Clinical Trials最新文献

{"title":"Proceedings of the University of Pennsylvania 15th annual conference on statistical issues in clinical trials: Advances in time-to-event analyses in clinical trials-challenges and opportunities.","authors":"Mary E Putt","doi":"10.1177/17407745241276119","DOIUrl":"https://doi.org/10.1177/17407745241276119","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Participant’s treatment guesses and adverse events in back pain trials: Nocebo in action?","authors":"Javier Muñoz Laguna, Hyangsook Lee, Eduard Poltavskiy, Jeehyoung Kim, Heejung Bang","doi":"10.1177/17407745241276124","DOIUrl":"https://doi.org/10.1177/17407745241276124","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"15th Annual University of Pennsylvania conference on statistical issues in clinical trial/advances in time to event analyses in clinical trials (morning panel discussion).","authors":"Pralay Mukhopadhyay, Douglas Schaubel, Mei-Cheng Wang","doi":"10.1177/17407745241272012","DOIUrl":"https://doi.org/10.1177/17407745241272012","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimands in clinical trials of complex disease processes.","authors":"Richard J Cook, Jerald F Lawless","doi":"10.1177/17407745241268054","DOIUrl":"https://doi.org/10.1177/17407745241268054","url":null,"abstract":"<p><p>Clinical trials with random assignment of treatment provide evidence about causal effects of an experimental treatment compared to standard care. However, when disease processes involve multiple types of possibly semi-competing events, specification of target estimands and causal inferences can be challenging. Intercurrent events such as study withdrawal, the introduction of rescue medication, and death further complicate matters. There has been much discussion about these issues in recent years, but guidance remains ambiguous. Some recommended approaches are formulated in terms of hypothetical settings that have little bearing in the real world. We discuss issues in formulating estimands, beginning with intercurrent events in the context of a linear model and then move on to more complex disease history processes amenable to multistate modeling. We elucidate the meaning of estimands implicit in some recommended approaches for dealing with intercurrent events and highlight the disconnect between estimands formulated in terms of potential outcomes and the real world.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on Astrachan et al. The transmutation of research risk in pragmatic clinical trials.","authors":"Jonathan Kimmelman","doi":"10.1177/17407745241266168","DOIUrl":"https://doi.org/10.1177/17407745241266168","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individualized clinical decisions within standard-of-care pragmatic clinical trials: Implications for consent.","authors":"Isabel M Astrachan, James Flory, Scott Yh Kim","doi":"10.1177/17407745241266155","DOIUrl":"https://doi.org/10.1177/17407745241266155","url":null,"abstract":"<p><p>Pragmatic clinical trials of standard-of-care interventions compare the relative merits of medical treatments already in use. Traditional research informed consent processes pose significant obstacles to these trials, raising the question of whether they may be conducted with alteration or waiver of informed consent. However, to even be eligible, such a trial in the United States must have no more than minimal research risk. We argue that standard-of-care pragmatic clinical trials can be designed to ensure that they are minimal research risk if the random assignment of an intervention in a pragmatic clinical trial can accommodate individualized, clinically motivated decision-making for each participant. Such a design will ensure that the patient-participants are not exposed to any risks beyond the clinical risks of the interventions, and thus, the trial will have minimal research risk. We explain the logic of this view by comparing three scenarios of standard-of-care pragmatic clinical trials: one with informed consent, one without informed consent, and one recently proposed design called Decision Architecture Randomization Trial. We then conclude by briefly showing that our proposal suggests a natural way to determine when to use an alteration versus a waiver of informed consent.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taking clinical decisions seriously in standard-of-care pragmatic clinical trials.","authors":"Isabel M Astrachan, James Flory, Scott Yh Kim","doi":"10.1177/17407745241266152","DOIUrl":"https://doi.org/10.1177/17407745241266152","url":null,"abstract":"","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to promote contraception use by female volunteers in Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia trial.","authors":"Christian Bustamante, Juan F Martinez, Alexander Navarro, Margarita Lopera, Gustavo Villegas, Sindy Duque, Natalia Acosta-Baena, Silvia Ríos-Romenets, Francisco Lopera","doi":"10.1177/17407745241264217","DOIUrl":"10.1177/17407745241264217","url":null,"abstract":"<p><strong>Background/aims: </strong>Including women of childbearing age in a clinical trial makes it necessary to consider two factors from a bioethical perspective: first, the lack of knowledge about the potential teratogenic effects of an investigational product, and also, the principle of justice not to exclude any population from the benefits of research. The most common way to address this issue is by requiring volunteers to use contraceptives before, during, and a few weeks after the clinical trial. This work presents all the strategies used to promote contraception use and prevent pregnancy during the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia clinical trial. Two characteristics of this trial make it of special interest for closely monitoring contraception use. One is that the trial lasted more than 7 years, and the other is that participants could be carriers of the E280A PSEN1 mutation, leading to a mild cognitive impairment as early as their late 30s.</p><p><strong>Methods: </strong>An individual medical evaluation to select the contraception method that best fits the volunteer was carried out during the screening visit, remitting to the gynecologist when necessary. All non-surgical contraception methods were supplied by the sponsor. Staff were trained on contraception counseling, correctly dispensing contraceptive drugs to volunteers, and identifying, reporting, and following up on pregnancies. Two comprehensive educational campaigns on contraception use were performed, and the intervention included all volunteers. In addition, volunteers were asked on an annual survey to evaluate the dispensing procedure. Finally, the effectiveness of these strategies was retrospectively evaluated, comparing by extrapolation the number of pregnancies presented throughout the trial with the General Fertility Rate in Colombia.</p><p><strong>Results: </strong>A total of 159 female volunteers were recruited. All strategies were implemented as planned, even during the COVID-19 contingency. Ten pregnancies occurred during the evaluation period (2015-2021). Two were planned; the rest were associated with a potential therapeutic failure or incorrect use of contraceptive methods for a contraceptive failure of 0.49% per year. Sixty percent of pregnancies led to an abortion, either miscarriage or therapeutic abortion. However, there was not enough data to associate the pregnancy outcome with the administration of the investigational product. Finally, we observed a lower fertility rate in women participating in the trial compared to the Colombian population.</p><p><strong>Conclusion: </strong>The lower rates of contraceptive failure and the decrease in the incidence of pregnancies in women participating in the trial compared to the Colombian population across the 7 years of evaluation suggest that the strategies used in API ADAD Colombia were adequate and effective in addressing contraception use.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of composite time-to-event endpoints in cardiovascular outcome trials.","authors":"Rachel Marceau West, Gregory Golm, Devan V Mehrotra","doi":"10.1177/17407745241267999","DOIUrl":"https://doi.org/10.1177/17407745241267999","url":null,"abstract":"<p><p>Composite time-to-event endpoints are commonly used in cardiovascular outcome trials. For example, the IMPROVE-IT trial comparing ezetimibe+simvastatin to placebo+simvastatin in 18,144 patients with acute coronary syndrome used a primary composite endpoint with five component outcomes: (1) cardiovascular death, (2) non-fatal stroke, (3) non-fatal myocardial infarction, (4) coronary revascularization ≥30 days after randomization, and (5) unstable angina requiring hospitalization. In such settings, the traditional analysis compares treatments using the observed time to the occurrence of the first (i.e. earliest) component outcome for each patient. This approach ignores information for subsequent outcome(s), possibly leading to reduced power to demonstrate the benefit of the test versus the control treatment. We use real data examples and simulations to contrast the traditional approach with several alternative approaches that use data for all the intra-patient component outcomes, not just the first.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statistical approaches for component-wise censored composite endpoints.","authors":"Anne Eaton","doi":"10.1177/17407745241265628","DOIUrl":"https://doi.org/10.1177/17407745241265628","url":null,"abstract":"<p><p>Composite endpoints defined as the time to the earliest of two or more events are often used as primary endpoints in clinical trials. Component-wise censoring arises when different components of the composite endpoint are censored differently. We focus on a composite of death and a non-fatal event where death time is right censored and the non-fatal event time is interval censored because the event can only be detected during study visits. Such data are most often analysed using methods for right censored data, treating the time the non-fatal event was first detected as the time it occurred. This can lead to bias, particularly when the time between assessments is long. We describe several approaches for estimating the event-free survival curve and the effect of treatment on event-free survival via the hazard ratio that are specifically designed to handle component-wise censoring. We apply the methods to a randomized study of breastfeeding versus formula feeding for infants of mothers infected with human immunodeficiency virus.</p>","PeriodicalId":10685,"journal":{"name":"Clinical Trials","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}