Clinical trial end point and surrogate

IMPORTANCE: Clinical trials for metastatic malignant neoplasms are increasingly being extended to patients with brain metastases. Despite the preeminence of progression-free survival (PFS) as a primary oncologic end point, the correlation of intracranial progression (ICP) and extracranial progression (ECP) events with overall survival (OS) is poorly understood for patients with brain metastases following stereotactic radiosurgery (SRS). OBJECTIVE: To determine the correlation of ICP and ECP with OS among patients with brain metastases completing an initial SRS course...

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by relentless growth of innumerable renal cysts bilaterally, associated with decline in glomerular filtration rate over the course of decades. The burden of ADPKD and its treatment is associated with a significant economic and societal cost. Despite several clinical studies conducted over the past decade, only one treatment has been approved by regulatory agencies to slow disease progression in ADPKD. Elucidating feasible endpoints and clear regulatory pathway may stimulate interest in developing and translating novel therapeutics...

BACKGROUND: An increasing number of clinical trials are being conducted exploring the efficacy of neoadjuvant immune checkpoint inhibitors. Surrogate end-points for overall survival (OS) are urgently needed. METHODS: Phase II or III trials of neoadjuvant immunotherapy that reported data on OS and surrogate end-points were identified from January 1, 2000, to November 25, 2022. Individual patient data, and trial-level data were requested from corresponding authors or extracted from eligible trials...

BACKGROUND: Predicting functional outcome in critically ill patients with traumatic brain injury (TBI) strongly influences end-of-life decisions and information for surrogate decision makers. Despite well-validated prognostic models, clinicians most often rely on their subjective perception of prognosis. In this study, we aimed to compare physicians' predictions with the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) prognostic model for predicting an unfavorable functional outcome at 6 months after moderate or severe TBI...

RESEARCH QUESTION: Pulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial N-methyl-d-aspartate (NMDA)-receptor agonist d-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain...

PURPOSE: Pathologic complete response (pCR) has prognostic importance and is frequently used as a primary end point, but doubts remain about its validity as a surrogate for event-free survival (EFS) and overall survival (OS) in human epidermal growth factor receptor 2 (HER2)-positive, early breast cancer. METHODS: We obtained individual-patient data from randomized trials of neoadjuvant anti-HER2 therapy that enrolled at least 100 patients, had data for pCR, EFS, and OS, and a median follow-up of at least 3 years...

BACKGROUND AIMS: Locoregional therapies, including transarterial chemoembolization (TACE), are recommended for the treatment of HCC; however, clinical trials evaluating their effectiveness have been complicated by a lack of validated surrogate outcomes. We aimed to evaluate if stage migration could serve as a potential surrogate of overall survival in patients undergoing TACE. APPROACH: We conducted a retrospective cohort study of adult patients with HCC who underwent TACE as initial therapy from 3 centers in the US from 2008 to 2019...

UNLABELLED: Deep vein thrombosis (DVT) is a preventable complication of critical illness, and this guideline aims to convey a pragmatic approach to the problem. Guidelines have multiplied over the last decade, and their utility has become increasingly conflicted as the reader interprets all suggestions or recommendations as something that must be followed. The nuances of grade of recommendation vs level of evidence are often ignored, and the difference between a "we suggest" vs a "we recommend" is overlooked...

BACKGROUND: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope. METHODS: We performed Bayesian meta-regression analyses on 66 CKD RCTs to evaluate associations between effects on GFR slope (the chronic slope and the total slope over 3 years, expressed as mean differences in ml/min per 1...

IMPORTANCE: Deprescribing is a promising approach to addressing the burden of polypharmacy. Few studies have initiated comprehensive deprescribing in the hospital setting among older patients requiring ongoing care in a postacute care (PAC) facility. OBJECTIVE: To evaluate the efficacy of a patient-centered deprescribing intervention among hospitalized older adults transitioning or being discharged to a PAC facility. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial of the Shed-MEDS (Best Possible Medication History, Evaluate, Deprescribing Recommendations, and Synthesis) deprescribing intervention was conducted between March 2016 and October 2020...

PURPOSE: Targeted tyrosine kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs) revolutionized the treatment of metastatic renal cell carcinoma (RCC). Efforts to translate these therapies into the adjuvant setting for local and locoregional RCC have been pursued over the past decade. We sought to provide an updated review of the literature regarding adjuvant therapy in RCC, as well as an analysis of patient characteristics that may portend the most favorable responses. MATERIALS AND METHODS: Using PubMed, Google Scholar, and Wiley Online Library, we reviewed articles between 2000 and 2022...

IMPORTANCE: The practice of using medical writers to communicate scientific information has gained popularity, but it may affect how and what information is communicated. OBJECTIVE: To assess characteristics of oncology trials that use medical writers and whether there is an association between the use of medical writers and trial success or the primary outcome evaluated. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included oncology trials testing a tumor-targeting intervention that were published in The Lancet, The Lancet Oncology, JAMA, JAMA Oncology, Journal of Clinical Oncology, and The New England Journal of Medicine between May 1, 2021, and May 1, 2022...

INTRODUCTION: IgA nephropathy (IgAN) is the commonest primary glomerulonephritis worldwide and may progress to end-stage kidney disease (ESKD) within a 10-20 year period. Its slowly progressive course has made clinical trials challenging to perform, however the acceptance of proteinuria reduction as a surrogate end point has significantly improved the feasibility of conducting clinical trials in IgAN, with several novel and repurposed therapies currently undergoing assessment. Already, interim results are demonstrating value to some of these, offering great hope to those with IgAN...

PURPOSE: Despite intensive treatment with surgery, radiation therapy, temozolomide (TMZ) chemotherapy, and tumor-treating fields, mortality of newly diagnosed glioblastoma (nGBM) remains very high. SurVaxM is a peptide vaccine conjugate that has been shown to activate the immune system against its target molecule survivin, which is highly expressed by glioblastoma cells. We conducted a phase IIa, open-label, multicenter trial evaluating the safety, immunologic effects, and survival of patients with nGBM receiving SurVaxM plus adjuvant TMZ following surgery and chemoradiation (ClinicalTrials...

Use of surrogate end-points such as progression-free survival (PFS) and other time-to-event (TTE) end-points is common in multiple myeloma (MM) clinical trials. This systematic review characterises all published randomised controlled trials (RCTs) in MM using PFS or other TTE end-points between 2005 and 2019 and assesses strength of surrogacy of PFS for overall survival (OS). The association between OS hazard ratios (HRs) and PFS HRs was evaluated with linear regression, and the coefficient of determination with Pearson's correlation...

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque...

SIGNIFICANCE STATEMENT: Glomerular volume, ischemic glomeruli, and global glomerulosclerosis are not consistently assessed on kidney transplant biopsies. The authors evaluated morphometric measures of glomerular volume, the percentage of global glomerulosclerosis, and the percentage of ischemic glomeruli and assessed changes in these measures over time to determine whether such changes predict late allograft failure. All three features increased from transplant to five-year biopsy. Kidneys with smaller glomeruli at 5 years had more global glomerulosclerosis and a higher percentage of ischemic-appearing glomeruli...

INTRODUCTION: Complete pathologic response (CPR) is an acceptable surrogate for survival in clinical trials but it occurs infrequently in patients with NSCLC receiving neoadjuvant chemotherapy (NCT). Therefore, we studied the impact of major pathologic response (MPR) for predicting survival of patients with NSCLC receiving NCT. We also tested a newly reported scoring system-the prognostic score (PRSC)-which combines T category, lymph node status, and MPR status. METHODS: We analyzed CPR and MPR, defined as 0% and less than or equal to 10% viable tumor cells, respectively, in 339 patients with NSCLC with various histologic types who had been treated with NCT followed by complete surgical resection...

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices...

Aim: The authors investigated surrogacy of radiology-based end points for clinical trials investigating immune checkpoint inhibitors in advanced hepatocellular carcinoma. Methods: Data were collected from electronic databases reporting median overall survival (OS), median progression-free survival (PFS) and objective response rate (ORR). Weighted Pearson correlation coefficients and 95% confidence intervals (CIs) were calculated. Results: 26 clinical trials (41 treatment arms, 5144 patients) were included. ORR (coefficient: 0...