Study design, result posting, and publication of late-stage cardiovascular trials

2020 ◽  
Author(s):  
Chris J Kapelios ◽  
Huseyin Naci ◽  
Panos E Vardas ◽  
Elias Mossialos
Keyword(s):  
Study Design ◽  
Late Stage ◽  
Scientific Literature ◽  
Late Phase ◽  
Open Label ◽  
Clinical Endpoints ◽  
Explanatory Factors ◽  
Study Protocols ◽  
Study Results ◽  
Design Result

Abstract Aims Pre-registration of study protocols in accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited. Methods and results We searched for interventional, late-phase cardiovascular disease (CVD) studies in adults registered in Clinicaltrials.gov. first posted after 1 January 2013 and completed up to 31 December 2018. Data on study design, result reporting, and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined. In total, 250 CVD trials were included in the analysis. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. One hundred and seventy-nine trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. The most common primary outcomes were non-clinical endpoints (76.0%), with only 17% of studies evaluating clinical endpoints. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P < 0.001 and 55.0% vs. 26.3%, P = 0.033, respectively). Sixty-three studies (25.2%) had results posted on clinicaltrials.gov, and 116 (46.4%) had results published in the scientific literature. In multivariate analysis, industry sponsorship was statistically significantly associated with results posting [odds ratio (OR): 3.38; 95% confidence interval (CI): 1.56–7.30, P = 0.002] and publication (OR: 0.41; 95% CI: 0.23–0.75, P = 0.004). Conclusion Among late-stage cardiovascular trials only one-fourth had results posted on clinicaltrials.gov and <50% had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Industry-sponsored studies were more likely to have their results posted, but less likely to have their results published in the scientific literature.

Study design, result reporting and publication of late-stage cardiovascular trials

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Kapelios ◽  
H Naci ◽  
P Vardas ◽  
E Mossialos
Keyword(s):  
Study Design ◽  
Late Stage ◽  
Late Phase ◽  
Phase Iii ◽  
Open Label ◽  
Explanatory Factors ◽  
Study Protocols ◽  
Study Results ◽  
Artery Disease ◽  
Design Result

Abstract Introduction Preregistration of study protocols in publicly accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on the characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited. Methods The purpose of this study was to perform a comprehensive analysis of the characteristics of late-stage, cardiovascular disease (CVD) trials registered in Clinicaltrials.gov. We searched for interventional, late-phase (annotated as phase III) CVD studies in adults first posted after 1/1/2013 and completed up to 31/12/2018. Data on study design, result reporting, result spinning and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined. Results The search yielded 352 studies. One hundred were excluded from further analysis because they were misclassified as CVD studies, while 2 were excluded as duplicate entries. In total, 250 CVD trials were included in the analysis. The most commonly studied fields were hypertension, coronary artery disease and heart failure. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. 179 trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P<0.001 and 55.0% vs. 26.3%, P=0.033, respectively). Sixty three studies (25.2%) had results posted on clinicaltrials.gov, and 116 (46.4%) had results published in the scientific literature. No clear indication of result spinning was found in 96 (85%) of published studies. In multivariate analysis, industry sponsorship was statistically significantly associated with results posting (OR: 3.56; 95% CI:1.67–7.60, P=0.001) and publication (OR: 0.41; 95% CI:0.23–0.75, P=0.004). Results spinning was associated with confirmation of the primary hypothesis (OR: 0.23; 95% CI: 0.07–0.75, P=0.015) and results posting (OR: 0.08; 95% CI: 0.01–0.65, P=0.018). Conclusions Among late-stage cardiovascular trials only 1/4 had their results posted on clinicaltrials.gov and less than half had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Having industry as a sponsor was independently associated with increased likelihood of results posting, but decreased likelihood of results publication. Results reporting was significantly associated with lower risk of results spinning. Funding Acknowledgement Type of funding source: None

The association of adaptive early phase study design and late phase study results in oncology using clinicaltrials.gov data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14078-e14078
Author(s):  
Donna Elise Levy ◽  
Srikanta Banerjee ◽  
Fred K Tabung
Keyword(s):  
Clinical Trials ◽  
Study Design ◽  
Late Stage ◽  
Early Phase ◽  
Late Phase ◽  
Adaptive Methods ◽  
Positive Outcome ◽  
Cancer Type ◽  
Traditional Methods ◽  
Phase Study

e14078 Background: Traditional methods such as the 3+3 design developed in the 1940s continue to be used in the majority of early phase oncology studies. Researchers have found that the traditional methods identify the appropriate dose level only 30% of the time. Patients are also exposed to sub-therapeutic doses due to the conservative methods. With these limitations on traditional design options, innovative methods need to be developed, adopted and assessed. Methods: This quantitative study assessed the association of the design methods (adaptive versus traditional) used for early phase oncology studies (adaptive versus traditional) and the outcome of late stage clinical trials. Differences by cancer type and by drug classification were also assessed. A sample of studies for this analysis was extracted from the National Institute of Health Clinical registry and results database. The data used for the analysis was extracted by the Clinical Trials Transformation Initiative (CTTI) Aggregate Analysis of ClinicalTrials.gov (AACT). Results: When assessing study design and outcome, there were lower odds of a positive outcome when adaptive methods were used though this association was not statistically significant (OR [95% highest posterior density (HPD)]:0.66 [0.20, 1.21]). Among the different drug types, using adaptive compared to traditional methods was associated with significantly higher odds of a positive outcome for taxanes, OR: 2.75, 95% HPD: 1.01, 5.16) and other, OR: 3.23, 95% HPD: 1.58, 5.46) but no association among studies of monoclonal antibodies or protein kinase inhibitors. There were no significant associations between early phase study design and outcome in late phase studies by cancer type (lung, breast, other). Conclusions: While results associated with the use of adaptive methods were not significant, further research should be conducted using all completed oncology clinical trials in the database to more precisely determine the relationship between adaptive study design in early phase oncology studies and outcomes in late stage studies. In addition, improvements in traditional versus adaptive design capture in the ClinicalTrials.gov database needs to be considered.

Design process for serious activities inspired by play and games: a problem solving with a board game from disengamement and gamification processes (Preprint)

2020 ◽  
Author(s):  
Stéphane Goria ◽  
Louise Dupet ◽  
Maëva Négroni ◽  
Gabriel Sega ◽  
Philippe Arnoux ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Serious Games ◽  
Diagnostic Method ◽  
Scientific Literature ◽  
Imaging Techniques ◽  
Point Of View ◽  
Board Game ◽  
Advantages And Disadvantages ◽  
Design Result

BACKGROUND most serious games and other game-based tools are designed as digital games or escape games. They are designed for learning or sometimes in the field of medicine as an aid to care. However, they can also be seen as an aid to research, in our case, to evaluate the advantages and disadvantages of imaging techniques for cancer detection. OBJECTIVE we present a case study of action research on the design of a serious board game intended to consider the advantages and weaknesses of a diagnostic method in a different ways. The goal was to better understand the principles of designing a tool using game or play. METHODS we explicitly implemented another process than gamification to develop a structure reminiscent of the game to highlight the strengths and weaknesses of different imaging techniques from the point of view of the respondents (in this case specialists not directly involved in the project). Based on this feedback and the scientific literature on this subject, we detail the main categories of games and games developed for serious use in order to understand their differences. Concerning the cancer research part to which game contributes, our method is based on questions asked to experts and practitioners of this specialty. RESULTS an expert point of view translation tool in the form of a game has been realized to apprehend a research in a different way. CONCLUSIONS we show with the help of a diagram, some possible design paths leading to this type of design result including two hidden dimensions to consider (the awareness of the game or play by the "player" and his role as a contributor or recipient).

scholarly journals Protocol for a randomised clinical trial of multimodal postconcussion symptom treatment and recovery: the Concussion Essentials study

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e041458
Author(s):  
Vicki Anderson ◽  
Vanessa C Rausa ◽  
Nicholas Anderson ◽  
Georgia Parkin ◽  
Cathriona Clarke ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Randomised Clinical Trial ◽  
Normal Activity ◽  
Secondary Outcome ◽  
Open Label ◽  
Human Research Ethics ◽  
Postconcussive Symptoms ◽  
Study Results ◽  
Registration Number ◽  
Initial Injury

IntroductionWhile most children recover from a concussion shortly after injury, approximately 30% experience persistent postconcussive symptoms (pPCS) beyond 1-month postinjury. Existing research into the treatment of pPCS have evaluated unimodal approaches, despite evidence suggesting that pPCS likely represent an interaction across various symptom clusters. The primary aim of this study is to evaluate the effectiveness of a multimodal, symptom-tailored intervention to accelerate symptom recovery and increase the proportion of children with resolved symptoms at 3 months postconcussion.Methods and analysisIn this open-label, assessor-blinded, randomised clinical trial, children with concussion aged 8–18 years will be recruited from The Royal Children’s Hospital (The RCH) emergency department, or referred by a clinician, within 17 days of initial injury. Based on parent ratings of their child’s PCS at ~10 days postinjury, symptomatic children (≥2 symptoms at least 1-point above those endorsed preinjury) will undergo a baseline assessment at 3 weeks postinjury and randomised into either Concussion Essentials (CE, n=108), a multimodal, interdisciplinary delivered, symptom-tailored treatment involving physiotherapy, psychology and education, or usual care (UC, n=108) study arms. CE participants will receive 1 hour of intervention each week, for up to 8 weeks or until pPCS resolve. A postprogramme assessment will be conducted at 3 months postinjury for all participants. Effectiveness of the CE intervention will be determined by the proportion of participants for whom pPCS have resolved at the postprogramme assessment (primary outcome) relative to the UC group. Secondary outcome analyses will examine whether children receiving CE are more likely to demonstrate resolution of pPCS, earlier return to normal activity, higher quality of life and a lower rate of utilisation of health services, compared with the UC group.Ethics and disseminationEthics were approved by The RCH Human Research Ethics Committee (HREC: 37100). Parent, and for mature minors, participant consent, will be obtained prior to commencement of the trial. Study results will be disseminated at international conferences and international peer-reviewed journals.Trial registration numberACTRN12617000418370; pre-results.

scholarly journals Robust Step Detection from Different Waist-Worn Sensor Positions: Implications for Clinical Studies

2020 ◽  
Vol 4 (1) ◽  
pp. 50-58
Author(s):  
Matthias  Tietsch ◽  
Amir Muaremi ◽  
Ieuan Clay ◽  
Felix Kluge ◽  
Holger Hoefling ◽  
...  
Keyword(s):  
Clinical Study ◽  
Clinical Studies ◽  
Neurological Diseases ◽  
Human Gait ◽  
Robust Solution ◽  
Step Detection ◽  
Study Protocols ◽  
Study Results ◽  
Wide Range ◽  
The Impact

Analyzing human gait with inertial sensors provides valuable insights into a wide range of health impairments, including many musculoskeletal and neurological diseases. A representative and reliable assessment of gait requires continuous monitoring over long periods and ideally takes place in the subjects’ habitual environment (real-world). An inconsistent sensor wearing position can affect gait characterization and influence clinical study results, thus clinical study protocols are typically highly proscriptive, instructing all participants to wear the sensor in a uniform manner. This restrictive approach improves data quality but reduces overall adherence. In this work, we analyze the impact of altering the sensor wearing position around the waist on sensor signal and step detection. We demonstrate that an asymmetrically worn sensor leads to additional odd-harmonic frequency components in the frequency spectrum. We propose a robust solution for step detection based on autocorrelation to overcome sensor position variation (sensitivity = 0.99, precision = 0.99). The proposed solution reduces the impact of inconsistent sensor positioning on gait characterization in clinical studies, thus providing more flexibility to protocol implementation and more freedom to participants to wear the sensor in the position most comfortable to them. This work is a first step towards truly position-agnostic gait assessment in clinical settings.

scholarly journals AGILE: a seamless phase I/IIa platform for the rapid evaluation of candidates for COVID-19 treatment: an update to the structured summary of a study protocol for a randomised platform trial letter

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gareth O. Griffiths ◽  
Richard FitzGerald ◽  
Thomas Jaki ◽  
Andrea Corkhill ◽  
Helen Reynolds ◽  
...  
Keyword(s):  
Phase I ◽  
Early Stage ◽  
Late Phase ◽  
Optimum Dose ◽  
Open Label ◽  
Link Type ◽  
Hospitalised Patients ◽  
Volunteer Study ◽  
The Uk ◽  
Phase Trial

Abstract Background There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/design AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol. Discussion Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tocilizumab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registration EudraCT Number: 2020-001860-27 14 March 2020 ClinicalTrials.gov Identifier: NCT04746183 19 February 2021 ISRCTN reference: 27106947

Safety of phosphatidylserine containing omega3 fatty acids in ADHD children: A double-blind placebo-controlled trial followed by an open-label extension

2013 ◽  
Vol 28 (6) ◽  
pp. 386-391 ◽  
Author(s):  
I. Manor ◽  
A. Magen ◽  
D. Keidar ◽  
S. Rosen ◽  
H. Tasker ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Rating Scale ◽  
Controlled Trial ◽  
Study Groups ◽  
Open Label ◽  
Double Blind ◽  
Blood Biochemical ◽  
Study Results ◽  
Open Label Extension ◽  
Safety Parameters

AbstractObjective:To evaluate the safety of phosphatidylserine (PS) enriched with omega3 fatty acids, mainly eicosapentaenoic (PS-Omega3) in children with attention-deficit hyperactivity disorder (ADHD).Methods:Two hundred children diagnosed with ADHD were randomised to receive either PS-Omega3 (300 mg PS-Omega3/day) or placebo for 15 weeks. One hundred and fifty children continued into an open-label extension for an additional 15 weeks in which they all consumed PS-Omega3 (150 mg PS-Omega3/day). Standard blood biochemical and haematological safety parameters, blood pressure, heart rate, weight and height were evaluated. Adverse events and the Side Effect Rating Scale were also assessed.Results:One hundred and sixty-two participants completed the double-blind phase. No significant differences were noted between the two study groups in any of the safety parameters evaluated. One hundred and forty participants completed the open-label phase. At the end of this phase, no significant changes from baseline were observed in any of the studied parameters among participants who consumed PS-Omega3 for 30 weeks.Conclusions:Study results demonstrate that consumption of PS-Omega3 by children with ADHD, as indicated in a 30-week evaluation period, is safe and well tolerated, without any negative effect on body weight or growth.

scholarly journals Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics

2016 ◽  
Vol 50 ◽  
pp. 5-15 ◽  
Author(s):  
George L. Jackson ◽  
Morris Weinberger ◽  
Miriam A. Kirshner ◽  
Karen M. Stechuchak ◽  
Stephanie D. Melnyk ◽  
...  
Keyword(s):  
Disease Management ◽  
Randomized Trial ◽  
Study Design ◽  
Open Label ◽  
Sample Characteristics ◽  
Baseline Sample

scholarly journals Treatment of early-stage breast cancer with percutaneous thermal ablation, an open-label randomised phase 2 screening trial: rationale and design of the THERMAC trial

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e052992
Author(s):  
Elles M F van de Voort ◽  
Gerson M Struik ◽  
Linetta B Koppert ◽  
Adriaan Moelker ◽  
Reno Debets ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Thermal Ablation ◽  
Surgical Excision ◽  
Maximum Diameter ◽  
Phase 2 ◽  
Open Label ◽  
Phase 3 ◽  
Complete Ablation ◽  
Study Results ◽  
Screening Trial

IntroductionBreast cancer is the most frequently diagnosed malignancy worldwide but almost half of the patients have an excellent prognosis with a 5-year survival rate of 98%–99%. These patients could potentially be treated with thermal ablation to avoid surgical excision, reduce treatment-related morbidity and increase patients’ quality of life without jeopardising treatment effectiveness. Previous studies showed highest complete ablation rates for radiofrequency, microwave and cryoablation. However, due to heterogeneity among studies, it is unknown which of these three techniques should be selected for a phase 3 comparative study.Methods and analysisThe aim of this phase 2 screening trial is to determine the efficacy rate of radiofrequency, microwave and cryoablation with the intention to select one treatment for further testing in a phase 3 trial. Additionally, exploratory data are obtained for the phase 3 trial. The design is a multicentre open-label randomised phase 2 screening trial. Patients with unifocal, invasive breast cancer with a maximum diameter of 2 cm without lymph node or distant metastases are included. Triple negative, Bloom-Richardson grade 3 tumours and patients with an indication for neoadjuvant chemotherapy will be excluded. Included patients will be allocated to receive one of the three thermal ablation techniques. Three months later surgical excision will be performed to determine the efficacy of thermal ablation. Treatment efficacy in terms of complete ablation rate will be assessed with CK 8/18 and H&E staining. Secondary outcomes include feasibility of the techniques in an outpatient setting, accuracy of MRI for complete ablation, patient satisfaction, adverse events, side effects, cosmetic outcome, system usability and immune response.Ethics and disseminationThis study protocol was approved by Medical Research Ethics Committee of the Erasmus Medical Center, Rotterdam, the Netherlands. Study results will be submitted for publication in peer-reviewed journals.Trial registration numberNL9205 (www.trialregister.nl); Pre-results.

scholarly journals AGILE: A Seamless Phase I/IIa Platform for the Rapid Evaluation of Candidates for COVID-19 treatment: An update to the structured summary of a study protocol for a randomised platform trial letter

2021 ◽  
Author(s):  
Gareth Owen Griffiths ◽  
Richard FitzGerald ◽  
Thomas Jaki ◽  
Andrea Corkhill ◽  
Helen Reynolds ◽  
...  
Keyword(s):  
Phase I ◽  
Early Stage ◽  
Late Phase ◽  
Optimum Dose ◽  
Open Label ◽  
University Of Oxford ◽  
Hospitalised Patients ◽  
Volunteer Study ◽  
The Uk ◽  
Phase Trial

Abstract Background:There is an urgent unmet clinical need for the identification of novel therapeutics for the treatment of COVID-19. A number of COVID-19 late phase trial platforms have been developed to investigate (often repurposed) drugs both in the UK and globally (e.g. RECOVERY led by the University of Oxford and SOLIDARITY led by WHO). There is a pressing need to investigate novel candidates within early phase trial platforms, from which promising candidates can feed into established later phase platforms. AGILE grew from a UK-wide collaboration to undertake early stage clinical evaluation of candidates for SARS-CoV-2 infection to accelerate national and global healthcare interventions. Methods/Design:AGILE is a seamless phase I/IIa platform study to establish the optimum dose, determine the activity and safety of each candidate and recommend whether it should be evaluated further. Each candidate is evaluated in its own trial, either as an open label single arm healthy volunteer study or in patients, randomising between candidate and control usually in a 2:1 allocation in favour of the candidate. Each dose is assessed sequentially for safety usually in cohorts of 6 patients. Once a phase II dose has been identified, efficacy is assessed by seamlessly expanding into a larger cohort. AGILE is completely flexible in that the core design in the master protocol can be adapted for each candidate based on prior knowledge of the candidate (i.e. population, primary endpoint and sample size can be amended). This information is detailed in each candidate specific trial protocol of the master protocol.Discussion:Few approved treatments for COVID-19 are available such as dexamethasone, remdesivir and tociluzimab in hospitalised patients. The AGILE platform aims to rapidly identify new efficacious and safe treatments to help end the current global COVID-19 pandemic. We currently have three candidate specific trials within this platform study that are open to recruitment. Trial registrations:EudraCT Number: 2020-001860-27 14th March 2020 ClinicalTrials.gov Identifier: NCT04746183ISRCTN reference: 27106947

Sign in / Sign up

Export Citation Format

Share Document