have recently been developed to identify the primary tumour in cancer of unknown primary tumour (CUP). However, the value of identifying the primary tumour in clinical practice for CUP patients remains questionable and difficult to prove in randomized trials.ObjectiveWe aimed to assess the clinical and economic value of primary tumour identification in CUP using a retrospective matched cohort study.MethodsWe used the Manitoba Cancer Registry to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients as having CUP if their primary tumour was found 6 months or more after initial diagnosis or never found during the course of disease. Otherwise, we considered patients to have metastatic cancer from a known primary tumour (CKP). We linked all patients with Manitoba Health databases to estimate their direct healthcare costs using a phase-of-care approach. We used the propensity score matching technique to match each CUP patient with a CKP patient on clinicopathologic characteristics. We compared treatment patterns, overall survival (OS) and phase-specific healthcare costs between the two patient groups and assessed association with OS using Cox regression adjustment.ResultsOf 5839 patients diagnosed with metastatic cancer, 395 had CUP (6.8%); 1:1 matching created a matched group of 395 CKP patients. CUP patients were less likely to receive surgery, radiation, hormonal and targeted therapy and more likely to receive cytotoxic empiric chemotherapeutic agents. Having CUP was associated with reduced OS (hazard ratio [HR] 1.31; 95% confidence interval 1.1-1.58), but this lost statistical significance with adjustment for treatment differences. CUP patients had a significant increase in the mean net cost of initial diagnostic workup before diagnosis and a significant reduction in the mean net cost of continuing cancer care.ConclusionIdentifying the primary tumour in CUP patients might enable the use of more effective therapies, improve OS and allow more efficient allocation of healthcare resources.

IntroductionXylitol (or 'birch sugar') is a naturally occurring sugar with antibacterial properties that has been used as a natural non-sugar sweetener in chewing gums, confectionery, toothpaste and medicines. In this preventative randomised trial, xylitol will be tested for the prevention of acute otitis media (AOM), a common and costly condition in young children. The primary outcome will be the incidence of AOM. Secondary outcomes will include upper respiratory tract infections (URTIs) and dental caries.Methods and analysisThis study will be a pragmatic, blinded (participant and parents, practitioners and analyst), two-armed superiority, placebo-controlled randomised trial with 1:1 allocation, stratified by clinical site. The trial will be conducted in the 11 primary care group practices participating in the TARGet Kids! research network in Canada. Eligible participants between the ages of 2-4 years will be randomly assigned to the intervention arm of regular xylitol syrup use or the control arm of regular sorbitol use for 6 months. We expect to recruit 236 participants, per treatment arm, to detect a 20% relative risk reduction in AOM episodes. AOM will be identified through chart review. The secondary outcomes of URTIs and dental caries will be identified through monthly phone calls with specified questions.Ethics and disseminationEthics approval from the Research Ethics Boards at the Hospital for Sick Children and St. Michael's Hospital has been obtained for this study and also for the TARGet Kids! research network. Results will be submitted for publication to a peer-reviewed journal and will be discussed with decision makers.Trial registration numberNCT03055091; Pre-results.

PurposeThe purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS).Materials and methodsWe used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have "occult" primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as "obvious." We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment.ResultsEighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences.ConclusionGI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

BackgroundResource and cost issues are a growing concern in health care. Thus, it is important to have an accurate estimate of the economic burden of care. Previous work has estimated the economic burden of cancer care for Canada; however, there is some concern this estimate is too low. The objective of this analysis was to provide a comprehensive revised estimate of this burden.MethodsWe used a case-control prevalence-based approach to estimate direct annual cancer costs from 2005 to 2012. We used patient-level administrative health care data from Ontario to correctly attribute health care costs to cancer. We employed the net cost method (cost difference between patients with cancer and control subjects without cancer) to account for costs directly and indirectly related to cancer and its sequelae. Using average patient-level cost estimates from Ontario, we applied proportions from national health expenditures data to obtain the economic burden of cancer care for Canada. All costs were adjusted to 2015 Canadian dollars.ResultsCosts of cancer care rose steadily over our analysis period, from $2.9 billion in 2005 to $7.5 billion in 2012, mostly owing to the increase in costs of hospital-based care. Most expenditures for health care services increased over time, with chemotherapy and radiation therapy expenditures accounting for the largest increases over the study period. Our cost estimates were larger than those in the Economic Burden of Illness in Canada 2005-2008 report for every year except 2005 and 2006.InterpretationThe economic burden of cancer care in Canada is substantial. Further research is needed to understand how the economic burden of cancer compares to that of other diseases.

Androgen-deprivation therapy (ADT) is an effective treatment for men with advanced prostate cancer, but loss of bone mineral density (BMD) is a major risk factor for fractures. This review compared the efficacy of available treatments to provide prescribing guidance to healthcare professionals. This is the first review to compare the effectiveness of different osteoporotic treatments (bisphosphonates, denosumab, toremifene, and raloxifene) on BMD in patients with non-metastatic prostate cancer on ADT using network meta-analysis. Results suggest that all evaluated treatments are effective in improving BMD compared to placebo. Zoledronic acid (ZA) was found to have a greater improvement in BMD compared to other active treatments at all three studied sites, except for risedronate, which had better BMD improvement compared to ZA at the femoral neck site in one small study. Our study did not identify evidence that one drug is unequivocally more effective than another. All drugs appeared to be effective in reducing the rate of bone loss. Healthcare professionals should also consider patient preference, costs, and local availability as part of the decision process.

BackgroundTelemedicine in the intensive care unit (tele-ICU) is expected to address geographic health disparities through more efficient resource allocation. Our previous economic evaluation demonstrated tele-ICU to be cost-effective in most cases and cost saving in some cases, compared to conventional intensive care unit (ICU) care without adequate intensivist coverage.IntroductionThis study's objective is to examine how to optimize the cost-effectiveness of tele-ICU use by selecting highest risk (i.e., both highest mortality and highest cost) subpopulations. We also explore potential cost savings.Materials and methodsWe conducted simulation analyses among a hypothetical adult ICU patient cohort defined by the literature, distinguishing four types of hospitals: urban tertiary (primary analysis), urban community, rural tertiary, and rural community. The selected tele-ICU use was assumed to affect per-patient ICU cost and hospital mortality among highest risk subpopulations (10-100% of all ICU patients), defined by an established illness-severity measure.ResultsWe found a U-shaped relationship between the economic efficiency and selected tele-ICU use among all 4 hospital types. Optimal cost-effectiveness was achieved when tele-ICU was applied to the 30-40% highest risk patients among all ICU patients (incremental cost-effectiveness ratio = $25,392 [2014 U.S. dollars] per extending a quality-adjusted life year) in urban tertiary hospitals (primary analysis). Our break-even analyses indicated that cost saving seems more feasible when reducing ICU medical care cost, rather than lowering the cost to operate telemedicine alone.Discussion and conclusionsA selected use of tele-ICU based on severity of illness is likely to improve tele-ICU cost-effectiveness. To achieve cost saving, tele-ICU must reduce more than just telemedicine-related cost.