Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study.

Background: The financial impact of cancer medicines on health systems is not well known. We describe temporal trends in expenditure on cancer medicines within the single-payer health system of Ontario, Canada, and the extent of clinical benefit these treatments offer.

Methods: In this cross-sectional study, we identified cancer medicines and expenditures from formularies and costing databases (the New Drug Funding Program, Ontario Drug Benefit Program, and The High-Cost Therapy Funding Program) during 10 consecutive years (April 1, 2012, to March 31, 2022) in Ontario, Canada.

Large numbers of patients are needed to obtain additional approvals for new cancer drugs: A retrospective cohort study.

Patients endure risk and uncertainty when they participate in clinical trials. We previously estimated that 12,217 patient-participants are required to bring a new cancer drug to market. However, many development efforts are aimed at extending the label of already approved drugs.

Bypassing phase 2 in cancer drug development erodes the risk/benefit balance in phase 3 trials.

Objectives: Drug developers sometimes launch phase 3 (P3) trials without supporting evidence from phase 2 (P2) trials. We call this practice "P2 bypass." The aims of this study were to estimate the prevalence of P2 bypass and to compare the safety and efficacy results for P3 trials that bypassed with those that did not.

Randomized Controlled Trials in Lung, Gastrointestinal, and Breast Cancers: An Overview of Global Research Activity.

Background: In this study, we compared and contrasted design characteristics, results, and publications of randomized controlled trials (RCTs) in gastrointestinal (GI), lung, and breast cancer. Methods: A PUBMED search identified phase III RCTs of anticancer therapy in GI, lung, and breast cancer published globally during the period 2014−2017. Descriptive statistics, chi-square tests, and the Kruskal−Wallis test were used to compare RCT design, results, and output across the cancer sites.

Cancer, Clinical Trials, and Canada: Our Contribution to Worldwide Randomized Controlled Trials.

Canada has a long tradition of leading practice-changing clinical trials in oncology. Here, we describe methodology, results, and interpretation of oncology RCTs with Canadian involvement compared to RCTs from other high-income countries (HICs). A literature search identified all RCTs evaluating anti-cancer therapies published 2014-2017.

Evolution of the Randomized Clinical Trial in the Era of Precision Oncology.

Importance: The randomized clinical trial (RCT) in oncology has evolved since its widespread adoption in the 1970s. In recent years, concerns have emerged regarding the use of putative surrogate end points, such as progression-free survival (PFS), and marginal effect sizes.

Objective: To describe contemporary trends in oncology RCTs and compare these findings with earlier eras of RCT design and output.

Application of Value Frameworks to the Design of Clinical Trials: The Canadian Cancer Trials Group Experience.

Background: Use of value framework thresholds in the design of clinical trials may increase the proportion of randomized controlled trials that identify clinically meaningful advances for patients. Existing frameworks have not been applied to the research output of a cooperative cancer trials group. We apply value frameworks to the randomized controlled trial output of the Canadian Cancer Trials Group (CCTG).

An Analysis of Contemporary Oncology Randomized Clinical Trials From Low/Middle-Income vs High-Income Countries.

Importance: The burden of cancer falls disproportionally on low-middle-income countries (LMICs). It is not well known how novel therapies are tested in current clinical trials and the extent to which they match global disease burden.

Objectives: To describe the design, results, and publication of oncology randomized clinical trials (RCTs) and examine the extent to which trials match global disease burden and how trial methods and results differ across economic settings.

Reliability of Oncology Value Framework Outputs: Concordance Between Independent Research Groups.

Research groups are increasingly utilizing value frameworks, but little is known of their reliability. To assess framework concordance and interrater reliability between two major value frameworks currently in use, we identified all previously published datasets containing both scores from the American Society of Clinical Oncology Value Framework (ASCO-VF) and grades from the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS). The intraclass correlation coefficient (ICC) was used to assess interrater reliability.

The fragility of phase 3 trials supporting FDA-approved anticancer medicines: a retrospective analysis.

Background: The fragility index of trial results-ie, the minimum number of changes from non-events to events resulting in loss of statistical significance-can provide a measure of confidence that a positive effect reported in a randomised controlled trial is real. We aimed to calculate the fragility index of randomised controlled trials supporting US Food and Drug Administration (FDA)-approved anticancer drugs.

Methods: This is a retrospective analysis of phase 3, randomised, controlled trials supporting anticancer drugs that were approved by the FDA between Jan 1, 2014, and Dec 31, 2018.

Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration Based on Single-Arm Trials.

This study uses the European Society of Medical Oncology Magnitude of Clinical Benefit Scale to evaluate the clinical benefit of anticancer drugs that gained approval by the US Food and Drug Administration based on single-arm rather than randomized clinical trials.

Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration.

Background: It is uncertain whether drugs approved by the US Food and Drug Administration (FDA) have clinically meaningful benefit as determined by validated scales such as the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).

Methods: We searched the Drugs@FDA website for applications of anticancer drugs from January 2006 to December 2016. Study characteristics, outcomes, and regulatory pathways were collected from drug labels and reports of registration trials.

Delivery of meaningful cancer care: a retrospective cohort study assessing cost and benefit with the ASCO and ESMO frameworks.

Background: The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have developed frameworks that quantify survival gains in light of toxicity and quality of life to assess the benefits of cancer therapies. We applied these frameworks to a cohort of contemporary randomised controlled trials to explore agreement between the two approaches and to assess the relation between treatment benefit and cost.

Methods: We identified all randomised controlled trials of systemic therapies in non-small-cell lung cancer, breast cancer, colorectal cancer, and pancreatic cancer published between Jan 1, 2011, and Dec 31, 2015, and assessed their abstracts and methods.

Disturbances in blood flow and 'medicine's greatest imitator'.

First described in 1959, intravascular lymphoma (IVL) remains one of the most clinically challenging diagnoses due to its diverse and non-specific clinical manifestations and evasiveness in detection by standard investigations. Indeed, IVL deserves the title of 'medicine's greatest imitator'. We highlight a case of IVL where the diagnosis came too late in the clinical course, detected by random skin biopsy.

A mitochondrial redox oxygen sensor in the pulmonary vasculature and ductus arteriosus.

The mammalian homeostatic oxygen sensing system (HOSS) initiates changes in vascular tone, respiration, and neurosecretion that optimize oxygen uptake and tissue oxygen delivery within seconds of detecting altered environmental or arterial PO2. The HOSS includes carotid body type 1 cells, adrenomedullary cells, neuroepithelial bodies, and smooth muscle cells (SMCs) in pulmonary arteries (PAs), ductus arteriosus (DA), and fetoplacental arteries. Hypoxic pulmonary vasoconstriction (HPV) optimizes ventilation-perfusion matching.