A survey of patients with laryngotracheal stenosis on future clinical trial design

2022 ◽  
pp. 174077452110657
Author(s):  
Ioan Lina ◽  
Alexandra Berges ◽  
Rafael Ospino ◽  
Kevin Motz ◽  
Ruth Davis ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Side Effects ◽  
Trial Design ◽  
Treatment Options ◽  
Clinical Trial Design ◽  
Trial Participation ◽  
Controlled Clinical Trial ◽  
Laryngotracheal Stenosis ◽  
Oral Ulcers ◽  
Gastrointestinal Side Effects

Background/Aims Laryngotracheal stenosis is a rare but devastating proximal airway fibrosis that restricts a patient’s ability to breathe. Treatment is primarily surgical and to date, there has never been a multi-institutional, randomized, prospective, and interventional clinical trial for a medical therapy to treat laryngotracheal stenosis. Therefore, we aimed to obtain patient feedback to guide successful trial design, recruitment, retention, and for identifying potential barriers to study participation. Methods Over 1000 members of an international laryngotracheal stenosis online support community (the Living with Idiopathic Subglottic Stenosis Facebook group) were sent two questionnaires for a proposed interventional double-blinded, randomized, placebo-controlled clinical trial. Results A total of 317 and 558 participants responded to the first and second surveys, respectively. The majority of participants (77%) were willing to consider enrollment, regardless of having a 50% chance of receiving placebo versus treatment (78%). The majority (84%) of participants were willing to travel 200 miles to participate for up to six in-person visits over 50 days. Specific side effects, including anemia/thrombocytopenia (72%) or risk of infection (69.3%) had the greatest impact on clinical trial participation with other side effects (peripheral edema (53%), oral ulcers (51%), and gastrointestinal side effects (41%)) having less impact. Conclusion Patients with laryngotracheal stenosis possess nuanced insight into their disease and treatment options. As a group, they are extremely motivated for better therapies. Future laryngotracheal stenosis clinical trials should focus on providing excellent side effect -related education and utilizing feedback from online advocacy groups to optimize recruitment and retention.

A novel, hybrid, single- and multi-site clinical trial design for CLN3 disease, an ultra-rare lysosomal storage disorder

2019 ◽  
Vol 16 (5) ◽  
pp. 555-560 ◽  
Author(s):  
Heather R Adams ◽  
Sara Defendorf ◽  
Amy Vierhile ◽  
Jonathan W Mink ◽  
Frederick J Marshall ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Rare Diseases ◽  
Trial Design ◽  
Neurodegenerative Disorder ◽  
Clinical Trial Design ◽  
Trial Participation ◽  
Local Participation ◽  
Cln3 Disease ◽  
Study Participants

Background Travel burden often substantially limits the ability of individuals to participate in clinical trials. Wide geographic dispersion of individuals with rare diseases poses an additional key challenge in the conduct of clinical trials for rare diseases. Novel technologies and methods can improve access to research by connecting participants in their homes and local communities to a distant research site. For clinical trials, however, understanding of factors important for transition from traditional multi-center trial models to local participation models is limited. We sought to test a novel, hybrid, single- and multi-site clinical trial design in the context of a trial for Juvenile Neuronal Ceroid Lipofuscinosis (CLN3 disease), a very rare pediatric neurodegenerative disorder. Methods We created a “hub and spoke” model for implementing a 22-week crossover clinical trial of mycophenolate compared with placebo, with two 8-week study arms. A single central site, the “hub,” conducted screening, consent, drug dispensing, and tolerability and efficacy assessments. Each participant identified a clinician to serve as a collaborating “spoke” site to perform local safety monitoring. Study participants traveled to the hub at the beginning and end of each study arm, and to their individual spoke site in the intervening weeks. Results A total of 18 spoke sites were established for 19 enrolled study participants. One potential participant was unable to identify a collaborating local site and was thus unable to participate. Study start-up required a median 6.7 months (interquartile range = 4.6–9.2 months). Only 33.3% (n = 6 of 18) of spoke site investigators had prior clinical trial experience, thus close collaboration with respect to study startup, training, and oversight was an important requirement. All but one participant completed all study visits; no study visits were missed due to travel requirements. Conclusions This study represents a step toward local trial participation for patients with rare diseases. Even in the context of close oversight, local participation models may be best suited for studies of compounds with well-understood side-effect profiles, for those with straightforward modes of administration, or for studies requiring extended follow-up periods.

scholarly journals Impact of a Dementia-friendly Program on Detection and Management of Patients with Cognitive Impairment and Delirium in Acute-care Hospital Units: A Controlled Clinical Trial Design

2021 ◽  
Author(s):  
Nina Mickelson Weldingh ◽  
Marte Rognstad Mellingsæter ◽  
Bendik Westlund Hegna ◽  
Jūratė Šaltytė Benth ◽  
Gunnar Einvik ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cognitive Impairment ◽  
Acute Care ◽  
Trial Design ◽  
Acute Care Hospital ◽  
Clinical Trial Design ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Care Hospital ◽  
Early Screening

Abstract Background: Frail older persons with cognitive impairment (CI) are at special risk of experiencing delirium during acute hospitalisation. The purpose of this study was to investigate whether a dementia-friendly hospital program contributes to improved detection and management of patients with CI and risk of delirium at an acute-care hospital in Norway. Furthermore, we aimed to explore whether the program affected the prevalence of delirium, pharmacological treatment, 30-day re-hospitalisation, 30-day mortality and institutionalisation afterwards. Methods: This study had a controlled clinical trial design with a historical control group. It was conducted at two different medical wards at a large acute-care hospital in Norway from September 2018 to December 2019. A total of 423 acute hospitalised patients 75 years of age or older were included in the study. Delirium screening and cognitive tests were recorded by research staff with the 4 ‘A’s Test (4AT) and the Confusion Assessment Measure (CAM), while demographic and medical information was recorded from the electronic medical records (EMR). Results: Implementation of the dementia-friendly hospital program did not show any significant changes in the identification of patients with CI. However, the share of patients screened with 4AT within 24 hours increased from 0% to 35.5% (P<.001). The proportion of the patients with CI identified by the clinical staff, who received measures to promote “dementia-friendly” care and reduce the risk for delirium increased by 32.2% (P<.001), compared to the control group. Furthermore, the number of patients with CI who were prescribed antipsychotic, hypnotic or sedative medications was reduced by 24.5% (P<.001). There were no differences in prevalence of delirium, 30-day readmission or 30-day mortality. Conclusions: A model for early screening and multifactorial non-pharmacological interventions for patients with CI and delirium may improve management of this patient group, and reduce prescriptions of antipsychotic, hypnotic and sedative medications. The implementation in clinical practice of early screening using quality improvement methodology deserves attention. Trial registration: The protocol of this study was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System with the registration number: NCT04737733 and date of registration: 03/02/2021.

Statistical modeling of a novel clinical trial design using neoadjuvant therapy (NAT) to personalize therapy in patients (pts) with triple-negative breast cancer (TNBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 595-595
Author(s):  
Stacy L. Moulder ◽  
Roland L. Bassett ◽  
Jason B White ◽  
Lei Huo ◽  
Senthil Damodaran ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Trial Design ◽  
Pathologic Complete Response ◽  
Clinical Trial Design ◽  
Trial Participation ◽  
Second Phase ◽  
Phase Ii Trials ◽  
Validation Data ◽  
Data Set ◽  
Experimental Drugs

595 Background: 40-50% of pts with TNBC develop pathologic complete response (pCR) with adriamycin/cyclophosphamide (AC)àtaxane (T) NAT; thus, most pts treated in randomized trials (RCTs) adding experimental drugs (ED) to standard NAT do not benefit from trial participation. A personalized trial design that enriches for non-pCR to standard NAT would diminish toxicity from ED in pts who do not need them and enrich ED in high-risk pts that are most likely to benefit. Methods: ARTEMIS (NCT02276443) is a non-randomized trial to study personalization of NAT in TNBC. Tumor biopsies were performed pre-NAT and volumetric change by ultrasound (VCU) after 4 cycles of AC (or upon clinical progression) assessed response. Pts with sensitive TNBC (VCU >=70% after AC) had T as the second phase of NAT. Pts with <70% VCU were offered phase II trials. pCR was assessed at surgical resection. 273 pts had available pCR status and 222 had complete data to generate a model predictive of response using multivariate logistic regression with common clinical factors. Data was randomly divided into training (n=111) and validation (n=111) sets. Results: 85 pts (38%) had pCR and VCU after AC x 4 was the strongest predictor of pCR. Other factors significant on multivariate analysis and included in the model were T stage (T1-4), stromal TIL, Ki67 and PD-L1. When applied to the validation data set, the accuracy of this model for predicting pCR was 76.6%, sensitivity 78.6% and specificity 75.4%. The PPV was 66.0% and the NPV was 85.2% with a ROC curve AUC of 82.4%. Using these data, ED exposure (table) was estimated for the ARTEMIS study design vs a 1:1 or a 2:1 RCT design (with an estimated pCR in control arm=40%), with a demonstrated benefit for personalization. Conclusions: This modeling indicates that personalization of NAT trials has the potential to enrich ED exposure for non-responsive disease as well as diminish ED exposure in pts likely to achieve pCR with standard NAT. Improved prediction of pCR would further enhance personalized trial design. Clinical trial information: NCT02276443 . [Table: see text]

Clinical Trial Design for Alcoholic Hepatitis

2017 ◽  
Vol 37 (04) ◽  
pp. 332-342 ◽  
Author(s):  
Gyongyi Szabo
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Trial Design ◽  
Alcoholic Hepatitis ◽  
Treatment Options ◽  
Clinical Trial Design ◽  
Therapeutic Interventions ◽  
Common Data Elements ◽  
Definition Of ◽  
Data Elements

AbstractAlcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months, treatment options are limited and ineffective. Recent advances on the understanding of the pathomechanisms of AH have identified numerous potential targets for new therapeutic interventions. Many of those targets are currently under preclinical testing and/or in human clinical trials for nonalcoholic steatohepatitis. Thus, the field of AH should be ready to launch new efforts and targeted clinical trials for this underserved patient population. There are remaining challenges in designing clinical trials in AH that include definition of the severity of disease, common data elements in clinical trial design, and selection of clinically meaningful endpoints. Future efforts and consensus meetings between regulatory agencies, academic and clinical experts, and industry will be instrumental to advance this emerging and greatly needed field of clinical investigations.

Sulfinpyrazone or Acetylsalicylic Acid to Prevent Postoperative Thrombus Formation in Arteriovenous Fistulas of Haemodialysis Patients

1979 ◽  
Author(s):  
F Albert ◽  
U Schmidt
Keyword(s):  
Side Effects ◽  
Acetylsalicylic Acid ◽  
Thrombus Formation ◽  
Significant Inhibition ◽  
High Rate ◽  
Controlled Clinical Trial ◽  
Arteriovenous Fistulas ◽  
Arteriovenous Shunts ◽  
Gastrointestinal Side Effects ◽  
Antithrombotic Efficacy

The effect of sulfinpyrazone (200 mg three times a day) and acetylsalicylic acid (500 mg three times a day) on the incidence of thrombosis of arteriovenous shunts was investigated in a controlled clinical trial. In 36 patients with chronic renal failure scheduled to begin haemodialysis the same operating team constructed a subcutaneous fistula in the distal forearm. During the first six weeks after the operation the antithrombotic efficacy proved to be good for both substances. No differences of thrombotic events between the two treatment groups were statistically significant. But in contrast to acetylsalicylic acid sulfinpyrazone made no significant inhibition of platelet - aggregation; sulfinpyrazone probably will prevent the clot formation by prolonging the shortened platelet survival in uraemic patients. In a high rate of patients given acetylsalicylic acid (10 out of 17) there were local bleeding and gastrointestinal side effects. In consequence we should prefer sulfinpyrazone, because in the sulfinpyrazone group side effects were minimal and in none patient withdrawal from the study was necessitated.

Integrating radiomics into clinical trial design

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Jessica J. Waninger ◽  
Michael D. Green ◽  
Catherine Cheze Le Rest ◽  
Benjamin Rosen ◽  
Issam El Naqa
Keyword(s):  
Clinical Trial ◽  
Trial Design ◽  
Clinical Trial Design
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