Update on the clinical trial landscape: analysis of ClinicalTrials.gov registration data, 2000-2020.

Background: The clinical trial landscape has evolved over the last two decades, shaped by advances in therapeutics and drug development and innovation in trial design and methods. The tracking of such changes became possible with trial registration, providing the public with a window into the massive clinical research enterprise. The ClinicalTrials.

Assessment of Trends in the Design, Accrual, and Completion of Trials Registered in ClinicalTrials.gov by Sponsor Type, 2000-2019.

Importance: ClinicalTrials.gov is a valuable resource that can be used to trace the state and nature of trials. Since its launch in 2000, more than 345 000 trials have been registered.

Wearable activity monitors to assess performance status and predict clinical outcomes in advanced cancer patients.

An objective evaluation of patient performance status (PS) is difficult because patients spend the majority of their time outside of the clinic, self-report to providers, and undergo dynamic changes throughout their treatment experience. Real-time, objective activity data may allow for a more accurate assessment of PS and physical function, while reducing the subjectivity and bias associated with current assessments. Consenting patients with advanced cancer wore a wearble activity monitor for three consecutive visits in a prospective, single-cohort clinical trial.

Why Public Comments Matter: The Case of the National Institutes of Health Policy on Single Institutional Review Board Review of Multicenter Studies.

Purpose: In 2014, the National Institutes of Health (NIH) requested public comments on a draft policy requiring NIH-funded, U.S.-based investigators to use a single institutional review board (sIRB) for ethical review of multicenter studies.

Wearable activity monitors in oncology trials: Current use of an emerging technology.

Background: Physical activity is an important outcome in oncology trials. Physical activity is commonly assessed using self-reported questionnaires, which are limited by recall and response biases. Recent advancements in wearable technology have provided oncologists with new opportunities to obtain real-time, objective physical activity data.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted.

Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial.

Background: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).

Methods: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks.

Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease.

Objective: Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment.

The transitioning from trials to extended follow-up studies.

Background: Investigators may elect to extend follow-up of participants enrolled in a randomized clinical trial after the trial comes to its planned end. The additional follow-up may be initiated to learn about longer term effects of treatments, including adverse events, costs related to treatment, or for reasons unrelated to treatment such as to observe the natural course of the disease using the established cohort from the trial.

Purpose: We examine transitioning from trials to extended follow-up studies when the goal of additional follow-up is to observe longer term treatment effects.

Changes in QTc interval in the citalopram for agitation in Alzheimer's disease (CitAD) randomized trial.

Background: A Food and Drug Administration (FDA) safety communication in August 2011 warned that citalopram was associated with a dose dependent risk of QT prolongation and recommended dose restriction in patients over the age of 60 but did not provide data for this age group.

Methods: CitAD was a randomized, double-masked, placebo-controlled, multicenter clinical trial for agitation in Alzheimer's disease (AD). Participants were assigned to citalopram (target dose of 30 mg/day) or placebo in a 1 ∶ 1 ratio.

HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined.

Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection.

Background: While inflammation predicts mortality in treated human immunodeficiency virus (HIV) infection, the prognostic significance of gut barrier dysfunction and phenotypic T-cell markers remains unclear.

Methods: We assessed immunologic predictors of mortality in a case-control study within the Longitudinal Study of the Ocular Complications of AIDS (LSOCA), using conditional logistic regression. Sixty-four case patients who died within 12 months of treatment-mediated viral suppression were each matched to 2 control individuals (total number of controls, 128) by duration of antiretroviral therapy-mediated viral suppression, nadir CD4(+) T-cell count, age, sex, and prior cytomegalovirus (CMV) retinitis.

Low proportions of CD28- CD8+ T cells expressing CD57 can be reversed by early ART initiation and predict mortality in treated HIV infection.

Background: Unlike cytomegalovirus (CMV) infection and aging, human immunodeficiency virus (HIV) decreases the proportion of CD28(-)CD8(+) T cells expressing CD57. Whether this abnormality predicts mortality in treated HIV infection and can be reversed by early antiretroviral therapy (ART) remains unknown.

Methods: We sampled recently HIV-infected individuals (<6 months) and HIV-uninfected controls and compared longitudinal changes in the proportion of CD28(-)CD8(+) T cells expressing CD57 between those who initiated ART early (<6 months) vs later (≥2 years).

Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial.

Importance: Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.

Objective: The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease.

Is sertraline treatment or depression remission in depressed Alzheimer patients associated with improved caregiver well being? Depression in Alzheimer's Disease Study 2.

Objective: We wanted to assess if sertraline treatment (versus placebo) or remission of depression at 12 weeks (versus nonremission) in Alzheimer patients is associated with improved caregiver well being.

Methods: We conducted a randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of sertraline for the treatment of depression in individuals with Alzheimer disease in five clinical research sites across the United States. Participants were caregivers of patients enrolled in the Depression in Alzheimer's Disease Study 2 (N = 131).

Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal disorder.

Background: Both hepatitis C virus (HCV) and human immunodeficiency virus (HIV) penetrate the central nervous system. HIV-associated neuroretinal disorder (HIV-NRD), a visual impairment of reduced contrast sensitivity and reading ability, is associated with cytokine dysregulation and genetic polymorphisms in the anti-inflammatory interleukin 10 (IL-10) signaling pathway. We investigated associations between HCV and HIV-NRD and between HCV and single-nucleotide polymorphisms (SNPs) in the IL-10 receptor 1 (IL10R1) gene.

Correlates of hypertension in patients with AIDS in the era of highly active antiretroviral therapy.

Background: It is unclear whether HIV-related factors modify risk of hypertension (HTN). In a cohort of patients with AIDS, the authors determined HTN incidence and prevalence and assessed associated traditional, HIV-specific, and retinal vasculature factors.

Methods: Prospective observational cohort included 2390 patients with AIDS (1998-2011).

Cognitive outcomes after sertaline treatment in patients with depression of Alzheimer disease.

Objectives: Although many depressed patients with Alzheimer disease (AD) are treated with antidepressants, the effect of such treatment on cognitive performance in these patients is not known. The authors report cognitive outcomes in patients with depression of AD (dAD) after a 24-week trial of sertraline or placebo.

Design: Placebo-controlled, randomized, double-blind trial.

Mortality in hepatitis C virus-infected patients with a diagnosis of AIDS in the era of combination antiretroviral therapy.

Background: Before the introduction of combination antiretroviral therapy (cART), patients infected with the human immunodeficiency virus (HIV) rarely died of liver disease. In resource-rich countries, cART dramatically increased longevity. As patients survived longer, hepatitis C virus (HCV) infection became a leading cause of death; however, because patients with AIDS continue to have 5-fold greater mortality than non-AIDS patients, it is unclear whether HCV infection increases mortality in them.

Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy.

Purpose: To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis.

Design: Prospective cohort study.

Methods: A total of 1600 participants with acquired immunodeficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least 1 follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing.

Citalopram for agitation in Alzheimer's disease: design and methods.

Background: Agitation is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer's disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms.