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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. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of systemic therapy RCTs in breast, colorectal, and non–small cell lung cancer published in 7 major journals between 2010 and 2020. This strategy replicates prior work and allows for comparison of trends with RCTs published between 1995 to 2004 and 2005 to 2009. MAIN OUTCOMES AND MEASURES: Data on RCT design, funding, results, and reporting were extracted from the published RCT report. Findings from the current period (2010-2020) were compared with data from RCTs published from 1995 to 2004 and 2005 to 2009. Descriptive and bivariate statistics were used to analyze temporal trends. RESULTS: The cohort included 298 RCTs (132 [44%] breast, 111 [37%] non–small cell lung cancer, 55 [19%] colorectal cancer). Experimental treatment included molecular inhibitor (171 of 298 [57%]), cytotoxic (83 of 298 [28%]), hormone (15 of 298 [5%]), and immune (24 of 298 [8%]) therapies. Sixty-nine percent (206 of 298) of RCTs were of palliative intent. The most common primary end point is now PFS; this has increased substantially over time (from 0% [0 of 167] to 18% [25 of 137] to 42% [125 of 298]; P < .001). Of 298 RCTs, 265 (89%) are now funded by industry (previously 95 of 167 [57%] and 107 of 137 [78%]; P < .001). Fifty-eight percent (173 of 298) of trials met their primary end point. Among positive trials, median improvement in overall survival and PFS was 3.4 and 2.9 months, respectively. More than one-third (117 of 298 [39%]) of reports used a professional medical writer; this increased substantially during the study period (from 3 of 27 [11%] in 2010 to 12 of 18 [67%] in 2020; P < .001). CONCLUSIONS AND RELEVANCE: This cohort study suggests that contemporary oncology RCTs now largely measure putative surrogate end points and are almost exclusively funded by the pharmaceutical industry. The increasing role of medical writers warrants attention. To demonstrate that new cancer treatments are high value, the oncology community needs to consider the extent to which study end points and target effect size provide meaningful benefit to patients.

Hemorrhagic shock (HS) is a setting in which both pulmonary and cutaneous perfusion may be impaired. The goals of this study were to evaluate the relationship between end-tidal (etCO2), transcutaneous (tPCO2), arterial carbon dioxide (PaCO2) and lactate during lethal HS and to assess the effect of progressive HS on those variables and on a new variable, the noninvasive CO2gradient (NICO2G or the difference between tPCO2and etCO2). Ten consciously sedated swine were hemorrhaged, by means of a computerized exponential protocol, of up to 80 estimated blood volume for 20 min. End-tidal carbon dioxide, tPCO2, PaCO2, and lactate measurements were taken at baseline and every 5 min thereafter, that is, after 25, 44, and 62 total blood volume hemorrhage (TBVH) and at cardiac arrest. Cardiac arrest occurred on average at 67 TBVH. Data were analyzed by linear regression and one-way repeated-measures analysis of variance and are presented as means ± SD. Forty-nine paired measurements were made. There was no overall relationship between NICO2variables and PaCO2: PaCO2vs. tPCO2(r2= 0.002, P= 0.78); PaCO2vs. etCO2(r2= 0.0002, P= 0.93). Rather, NICO2G increased at each level of blood loss: 4.0 ± 24.9 at baseline, 6.3 ± 35.7 at 25 TBVH, 25.0 ± 37.6 at 44 TBVH, 55.0 ± 33.9 at 62 TBVH, and 70.0 ± 33.2 at cardiac arrest (P< 0.05). Similarly, tPCO2increased and etCO2decreased at each level. Linear regression of NICO2G and lactate showed a better correlation than was observed for the other two variables: NICO2G, r2= 0.58; tPCO2, r2= 0.46; etCO2, r2= 0.26. During HS, NICO2monitors lose accuracy for approximating the PaCO2but gain usefulness as hemodynamic monitors. Also, by combining data from two different organ systems, NICO2G demonstrated improved correlation with lactate than did either etCO2or tPCO2alone.

The electrostatic force on an ‘almost sinusoidal’ surface due to a line charge situated symmetrically above a crest is calculated. This force is then compared to the force on a perfectly smooth sheet.