Adaptive designs undertaken in clinical research: a review of registered clinical trials

Adaptive designs have the potential to improve efficiency in the evaluation of new medical treatments in comparison to traditional fixed sample size designs. However, they are still not widely used in practice in clinical research. Little research has been conducted to investigate what adaptive designs are being undertaken. This review highlights the current state of registered adaptive designs and their characteristics. The review looked at phase II, II/III and III trials registered on ClinicalTrials.gov from 29 February 2000 to 1 June 2014, supplemented with trials from the National Institute for Health Research register and known adaptive trials. A range of adaptive design search terms were applied to the trials extracted from each database. Characteristics of the adaptive designs were then recorded including funder, therapeutic area and type of adaptation. The results in the paper suggest that the use of adaptive designs has increased. They seem to be most often used in phase II trials and in oncology. In phase III trials, the most popular form of adaptation is the group sequential design. The review failed to capture all trials with adaptive designs, which suggests that the reporting of adaptive designs, such as in clinical trials registers, needs much improving. We recommend that clinical trial registers should contain sections dedicated to the type and scope of the adaptation and that the term 'adaptive design' should be included in the trial title or at least in the brief summary or design sections

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Additional file 3 of Adaptive designs undertaken in clinical research: a review of registered clinical trials

Case studies. XLSX file containing a list of the trials used in the review. Trial number, title and URL are provided. (XLSX 35.2 kb

Additional file 1 of Adaptive designs undertaken in clinical research: a review of registered clinical trials

Search terms. PDF with a table of the final selection of search terms used in the review. (PDF 6.19 kb

Additional file 2 of Adaptive designs undertaken in clinical research: a review of registered clinical trials

Table of summary statistics. PDF containing a table of summary statistics by phase and funder type. Counts and percentages are presented for categorical variables whilst medians and interquartile ranges are presented for continuous variables. (PDF 19.5 kb

MIGHTEE-H i:The M_{H i}- M_∗relation over the last billion years

We study the relation over the last billion years using the MIGHTEE-H i sample. We first model the upper envelope of the relation with a Bayesian technique applied to a total number of 249 H i-selected galaxies, without binning the data sets, while taking account of the intrinsic scatter. We fit the envelope with both linear and non-linear models, and find that the non-linear model is preferred over the linear one with a measured transition stellar mass of log10(M∗/M⊙) = 9.15 ± 0.87, beyond which the slope flattens. This finding supports the view that the lack of H i gas is ultimately responsible for the decreasing star formation rate observed in the massive main-sequence galaxies. For spirals alone, which are biased towards the massive galaxies in our sample, the slope beyond the transition mass is shallower than for the full sample, indicative of distinct gas processes ongoing for the spirals/high-mass galaxies from other types with lower stellar masses. We then create mock catalogues for the MIGHTEE-H i detections and non-detections with two main galaxy populations of late and early-type galaxies to measure the underlying relation. We find that the turnover in this relation persists whether considering the two galaxy populations as a whole or separately. We note that an underlying linear relation could mimic this turnover in the observed scaling relation, but a model with a turnover is strongly preferred. Measurements on the logarithmic average of H i masses against the stellar mass are provided as a benchmark for future studies.</p

Considering planned change anew: stretching large group interventions strategically, emotionally and meaningfully

Large Group Interventions, methods for involving “the whole system” in a change process, are important contemporary planned organizational change approaches. They are well known to practitioners but unfamiliar to many organizational researchers, despite the fact that these interventions address crucial issues about which many organizational researchers are concerned. On the other hand, these interventions do not appear to be informed by contemporary developments in organizational theorizing. This disconnect on both sides is problematic. We describe such interventions and their importance; illustrate them with extended descriptions of particular Future Search and Whole‐Scale™ change interventions; summarize research on strategy, emotion, and sensemaking that may inform them; and suggest questions about the interventions that may stimulate research and reflection on practice. We also discuss conditions that may foster effective engagement between Large Group Interventions practitioners and organizational researchers. Our approach represents a way to conduct a review that combines scholarly literature and skilled practice and to initiate a dialog between them

MIGHTEE-H\u2009i: the baryonic Tully\u2013Fisher relation over the last billion years

Using a sample of 67 galaxies from the MeerKAT International GigaHertz Tiered Extragalactic Exploration Survey Early Science data, we study the H\u2009i-based baryonic Tully\u2013Fisher relation (bTFr), covering a period of 3c1 billion years (0 64 z 64 0.081). We consider the bTFr based on two different rotational velocity measures: the width of the global H\u2009i profile and Vout, measured as the outermost rotational velocity from the resolved H\u2009i rotation curves. Both relations exhibit very low intrinsic scatter orthogonal to the best-fitting relation (\u3c3 a5 = 0.07 \ub1 0.01), comparable to the SPARC sample at z 43 0. The slopes of the relations are similar and consistent with the z 43 0 studies (\u20603.66+0.35 120.29 for W50 and 3.47+0.37 120.30 for Vout). We find no evidence that the bTFr has evolved over the last billion years, and all galaxies in our sample are consistent with the same relation independent of redshift and the rotational velocity measure. Our results set-up a reference for all future studies of the H\u2009i-based bTFr as a function of redshift that will be conducted with the ongoing deep SKA pathfinders surveys

MIGHTEE-HI: The MHI−M⋆M_{\rm HI}-M_{\star} relation over the last billion years

We measure the $M_{\rm HI}-M_{\star}$ relation over the last billion years down to $M_{\rm HI}\sim 10^7 M_{\odot}$ using the MIGHTEE Early Science data with a Bayesian technique. This technique is applied to the HI detections, without binning the datasets, while taking account of the intrinsic scatter in the $M_{\rm HI}-M_{\star}$ relation. We divide the full sample of 249 galaxies into 161 spirals, 64 irregulars, 15 mergers, and 9 elliptical galaxies to measure their $M_{\rm HI}-M_{\star}$ relations. We fit this relation with both linear and non-linear models, and find that the non-linear model is preferred over the linear one for the full HI-selected sample with a measured transition stellar mass of $\log_{10}(M_\star$/$M_{\odot})$ = $9.15^{+0.8}_{-0.95}$, beyond which the measured slope flattens. This finding supports the view that the lack of HI gas is ultimately responsible for the decreasing star formation rate observed in the massive main sequence galaxies. For the spiral galaxies alone, which are biased towards those galaxies with the highest stellar masses in our sample, the slope beyond the transition mass is shallower than for the full sample, indicative of distinct gas processes ongoing for the spirals/high-mass galaxies from other types of galaxies with lower stellar masses. We also observe a moderate evolution of the $M_{\rm HI}-M_{\star}$ relation when splitting our samples into two redshift bins over the last billion years, which can largely be attributed to the effect of sample selection and hence highlights the potential of the full MIGHTEE survey.Comment: 14 pages, submitted to MNRA