scholarly journals Detection of Clenbuterol-Induced Changes in Heart Rate Using At-Home Recorded Smartwatch Data: Randomized Controlled Trial

10.2196/31890 ◽  
2021 ◽  
Vol 5 (12) ◽  
pp. e31890
Author(s):  
Willem O Elzinga ◽  
Samantha Prins ◽  
Laura G J M Borghans ◽  
Pim Gal ◽  
Gabriel A Vargas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Heart Rate ◽  
Clinical Trials ◽  
Treatment Effects ◽  
Controlled Trial ◽  
Intraclass Correlation ◽  
Effect Sizes ◽  
Detectable Effect ◽  
Sleep State ◽  
Induced Changes

Background Although electrocardiography is the gold standard for heart rate (HR) recording in clinical trials, the increasing availability of smartwatch-based HR monitors opens up possibilities for drug development studies. Smartwatches allow for inexpensive, unobtrusive, and continuous HR estimation for potential detection of treatment effects outside the clinic, during daily life. Objective The aim of this study is to evaluate the repeatability and sensitivity of smartwatch-based HR estimates collected during a randomized clinical trial. Methods The data were collected as part of a multiple-dose, investigator-blinded, randomized, placebo-controlled, parallel-group study of 12 patients with Parkinson disease. After a 6-day baseline period, 4 and 8 patients were treated for 7 days with an ascending dose of placebo and clenbuterol, respectively. Throughout the study, the smartwatch provided HR and sleep state estimates. The HR estimates were quantified as the 2.5th, 50th, and 97.5th percentiles within awake and asleep segments. Linear mixed models were used to calculate the following: (1) the intraclass correlation coefficient (ICC) of estimated sleep durations, (2) the ICC and minimum detectable effect (MDE) of the HR estimates, and (3) the effect sizes of the HR estimates. Results Sleep duration was moderately repeatable (ICC=0.64) and was not significantly affected by study day (P=.83), clenbuterol (P=.43), and study day by clenbuterol (P=.73). Clenbuterol-induced changes were detected in the asleep HR as of the first night (+3.79 beats per minute [bpm], P=.04) and in the awake HR as of the third day (+8.79 bpm, P=.001). The median HR while asleep had the highest repeatability (ICC=0.70). The MDE (N=12) was found to be smaller when patients were asleep (6.8 bpm to 11.7 bpm) than while awake (10.7 bpm to 22.1 bpm). Overall, the effect sizes for clenbuterol-induced changes were higher while asleep (0.49 to 2.75) than while awake (0.08 to 1.94). Conclusions We demonstrated the feasibility of using smartwatch-based HR estimates to detect clenbuterol-induced changes during clinical trials. The asleep HR estimates were most repeatable and sensitive to treatment effects. We conclude that smartwatch-based HR estimates obtained during daily living in a clinical trial can be used to detect and track treatment effects. Trial Registration Netherlands Trials Register NL8002; https://www.trialregister.nl/trial/8002

scholarly journals Detection of Clenbuterol-Induced Changes in Heart Rate Using At-Home Recorded Smartwatch Data: Randomized Controlled Trial (Preprint)

2021 ◽  
Author(s):  
Willem O Elzinga ◽  
Samantha Prins ◽  
Laura G J M Borghans ◽  
Pim Gal ◽  
Gabriel A Vargas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Heart Rate ◽  
Clinical Trials ◽  
Treatment Effects ◽  
Controlled Trial ◽  
Intraclass Correlation ◽  
Effect Sizes ◽  
Detectable Effect ◽  
Sleep State ◽  
Induced Changes

BACKGROUND Although electrocardiography is the gold standard for heart rate (HR) recording in clinical trials, the increasing availability of smartwatch-based HR monitors opens up possibilities for drug development studies. Smartwatches allow for inexpensive, unobtrusive, and continuous HR estimation for potential detection of treatment effects outside the clinic, during daily life. OBJECTIVE The aim of this study is to evaluate the repeatability and sensitivity of smartwatch-based HR estimates collected during a randomized clinical trial. METHODS The data were collected as part of a multiple-dose, investigator-blinded, randomized, placebo-controlled, parallel-group study of 12 patients with Parkinson disease. After a 6-day baseline period, 4 and 8 patients were treated for 7 days with an ascending dose of placebo and clenbuterol, respectively. Throughout the study, the smartwatch provided HR and sleep state estimates. The HR estimates were quantified as the 2.5th, 50th, and 97.5th percentiles within awake and asleep segments. Linear mixed models were used to calculate the following: (1) the intraclass correlation coefficient (ICC) of estimated sleep durations, (2) the ICC and minimum detectable effect (MDE) of the HR estimates, and (3) the effect sizes of the HR estimates. RESULTS Sleep duration was moderately repeatable (ICC=0.64) and was not significantly affected by study day (<i>P</i>=.83), clenbuterol (<i>P</i>=.43), and study day by clenbuterol (<i>P</i>=.73). Clenbuterol-induced changes were detected in the asleep HR as of the first night (+3.79 beats per minute [bpm], <i>P</i>=.04) and in the awake HR as of the third day (+8.79 bpm, <i>P</i>=.001). The median HR while asleep had the highest repeatability (ICC=0.70). The MDE (N=12) was found to be smaller when patients were asleep (6.8 bpm to 11.7 bpm) than while awake (10.7 bpm to 22.1 bpm). Overall, the effect sizes for clenbuterol-induced changes were higher while asleep (0.49 to 2.75) than while awake (0.08 to 1.94). CONCLUSIONS We demonstrated the feasibility of using smartwatch-based HR estimates to detect clenbuterol-induced changes during clinical trials. The asleep HR estimates were most repeatable and sensitive to treatment effects. We conclude that smartwatch-based HR estimates obtained during daily living in a clinical trial can be used to detect and track treatment effects. CLINICALTRIAL Netherlands Trials Register NL8002; https://www.trialregister.nl/trial/8002

Proposals for Sample Size Calculation Programs

2007 ◽  
Vol 46 (06) ◽  
pp. 655-661 ◽  
Author(s):  
H. Heinzl ◽  
A. Benner ◽  
C. Ittrich ◽  
M. Mittlböck
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sample Size ◽  
Sample Size Calculation ◽  
Effect Sizes ◽  
Detectable Effect ◽  
Planning Stage ◽  
Type Iii ◽  
Error Risk ◽  
Q Values

Summary Objectives : Numerous sample size calculation programs are available nowadays. They include both commercial products as well as public domain and open source applications. We propose modifications for these programs in order to even better support statistical consultation during the planning stage of a two-armed clinical trial. Methods : Directional two-sided tests are commonly used for two-armed clinical trials. This may lead to a non-negligible Type III error risk in a severely underpowered study. In the case of a reasonably sized study the question for the so-called auxiliary alternative may evolve. Results : We propose that sample size calculation programs should be able to compute i) Type III errors and the so-called (q-values, ii) minimum sample sizes required to keep the (q-values below pre-specified levels, and iii) detectable effect sizes of the so-called auxiliary alternatives. Conclusions : Proposals iand ii are intended to help prevent irresponsibly underpowered clinical trials, whereas the proposal iii is meant as additional assistance for the planning of reasonably sized clinical trials.

scholarly journals Applicability of Dmax Method on Heart Rate Variability to Estimate the Lactate Thresholds in Male Runners

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Eduardo Marcel Fernandes Nascimento ◽  
Diego Antunes ◽  
Paulo Cesar do Nascimento Salvador ◽  
Fernando Klitzke Borszcz ◽  
Ricardo Dantas de Lucas
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Blood Lactate ◽  
Standard Error ◽  
Intraclass Correlation ◽  
Effect Sizes ◽  
Initial Speed ◽  
Limits Of Agreement ◽  
Aerobic Threshold ◽  
Post Hoc

Introduction. The purpose of this study was to evaluate the application of the Dmax method on heart rate variability (HRV) to estimate the lactate thresholds (LT), during a maximal incremental running test (MIRT). Methods. Nineteen male runners performed two MIRTs, with the initial speed at 8 km·h−1 and increments of 1 km·h−1 every 3 minutes, until exhaustion. Measures of HRV and blood lactate concentrations were obtained, and lactate (LT1 and LT2) and HRV (HRVTDMAX1 and HRVTDMAX2) thresholds were identified. ANOVA with Scheffe’s post hoc test, effect sizes (d), the bias ± 95% limits of agreement (LoA), standard error of the estimate (SEE), Pearson’s (r), and intraclass correlation coefficient (ICC) were calculated to assess validity. Results. No significant differences were observed between HRVTDMAX1 and LT1 when expressed for speed (12.1 ± 1.4 km·h−1 and 11.2 ± 2.1 km·h−1; p=0.55; d = 0.45; r = 0.46; bias ± LoA = 0.8 ± 3.7 km·h−1; SEE = 1.2 km·h−1 (95% CI, 0.9–1.9)). Significant differences were observed between HRVTDMAX2 and LT2 when expressed for speed (12.0 ± 1.2 km·h−1 and 14.1 ± 2.5 km·h−1; p=0.00; d = 1.21; r = 0.48; bias ± LoA = −1.0 ± 1.8 km·h−1; SEE = 1.1 km·h−1 (95% CI, 0.8–1.6)), respectively. Reproducibility values were found for the LT1 (ICC = 0.90; bias ± LoA = −0.7 ± 2.0 km·h−1), LT2 (ICC = 0.97; bias ± LoA = −0.1 ± 1.1 km·h−1), HRVTDMAX1 (ICC = 0.48; bias ± LoA = −0.2 ± 3.4 km·h−1), and HRVTDMAX2 (ICC = 0.30; bias ± LoA = 0.3 ± 3.5 km·h−1). Conclusions. The Dmax method applied over a HRV dataset allowed the identification of LT1 that is close to aerobic threshold, during a MIRT.

Barriers to participation in breast cancer trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6593-6593
Author(s):  
O. Herasme ◽  
J. Goldberg ◽  
R. Sandoval ◽  
C. Harris ◽  
Y. Ortiz-Pride ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Child Care ◽  
Cancer Patients ◽  
Controlled Trial ◽  
Demographic Factors ◽  
Trial Participation ◽  
Barriers To Participation ◽  
Cancer Trials

6593 Background: Clinical cancer trials allow investigators to test the effectiveness and safety of new cancer drugs and treatments. Historically, fewer that 5% of cancer patients have participated in clinical trials. The purpose of this study was to assess attitudes, beliefs, and practical barriers to clinical trial recruitment. Methods: Women were recruited in the Herbert Irving Comprehensive Cancer Center while waiting for routine breast screening or for oncology care in connection with a diagnosis of breast cancer. The 29-item survey questionnaire covered demographic factors, prior cancer diagnosis or risk factors, past experience with clinical trials if any, willingness to participate in different types of trials, and attitudinal and practical barriers to participation. Results: Of 329 respondents, 48.9% were non- Hispanic white, 10.9% non-Hispanic black, 34.9% Hispanic, and 5.30% other/unknown. The mean age of participants was 52.5 (SD=12.1). Of 131 (39.8%) participants reporting that they had been asked to participate in clinical trial, 82 were white, 17 black and 32 Hispanic. Of those who enrolled, 64 were white, 14 were black, and 19 Hispanic. Of those asked to participate 56/63 breast cancer patients (88.9%) and 44/68 others (64.7%) enrolled (P=0.002). Of 48 who reported that they had child care responsibilities, 33 enrolled (68.8) compared to 67/83 (80.7%) of those without such responsibilities (P=0.07). Of the total sample, 88/220 (40.0%) of those without childcare responsibilities but only 32/109 (29.4) said they would be willing to participate in a placebo-controlled trial. Respondents were twice as likely to say they would participate in a trial comparing two active agents as a placebo-controlled trial. Conclusion: Our findings suggest that being asked to participate in a clinical trial may be associated with demographic factors, and that specific circumstances, such as child care responsibilities, may also affect trial participation. Awareness of these barriers may help investigators to develop effective strategies for overcoming them and for improving trial participation overall. No significant financial relationships to disclose.

Trifluoperazine (“Stelazine”) a Controlled Clinical Trial in Chronic Schizophrenia

1961 ◽  
Vol 107 (447) ◽  
pp. 250-257 ◽  
Author(s):  
W. J. Stanley ◽  
D. Walton
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Controlled Trial ◽  
Pernicious Anaemia ◽  
Chronic Schizophrenia ◽  
Mental Illnesses ◽  
Controlled Clinical Trial ◽  
Vitamin B ◽  
Uncontrolled Trial ◽  
New Compounds

So many new compounds are now being introduced for the treatment of psychiatric disorders that it is difficult for the clinician to assess the accuracy of the claims made for them. If a form of therapy is one hundred per cent. effective in a disease which was previously one hundred per cent. fatal, for example vitamin B12 in pernicious anaemia, the question of a controlled trial does not arise. But even the manufacturers do not claim such a degree of effectiveness for drugs advocated for the treatment of mental illnesses, and in addition the natural course of such illnesses is very variable, so that it is essential that clinical trials of these drugs should be controlled. Foulds (1958) has reviewed British and American clinical trials of drugs in psychiatry during the years 1951 to 1956, and has shown that the less controlled a trial, the more likely it is to result in a favourable report on the drug being tested, presumably because of bias on the part of the clinician. Forrester (1958), however, on the basis of a completely uncontrolled trial of Stelazine on only twenty-five patients, concluded that “the amount of improvement in a few cases was not sufficient to encourage the further use of the drug”.

scholarly journals Challenges for funders in monitoring compliance with policies on clinical trials registration and reporting: analysis of funding and registry data in the UK

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e035283 ◽  
Author(s):  
Rachel L Knowles ◽  
Kam Pou Ha ◽  
Julia Mueller ◽  
Frances Rawle ◽  
Rosa Parker
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Medical Research ◽  
Research Funding ◽  
Controlled Trial ◽  
Monitoring Systems ◽  
Clinical Trial Registry ◽  
Funding Body ◽  
The Uk ◽  
Research Funding Body

ObjectivesTo evaluate compliance by researchers with funder requirements on clinical trial transparency, including identifying key areas for improvement; to assess the completeness, accuracy and suitability for annual compliance monitoring of the data routinely collected by a research funding body.DesignDescriptive analysis of clinical trials funded between February 2011 and January 2017 against funder policy requirements.SettingPublic medical research funding body in the UK.Data sourcesRelevant clinical trials were identified from grant application details, post-award grant monitoring systems and the International Standard Randomised Controlled Trial Number (ISRCTN) registry.Main outcome measureThe proportion of all Medical Research Council (MRC)-funded clinical trials that were (a) registered in a clinical trial registry and (b) publicly reported summary results within 2 years of completion.ResultsThere were 175 grants awarded that included a clinical trial and all trials were registered in a public trials registry. Of 62 trials completed for over 24 months, 42 (68%) had publicly reported the main findings by 24 months after trial completion; 18 of these achieved this within 12 months of completion. 11 (18%) trials took >24 months to report and 9 (15%) completed trials had not yet reported findings. Five datasets were shared with other researchers.ConclusionsCompliance with the funder policy requirements on trial registration was excellent. Reporting of the main findings was achieved for most trials within 24 months of completion; however, the number of unreported trials remains a concern and should be a focus for future funder policy initiatives. Identifying trials from grant management and grant monitoring systems was challenging therefore funders should ensure investigators reliably provide trial registries with information and regularly update entries with details of trial publications and protocols.

The future of multiple sclerosis therapies: redesigning multiple sclerosis clinical trials in a new therapeutic eraa

2005 ◽  
Vol 11 (6) ◽  
pp. 669-676 ◽  
Author(s):  
H F McFarland ◽  
S C Reingold
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Controlled Trial ◽  
International Workshop ◽  
Regulatory Approval ◽  
Ethical Considerations ◽  
New Therapies ◽  
Clinical Trial Designs ◽  
New Strategies

Due to past success in testing and gaining regulatory approval for a variety of therapies in multiple sclerosis (MS), the conduct of future clinical trials has become increasingly problematic. An international workshop has met to discuss the issues facing the MS clinical trial community and to examine possible new strategies for the design of trials. Particular focus has been placed on trials that either avoid the use of a placebo because of ethical considerations or on designs that allow new therapies to be studied more rapidly or with fewer patients than needed in a conventional placebo-controlled trial. The discussions resulting from the workshop should provide a basis for the examination and implementation of innovative clinical trial designs in MS.

Clinical trial design: the neglected problem of asymmetrical transfer in cross-over trials

1983 ◽  
Vol 13 (4) ◽  
pp. 867-873 ◽  
Author(s):  
Keith Millar
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Trial Design ◽  
Treatment Effects ◽  
Clinical Trial Design ◽  
Analyse Data ◽  
Order Of Administration

SynopsisThe paper illustrates drawbacks of the popular cross-over design in clinical trials in psychiatry where treatment effects become distorted by, and confounded with, the effects of their order of administration. It is argued that research workers should analyse data from cross-over trials for asymmetries due to order of treatment and seriously doubt the reliability of data if such effects are found. The problem is avoided by the use of separate-groups designs.

scholarly journals Real-world effects of ACE inhibitors and Angiotensin Receptor Blockers: protocol for an emulation study of the ONTARGET trial using electronic health records

2021 ◽  
Author(s):  
Paris Baptiste ◽  
Angel YS Wong ◽  
Anna Schultze ◽  
Marianne Cunnington ◽  
Johannes FE Mann ◽  
...  
Keyword(s):  
Primary Care ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Cohort Study ◽  
Treatment Effects ◽  
Dual Therapy ◽  
List Type ◽  
Exclusion Criteria ◽  
Eligibility Criteria ◽  
Specific Effects

ABSTRACTIntroductionCardiovascular disease (CVD) is a leading cause of death globally, responsible for nearly 18 million deaths worldwide in 2017. Medications to reduce the risk of cardiovascular events are prescribed based upon evidence from clinical trials which explore treatment effects in an indicated sample of the general population. However, these results may not be fully generalisable because of trial eligibility criteria that generally restrict to younger patients with fewer comorbidities. Therefore, evidence of effectiveness of medications for groups underrepresented in clinical trials such as those over 75 years, from ethnic minority backgrounds or with low kidney function may be limited.The ONTARGET trial studied the effects of an angiotensin-converting-enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) separately and in combination on cardiovascular event reduction. Using individual anonymised data from this study, in collaboration with the original trial investigators, we aim to investigate clinical trial replicability within routinely-collected patient data. If the original trial results are replicable, we will assess treatment effects and risk in groups underrepresented and excluded from the original clinical trial.Methods and analysisWe will develop a cohort analogous to the ONTARGET trial within CPRD between 1 January 2001 to 31 July 2019 using the trial eligibility criteria and propensity score matching. The primary outcome, as in the trial, is a composite of cardiovascular death, non-fatal MI, non-fatal stroke and hospitalisation for congestive heart-failure, examined in a time-to-event analysis. If results from the cohort study fall within pre-specified limits, we will expand the cohort to include those with advanced kidney dysfunction and increase the proportion of elderly participants and those from ethnicity minority backgrounds.We will then compare the risk of adverse events and association with long-term outcomes in the clinical trial, with that seen in a directly comparable sample of those attending NHS primary care.STRENGTHS AND LIMITATIONSStrengthsLarge cohort study giving power to look at effects within subgroups underrepresented in the clinical trialAccess to individual patient level data from a landmark trial to support creation of a trial-analogous cohortNovelty of studying treatment effects of dual therapy in real-world settingsLimitationsThere may be differences between the trial population and the observational cohort due to the level of detail on inclusion/exclusion criteria provided by the trialDrug-specific effects are unlikely to be able to be investigated due to small numbers in the dual-therapy arm: class-specific effects will be studied insteadMisclassification by primary care coding may lead to inaccurate replication of trial inclusion and exclusion criteria.

scholarly journals O-EGS06 Trials and Tribulations: Educational Impact and Recommendations from the Implementation of Student-Led Recruitment in a Clinical Trial

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
William Cambridge ◽  
Aya Riad ◽  
David Henshall ◽  
Heather McAdam ◽  
James Glasbey ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Medical Students ◽  
Academic Career ◽  
Controlled Trial ◽  
Recruitment Rate ◽  
University Teaching ◽  
Teaching Hospitals ◽  
Free Text ◽  
Training Support

Abstract Background Medical students have an essential role in medical research, yet often feel unprepared and lack opportunities for involvement as recruiters within research studies. This study aimed to understand the educational effect of involvement in clinical trial recruitment on medical students, and to derive generalisable future recommendations. Methods Tracking wound infection with smartphone technology (TWIST) was a randomised controlled trial enrolling adult emergency abdominal surgery patients across two university teaching hospitals. All recruiters underwent pre-recruitment training based on “Generating Student Recruiters for Randomised Trials” (GRANULE) principles, and completed pre-and post-recruitment surveys. Respondent agreement with statements were assessed using 5-point Likert scales (from 1 [“strongly disagree”] to 5 [“strongly agree”]). Quantitative data were analysed using paired t-tests to compare differences pre- and post-involvement, and a thematic analysis approach adopted for anonymised free-text answers. Results Of 492 patients recruited to TWIST from 2016 to 2020, 86.0% (n = 423) were recruited by medical students. Following student involvement, the monthly recruitment rate tripled (4.8 to 15.7 patients). Thirty student recruiters (96.8%), completed both surveys, reporting significant improvements in clinical and academic competencies. This included increased confidence in gaining and documenting consent, as well as interest in pursuing a clinical-academic career. Over half (58.2%) felt the undergraduate curriculum had not prepared them for involvement in clinical trials (mean:2.47, SD: 0.94). There were three emergent themes regarding recommendations for involvement of students, based on their engagement, preparation, and support during recruitment. Conclusions Student recruitment in clinical trials is feasible and provides a route to developing a research-active medical workforce. It also accelerates recruitment to clinical trials, as well as benefiting students through development of clinical competencies and provision of additional exposure to research. Adequate training, support, and selection of suitable trials are essential for successful student engagement.

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