Inappropriate censoring in Kaplan-Meier analyses

Edward Lynn Kaplan and Paul Meier worked separately analysing survival time data, both as graduate students at Princeton University and after graduation. 1 Kaplan EL Meier P Nonparametric estimation from incomplete observations. J Am Statist Assoc. 1958; 53: 457-481 Crossref Scopus (47473) Google Scholar In 1954, they independently submitted manuscripts to the Journal of the American Statistical Association, at which time John Tukey, their PhD mentor at Princeton and the journal's editor, convinced them to combine their work into one manuscript. Leveraging external data in the design and analysis of clinical trials in neuro-oncologyIntegration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions). Based on a series of presentations at the 2020 Clinical Trials Think Tank hosted by the Society of Neuro-Oncology, we provide an overview on the use of external control data representative of the standard of care in the design and analysis of clinical trials. Full-Text PDF Basket clinical trial design for targeted therapies for cancer: a French National Authority for Health statement for health technology assessmentDuring the past decade, health technology assessment bodies have faced new challenges in establishing the benefits of new drugs for individuals and health-care systems. A topic of increasing importance to the field of oncology is the so-called agnostic regulatory approval of targeted therapies for cancer (independent of tumour location and histology) granted on the basis of basket trials. Basket trials in oncology offer the advantage of simultaneously evaluating treatments for multiple tumours, even rare cancers, in a single clinical trial. Full-Text PDF Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extensionThe 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and molecular pathology practices within trials have not been codified or formalised. We developed international consensus reporting guidelines for cellular and molecular pathology content in clinical trial protocols (the SPIRIT-Path extension) using an international Delphi process, which assesses candidate items generated from a previous systematic review, followed by an expert consensus meeting. Full-Text PDF Late phase 1 studies: concepts and outcomesOver the past two decades, targeted therapies have become cornerstone treatments for numerous cancers with oncogene addiction. Unfortunately, their effectiveness reduces over time and most patients who receive targeted therapies relapse within 12 months. The emergence of drug-resistance mechanisms in tumours paved the way for next-generation inhibitors. However, insufficient concentration of targeted therapy is a frequent but poorly explored mechanism of treatment failure. Additionally, the maximum tolerated dose (MTD) is not always reached in phase studies, and the recommended phase 2 dose is mostly based on benefit–risk ratio and pharmacokinetic considerations, which could result in a suboptimal dose. Full-Text PDF