Background: SURMOUNT-4 was a Phase 3 clinical trial evaluating the safety and efficacy of tirzepatide in adults living with obesity or overweight. The method of delivery for tirzepatide was via a ...weekly, single-use injection pen device. The aim of this qualitative interview study was to better understand the ease-of-use of the pen device used to administer the study medication. Methods: Exit interviews were conducted with a random sample of US-based participants who had completed their Week 88 primary endpoint and Week 92 safety follow-up visits in SURMOUNT-4. A semi-structured discussion guide was used to understand the participant experience of the study, including use of the single-use pen device. Participants also completed an Injection Device Experience Questionnaire (ID-EQ) during their interview. As of May 30, 2023, interviews are on-going; n = 79 have been completed. The intended total sample size is n = 90 interviews. Results: Most participants reported that the single-use pen device was easy to use, and this was reflected in their responses to the IDEQ item "Overall, the device is easy to use": 91% responded "Strongly Agree", and 9% responded "Agree." Participants commented that the device was convenient due to being pre-filled and packaged as an allin-one device, that administration was simple and required minimal steps to inject each dose, that using the device took very little time, and that the needle was small and caused little to no pain. The requirement for the drug (and therefore the device) to be kept refridgerated was the key limitation mentioned. Conclusions: Qualitative exit interview methodology was utilized to understand participants' overall experience during SURMOUNT-4. Participants in the SURMOUNT-4 clinical trial found the single-use injection pen device to be easy to use and convenient.
To update the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases by surveying international experts regarding previous uncertainties within the ...2002 consensus, changes that may be necessary based on practice pattern changes and research findings since that time.
A two-phase survey was used to determine revisions and new additions to the 2002 consensus. A total of 49 experts from the American Society for Radiation Oncology, the European Society for Therapeutic Radiology and Oncology, the Faculty of Radiation Oncology of the Royal Australian and New Zealand College of Radiologists, and the Canadian Association of Radiation Oncology who are directly involved in the care of patients with bone metastases participated in this survey.
Consensus was established in areas involving response definitions, eligibility criteria for future trials, reirradiation, changes in systemic therapy, radiation techniques, parameters at follow-up, and timing of assessments.
An outline for trials in bone metastases was updated based on survey and consensus. Investigators leading trials in bone metastases are encouraged to adopt the revised guideline to promote consistent reporting. Areas for future research were identified. It is intended for the consensus to be re-examined in the future on a regular basis.
Purpose of Review
Randomized controlled trials (RCTs) in heart failure (HF) are becoming increasingly complex and expensive to conduct and if positive deliver expensive therapy tested only in ...selected populations.
Recent Findings
Electronic health records and clinical cardiovascular quality registries are providing opportunities for pragmatic and registry-based prospective randomized clinical trials (RRCTs). Simplified regulatory, ethics, and consent procedures; recruitment integrated into real-world care; and simplified or automated baseline and outcome collection allow assessment of study power and feasibility, fast and efficient recruitment, delivery of generalizable findings at low cost, and potentially evidence-based and novel use of generic drugs with low costs to society.
Summary
There have been no RRCTs in HF to date. Major challenges include generating funding, international collaboration, and the monitoring of safety and adherence for chronic HF treatments. Here, we use the Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF), to be conducted in the Swedish Heart Failure Registry, to exemplify the advantages and challenges of HF RRCTs.
A balanced treatment of the theories, methodologies, and design issues involved in clinical trials using statistical methods There has been enormous interest and development in Bayesian adaptive ...designs, especially for early phases of clinical trials. However, for phase III trials, frequentist methods still play a dominant role through controlling type I and type II errors in the hypothesis testing framework. From practical perspectives, Clinical Trial Design: Bayesian and Frequentist Adaptive Methods provides comprehensive coverage of both Bayesian and frequentist approaches to all phases of clinical trial design. Before underpinning various adaptive methods, the book establishes an overview of the fundamentals of clinical trials as well as a comparison of Bayesian and frequentist statistics. Recognizing that clinical trial design is one of the most important and useful skills in the pharmaceutical industry, this book provides detailed discussions on a variety of statistical designs, their properties, and operating characteristics for phase I, II, and III clinical trials as well as an introduction to phase IV trials. Many practical issues and challenges arising in clinical trials are addressed. Additional topics of coverage include: Risk and benefit analysis for toxicity and efficacy trade-offs Bayesian predictive probability trial monitoring Bayesian adaptive randomization Late onset toxicity and response Dose finding in drug combination trials Targeted therapy designs The author utilizes cutting-edge clinical trial designs and statistical methods that have been employed at the world's leading medical centers as well as in the pharmaceutical industry. The software used throughout the book is freely available on the book's related website, equipping readers with the necessary tools for designing clinical trials. Clinical Trial Design is an excellent book for courses on the topic at the graduate level. The book also serves as a valuable reference for statisticians and biostatisticians in the pharmaceutical industry as well as for researchers and practitioners who design, conduct, and monitor clinical trials in their everyday work.
This paper proposes a two‐stage phase I‐II clinical trial design to optimize dose‐schedule regimes of an experimental agent within ordered disease subgroups in terms of the toxicity‐efficacy ...trade‐off. The design is motivated by settings where prior biological information indicates it is certain that efficacy will improve with ordinal subgroup level. We formulate a flexible Bayesian hierarchical model to account for associations among subgroups and regimes, and to characterize ordered subgroup effects. Sequentially adaptive decision‐making is complicated by the problem, arising from the motivating application, that efficacy is scored on day 90 and toxicity is evaluated within 30 days from the start of therapy, while the patient accrual rate is fast relative to these outcome evaluation intervals. To deal with this in a practical manner, we take a likelihood‐based approach that treats unobserved toxicity and efficacy outcomes as missing values, and use elicited utilities that quantify the efficacy‐toxicity trade‐off as a decision criterion. Adaptive randomization is used to assign patients to regimes while accounting for subgroups, with randomization probabilities depending on the posterior predictive distributions of utilities. A simulation study is presented to evaluate the design's performance under a variety of scenarios, and to assess its sensitivity to the amount of missing data, the prior, and model misspecification.
Randomised trials use the play of chance to assign participants to comparison groups. The unpredictability of the process, if not subverted, should prevent systematic differences between comparison ...groups (selection bias), provided that a sufficient number of people are randomised.
To assess the effects of randomisation and concealment of allocation on the results of healthcare trials.
We searched the Cochrane Methodology Register, MEDLINE, SciSearch, reference lists up to August 2000 and used personal communication.
Cohorts of trials, systematic reviews or meta-analyses of healthcare interventions that compared outcomes or prognostic factors for one of the following comparisons: randomised versus non-randomised trials, randomised trials with adequately versus inadequately concealed allocation, or high versus low quality trials where selection bias could not be separated from other sources of bias.
One of us went through all of the citations in the Cochrane Methodology Register and accumulated reference lists. Studies that appeared to meet the inclusion criteria were retrieved and assessed independently by two of the reviewers. The methodological quality of included studies was appraised and information extracted by one of us and checked by a second. Tabular summaries of the results were prepared for each comparison and the results across studies were assessed qualitatively to identify common trends or discrepancies.
We identified 32 studies including over 3000 trials. Twenty-two studies compared randomised versus non-randomised trials, three compared adequately versus inadequately concealed allocation, and nine compared high versus low quality trials (some studies included more than one comparison). Five studies were of high methodological quality. In 15 of the 22 studies that compared randomised and non-randomised trials of the same intervention, important differences were found in the estimates of effect. Some of these differences were due to a poorer prognosis in the control groups in the non-randomised trials. The results of the other seven studies that compared randomised and non-randomised trials across different interventions are less clear. Comparisons of adequately and inadequately concealed allocation in randomised trials of the same intervention provided high quality evidence that concealment can be crucial in achieving similar treatment groups and, therefore, unbiased estimates of treatment effects. Studies with inadequate concealment tended to overestimate treatment effects. Comparisons of high and low quality trials of the same intervention have found important differences in estimates of effect, but it is not possible to determine the extent to which these differences can be attributed to randomisation or concealment of allocation. Omitting comparisons between randomised trials and non-randomised trials using historical controls did not substantially alter the results or conclusions of our review.
On average, non-randomised trials and randomised trials with inadequate concealment of allocation tend to result in larger estimates of effect than randomised trials with adequately concealed allocation. However, it is not generally possible to predict the magnitude, or even the direction, of possible selection biases and consequent distortions of treatment effects.
Adaptive Designs for Clinical Trials Bhatt, Deepak L; Mehta, Cyrus
The New England journal of medicine,
2016-Jul-07, Letnik:
375, Številka:
1
Journal Article
PDF
