Oncology modeling for fun and profit! Key steps for busy analysts in health technology assessment

In evaluating new oncology medicines, two common modeling approaches are state transition (e.g., Markov and semi-Markov) and partitioned survival. Partitioned survival models have become more prominent in oncology health technology assessment processes in recent years. Our experience in conducting and evaluating models for economic evaluation has highlighted many important and practical pitfalls. As there is little guidance available on best practices for those who wish to conduct them, we provide guidance in the form of 'Key steps for busy analysts,' who may have very little time and require highly favorable results. Our guidance highlights the continued need for rigorous conduct and transparent reporting of economic evaluations regardless of the modeling approach taken, and the importance of modeling that better reflects reality, which includes better approaches to considering plausibility, estimating relative treatment effects, dealing with post-progression effects, and appropriate characterization of the uncertainty from modeling itself

Impact of smoking on health system costs among cancer patients in a retrospective cohort study in Ontario, Canada

Objective Smoking is the main modifiable cancer risk factor. The objective of this study was to examine the impact of smoking on health system costs among newly diagnosed adult patients with cancer. Specifically, costs of patients with cancer who were current smokers were compared with those of non-smokers from a publicly funded health system perspective. Methods This population-based cohort study of patients with cancer used administrative databases to identify smokers and non-smokers (1 April 2014-31 March 2016) and their healthcare costs in the 12-24 months following a cancer diagnosis. The health services included were hospitalisations, emergency room visits, drugs, home care services and physician services (from the time of diagnosis onwards). The difference in cost (ie, incremental cost) between patients with cancer who were smokers and those who were non-smokers was estimated using a generalised linear model (with log link and gamma distribution), and adjusted for age, sex, neighbourhood income, rurality, cancer site, cancer stage, geographical region and comorbidities. Results This study identified 3606 smokers and 14 911 non-smokers. Smokers were significantly younger (61 vs 65 years), more likely to be male (53%), lived in poorer neighbourhoods, had more advanced cancer stage,and were more likely to die within 1 year of diagnosis, compared with non-smokers. The regression model revealed that, on average, smokers had significantly higher monthly healthcare costs ($5091) than non-smokers ($4847), p<0.05. Conclusions Smoking status has a significant impact on healthcare costs among patients with cancer. On average, smokers incurred higher healthcare costs than non-smokers. These findings provide a further rationale for efforts to introduce evidence-based smoking cessation programmes as a standard of care for patients with cancer as they have the potential not only to improve patients' outcomes but also to reduce the economic burden of smoking on the healthcare system

Estimates and predictors of health care costs of esophageal adenocarcinoma : A population-based cohort study

Background: Esophageal adenocarcinoma (EAC) incidence is increasing rapidly. Esophageal cancer has the second lowest 5-year survival rate of people diagnosed with cancer in Canada. Given the poor survival and the potential for further increases in incidence, phase-specific cost estimates constitute an important input for economic evaluation of prevention, screening, and treatment interventions. The study aims to estimate phase-specific net direct medical costs of care attributable to EAC, costs stratified by cancer stage and treatment, and predictors of total net costs of care for EAC. Methods: A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data from 2003 to 2011. The mean net costs of EAC care per 30 patient-days (2016 CAD) were estimated from the payer perspective using phase of care approach and generalized estimating equations. Predictors of net cost by phase of care were based on a generalized estimating equations model with a logarithmic link and gamma distribution adjusting for sociodemographic and clinical factors. Results: The mean net costs of EAC care per 30 patient-days were $1016 (95$955-$1078) in the initial phase,$669 (95% CI, $594-$743) in the continuing care phase, and $8678 (95$8217-$9139) in the terminal phase. Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the highest cost, particularly in the terminal phase. Strong predictors of higher net costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy, radiotherapy alone, surgery alone, and chemotherapy alone in the initial and continuing care phases, stage III-IV disease and patients diagnosed with EAC later in a calendar year (2007-2011) in the initial and terminal phases, comorbidity in the continuing care phase, and older age at diagnosis (70-74 years), and geographic region in the terminal phase. Conclusions: Costs of care vary by phase of care, stage at diagnosis, and type of treatment for EAC. These cost estimates provide information to guide future resource allocation decisions, and clinical and policy interventions to reduce the burden of EAC

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination:A systematic review and meta-analysis

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.</p

Clinical management and infection control of SARS: Lessons learned

AbstractThe outbreak of severe acute respiratory syndrome (SARS) in 2003 was the first emergence of an important human pathogen in the 21st century. Responding to the epidemic provided clinicians with extensive experience in diagnosing and treating a novel respiratory viral disease. In this article, we review the experience of the SARS epidemic, focusing on measures taken to identify and isolate patients, prevent the transmission of infection to healthcare workers and develop effective therapies. Lessons learned from the SARS epidemic will be especially important in responding to the current emergence of another highly pathogenic human coronavirus, the agent of Middle East respiratory syndrome (MERS), and to the recently emerging H7N9 influenza A virus in China. This paper forms part of a symposium in Antiviral Research on “From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System

© 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Objectives To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payer's perspective, using data from a recently published Bayesian network meta-analysis. Methods Analysis was conducted through a three-state Markov model and used data on the progression of disease with treatment from the gemcitabine arms of randomized controlled trials combined with estimates from the network meta-analysis for the newer regimens. Estimates of health care costs were obtained from local providers, and utilities were derived from the literature. The model estimates the effect of treatment regimens on costs and quality-adjusted life-years (QALYs) discounted at 5% per annum. Results At a willingness-to-pay (WTP) threshold of greater than $30,666 per QALY, FOLFIRINOX would be the most optimal regimen. For a WTP threshold of$50,000 per QALY, the probability that FOLFIRINOX would be optimal was 57.8%. There was no price reduction for nab-paclitaxel when GnP was optimal. Conclusions From a Canadian public health payer's perspective at the present time and drug prices, FOLFIRINOX is the optimal regimen on the basis of the cost-effectiveness criterion. GnP is not cost-effective regardless of the WTP threshold

Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysisResearch in context

Summary: Background: Patients with small cell lung cancer (SCLC) are at high risk for brain metastases. Prophylactic cranial irradiation (PCI) is recommended in this population to reduce the incidence of brain metastases and prolong survival. We aimed to assesses the efficacy of PCI in this population in the era of routine brain imaging. To our knowledge, this is the first systematic review and meta-analysis to examine the use among patients who were radiographically confirmed not to have brain metastases after completion of first-line therapy. Methods: In this systematic review and meta-analysis, cohort studies and controlled trials reporting on the use of PCI for patients SCLC were identified in EMBASE, MEDLINE, CENTRAL, and grey literature sources. The literature search was conducted on November 12, 2023. Summary data were extracted. Random-effects meta-analyses pooled hazard ratios (HR) for the primary outcome of overall survival between PCI and no intervention groups. This study is registered with the Open Science Framework, DOI:10.17605/OSF.IO/BC359, and PROSPERO, CRD42021249466. Findings: Of 4318 identified records, 223 were eligible for inclusion. 109 reported on overall survival in formats amenable to meta-analysis; PCI was associated with longer survival in all patients with SCLC (HR 0.59; 95% CI, 0.55–0.63; p < 0.001; n = 56,770 patients), patients with limited stage disease (HR 0.60; 95% CI, 0.55–0.65; p < 0.001; n = 78 studies; n = 27,137 patients), and patients with extensive stage disease (HR 0.59; 95% CI, 0.51–0.70; p < 0.001; n = 28 studies; n = 26,467 patients). Between-study heterogeneity was significant when pooled amongst all studies (I2 = 73.6%; 95% CI 68.4%–77.9%). Subgroup analysis did not reveal sources of heterogeneity. In a subgroup analysis on studies that used magnetic resonance imaging to exclude presence of brain metastases at restaging among all patients, overall survival did not differ significantly between patients who did or did not receive PCI (HR 0.74; 95% CI, 0.52–1.05; p = 0.08; n = 9 studies; n = 1384 patients). Interpretation: Our findings suggested that administration of PCI is associated with a survival benefit, but not when considering studies that radiographically confirmed absence of brain metastases, suggesting that the survival benefit conferred by PCI might be therapeutic rather than prophylactic. Funding: No funding