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Patient Education and Counseling Sep 2020Oncology clinical trials use a variety of clinical endpoints. Patients' understanding of the differences between clinical endpoints is important because misperceptions... (Review)
Review
OBJECTIVES
Oncology clinical trials use a variety of clinical endpoints. Patients' understanding of the differences between clinical endpoints is important because misperceptions of treatment efficacy may affect treatment decisions. The objective of this literature review is to find and synthesize available empirical publications assessing patients' understanding of common oncology clinical endpoints.
METHODS
We conducted a literature search of 5 databases and 3 conferences, limiting the search to articles and abstracts published in English through September 2018. We reviewed the titles and abstracts for inclusion, then reviewed full texts to determine if they reported empirical research studies focused on (1) clinical endpoints, (2) oncology, and (3) patient understanding. The original search identified 497publications, of which 13 met the inclusion criteria.
RESULTS
Available literature yields little information on this topic.The few publications that do exist suggest that healthcare professionals and cancer patients generally do not discuss clinical endpoint concepts and that patients can be confused about the purpose of a treatment based on misperceptions about endpoints.
CONCLUSIONS
Research is needed on how to discuss oncology clinical endpoints with patients.
PRACTICE IMPLICATIONS
Patient-friendly definitions of clinical endpoints may help healthcare providers communicate important information about treatments to patients.
Topics: Clinical Trials as Topic; Comprehension; Disease-Free Survival; Endpoint Determination; Humans; Medical Oncology; Neoplasms; Patient Education as Topic; Patients
PubMed: 32273145
DOI: 10.1016/j.pec.2020.03.018 -
European Journal of Heart Failure Aug 2022Prognostic enrichment strategies can make trials more efficient, although potentially at the cost of diminishing external validity. Whether using a risk score to...
AIMS
Prognostic enrichment strategies can make trials more efficient, although potentially at the cost of diminishing external validity. Whether using a risk score to identify a population at increased mortality risk could improve trial efficiency is uncertain. We aimed to assess whether Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER-HF), a previously validated risk score, could improve clinical trial efficiency.
METHODS AND RESULTS
Mortality rates and association of MARKER-HF with all-cause death by 1 year were evaluated in four community-based heart failure (HF) and five HF clinical trial cohorts. Sample size required to assess effects of an investigational therapy on mortality was calculated assuming varying underlying MARKER-HF risk and proposed treatment effect profiles. Patients from community-based HF cohorts (n = 11 297) had higher observed mortality and MARKER-HF scores than did clinical trial patients (n = 13 165) with HF with either reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). MARKER-HF score was strongly associated with risk of 1-year mortality both in the community (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.44-1.52) and clinical trial cohorts with HFrEF (HR 1.41, 95% CI 1.30-1.54), and HFpEF (HR 1.74, 95% CI 1.53-1.98), per 0.1 increase in MARKER-HF. Using MARKER-HF to identify patients for a hypothetical clinical trial assessing mortality reduction with an intervention, enabled a reduction in sample size required to show benefit.
CONCLUSION
Using a reliable predictor of mortality such as MARKER-HF to enrich clinical trial populations provides a potential strategy to improve efficiency by requiring a smaller sample size to demonstrate a clinical benefit.
Topics: Clinical Trials as Topic; Heart Failure; Humans; Machine Learning; Prognosis; Risk Factors; Stroke Volume; Ventricular Function, Left
PubMed: 35508918
DOI: 10.1002/ejhf.2528 -
Fertility and Sterility Jan 2020Although chemotherapy is no complete substitute for psychotherapy in the treatment of impotence of the male patient, nevertheless, in cases where psychologic and/or...
Although chemotherapy is no complete substitute for psychotherapy in the treatment of impotence of the male patient, nevertheless, in cases where psychologic and/or somatic failure plays a role as etiologic agent then indeed chemotherapy is indicated. -T. Jakobovits.
Topics: Age of Onset; Clinical Trials as Topic; Health Knowledge, Attitudes, Practice; Humans; Hypogonadism; Male
PubMed: 32033739
DOI: 10.1016/j.fertnstert.2019.10.020 -
Epilepsy & Behavior : E&B Oct 2020On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from... (Review)
Review
On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from preclinical models to clinical prognostication. The conference featured regulatory agencies, academic laboratories, and healthcare companies involved in emerging epilepsy therapies and research. The program included discussions around funding and support for investigations in epilepsy and neurologic research, clinical trial design and integrated outcome measures for people with epilepsy, and drug development and upcoming disease-modifying therapies. Finally, the conference included updates from the preclinical, clinical, and device pipeline. Summaries of the talks are provided in this paper, with the various pipeline therapeutics in the listed tables to be outlined in a subsequent publication.
Topics: Animals; Anticonvulsants; Clinical Trials as Topic; Congresses as Topic; Device Approval; Drug Development; Epilepsy; Florida; Genetic Testing; Humans; Mass Screening; National Institute of Neurological Disorders and Stroke (U.S.); United States
PubMed: 32563052
DOI: 10.1016/j.yebeh.2020.107189 -
BMC Medical Research Methodology Apr 2022Pediatric population presents several barriers for clinical trial design and analysis, including ethical constraints on the sample size and slow accrual rate. Bayesian...
BACKGROUND
Pediatric population presents several barriers for clinical trial design and analysis, including ethical constraints on the sample size and slow accrual rate. Bayesian adaptive design methods could be considered to address these challenges in pediatric clinical trials.
METHODS
We developed an innovative Bayesian adaptive design method and demonstrated the approach as a re-design of a published phase III pediatric trial. The innovative design used early success criteria based on skeptical prior and early futility criteria based on enthusiastic prior extrapolated from a historical adult trial, and the early and late stopping boundaries were calibrated to ensure a one-sided type I error of 2.5%. We also constructed several alternative designs which incorporated only one type of prior belief and the same stopping boundaries. To identify a preferred design, we compared operating characteristics including power, expected trial size and trial duration for all the candidate adaptive designs via simulation when performing an increasing number of equally spaced interim analyses.
RESULTS
When performing an increasing number of equally spaced interim analyses, the innovative Bayesian adaptive trial design incorporating both skeptical and enthusiastic priors at both interim and final analyses outperforms alternative designs which only consider one type of prior belief, because it allows more reduction in sample size and trial duration while still offering good trial design properties including controlled type I error rate and sufficient power.
CONCLUSIONS
Designing a Bayesian adaptive pediatric trial with both skeptical and enthusiastic priors can be an efficient and robust approach for early trial stopping, thus potentially saving time and money for trial conduction.
Topics: Bayes Theorem; Child; Clinical Trials as Topic; Computer Simulation; Humans; Medical Futility; Research Design; Sample Size
PubMed: 35448963
DOI: 10.1186/s12874-022-01569-x -
Biostatistics (Oxford, England) Dec 2023Trial-level surrogates are useful tools for improving the speed and cost effectiveness of trials but surrogates that have not been properly evaluated can cause...
Trial-level surrogates are useful tools for improving the speed and cost effectiveness of trials but surrogates that have not been properly evaluated can cause misleading results. The evaluation procedure is often contextual and depends on the type of trial setting. There have been many proposed methods for trial-level surrogate evaluation, but none, to our knowledge, for the specific setting of platform studies. As platform studies are becoming more popular, methods for surrogate evaluation using them are needed. These studies also offer a rich data resource for surrogate evaluation that would not normally be possible. However, they also offer a set of statistical issues including heterogeneity of the study population, treatments, implementation, and even potentially the quality of the surrogate. We propose the use of a hierarchical Bayesian semiparametric model for the evaluation of potential surrogates using nonparametric priors for the distribution of true effects based on Dirichlet process mixtures. The motivation for this approach is to flexibly model relationships between the treatment effect on the surrogate and the treatment effect on the outcome and also to identify potential clusters with differential surrogate value in a data-driven manner so that treatment effects on the surrogate can be used to reliably predict treatment effects on the clinical outcome. In simulations, we find that our proposed method is superior to a simple, but fairly standard, hierarchical Bayesian method. We demonstrate how our method can be used in a simulated illustrative example (based on the ProBio trial), in which we are able to identify clusters where the surrogate is, and is not useful. We plan to apply our method to the ProBio trial, once it is completed.
Topics: Humans; Bayes Theorem; Treatment Outcome; Clinical Trials as Topic
PubMed: 36610075
DOI: 10.1093/biostatistics/kxac053 -
Spinal Cord Sep 2019Traumatic spinal cord injury (SCI) leads to immediate neuronal and axonal damage at the focal injury site and triggers secondary pathologic series of events resulting... (Review)
Review
Traumatic spinal cord injury (SCI) leads to immediate neuronal and axonal damage at the focal injury site and triggers secondary pathologic series of events resulting in sensorimotor and autonomic dysfunction below the level of injury. Although there is no cure for SCI, neuroprotective and regenerative therapies show promising results at the preclinical stage. There is a pressing need to develop non-invasive outcome measures that can indicate whether a candidate therapeutic agent or a cocktail of therapeutic agents are positively altering the underlying disease processes. Recent conventional MRI studies have quantified spinal cord lesion characteristics and elucidated their relationship between severity of injury to clinical impairment and recovery. Next to the quantification of the primary cord damage, quantitative MRI measures of spinal cord (rostrocaudally to the lesion site) and brain integrity have demonstrated progressive and specific neurodegeneration of afferent and efferent neuronal pathways. MRI could therefore play a key role to ultimately uncover the relationship between clinical impairment/recovery and injury-induced neurodegenerative changes in the spinal cord and brain. Moreover, neuroimaging biomarkers hold promises to improve clinical trial design and efficiency through better patient stratification. The purpose of this narrative review is therefore to propose a guideline of clinically available MRI sequences and their derived neuroimaging biomarkers that have the potential to assess tissue damage at the macro- and microstructural level after SCI. In this piece, we make a recommendation for the use of key MRI sequences-both conventional and advanced-for clinical work-up and clinical trials.
Topics: Brain; Clinical Trials as Topic; Humans; Magnetic Resonance Imaging; Neuroimaging; Practice Guidelines as Topic; Spinal Cord Injuries
PubMed: 31267015
DOI: 10.1038/s41393-019-0309-x -
Clinical Trials (London, England) Oct 2021The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid...
The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.
Topics: COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Humans; Pandemics; State Medicine; United Kingdom
PubMed: 34154428
DOI: 10.1177/17407745211024764 -
Translational Neurodegeneration May 2024The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have... (Review)
Review
The use of biomarker-led clinical trial designs has been transformative for investigating amyloid-targeting therapies for Alzheimer's disease (AD). The designs have ensured the correct selection of patients on these trials, supported target engagement and have been used to support claims of disease modification and clinical efficacy. Ultimately, this has recently led to approval of disease-modifying, amyloid-targeting therapies for AD; something that should be noted for clinical trials investigating tau-targeting therapies for AD. There is a clear overlap of the purpose of biomarker use at each stage of clinical development between amyloid-targeting and tau-targeting clinical trials. However, there are differences within the potential context of use and interpretation for some biomarkers in particular measurements of amyloid and utility of soluble, phosphorylated tau biomarkers. Given the complexities of tau in health and disease, it is paramount that therapies target disease-relevant tau and, in parallel, appropriate assays of target engagement are developed. Tau positron emission tomography, fluid biomarkers reflecting tau pathology and downstream measures of neurodegeneration will be important both for participant recruitment and for monitoring disease-modification in tau-targeting clinical trials. Bespoke design of biomarker strategies and interpretations for different modalities and tau-based targets should also be considered.
Topics: Alzheimer Disease; Humans; tau Proteins; Biomarkers; Clinical Trials as Topic
PubMed: 38773569
DOI: 10.1186/s40035-024-00417-w -
Physica Medica : PM : An International... Aug 2022The roles and responsibilities of medical physicists (MPs) are growing together with the evolving science and technology. The complexity of today's clinical trials...
INTRODUCTION
The roles and responsibilities of medical physicists (MPs) are growing together with the evolving science and technology. The complexity of today's clinical trials requires the skills and knowledge of MPs for their safe and efficient implementation. However, it is unclear to what extent the skillsets offered by MPs are being exploited in clinical trials across Europe.
METHODS
The EFOMP Working Group on the role of Medical Physics Experts in Clinical Trials has designed a survey that targeted all 36 current National Member Organisations, receiving a response from 31 countries. The survey included both quantitative and qualitative queries regarding the involvement of MPs in trial design, setup, and coordination, either as trial team members or principal investigators.
RESULTS
The extent of MPs involvement in clinical trials greatly varies across European countries. The results showed disparities between the roles played by MPs in trial design, conduct or data processing. Similarly, differences among the 31 European countries that responded to the survey were found regarding the existence of national bodies responsible for trials or the available training offered to MPs. The role of principal investigator or co-investigator was reported by 12 countries (39%), a sign of efficient collaboration with medical doctors in designing and implementing clinical studies.
CONCLUSION
Organisation of specific training courses and guideline development for clinical trial design and conduct would encourage the involvement of a larger number of MPs in all stages of trials across Europe, leading to a better standardisation of clinical practice.
Topics: Clinical Trials as Topic; Europe; Humans; Physician's Role; Surveys and Questionnaires
PubMed: 35717777
DOI: 10.1016/j.ejmp.2022.06.008