The neoadjuvant and adjuvant use of immune checkpoint inhibitors (ICIs) in early stage non-small cell lung cancer (NSCLC) is increasing, with pembrolizumab approved as adjuvant therapy following surgical resection and chemotherapy by the U.S. Food and Drug Administration in early 2023. However, clinical trials of these agents have several key limitations including the use of surrogate endpoints that have not been validated and a lack of demonstrated survival benefit. Further data supporting the benefits of ICIs in this setting are necessary to justify their use at the cost of greater financial burdens, time, and adverse effects.

Introduction

The number of oncologic drugs approved by the US Food and Drug Administration (FDA) on the basis of surrogate endpoints is rising. However, many surrogates have not demonstrated a correlation with clinically meaningful outcomes like overall survival. We sought to investigate surrogate validation studies conducted by the FDA over the past 17 years.

Methods

We reviewed analyses of surrogate outcomes published by the FDA from 2005 to 2022. Data extracted included the number of clinical trials included in each analysis, the associations of surrogate outcomes with OS or other surrogates, and the authors' interpretation of these associations.

Results

Of the 15 surrogate analyses conducted by the FDA, only one demonstrated a strong correlation between a surrogate outcome and overall survival. 87% only included clinical trials submitted to the FDA in their analysis, and all were published from 2014 onwards.

Discussion

The vast majority of FDA analyses of surrogate outcomes did not find strong correlations between surrogates and overall survival, raising concern about the use of such outcomes as endpoints in clinical trials. As most studies were based on limited data, further research is required to assess the true validity of surrogate outcomes.

Policy summary

Drugs approved on the basis of surrogates that are not associated with clinically meaningful outcomes can cause significant harm to patients. Until surrogate outcomes have been thoroughly and robustly validated, they should be used with caution in drug approval decisions.

Methamphetamine (meth) is a highly addictive stimulant with harmful effects that lead to cardiovascular disease and stroke. Rates of meth use have been growing with an estimated 24 million users worldwide as of 2015. Despite a strong association between meth use and increased cerebrovascular risk, detailed descriptions of clinical and neuroradiologic characteristics in larger cohorts are lacking.

Abstract: The health disparities research field is rapidly evolving, but not all populations may be adequately represented in research on disparities. This study characterizes the current state of disparities literature and identifies trends, gaps, and opportunities in the field through bibliometric analysis. 260 articles published between January 2020 and August 2022, of which 95% focused on health disparities, were included in the analysis. 67% of studies investigated disparities across racial or ethnic groups, and all 9 articles on physician employment investigated disparities in gender. The majority of studies focused on adults, with 71% of studies having mean or median ages of subjects between 40 and 80 years. Articles on cancer and cardiovascular conditions comprised 34% of health-related disparity studies. Our results highlight a need to study disparities in pediatric and young adult populations. Such research can identify targets of early intervention that may improve long-term health and reduce disparities presenting in late adulthood.