scholarly journals Bayesian Utility-Based Designs for Subgroup-Specific Treatment Comparison and Early-Phase Dose Optimization in Oncology Clinical Trials

2019 ◽  
pp. 1-7
Author(s):  
Peter F. Thall
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Patient Outcomes ◽  
Early Phase ◽  
Operating Characteristics ◽  
Treatment Comparison ◽  
Trade Offs ◽  
Patient Heterogeneity ◽  
Clinical Trial Designs

PURPOSE Despite the fact that almost any sample of patients with a particular disease is heterogeneous, most clinical trial designs ignore the possibility that treatment or dose effects may differ between prognostic or biologically defined subgroups. This article reviews two clinical trial designs that make subgroup-specific decisions and compares each to a simpler design that ignores patient heterogeneity. The purpose is to illustrate the benefits of accounting prospectively for treatment-subgroup interactions and how utilities may be used to quantify risk-benefit trade-offs. METHODS Two Bayesian clinical trial designs that perform subgroup-specific decision making and inference based on elicited utilities of patient outcomes are reviewed. The first is a randomized comparative trial of nutritional prehabilitation for patients undergoing esophageal resection that has two prognostic subgroups and is based on postoperative morbidity score. The second is a sequentially adaptive trial of natural killer cells for treating hematologic malignancies that is based on five time-to-event outcomes and that performs safety monitoring and optimizes cell dose within six disease subgroups. Computer simulations under a range of different scenarios are presented for each design to establish its operating characteristics and compare it to a more conventional design that ignores patient heterogeneity. RESULTS Each design has attractive operating characteristics, is greatly superior to a simplified design that ignores patient subgroups, is robust to deviations from its assumed statistical model, and is feasible to use for conducting trials. CONCLUSION Bayesian designs that make subgroup-specific decisions in randomized comparative trials or sequentially adaptive early-phase dose-finding trials are superior to designs that ignore patient heterogeneity. Using elicited utilities of complex patient outcomes to quantify risk-benefit trade-offs provides a practical and ethical basis for decision making and treatment evaluation in clinical trials.

Compliance with dietary guidelines and its relationship with symptoms and clinical outcomes in patients with advanced cancer in early-phase oncology clinical trials.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 199-199
Author(s):  
Goldy George ◽  
Alan J Kim ◽  
Melat Gebremeskel ◽  
Meryna Manandhar ◽  
Harsha M Pradeep ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Advanced Cancer ◽  
Early Phase ◽  
Symptom Burden ◽  
Whole Grains ◽  
Dietary Guidelines ◽  
Early Phase Clinical Trial ◽  
Dietary Guidelines For Americans ◽  
Phase Clinical Trial

199 Background: We examined compliance with the Dietary Guidelines for Americans and its association with symptom burden and clinical outcomes in patients with advanced cancer in early-phase clinical trials testing novel immunotherapeutic and targeted agents. Methods: Patients starting an early-phase clinical trial (ECOG-PS = 0-1) were recruited into a prospective, longitudinal design with assessments at baseline and at the end of Cycle 1. Diet and symptom burden were assessed using the validated National Cancer Institute Diet History Questionnaire (NCI-DHQ) and the MD Anderson Symptom Inventory, respectively. Compliance with the Dietary Guidelines for Americans recommendations was measured via the Healthy Eating Index (HEI) (a measure of dietary intake per total energy), computed from NCI-DHQ food group and nutrient scores; higher HEI scores indicate greater compliance with dietary guidance recommendations (possible range = 0–100). Statistical tests included Spearman rank correlations (rho), and Cox proportional hazards models. Results: Among early-phase clinical trial patients [N = 40; 50% female; 80% Non-Hispanic White; 80% ECOG = 1; 36% on trials including an immunotherapeutic agent and 64% on targeted therapy trials; mean age = 55y; mean BMI = 28], mean HEI was 69, compared to 59 for the US general population. The proportion of phase I clinical trial patients who met adequacy guidelines were 80% for whole fruit, 73% for total protein foods, 55% for seafood and plant proteins, 55% for total fruit, 50% for greens and beans, 28% for total vegetables, 15% for fatty acids [(PUFAs + MUFAs)/SFAs ≥2.5], 13% for dairy, and 0% for whole grains. The proportion of patients who met moderation guidelines were 28% for refined grains, 28% for added sugar, 13% for saturated fat, and 0% for sodium. Female patients had higher HEI scores than male patients (73 vs. 65, P = 0.004). Patients who were normal weight (BMI < 25) had higher scores for meeting the moderation in sugar intake guideline than overweight patients (BMI≥25) (7.7 vs. 5.5, P = 0.031). Higher intakes of cooked lean meat from beef, pork, veal, lamb, and game were linked to prolonged overall survival (HR = 0.5, 95%CI = 0.26, 0.96, P = 0.039). In immunotherapy patients, greater compliance with seafood and plant protein recommendations was associated with less fatigue at end of Cycle 1 (rho = -0.7, P = 0.008); in targeted therapy patients, higher glycemic load was associated with worse pain (rho = 0.7, P = 0.004). Conclusions: Diets of these early-phase clinical trial patients overall were congruent with recommendations in the Dietary Guidelines for Americans. However, increasing intakes of whole grains and reducing sodium intakes may be useful dietary goals for this population. Also, dietary factors may influence symptoms, such as fatigue and pain, in early-phase clinical trial patients with advanced cancer.

Current Advances in Clinical Trials for Rare Disease Populations: Spotlight on the Patient

2021 ◽  
Vol 16 ◽  
Author(s):  
Erica Winter ◽  
Scott Schliebner
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Drug Development ◽  
Rare Disease ◽  
Rare Diseases ◽  
Statistical Analyses ◽  
Clinical Trial Designs ◽  
Novel Approaches

: Characterized by small, highly heterogeneous patient populations, rare disease trials magnify the challenges often encountered in traditional clinical trials. In recent years, there have been increased efforts by stakeholders to improve drug development in rare diseases through novel approaches to clinical trial designs and statistical analyses. We highlight and discuss some of the current and emerging approaches aimed at overcoming challenges in rare disease clinical trials, with a focus on the ultimate stakeholder, the patient.

scholarly journals ACTA A Tool for Argumentative Clinical Trial Analysis

2019 ◽  
Author(s):  
Tobias Mayer ◽  
Elena Cabrio ◽  
Serena Villata
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Online Discussion ◽  
Trial Analysis ◽  
Persuasive Essays

Argumentative analysis of textual documents of various nature (e.g., persuasive essays, online discussion blogs, scientific articles) allows to detect the main argumentative components (i.e., premises and claims) present in the text and to predict whether these components are connected to each other by argumentative relations (e.g., support and attack), leading to the identification of (possibly complex) argumentative structures. Given the importance of argument-based decision making in medicine, in this demo paper we introduce ACTA, a tool for automating the argumentative analysis of clinical trials. The tool is designed to support doctors and clinicians in identifying the document(s) of interest about a certain disease, and in analyzing the main argumentative content and PICO elements.

Increasing Health Literacy to Improve Clinical Trial Recruitment

2018 ◽  
pp. 94-108
Author(s):  
Saliha Akhtar
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Informed Consent ◽  
Health Literacy ◽  
Trial Recruitment ◽  
Negative Perception ◽  
Consent Forms ◽  
Clinical Trial Recruitment ◽  
And Training

Health literacy has been found to be linked to healthcare understanding and decision making. Therefore, it makes sense why individuals who do not understand clinical trials will be less likely to want to enroll in one. In fact, three major barriers found in the literature that prevent potential participants from enrolling in clinical trials include a distrust or negative perception, lack of understanding, and lack of accessible and affordable healthcare. Hence, there is a need to increase potential participants' healthcare understanding so that they can make the best healthcare decisions for themselves. Strategies suggested to help increase potential participants' health literacy include revising informed consent forms, utilizing culturally targeted statements, using a variety of material, and training investigative site personnel. These proposed strategies may help increase health literacy, which in turn could improve clinical trial recruitment. Furthermore, these strategies focus on different elements of health literacy and coupled together may bring the most improvement.

Simulation Modeling as a Decision-Making Aid in Economic Evaluation for Randomized Clinical Trials

2011 ◽  
pp. 1738-1758
Author(s):  
Tillal Eldabi ◽  
Robert D. Macredie ◽  
Ray J. Paul
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Economic Evaluation ◽  
Simulation Model ◽  
Randomized Clinical Trial ◽  
Simulation Modeling ◽  
Randomized Clinical Trials ◽  
Healthcare Systems ◽  
Modeling Process

This chapter reports on the use of simulation in supporting decision-making about what data to collect in a randomized clinical trial (RCT). We show how simulation also allows the identification of critical variables in the RCT by measuring their effects on the simulation model’s “behavior.” Healthcare systems pose many of the challenges, including difficulty in understanding the system being studied, uncertainty over which data to collect, and problems of communication between problem owners. In this chapter we show how simulation also allows the identification of critical variables in the RCT by measuring their effects on the simulation model’s “behavior.” The experience of developing the simulation model leads us to suggest simple but extremely valuable lessons. The first relates to the inclusion of stakeholders in the modeling process and the accessibility of the resulting models. The ownership and confidence felt by stakeholders in our case is, we feel, extremely important and may provide an example to others developing models.

scholarly journals Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions

2020 ◽  
Vol 16 (9) ◽  
pp. e859-e867
Author(s):  
Rachel S. Hianik ◽  
Gavin P. Campbell ◽  
Eli Abernethy ◽  
Colleen Lewis ◽  
Christina S. Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Phase I ◽  
Shared Decision Making ◽  
Phase I Trial ◽  
Performance Status ◽  
Shared Decision ◽  
Phase I Clinical Trials ◽  
Decision Making Model

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient’s opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

scholarly journals Molecular profiling of metastatic bladder cancer early-phase clinical trial participants predicts patient outcomes

2020 ◽  
pp. molcanres.0751.2020
Author(s):  
Omar Alhalabi ◽  
Andrew W Hahn ◽  
Pavlos Msaouel ◽  
Alexander Y Andreev-Drakhlin ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bladder Cancer ◽  
Patient Outcomes ◽  
Early Phase ◽  
Molecular Profiling ◽  
Early Phase Clinical Trial ◽  
Metastatic Bladder Cancer ◽  
Phase Clinical Trial ◽  
Trial Participants

scholarly journals INFORMED CONSENT IN CLINICAL TRIALS FOR PERSONS WITH DEMENTIA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S28-S28 ◽  
Author(s):  
Joan G Carpenter
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Informed Consent ◽  
Nursing Homes ◽  
Decision Maker ◽  
Surrogate Decision Maker ◽  
Decision Making Capacity ◽  
Consent Document ◽  
Surrogate Decision

Abstract Informed consent is one of the most important processes during the implementation of a clinical trial; special attention must be given to meeting the needs of persons with dementia in nursing homes who have impaired decision making capacity. We overcame several challenges during enrollment and consent of potential participants in a pilot clinical trial including: (1) the consent document was designed for legally authorized representatives however some potential participants were capable of making their own decisions; (2) the written document was lengthy yet all seven pages were required by the IRB; (3) the required legal wording was difficult to understand and deterred potential participants; and (4) the primary mode of communication was via phone. We tailored assent and informed consent procedures to persons with dementia and their legally authorized representative/surrogate decision maker to avoid risking an incomplete trial and to improve generalizability of trial results to all persons with dementia.

scholarly journals An adaptive two-arm clinical trial using early endpoints to inform decision making: design for a study of sub-acromial spacers for repair of rotator cuff tendon tears

Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Nick Parsons ◽  
Nigel Stallard ◽  
Helen Parsons ◽  
Philip Wells ◽  
Martin Underwood ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Rotator Cuff ◽  
Surgical Procedures ◽  
Adaptive Designs ◽  
Operating Characteristics ◽  
Worked Example ◽  
Patient Reported ◽  
Design Characteristics ◽  
Inform Decision Making

Abstract Background There is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked example, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures. Methods Test statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described. Results Simulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked example, with code in R, provides a practical demonstration of how the design might work in a real study. Conclusions In summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study. Trial registration ISRCTN Registry, ISRCTN17825590. Registered on 5 March 2018.

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