Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 56 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 4028 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 44 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 56 trial 15 COVID-19 11 patient 10 clinical 5 research 5 datum 3 covid-19 2 treatment 2 study 2 pandemic 2 day 2 SARS 1 vaccine 1 user 1 tablet 1 surfactant 1 site 1 score 1 safety 1 result 1 respiratory 1 rapid 1 pwd 1 policy 1 plague 1 phase 1 participant 1 pangolin 1 outcome 1 old 1 network 1 nasal 1 mask 1 intervention 1 infection 1 impact 1 ice 1 iPad 1 hydroxychloroquine 1 home 1 gender 1 figure 1 exacerbation 1 error 1 drug 1 difference 1 device 1 container 1 consent 1 condition Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 3705 trial 1176 patient 1091 study 843 treatment 816 datum 801 research 721 % 630 analysis 512 participant 471 time 469 pandemic 462 outcome 457 effect 433 result 400 care 391 drug 390 safety 373 group 370 intervention 368 disease 349 use 344 vaccine 329 risk 329 day 317 phase 312 review 306 number 305 child 299 author 291 evidence 289 design 285 health 285 case 279 protocol 260 information 258 site 253 event 230 investigator 228 therapy 228 consent 222 cancer 214 infection 213 user 209 method 205 impact 204 process 192 efficacy 185 control 183 response 175 difference Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 510 COVID-19 194 GenV 124 Health 114 SARS 110 al 103 Clinical 93 et 91 Phase 90 Fig 89 • 79 Trials 77 CoV-2 77 China 76 COPD 73 Table 73 . 72 Research 70 IT 67 iPad 64 Data 63 RCTs 63 RCT 60 Trial 59 CI 55 meta 54 US 52 United 50 Committee 49 FDA 47 Coronavirus 46 University 46 National 46 March 45 TCM 45 States 45 International 44 sha 42 II 42 ClinicalTrials.gov 41 remdesivir 41 World 41 Medical 38 Korea 38 Hydroxychloroquine 37 hydroxychloroquine 37 Group 37 DOI 36 MERS 36 April 35 Organization Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 880 we 706 it 355 they 122 i 92 them 75 he 50 you 47 us 24 she 22 one 21 itself 20 themselves 19 him 6 me 3 himself 3 her 2 ourselves 2 mg 1 s 1 myself 1 il-12 1 em 1 aptt Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 7346 be 1266 have 758 use 473 include 400 do 324 report 324 base 274 provide 266 make 255 control 251 need 240 show 235 require 230 conduct 222 consider 216 follow 215 compare 207 identify 202 relate 195 assess 189 give 182 take 181 increase 174 develop 164 treat 160 find 153 lead 150 evaluate 146 reduce 145 miss 143 receive 137 perform 135 define 135 collect 131 see 126 remain 123 participate 123 allow 120 suggest 118 improve 114 support 111 test 111 ensure 109 continue 108 publish 102 randomize 100 associate 99 register 99 exist 99 describe Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 1286 clinical 1000 not 493 - 431 such 397 more 394 also 351 other 310 well 272 only 271 first 261 new 252 high 233 randomized 228 however 223 respiratory 214 available 213 medical 204 most 196 primary 194 e.g. 193 as 193 adverse 188 non 188 large 188 covid-19 187 many 181 different 179 severe 173 low 169 statistical 167 standard 162 acute 156 additional 154 potential 152 possible 151 patient 151 multiple 151 important 133 randomised 128 specific 125 even 123 likely 117 systematic 114 significant 114 relevant 112 early 111 further 109 same 108 single 107 public Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 72 most 54 good 45 least 32 Most 21 high 20 large 8 great 5 short 4 bad 3 long 3 late 3 early 3 big 2 t.t 1 small 1 safe 1 old 1 new 1 low 1 hard 1 fit 1 few 1 common 1 broad 1 MOST 1 -Off Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 132 most 24 least 10 well 2 long 1 worst Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 17 doi.org 3 www 3 covid-nma.com 2 www.researchprotection.org 2 www.irct.ir 2 orcid.org 2 mcri.figshare.com 2 github.com 2 clinicaltrials.gov 1 zenodo.org 1 www.who.int 1 www.rilintech.comt 1 www.polio-vaccine.com 1 www.medresman.org 1 www.medresman 1 www.frontiersin.org 1 www.biomedcentral.com 1 patienterstatningen.dk 1 ourworldindata.org 1 fundingawards.nihr.ac.uk 1 creativecommons.org 1 creat 1 bioinfo.ieo.it Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 7 http://doi.org/10 3 http://www 3 http://doi.org/10.1101/2020.05.30.20117523 2 http://www.irct.ir/trial/46946 2 http://doi.org/10.1101/2020.03.05.20031476 2 http://doi.org/10.1038/s41598-020-65898-x 2 http://covid-nma.com 1 http://zenodo.org/record/3903347#.XwLasUBuI2x 1 http://www.who.int/ictrp/en/ 1 http://www.rilintech.comt 1 http://www.researchprotection.org/InformedConsent/InformedConsent.html 1 http://www.researchprotection.org 1 http://www.polio-vaccine.com/fr/ 1 http://www.medresman.org 1 http://www.medresman 1 http://www.frontiersin.org/articles/10.3389/fmed 1 http://www.biomedcentral.com/content/ 1 http://patienterstatningen.dk/ 1 http://ourworldindata.org/coronavirus-source-data 1 http://orcid.org/0000-0002-8119-8439 1 http://orcid.org/0000-0002-3520-1342 1 http://mcri.figshare.com/projects/Generation_Victoria/35822 1 http://mcri.figshare.com/projects/Generation_ 1 http://github.com/pcmdpc/COVID-19 1 http://github.com/CSSEGISandData/COVID-19 1 http://fundingawards.nihr.ac.uk/search 1 http://doi.org/10.1038/s41598-020-73466-6 1 http://doi.org/10.1038/s41598-020-65898-x.Correspondence 1 http://doi.org/10.1016/j.jecp.2020 1 http://creativecommons.org/licenses/by/4.0/ 1 http://creat 1 http://covid-nma.com/ 1 http://clinicaltrials.gov/ct2/home 1 http://clinicaltrials.gov/ 1 http://bioinfo.ieo.it/shiny/app/CovidCT Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 20 live@home.path 2 awake.prone.meta.trial@gmail.com 1 moeininm@mums.ac.ir 1 ingra107@umn.edu Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 9 analysis showed evidence 6 use is not 5 patients are not 5 patients do not 5 trials did not 4 trials showed evidence 3 pandemic has not 3 participant is unable 3 patients are randomly 3 results were not 3 study are available 3 study did not 3 trial did not 3 trial showed evidence 3 trial was not 3 trials are typically 3 trials showed statistically 2 analysis is comparison 2 authors have not 2 care reduces all 2 care showed evidence 2 children made efficient 2 covid-19 are also 2 covid-19 has greatly 2 data are also 2 data are available 2 data are not 2 data were available 2 data were not 2 drug developing landscape 2 intervention is not 2 interventions are currently 2 outcome is resource 2 outcomes were admission 2 outcomes were all 2 pandemic related ices 2 pandemic related reasons 2 participants compared colchicine 2 patient is unable 2 patient reported outcome 2 review was only 2 study is not 2 study reports guidelines 2 time is more 2 treatments are effective 2 trial has also 2 trial is currently 2 trial is not 2 trial was open 2 trials are often Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 16 analysis showed no evidence 1 analysis showed no difference 1 children are not just 1 children do not simply 1 covid-19 has no effect 1 data did not explicitly 1 data found no benefit 1 data were not available 1 diseases are not well 1 drug was not yet 1 effects are not always 1 intervention is not merely 1 intervention is not often 1 pandemic is not surprising 1 participant is not possible 1 patient has no disease 1 patients are not reluctant 1 patients showing no difference 1 research is not well 1 results were not available 1 results were not statistically 1 safety has not yet 1 studies did not formally 1 treatment are not available 1 treatment is not worse 1 trial found no reduction 1 trial is not able 1 trial was not eligible 1 trials did not explicitly 1 trials shows no difference 1 trials was not effective 1 trials were not possible 1 use is not necessarily 1 use is not protective 1 use is not typically 1 used were not previously A rudimentary bibliography -------------------------- id = cord-309582-ihrj84hr author = AlNaamani, Khalid title = Medical research during the COVID-19 pandemic date = 2020-08-06 keywords = COVID-19; SARS; trial summary = Despite the dedication of enormous resources, the advancement in health care systems and collaboration between different investigators across the world, only a small number of patients over the last decade have in fact benefited from clinical research performed during different outbreaks of respiratory viruses such as was the case for the severe acute respiratory syndrome (SARS), the HIN1 flu virus (swine flu) or the Middle East Respiratory Syndrome. An example of unpublished results that need to be widely acknowledged because of a negative outcome leading to early termination is that of a Brazilian study (CloroCovid19 ) which was a parallel, double-blind, randomized, phase IIb clinical trial, which started on March 23, 2020, aiming to assess safety and efficacy of Chloroquine diphosphate (CQ) in the treatment of hospitalized patients with severe respiratory syndrome secondary to SARS-CoV-2 infection. doi = 10.12998/wjcc.v8.i15.3156 id = cord-322534-eikz07zz author = Allahyari, Abolghasem title = Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial date = 2020-06-26 keywords = patient; trial summary = title: Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: a structured summary of a study protocol for a randomised controlled trial OBJECTIVES: In this study, we investigate the effect of hydroxychloroquine on the prevention of Novel Coronavirus Disease (COVID-19) in cancer patients being treated. Trial registration: This trial has been registered by the title of "Effect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment" in Iranian Registry of Clinical Trials (IRCT) with code "IRCT20200405046958N1", https://www.irct.ir/trial/46946. Trial registration: This trial has been registered by the title of "Effect of Hydroxychloroquine on Novel Coronavirus Disease (COVID-19) prevention in cancer patients under treatment" in Iranian Registry of Clinical Trials (IRCT) with code "IRCT20200405046958N1", https://www.irct.ir/trial/46946. Also, the help of Clinical Research Development Unit of Akbar Hospital (affiliated to Mashhad University of Medical Sciences, Mashhad, Iran) in designing the study and methodological issues is highly appreciated. The trial has been approved by the Ethical Committee of Mashhad University of Medical Sciences, Iran. doi = 10.1186/s13063-020-04485-x id = cord-334667-0cah15lg author = Arabi, Yaseen M. title = Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial date = 2020-01-03 keywords = MERS; day; trial summary = title: Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial ABSTRACT: The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. Baseline characteristics will be presented for the two study groups (Additional file 1: Table S1 ) including age, sex, and body mass index, the presence of co-infections, nosocomial versus community-acquired MERS infection, Acute Physiology and Chronic Health Evaluation (APA-CHE) II scores, Sequential Organ Failure Assessment scores, and the Karnofsky Performance Status Scale score [3] . The MIRACLE trial investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant Interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. doi = 10.1186/s13063-019-3846-x id = cord-334433-oudvxb4d author = Beane, Joal D. title = Conducting Clinical Trials in the Time of a Pandemic date = 2020-06-08 keywords = clinical; trial summary = Responses to mitigate the effects of the pandemichave included: 1) thedevelopment of strategies to support research programs during unforeseen economic loss, 2)establishment of institutionalguidelines for clinical trials, 3)measures to ensure a healthy clinical research team, 4) useof innovative technologies to maintain access to clinical trials, 5) amendment of protocols to avoid costly trial closures, and 6) the strategic reopening of suspended clinical trials. Efforts to modify protocols in order to comply with the emergency public health response and the guidelines established by the FDA and IRBareencouraged.Investigators need to prioritize collection of data, focusing on the primary endpoint and important secondary endpoints to remain in compliance.Clinical protocols should be reexamined thoroughly and amendments should be made to reduce superfluous clinical visits.While many protocol changes typically required an amendment and lengthy review process, to avoid costly delays, reviews of amendments at our institution are being waived or expedited if the adjustment pertains to patient safety in the setting of COVID-19. doi = 10.1097/sla.0000000000004114 id = cord-135406-ztgrxucb author = Ben-Michael, Eli title = A trial emulation approach for policy evaluations with group-level longitudinal data date = 2020-11-11 keywords = difference; policy; trial summary = While these methods are less common in epidemiology, epidemiologic researchers are well accustomed to handling similar complexities in studies of individual-level interventions."Target trial emulation"emphasizes the need to carefully design a non-experimental study in terms of inclusion and exclusion criteria, covariates, exposure definition, and outcome measurement -and the timing of those variables. We argue that policy evaluations using group-level longitudinal ("panel") data need to take a similar careful approach to study design, which we refer to as"policy trial emulation."This is especially important when intervention timing varies across jurisdictions; the main idea is to construct target trials separately for each"treatment cohort"(states that implement the policy at the same time) and then aggregate. 4 5 In this paper, we argue that policy evaluations using panel data need to take a similarly careful approach to study design, which we refer to as "policy trial emulation." The main idea is to construct target trials separately for each "treatment cohort" (states that implement the policy at the same time) and then aggregate. doi = nan id = cord-279197-cesemos0 author = Block, Keith I. title = Integrative Cancer Therapies: Learning From COVID-19 date = 2020-06-21 keywords = COVID-19; cancer; patient; trial summary = Not only has COVID-19 suddenly converted us to a reliance on telehealth that is likely to persist in the future, it has also highlighted the use of some integrative therapies commonly used by cancer patients that have previously been thought to be too controversial for conventional clinics, but that might bear further research attention. For instance, 3 meta-analyses of randomized trials of chemotherapy in colorectal cancer patients found that performance status predicted mortality, [12] [13] [14] in addition to treatment side effects. Along with the previously published beneficial effects of parenteral fish oil emulsions in cancer patients, 30 these vitamin C trials raise the question of the potentials of other unconventional intravenous treatments in cancer patients. Pooled safety and efficacy analysis examining the effect of performance status on outcomes in nine first-line treatment trials using individual data from patients with metastatic colorectal cancer doi = 10.1177/1534735420932652 id = cord-348244-1py0k53e author = Buyse, Marc title = Central statistical monitoring of investigator-led clinical trials in oncology date = 2020-06-23 keywords = clinical; datum; trial summary = We describe the principles of central statistical monitoring, provide examples of its use, and argue that it could help drive down the cost of randomized clinical trials, especially investigator-led trials, whilst improving their quality. Yet, there is no evidence showing that extensive data monitoring has any major impact on the quality of clinical-trial data, and none of the randomized studies assessing more intensive versus less intensive monitoring has shown any difference in terms of clinically relevant treatment outcomes [18] [19] [20] [21] [22] . Both types of trials may benefit from central statistical monitoring of the data; industry-sponsored trials to target centers that are detected as having potential data quality issues, which may require an on-site audit, and investigatorled trials as the primary method for checking data quality. An evidence-based study of the cost for data monitoring in clinical trials A statistical approach to central monitoring of data quality in clinical trials doi = 10.1007/s10147-020-01726-6 id = cord-031978-l6nlrv9h author = Chauvenet, Alienor title = Panel sampling in health research date = 2020-09-16 keywords = treatment; trial summary = Carsten Hjorthøj and colleagues question the extent to which the effects of cannabidiol as a pharmacological treatment for cannabis use disorder might be clinically meaningful. The Lancet Psychiatry, Matthias Pierce and colleagues 1,2 identify the importance of sampling in studying mental health effects of COVID-19. It seems that self-selected commercial survey panels in general might be biased towards mentally unhealthy or unhappy individuals. Despite great interest in the discontinuation of antipsychotic medication, few individuals can equally accept either treatment group in a randomised discontinuation trial, because the decision to maintain or discontinue is too important to be left to randomisation. Second, clinical cohort studies including individuals who discontinue antipsychotic medication should be done to generate precise knowledge about the proportion and The Dutch MESIFOS study 1 found that more patients achieved long term functional remission in the group who were assigned to early discontinuation of antipsychotic medication after 6 months of remission, compared with those who were assigned to maintenance treatment. doi = 10.1016/s2215-0366(20)30358-8 id = cord-267608-0odu8lus author = Chen, Daohong title = Innovative highlights of clinical drug trial design date = 2020-06-03 keywords = clinical; drug; study; trial summary = Accordingly taking the advantage of interim analysis based on novel biomarker approach for detecting the pathogenesis-specific molecular alteration(s), an adaptive clinical study can select the drug-sensitive sub-population from patients with initially targeted disease or an alternative indication, to continue the investigation for an optimized therapeutic efficacy [7] . While human bioequivalence study is increasingly contributing to evaluation of emerging formulation and bio-similar agents besides chemical generics [4] , several adaptive trial designs have been capable of translating the scientific breakthroughs into novel therapeutic benefits with shorter processing time and lower financial costs, to address the unmet clinical needs [3, 19] . Of note, to preserve the strength of clear defining efficacy and safety of tested drugs, the innovative designs of clinical study are substantially overlapped with classic trial protocols of three phases which still serve as the mainstream approach of clinical investigation [3, 7] . doi = 10.1016/j.trsl.2020.05.007 id = cord-018677-gmitz3gg author = Clemens, John D. title = Sequential stages of clinical trials and overview of issues to be considered date = 2005 keywords = Phase; United; trial; vaccine summary = In these studies volunteers are typically allocated at random to receive the vaccine or a comparison agent, usually a placebo, and are then challenged at a defined interval after vaccination with an inoculum of the pathogen predicted to cause the target disease in nearly 100% of the control group. Phase III studies are designed as randomized, controlled trials with clear hypotheses, and are conducted in the target group for whom vaccine licensure is desired and in a population that normally experiences the target infection. Definition of immunological correlates of vaccine protection is very important because such correlates permit assessments of the protection of the tested vaccine and ones suitably similar to it in small, short-term studies with immunological endpoints, without resort to full-scale, Phase III efficacy trials with clinical infection endpoints. The successive phases of clinical evaluation of vaccine candidates allow for acquisition of critical information about vaccine safety, immunogenicity, excretion, transmission, and protection in an incremental fashion, while minimizing the risks to subjects who volunteer to participate in these studies. doi = 10.1007/3-7643-7381-4_11 id = cord-276092-4e4muqnu author = Dal-Re, Rafael title = Waste in COVID-19 clinical trials conducted in western Europe date = 2020-07-07 keywords = trial summary = A cross-sectional analysis was carried out based on a series of searches conducted on May 20-21, 2020 looking for non-industry-sponsored, ongoing trials, aiming to assess medicines or convalescent plasma for the treatment of COVID-19 patients, in the 5 largest European countries and 2 regions (Benelux, Scandinavia). The following information was extracted from each trial: single-arm or randomized controlled trial (RCT), blinding, and planned sample size; whether the trial was multicenter, had a control (standard of care) arm and a Data Monitoring Committee. Limited useful information should be expected from single-arm trials, RCTs recruiting ≤50 participants/arm and those with no standard of care arm. However, it should be highlighted that it is rather surprising why some trials carried out in all the countries/regions included in this study seemed not to be registered on the EudraCT database (from which the EU-CTR obtains all the information), something that should be expected from all trials conducted with medicines in Europe. doi = 10.1016/j.ejim.2020.07.002 id = cord-271514-sls3bsm0 author = Dean, Natalie E. title = Ensemble Forecast Modeling for the Design of COVID-19 Vaccine Efficacy Trials date = 2020-09-15 keywords = site; trial summary = We recommend the use of ensemble forecast modeling – combining projections from independent modeling groups – to guide investigators identifying suitable sites for COVID-19 vaccine efficacy trials. In this paper, we describe a simplified framework for the use of ensemble modeling to guide the selection and continued evaluation of sites for a vaccine efficacy trial, with a focus on the COVID-19 pandemic. Suggested guidelines are the ability to: (i) capture all geographic areas in the candidate list of sites, (ii) disaggregate to at least the first administrative level (e.g. state, province), though finer levels may be preferred for certain planning activities, (iii) project the COVID-19 symptomatic cumulative incidence, i.e. the number of new symptomatic infections of any severity divided by the total population size during a pre-specified period (three months suggested), and (iv) produce a minimum of 1000 simulated epidemics. We describe an ensemble modeling procedure to inform site selection for a vaccine efficacy trial planned during an ongoing epidemic. doi = 10.1016/j.vaccine.2020.09.031 id = cord-263088-zj14ro5j author = DiPaola, Joshua D. title = Investigating the use of sensory information to detect and track prey by the Sunda pangolin (Manis javanica) with conservation in mind date = 2020-06-17 keywords = Manis; condition; container; pangolin; trial summary = All trials across the ''olfactory'' , ''visual'' , and ''acoustic'' conditions of phase I were pseudo-randomised within a session so that each session consisted of an equal number of trials of left and right correct choices (based on the side of the chamber in which a container was placed), no one side was baited with food more than three consecutive times in a row, and the first three trials for each session across all conditions were always tests rather than controls to avoid a frustration effect. Phase I control containers (i.e., opaque with solid lids) were used as the stimulus containers in the test trials for this condition as we wanted the subject to make olfactory decisions based on the trail scent without being influenced by the odor of the food inside the container. doi = 10.1038/s41598-020-65898-x id = cord-005705-j765ruj1 author = Dreyfuss, Didier title = Is it better to consent to an RCT or to care?: Μηδεν αγαν (“nothing in excess”) date = 2004-12-17 keywords = ARDS; consent; patient; research; trial summary = Another contention of the present paper is this [14] : critical care physicians may still believe that RCTs remain the best tool for improving knowledge and care, and in this case they must accept to use the means needed to achieve the end and therefore to insist on mandatory informed consent from the patient or proxy; or they may realize that the game is not worth the candle and they must then turn to other forms of research that are ranked less highly in the pyramid of evidence-based medicine [15] . Before discussing the problem of informed consent to research a critical appraisal of the scientific and ethical validity of RCTs in critical care medicine is in order. doi = 10.1007/s00134-004-2493-0 id = cord-048447-chz8luni author = Duffett, Mark title = Surfactant therapy for acute respiratory failure in children: a systematic review and meta-analysis date = 2007-06-15 keywords = respiratory; surfactant; trial summary = The primary objective of the systematic review is to assess the effect of the administration of pulmonary surfactant compared with no therapy or with placebo on all-cause mortality (at or before hospital discharge) in mechanically ventilated children with acute respiratory failure. We used the following characteristics to assess the methodologic quality: allocation concealment (sealed envelopes or central randomization were considered adequate), blinding (which of the trial personnel and caregivers were blinded, and the methods used to ensure blinding), completeness of followup (assessed by the number of patients randomized for whom there were no outcomes), similarity of the groups at baseline (with respect to known prognostic factors: age, aetiology, severity of illness as measured by the Pediatric Risk of Mortality score, and immunosuppression), whether a standard or recommended strategy for mechanical ventilation was used, and whether a priori criteria for the use of co-interventions were used. doi = 10.1186/cc5944 id = cord-344705-co0nk7pt author = Eichler, Hans‐Georg title = Clinical trials for Covid‐19: can we better use the short window of opportunity? date = 2020-05-14 keywords = clinical; covid-19; trial summary = We here discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision‐relevant clinical trials. Many small stand-alone trials and observational studies of single-agent interventions are currently running or in planning; many of these will likely not deliver robust results that could support regulatory and patient-level treatment decisions. We here discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision-relevant clinical trials. Now is the time to ensure that the window of opportunity will not shut, both for patients in need of treatment and for researchers to conduct clinical trials that deliver. doi = 10.1002/cpt.1891 id = cord-345095-1li57v0j author = Felix, Carol title = Clinical Research in the Time of COVID-19 date = 2020-10-01 keywords = trial summary = The need for clinical trials, the improved treatments they elucidate, and the US Food and Drug Administration (FDA) approval providing public access to these new and better treatments will remain. The pandemic does not end medical research, and it may, in fact, point us in a new and better direction for implementing clinical trials. 1 Academic institutions will do robust research again, and those institutions most prepared to pick up research at prepandemic levels will be those that follow FDA guidelines to facilitate and continue running clinical trials even during the spread of COVID-19. So, how do we run clinical trials in the time of COVID-19? Until a vaccine is developed, and likely even after that if COVID-19 becomes a seasonal norm, we will have to weigh the risks and benefits of everything we do, including medical visits and research appointments. FDA Guidance on conduct of clinical trials of medical products during COVID-19 public health emergency: guidance for industry, investigators, and institutional review boards doi = 10.1016/j.ijrobp.2020.06.059 id = cord-356040-qdpkidn8 author = Ghazawi, Feras M. title = Infection risk of dermatologic therapeutics during the COVID‐19 pandemic: an evidence‐based recalibration date = 2020-07-03 keywords = infection; patient; trial summary = Recommendations were made recently to limit or stop the use of oral and systemic immunotherapies for skin diseases due to potential risks to the patients during the current severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) COVID‐19 pandemic. We performed a literature review to approximate the risk of SARS‐CoV‐2 infection, including available data on the roles of relevant cytokines, cell subsets, and their mediators in eliciting an optimal immune response against respiratory viruses in murine gene deletion models and humans with congenital deficiencies were reviewed for viral infections risk and if possible coronaviruses specifically. A randomized, open-label, controlled trial for the efficacy and safety of Adalimumab Injection in the treatment of patients with severe novel coronavirus pneumonia (COVID-19) Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2) doi = 10.1111/ijd.15028 id = cord-269716-x3b0qphd author = Hopper, Lydia M. title = Problem solving flexibility across early development date = 2020-08-26 keywords = Hopper; child; old; phase; trial summary = For all children and action sequences used, in the first trial of Phase 2, 7 of the 20 2year-olds (35.00%), 14 of the 22 3-year-olds (63.64%), and 13 of the 19 4-year-olds (68.42%) used the (newly available) most efficient method (i.e., they removed only the lower two of five straws from the tube), highlighting their recognition of the changed task demands. In spite of this, after correcting for multiple comparisons, post hoc pairwise comparisons revealed no significant difference across age groups when comparing the numbers of children whose responses in the first trial of Phase 2 responses were efficient: 4-year-olds versus 2year-olds, t(35.92) = À2.41, p = .021, 95% CI [À0.68, À0.06]; 4-year-olds versus 3-year-olds, Considering all 4 trials that children completed in Phase 2, on average children removed significantly fewer straws per trial in Phase 2 than they did in Phase 1, highlighting their understanding of the changed task demands. doi = 10.1016/j.jecp.2020.104966 id = cord-344491-93ggxzxu author = Husebo, Bettina Sandgathe title = LIVE@Home.Path—innovating the clinical pathway for home-dwelling people with dementia and their caregivers: study protocol for a mixed-method, stepped-wedge, randomized controlled trial date = 2020-06-09 keywords = Health; Norway; home; intervention; pwd; trial summary = In the COSMOS trial, a randomized implementation hybrid trial carried out in Norwegian nursing homes during 2014-2015, our group successfully developed, implemented and effect evaluated a multicomponent intervention addressing COmmunication, Systematic assessment and treatment of pain, Medication review, Organization of activities and Safety [22] . In practice in the LIVE@Home.Path: the coordinator will encourage and facilitate that both the PWD and the caregiver participate in local educational programs arranged by the municipality or the specialist health services several times yearly. PWDs are eligible for inclusion if they: are aged ≥ 65 years; are home-dwelling; have a minimum 1 h/week regular face-to-face contact with the caregiver; are diagnosed with dementia according to standardized protocol [60] ; have Mini-Mental State Examination (MMSE) score of 15-25; have a Functional Assessment Staging Test (FAST) score of 4-7; and provide written informed consent. A randomized controlled trial of a community-based dementia care coordination intervention: effects of MIND at Home on caregiver outcomes doi = 10.1186/s13063-020-04414-y id = cord-283197-jjye8t6j author = Ingraham, Nicholas E. title = Fact Versus Science Fiction: Fighting Coronavirus Disease 2019 Requires the Wisdom to Know the Difference date = 2020-04-29 keywords = SARS; hydroxychloroquine; trial summary = This commentary uses a recent study of hydroxychloroquine to demonstrate the dire need for randomized clinical trials, but more importantly, to explore the potential consequences of misinformation, how fear fuels its impact, and offer guidance to maintain scientific integrity without relinquishing hope. As of March 25, there remains no randomized control trial in humans with evidence that chloroquine or hydroxychloroquine is beneficial in SARS-CoV or SARS-CoV-2. Premature acceptance of efficacy is not new (swine flu vaccination [10] or recombinant human activated protein C [11] ), but it is these prior experiences that influence current standards to require high quality and often multiple randomized control trials to change practice. However, despite warnings from healthcare leaders and public health agencies, there continues to be a premature adoption of hydroxychloroquine as treatment based on limited preclinical data and misinformed interpretation of a nonrandomized study. doi = 10.1097/cce.0000000000000108 id = cord-346842-ip4i3bdk author = Jeon, JuYeun title = The Impact of COVID-19 on the Conduct of Clinical Trials for Medical Products in Korea date = 2020-09-07 keywords = COVID-19; Korea; trial summary = METHODS: The impact on subject''s scheduled visits and major milestones of clinical trials in Korea were measured by conducting a survey among clinical project manager (CPMs) working at global clinical research organization. New approaches were necessary in clinical trials to eliminate the risk of infection by complying with the guideline and enable subjects to continue to participate in trials if no better alternative treatment options were available, for protecting the subjects'' safety and well-being. The study evaluated the impact of the COVID-19 epidemic and the KCDC disease control guideline on the conduct of clinical research in Korea, on subjects, investigators, monitor, pharmaceutical companies, Institutional Review Boards (IRBs) and regulatory authorities (RAs), in order to suggest recommendations for conducting clinical trials during the pandemic. The survey was distributed to total 140 clinical project manager (CPMs) who were working at global clinical research organization and responsible for trials performed in Korea, according to method of simple random sampling from February 24, 2020 to March 7, 2020. doi = 10.3346/jkms.2020.35.e329 id = cord-350062-6xsh2pis author = Juul, Sophie title = Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project) date = 2020-09-17 keywords = COVID-19; trial summary = Meta-analyses and trial sequential analyses showed that we could exclude the possibility that hydroxychloroquine versus standard care reduced the risk of all-cause mortality (RR 1.07; 95% CI 0.97–1.19; p = 0.17; I(2) = 0%; 7 trials; low certainty) and serious adverse events (RR 1.07; 95% CI 0.96–1.18; p = 0.21; I(2) = 0%; 7 trials; low certainty) by 20% or more, and meta-analysis showed evidence of a harmful effect on nonserious adverse events (RR 2.40; 95% CI 2.01–2.87; p < 0.00001; I(2) = 90%; 6 trials; very low certainty). Random-effects meta-analysis showed no evidence of a difference between lopinavir-ritonavir versus standard care on serious adverse events (RR 0.64; 95% CI 0.39-1.04; p = 0.07, I 2 = 0%; 2 trials; very low certainty) (S10 Fig, S7 Table) . Random-effects meta-analysis showed no evidence of a difference between lopinavir-ritonavir versus standard care on adverse events not considered as serious (RR 1.14; 95% CI 0.85-1.53; p = 0.38, I 2 = 75%; 2 trials; very low certainty) (S12 Fig; S7 Table) . doi = 10.1371/journal.pmed.1003293 id = cord-302448-2r4rtixg author = Kharma, Nadir title = Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, The ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial date = 2020-09-07 keywords = patient; trial summary = title: Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, The ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. To prove the positive effect of anticoagulation with bivalirudin intravenously on gas-exchange in patients with COVID-19 and respiratory failure on invasive mechanical ventilation. Inclusion criteria: all adult patients admitted to the ICU who are COVID positive tested and in need for mechanical ventilation are eligible for inclusion. doi = 10.1186/s13063-020-04689-1 id = cord-031315-p7jb4gf2 author = Kong, Qing title = Efficacy and safety of Jia Wei Bushen Yiqi formulas as an adjunct therapy to systemic glucocorticoids on acute exacerbation of COPD: study protocol for a randomized, double-blinded, multi-center, placebo-controlled clinical trial date = 2020-09-03 keywords = COPD; China; TCM; day; exacerbation; trial summary = title: Efficacy and safety of Jia Wei Bushen Yiqi formulas as an adjunct therapy to systemic glucocorticoids on acute exacerbation of COPD: study protocol for a randomized, double-blinded, multi-center, placebo-controlled clinical trial The present study aims to evaluate the efficacy and safety of Jia Wei Bushen Yiqi (JWBY) formulas in patients who suffer from COPD exacerbations and to investigate whether the short-term (5-days) systemic glucocorticoid therapy is non-inferior to the long-term (9-day) regime. On one hand, a dose of 40 mg prednisone (a common oral systemic glucocorticoid) daily for 5 days has been recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Science Committee Report based on the REDUCE randomized clinical trial since 2015 [24] . We conducted a randomized and placebo-controlled trial enrolling stable COPD patients in 2014, which illustrated that TCM formulas called Bushen Yiqi (BY) formulas can improve the lung function, reduce the frequency of acute exacerbation of COPD, and modulate the HPA axis [35] . doi = 10.1186/s13063-020-04669-5 id = cord-335198-qp964238 author = Kotsimbos, T. title = Pandemic Treatments on Trial: The bigger picture date = 2020-08-03 keywords = COVID19; patient; trial summary = Given the stated extremes above, there is a clear trade-off between "doing all that one can for individual patients with currently available information in a timely manner and despite significant uncertainty" and "group treatment of individuals to be enrolled in properly conducted but costly (effort, time and money) clinical trials for specific therapeutic approaches that will help inform the evidence-base for future patients". And how do we quickly establish and conduct difficult and costly randomized, controlled clinical trials for the most promising old and new therapies where there is a clear equipoise between possible benefits and potential risks? Paradoxically, the almost immediate establishment of a well-designed RCT to test the combination antiviral treatment lopinavir-ritonavir in Wuhan, China during the beginning of the pandemic exemplified this tension in a most unusual way when trial recruitment ceased early due to falling COVID19 case numbers (7). doi = 10.1183/13993003.02281-2020 id = cord-266573-vfl08i2p author = Largent, Emily A title = Paying Participants in COVID-19 Trials date = 2020-05-29 keywords = COVID-19; research; trial summary = Given increased risk of undue influence against pandemic background conditions, incentive payment should be avoided unless essential to recruitment and retention in important trials whose social value outweighs this risk. Given the pandemic''s devastating economic effects, as well as the fact that risks may be higher or more uncertain in COVID-19 trials than in nonpandemic research, there is an increased likelihood of undue influence stemming from incentive payments. Rather, in light of pandemic circumstances-similar features of which may be replicated in other contexts, including research conducted in low-and middle-income countries or with participants whose nonresearch options are limited even in the absence of a pandemic-offers of compensation may raise ethical concerns akin to incentives [14] . Acknowledging this challenge, the best IRBs can do is to minimize the possibility of undue influence for trial participants on the whole by making it unlikely for research participation to constitute an objectively unreasonable choice for members of the target study population. doi = 10.1093/infdis/jiaa284 id = cord-348306-e8hdx4u2 author = Li, Jie title = Meta-trial of awake prone positioning with nasal high flow therapy: Invitation to join a pandemic collaborative research effort date = 2020-07-24 keywords = trial summary = title: Meta-trial of awake prone positioning with nasal high flow therapy: Invitation to join a pandemic collaborative research effort We take the example of such a meta-trial, set up to investigate prone positioning among awake patients undergoing nasal high flow therapy and invite journal readers to join this collaborative research effort.  A meta-trial, with harmonized inclusion and outcome criteria and a global interim analysis plan, may enable to get a high level of evidence within the short period of time required by the pandemic, through performing a prospective meta-analysis of the generated data across countries.  A meta-trial, with harmonized inclusion and outcome criteria and a global interim analysis plan, may enable to get a high level of evidence within the short period of time required by the pandemic, through performing a prospective meta-analysis of the generated data across countries. doi = 10.1016/j.jcrc.2020.07.020 id = cord-338588-rc1h4drd author = Li, Xuanyi title = Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis date = 2020-10-16 keywords = author; gender; impact; network; score; trial summary = Seminal events (Fig. 1C) are likely a driver of preferential attachment 35 , and may The network is overwhelmingly dominated by men until 1980, when a trend towards increasing authorship by women begins to be seen; however, representation by women in first/last authorship remains low; gray shaded lines are 95% confidence intervals of the LOESS curves; (B) Men tend on average to have a longer productive period and to achieve a higher author impact score than women (P < 0.001 for both comparisons); (C) Men tend on average to be more central and have more collaborations outside of their subspecialty. While there is much to be applauded in the continued success of translating research findings into the clinic, we observed clear gender disparities within the cancer clinical trialist network: women have a statistically significantly lower final impact score, shorter productive period, less centrality, and less collaboration with those outside of their primary subspecialty. doi = 10.1038/s41598-020-73466-6 id = cord-347189-i9rzo3j0 author = Lorusso, Domenica title = Clinical research disruption in the post-COVID-19 era: will the pandemic lead to change? date = 2020-10-13 keywords = COVID-19; clinical; trial summary = The COVID-19 pandemic suggests that it is possible to alleviate redundancy in clinical trials, and while preserving the rigour of a study, can offer a new, less burdened and more inclusive vision of clinical research for the scientific community of tomorrow. Data from China reported that patients with cancer who are infected with COVID-19 are at 3.5 times the risk of requiring mechanical ventilation or intensive care unit (ICU) admission, compared with the general population. 4 Although conversion to telemedicine has maintained the continuity of care for many patients, the COVID-19 pandemic has massively disrupted clinical research and many cancer centres halted clinical trial activities including patient recruitment. COVID-19 has pointed out that sometimes, high level of bureaucracy in research rules place unnecessary burdens on patients and clinicians and it suggests that it is time to alleviate bureaucracy and introduce some practical changes into research organisation that will possibly promote patient access to trials and reduce the costs of the clinical research. doi = 10.1136/esmoopen-2020-000924 id = cord-267699-h7ftu3ax author = MacIntyre, C. Raina title = A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS date = 2020-04-30 keywords = COVID-19; mask; trial summary = title: A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. The aim of this study was to review the randomised controlled trials evidence for use of masks and respirators by the community, health care workers and sick patients for prevention of infection. (17) We conducted a randomised controlled trial comparing the targeted strategy tested in the two North American studies, with the wearing of respiratory protection during an entire shift, and showed efficacy for continual (but not targeted) use of a respirator (19) . doi = 10.1016/j.ijnurstu.2020.103629 id = cord-026998-vlmoa5dr author = McCulloch, Peter title = COVID-19 has no effect on gravity date = 2020-06-03 keywords = research; trial summary = The Adaptive COVID-19 Treatment Trial of remdesivir was highlighted before any details were available even on preprint servers, and inferences made publicly about mortality reduction, although the trial did not show this. The laws of scientific inference and statistics have not been affected by the virus, and studies whose design guarantees they cannot produce a valid result still will not do so during the crisis. The crisis has shown that the normal processes of peer review and prioritization, both in funding and in publication, can be radically accelerated, but should be robust to protect the conduct of meaningful clinical research. We hope the research world, like the rest of society, will keep some of the helpful adaptations it has made to cope with the crisis. FDA will reportedly authorize use of remdesivir for Covid-19 after trial shows ''positive effect'' on recovery time doi = 10.1136/bmjsit-2020-000046 id = cord-160526-27kmder5 author = Meyer, R. Daniel title = Statistical Issues and Recommendations for Clinical Trials Conducted During the COVID-19 Pandemic date = 2020-05-21 keywords = covid-19; datum; ice; pandemic; trial summary = A number of strategies and recommendations are put forward to assess and address issues related to estimands, missing data, validity and modifications of statistical analysis methods, need for additional analyses, ability to meet objectives and overall trial interpretability. It should continue throughout the conduct of the study in light of the evolving situation and accumulating data, considering regional differences in the infection status and pandemic Determine what additional information needs to be collected in the study database or in the form of input from study investigators in order to adequately monitor, document, and address pandemic-related issues (feasibility to obtain such information and its quality may vary and this needs to be considered as part of the risk factors);  Understand reasons for treatment or study discontinuation and the impact on planned estimands and intercurrent events; doi = nan id = cord-327738-i400ynjp author = Milner, Ross title = Is it Ethically Appropriate to Continue Surgical Clinical Trials During the COVID-19 Pandemic? EDITED BY DR SARR date = 2020-04-27 keywords = clinical; trial summary = We discuss here the ethics of clinical trial care within the surgical specialties and the the pros and cons of participation in clinical trial during the COVID-19 pandemic, with a specific focus on surgical oncology and vascular surgery. The current need for social distancing and limitations of health care resources has shifted priorities appropriately, but completely halting clinical trials would hinder dramatically the delopment of novel treatment sand leave patients currently enrolled in these trials without access to potentially life-saving medications. Before continuing to enroll patients in surgical trials, we believe that surgeons must carefully consider the type of trial, the institutional status with respect to scarce resources, and the potential risk/benefit ratio to patients and health care workers involved. Medically-necessary, time-sensitive procedures: A scoring system to ethically and efficiently manage resource scarcity and provider risk during the COVID-19 pandemic doi = 10.1016/j.surg.2020.04.024 id = cord-294651-iy0h2pyf author = Nasrallah, Ali A. title = A large number of COVID-19 interventional clinical trials were registered soon after the pandemic onset: a descriptive analysis date = 2020-06-08 keywords = COVID-19; Coronavirus; trial summary = Abstract Background There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the Coronavirus disease 2019 (COVID-19) pandemic. Randomized control trials (RCTs) are needed to provide unbiased evidence to guide the clinical care and public health practices aimed to control COVID-19 outbreak [16] . We included the following variables for our analysis: study ID, source register unique identifier, original registry, public title, primary sponsor, location (country and region), recruitment status, age range, gender, target size, study design, phase, publication (yes/no, count, and URL), intervention (category, subcategory, and name), primary outcomes, registration date, enrollment date, retrospective label, and trial URL. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial doi = 10.1016/j.jclinepi.2020.06.005 id = cord-281400-ho2m7nqn author = Nguyen, Van Thu title = Research response to COVID-19 needed better coordination and collaboration: a living mapping of registered trials date = 2020-10-21 keywords = COVID-19; research; trial summary = We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered. We systematically search the platform every week for all RCTs evaluating preventive interventions and treatments for COVID-19 and created a publicly available interactive mapping tool at https://covid-nma.com to visualize all trials registered. Up to August J o u r n a l P r e -p r o o f In certain countries, the sample size is relatively small for trials evaluating COVID-19 treatments ( Timing of research response to the evolution of the pandemic In Europe, Spain registered only 2/93 trials (2%) before the peak (i.e., March 27, 2020. Our interactive living mapping of COVID-19 research was designed to help decision makers use data from clinical registries for an up-to-date picture of all research questions being investigated so as to prioritize research and avoid waste in research (26) . doi = 10.1016/j.jclinepi.2020.10.010 id = cord-352177-05sku8a8 author = Pahus, Laurie title = Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials? date = 2020-08-13 keywords = clinical; patient; trial summary = To additionally explain patient willingness to participate in new-drug studies or research associated with pharmaceutical companies or with public institutions, further models used the same predictive variables as for the first model, plus distrustgroup-membership as an additional explanatory variable. Our study aimed at evaluating variables associated with patient willingness to participate in different categories of clinical trials and at identifying a potential recruitment bias in clinical trials related to patient distrust in the pharmaceutical industry and healthcare systems. Several studies have previously evaluated such rates and highlighted that altruism, hope for personal benefit, contribution to advances in science as well as financial benefit are the main reasons for agreeing to participate, whereas fear of adverse events, impossibility to cope with the logistic constraints accompanying participation, poor knowledge about or negative perception of clinical trials and distrust in pharmaceutical industry are potential barriers [20] [21] [22] [23] . Distrust in pharmaceutical companies is associated with a specific patient profile and with refusal to participate in pre-marketing industry-sponsored drug trials. doi = 10.1186/s12910-020-00509-y id = cord-004647-0fuy5tlp author = Patson, Noel title = Systematic review of statistical methods for safety data in malaria chemoprevention in pregnancy trials date = 2020-03-20 keywords = analysis; datum; safety; trial summary = METHODS: The search included five databases (PubMed, Embase, Scopus, Malaria in Pregnancy Library and Cochrane Central Register of Controlled Trials) to identify original English articles reporting Phase III randomized controlled trials (RCTs) on anti-malarial drugs for malaria prevention in pregnancy published from January 2010 to July 2019. This review, therefore, aims at identifying applied statistical methods and their appropriateness in the analysis of safety data in anti-malarial drugs for malaria prevention during pregnancy clinical trials. This review sought to provide a detailed overview of the actual practice of the statistical analysis of safety data in the unique setting of drug trials for the preventions of malaria in pregnancy as reflected published literature. Advantageously, methods based on causal inference framework, such as mediation analysis [28] [29] [30] [31] could be adapted/extended to assess the influence of the AEs on non-adherence in RCTs. Despite about three-quarters of the trials reporting p-values after comparing safety outcomes by treatment arms, only about half of the reviewed trials adhered to International Harmonisation Conference Guideline E9 in reporting of confidence intervals in quantifying the safety effect size [3, 4] . doi = 10.1186/s12936-020-03190-z id = cord-326331-g4o3forj author = Rai, Ansaar T title = Neuroendovascular clinical trials disruptions due to COVID-19 potential future challenges and opportunities date = 2020-06-30 keywords = COVID-19; clinical; trial summary = METHODS: A survey-based study focused on randomized controlled trials (RCTs) and single-arm studies for acute ischemic stroke and cerebral aneurysms was developed by a group of senior neurointerventionalists and sent to sites identified through the clinical trials website (https://clinicaltrials.gov/), study sponsors, and physician investigators. The Food and Drug Administration (FDA) published its guidance on the ''Conduct Of Clinical Trials Of Medical Products During COVID19 Pandemic'' for the industry, investigators, and institutional review boards in March 2020 and updated these on April 2, 2020 (https://www. These were identified by the writing group and fell into four categories: general disruption caused by trial suspensions and missed opportunities of enrollment, compromised trial quality due to inability of timely clinical and imaging follow-up, inability to enroll neurologically debilitated patients because legally authorized representatives were not at hand for face to face consent and dated remote consent procedures did not apply and, finally, personal effect of compensation or working conditions on study staff. doi = 10.1136/neurintsurg-2020-016502 id = cord-030531-4uucx9ss author = Randremanana, Rindra Vatosoa title = An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial date = 2020-08-17 keywords = Madagascar; ciprofloxacin; patient; plague; trial summary = All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11. The secondary objective is to collect data on the effectiveness of ciprofloxacin in the treatment of pneumonic plague, although the trial is not able to formally assess the non-inferiority of ciprofloxacin monotherapy compared to streptomycin and ciprofloxacin combination therapy in pneumonic plague, Considering the operational and practical complexities of a plague RCT, the study also has additional exploratory objectives to optimize investments: to evaluate the level and kinetics of anti-Y. doi = 10.1186/s13063-020-04642-2 id = cord-004339-7nwpic3d author = Rennie, Katherine J. title = Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction date = 2020-02-13 keywords = NAIROS; nasal; outcome; participant; patient; trial summary = Secondly, consent to have the discussion about the NAIROS trial with the investigator audio-recorded and their details passed onto • Any prior septal surgery • Systemic inflammatory disease or the use of any current oral steroid treatment within the past 2 weeks • Granulomatosis with polyangiitis • Nasendoscopic evidence of unrelated associated pathology, e.g. adenoid pad, septal perforation, chronic rhinosinusitis indicated by the presence of polyposis or pus • Any history of intranasal recreational drug use within the past 6 months • Breast-feeding, pregnancy or intended pregnancy for the duration of involvement in the trial • Bleeding diathesis • Therapeutic anticoagulation (warfarin/novel oral anti-coagulant (NOAC) therapy) • Clinically significant contraindication to general anaesthesia • Patients known to be immuno-compromised • Those in whom an external bony deformity substantially contributes to the nasal obstruction a member of the qualitative team for a telephone interview. doi = 10.1186/s13063-020-4081-1 id = cord-282261-wcmc5mh6 author = Rhodus, Elizabeth K. title = COVID-19 and geriatric clinical trials research date = 2020-09-16 keywords = COVID-19; clinical; trial summary = The COVID-19 crisis affects every aspect of clinical trial research engagement including: recruitment and retention; ability to ensure participant safety while engaged in experimental interventions; study procedures, including consideration of remote assessments, impact on populations with health disparities, and generalizability of future results; outcome measures, including biomarker assessment; impact on the clinical trial workforce, including attrition; impact on dissemination of results and scientific collaborations, which move the clinical trial infrastructure forward; current and future funding allocations; and regulatory considerations in regards to management of altered study conduct and change of outcome measures (Fig. 1) . The purpose of this article is to highlight the impact of disasters such as the COVID-19 pandemic on geriatric clinical trials research and propose approaches for the scientific community to continue pushing forward. The vulnerability of older adults to COVID-19 is a critical reminder for the need to prepare for disasters during clinical trial design. doi = 10.1007/s40520-020-01705-x id = cord-331133-6zu44fn2 author = Riley, William T title = Rapid, responsive, relevant (R3) research: a call for a rapid learning health research enterprise date = 2013-05-10 keywords = rapid; research; trial summary = To produce more rapid, responsive, and relevant research, we propose approaches that increase relevance via greater stakeholder involvement, speed research via innovative designs, streamline review processes, and create and/or better leverage research infrastructure. Research infrastructures such as rapid learning systems and other health information technologies can be leveraged to rapidly evaluate new and existing treatments, and alleviate the extensive recruitment delays common in traditional research. What are needed are "rapid-learning research systems" that integrate researchers, funders, health systems, practitioners, and community partners asking clinically relevant questions, using efficient and innovative research designs, and leveraging rich, longitudinal data sets from millions of patients. Broad stakeholder engagement involving patients, providers, health plans, policy makers and other relevant stakeholders may seem counterintuitive as a strategy to speed research, but this time investment has the potential to improve the recruitment and retention of study participants, thus increasing the pace of conducting the study. doi = 10.1186/2001-1326-2-10 id = cord-331206-m938suxh author = Rodgers, F. title = Missing clinical trial data: the knowledge gap in the safety of potential COVID-19 drugs date = 2020-06-03 keywords = COVID-19; June; result; trial summary = However, availability of safety information is limited by a lack of timely reporting of clinical trial results on public registries or through academic publication. We aimed to analyse the knowledge gap in safety data by quantifying the number of missing clinical trial results for drugs potentially being repurposed for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for timely result reporting (within 395 days of the primary completion date). We reviewed the number of completed or terminated trials that have not reported results for an extensive, list of medications being repurposed for COVID-19, looking at all previous indications for these drugs. . https://doi.org/10.1101/2020.05.30.20117523 doi: medRxiv preprint Discussion 40.4% of the completed clinical trials for drugs that may be repurposed for COVID-19 were not found to report results on either ClinicalTrials.gov or through academic publication (Table 2 ). doi = 10.1101/2020.05.30.20117523 id = cord-324607-rpwccvqi author = Rojek, Amanda M title = Core Minimal Datasets to Advance Clinical Research for Priority Epidemic Diseases date = 2020-02-15 keywords = clinical; trial summary = Among the noteworthy successes of vaccine trials, and the commendable efforts to implement clinical treatment trials during Ebola outbreaks, we should also focus on strengthening the collection and curation of epidemiological and observational data that can improve the conception and design of clinical research. Table 1 identifies some key domains that could contribute to a core minimal dataset that informs clinical trial design for each priority pathogen. While these data have their most important benefits in improving patient management (through better recognition of disease complications and informing supportive care) and public health control, patient-based data are also used to determine key parameters for clinical trials, such as the inclusion criteria, the nature and rate of clinically relevant outcomes, and potential confounders. A systematic review and meta-analysis of patient data from the west Africa (2013-16) Ebola virus disease epidemic doi = 10.1093/cid/ciz760 id = cord-287507-1xb2hipt author = Rubio-San-Simón, A. title = Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP) date = 2020-05-29 keywords = COVID-19; trial summary = title: Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP) METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. Cancer research is particularly challenging, because patients are remarkably vulnerable: their baseline condition needs close surveillance and delays in diagnosis or treatment are potentially fatal [9] ; in parallel, cancer patients are at increased risk for severe COVID-19 disease [10] [11] [12] We evaluated the impact of the COVID-19 pandemic on the early phase clinical trial activity in paediatric oncology during the first month of state of alarm in Spain (14th March-12th April 2020). doi = 10.1007/s12094-020-02399-3 id = cord-345762-khvcoqti author = Scott, Ian A. title = COVID‐19 pandemic and the tension between the need to act and the need to know date = 2020-08-06 keywords = COVID-19; patient; trial summary = The false promise of rushed science A pandemic as serious as COVID-19 will compel some clinicians and patients to try unproven therapies based on theory, in vitro data, animal models, clinical anecdotes, observational studies and uncontrolled trials that may later be shown to be misleading. Hopefully, the same problems will not occur with remdesivir, whichdespite limited and conflicting evidence of clinical improvement from only two placebo-controlled RCT 19, 20 and one non-controlled cohort study 5has now become a ''standard of care'' in the United States for COVID-19 patients with severe pneumonia. Separating out these effects, and determining which drugs to use and when (early in the disease course or only at deterioration), will likely require large-scale trials with multiple treatment arms that are sufficiently powered to enable analyses of primary and, where indicated, secondary outcomes across different patient subgroups. doi = 10.1111/imj.14929 id = cord-316626-258rbcwb author = Serpa Neto, Ary title = Will Evidence-based Medicine Survive the COVID-19 Pandemic? date = 2020-09-17 keywords = bayesian; trial summary = One major challenge during the pandemic is to design clinical trials that can mitigate these concerns and quickly identify effective or harmful interventions to improve patient outcomes. In a pandemic with more than 75,000 new cases per day, the use of a Bayesian adaptive trial design can quickly incorporate existing evidence, drop interventions that have a higher probability of futility, redirect patients to be randomized to the most promising ones, and constantly include new and potential candidate interventions. 1144-1153) (13) describe the study protocol of a randomized, doubleblind, placebo-controlled clinical trial (ORCHID trial) assessing the impact of hydroxychloroquine in hospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and symptoms of acute respiratory infection. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial Rationale and design of ORCHID: a randomized placebo-controlled clinical trial of hydroxychloroquine for adults hospitalized with COVID-19 doi = 10.1513/annalsats.202006-587ed id = cord-284502-nesvd10a author = Singh, Arjun Gurmeet title = Clinical trials during COVID‐19 date = 2020-05-02 keywords = trial summary = Sponsors need to take into account the national guidelines and restrictive measures imposed including limitations of trial participants and staff confinements and their ability to perform visits, interviews and forms, and notification of adverse effects. The risk-benefit section of protocols should include the additional risks that the participant and trial workers could encounter due to COVID-19 with adequate risk mitigation measures. Clinical investigators and sponsors should consult their Institutional Review Boards (IRBs) or Institutional Ethics Committees (IECs) in deciding if the participants'' safety and rights are best served and protected by participating in the ongoing study or by discontinuing the IMP, intervention or even participation in the trial. Since trial participants may not be able to visit the site for the protocol specific visits and investigations, sponsors should evaluate if alternate measures such as virtual visits, alternate locations for assessment, including imaging centers and labs, could suffice when necessary, only after ensuring the safety of the participant. doi = 10.1002/hed.26223 id = cord-331487-jh34klbg author = Sivapalan, Pradeesh title = Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial date = 2020-06-10 keywords = Azithromycin; COVID-19; patient; study; treatment; trial summary = OBJECTIVES: The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of noninvasive ventilation, treatment in the intensive care unit and death. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). doi = 10.1186/s13063-020-04409-9 id = cord-286288-gduhterq author = Spitzer, Ernest title = Cardiovascular Clinical Trials in a Pandemic: Immediate Implications of Coronavirus Disease 2019 date = 2020-05-01 keywords = datum; pandemic; trial summary = Nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. Trials in patient populations with acute presentations (e.g. ST-elevation MI [STEMI]) may identify potentially suitable trial candidates; however, the capacity to comply with study procedures needs to be assessed, as well as considerations related to patient safety during follow-up. Participants in the follow-up phase (when they are generally at home) constitute a higher-risk population in the Reduced capacity at investigational sites will impact on availability to perform study visits (or phone calls) to assess and confirm eligibility, enter data in electronic case report forms (eCRFs), to report (serious) adverse events and to follow the protocol in general. The participation of several committees in clinical trials ensures proper scientific and operational oversight, data integrity and quality, as well as patient safety. doi = 10.15420/cfr.2020.07 id = cord-286144-6wtk5y7c author = Tini, Giulia title = Semantic and Geographical Analysis of COVID-19 Trials Reveals a Fragmented Clinical Research Landscape Likely to Impair Informativeness date = 2020-06-29 keywords = covid-19; figure; trial summary = Results: We observe a clear prevalence of monocentric trials with highly heterogeneous endpoints and a significant disconnect between geographic distribution and disease prevalence, implying that most countries would need to recruit unrealistic percentages of their total prevalent cases to fulfill enrolment. In the present work, we defined structured semantic ontologies with controlled vocabularies to categorize trial interventions, study endpoints, and study designs, and we conducted an analysis of the growth rate, geographical distribution, and trial characteristics of COVID-19-related trials, highlighting a number of relevant features that may impair the possibility of obtaining reliable and transferable results within the current framework. We highlight a number of peculiar characteristics of this clinical research landscape: extremely rapid growth, substantial geographical and methodological incoherence, an unusual funding pattern, prevalence of monocentric trials, and extreme heterogeneity in the interventions tested. doi = 10.3389/fmed.2020.00367 id = cord-032607-bn8g02gi author = Wake, Melissa title = Integrating trials into a whole-population cohort of children and parents: statement of intent (trials) for the Generation Victoria (GenV) cohort date = 2020-09-24 keywords = Fig; GenV; Victoria; cohort; datum; trial summary = Keywords: Research methodology, Randomization, Registry trials, Multiple baseline randomized trials, Trials within cohorts, Population studies, Generation Victoria (GenV), Clinical trial as topic, Children, Intervention Background Randomized controlled trials (RCT) provide high-quality evidence with regards to the effectiveness of therapies and prevention and are critical to guide translation and optimal resource allocation. If feasibility (potentially demonstrated through pilot studies) and mutual alignment appear likely [29] , the trial would proceed to a partnering agreement that defines at least the following 8 items: 1) Which GenV trial model is being followed; 2) Design and high-level (or draft) protocol; 3) Timelines; 4) Data sharing and governance plans; 5) Status of ethical approval; 6) Communication with participants, including information statement and consent; 7) Trial oversight and 8) Capacity assessment, including trial quality, human resource and funding. doi = 10.1186/s12874-020-01111-x id = cord-310272-utqyuy0n author = Zamani, Efpraxia D. title = Appropriating Information Technology Artefacts through Trial and Error: The Case of the Tablet date = 2020-09-18 keywords = appropriation; device; error; iPad; tablet; trial; user summary = doi = 10.1007/s10796-020-10067-8 id = cord-280020-nrnc8u28 author = Zhao, Yang title = Appealing for Efficient, Well Organized Clinical Trials on COVID-19 date = 2020-03-07 keywords = trial summary = We reviewed the characteristics of interventional trials from Chinese Clinical Trial Registration (ChiCTR) and ClinicalTrials.gov. We found some studies with potential defects including unreasonable design, inappropriate primary endpoint definition, insufficient sample size and ethical issue. Herein, we reviewed the characteristics of interventional trials from Chinese Clinical Trial Registration (ChiCTR) and Two authors (Zhao and Shen) were independently responsible for collecting the relevant information, including clinical phase, study design, presence or absence of randomization, blinding, sample size, severity of disease and source of samples. Through analyzing currently-registered interventional trials, we found some studies with potential defects including unreasonable design, inappropriate PE definition, small sample size and ethical issue. https://doi.org/10.1101/2020.03.05.20031476 doi: medRxiv preprint As appealed by some Chinese scientists recently, clinical trials on COVID-19 should be designed based on scientific rules (appropriate controls, randomization, blinding, and sufficient sample size)，ethics and patients'' benefits 5 CC-BY-NC 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity. doi = 10.1101/2020.03.05.20031476 id = cord-279637-n8acd6hj author = van der Plas, J.L. title = How to expedite early phase SARS‐CoV‐2 vaccine trials in pandemic setting – a practical perspective date = 2020-06-19 keywords = trial summary = authors: van der Plas, J.L.; Roestenberg, M.; Cohen, A.F.; Kamerling, I.M.C. title: How to expedite early phase SARS‐CoV‐2 vaccine trials in pandemic setting – a practical perspective After preclinical studies and manufacturing processes, a rate-limiting step in vaccine development is the conduct of clinical trials. In the current COVID-19 pandemic it is more important than ever to identify and select the most promising vaccine candidates as early as possible and stop clinical development for failing candidates to avoid wasting valuable time and resources. Here, we discuss several practical suggestions that could accelerate early phase vaccine trials in the COVID-19 pandemic. Recruitment and screening of participants are time consuming activities in early phase clinical trials. Significant time can be saved if potential participants can be identified, counseled and general health status assessed before the formal clinical trial approval. doi = 10.1111/bcp.14435