Randomize the First Patient!

Tc, Chalmers

doi:10.1056/nejm197701132960214

Cited by 47 publications

(9 citation statements)

References 6 publications

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“…Unfortunately, the main result of the RCTs conducted years after proved not to be in favour of the laparoscopic approach, by which time it was too late [ 19 ]. This is a further argument for the standpoint introduced by Chalmers: “ When new interventions are assessed we should always randomise the first patient ” [ 20 , 21 ].…”

Section: Resultsmentioning

confidence: 99%

Specific barriers to the conduct of randomised clinical trials on medical devices

Neugebauer

Rath

Antoine

et al. 2017

Trials

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BackgroundMedical devices play an important role in the diagnosis, prevention, treatment and care of diseases. However, compared to pharmaceuticals, there is no rigorous formal regulation for demonstration of benefits and exclusion of harms to patients. The medical device industry argues that the classical evidence hierarchy cannot be applied for medical devices, as randomised clinical trials are impossible to perform. This article aims to identify the barriers for randomised clinical trials on medical devices.MethodsSystematic literature searches without meta-analysis and internal European Clinical Research Infrastructure Network (ECRIN) communications taking place during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.ResultsIn addition to the barriers that exist for all trials, we identified three major barriers for randomised clinical trials on medical devices, namely: (1) randomisation, including timing of assessment, acceptability, blinding, choice of the comparator group and considerations on the learning curve; (2) difficulties in determining appropriate outcomes; and (3) the lack of scientific advice, regulations and transparency.ConclusionsThe present review offers potential solutions to break down the barriers identified, and argues for applying the randomised clinical trial design when assessing the benefits and harms of medical devices.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2168-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Specific barriers to the conduct of randomised clinical trials on medical devices

Neugebauer

Rath

Antoine

et al. 2017

Trials

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“…Thomas Chalmers highlighted in 1977 the need to 'Randomize the first patient' 19 , and a reassuring 75.5% of trials are indeed randomized. However, we identified areas of concern.…”

Section: Discussionmentioning

confidence: 99%

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

et al. 2020

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Background: Never before have clinical trials drawn as much public attention as those testing interventions for COVID-19. We aimed to describe the worldwide COVID-19 clinical research response and its evolution over the first 100 days of the pandemic. Methods: Descriptive analysis of planned, ongoing or completed trials by April 9, 2020 testing any intervention to treat or prevent COVID-19, systematically identified in trial registries, preprint servers, and literature databases. A survey was conducted of all trials to assess their recruitment status up to July 6, 2020. Results: Most of the 689 trials (overall target sample size 396,366) were small (median sample size 120; interquartile range [IQR] 60-300) but randomized (75.8%; n=522) and were often conducted in China (51.1%; n=352) or the USA (11%; n=76). 525 trials (76.2%) planned to include 155,571 hospitalized patients, and 25 (3.6%) planned to include 96,821 health-care workers. Treatments were evaluated in 607 trials (88.1%), frequently antivirals (n=144) or antimalarials (n=112); 78 trials (11.3%) focused on prevention, including 14 vaccine trials. No trial investigated social distancing. Interventions tested in 11 trials with >5,000 participants were also tested in 169 smaller trials (median sample size 273; IQR 90-700). Hydroxychloroquine alone was investigated in 110 trials. While 414 trials (60.0%) expected completion in 2020, only 35 trials (4.1%; 3,071 participants) were completed by July 6. Of 112 trials with detailed recruitment information, 55 had recruited <20% of the targeted sample; 27 between 20-50%; and 30 over 50% (median 14.8% [IQR 2.0-62.0%]). Conclusions: The size and speed of the COVID-19 clinical trials agenda is unprecedented. However, most trials were small investigating a small fraction of treatment options. The feasibility of this research agenda is questionable, and many trials may end in futility, wasting research resources. Much better coordination is needed to respond to global health threats.

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“…A well-designed and well-conducted RCT is considered the gold standard in clinical research. RCTs rank top of the evidence hierarchy compared to other research approaches, as they employ the design least affected by bias, surpassed only by a systematic review of combinable, well-conducted RCTs [ 3 , 4 , 23 – 25 ]. But like any type of research, RCTs have their advantages and disadvantages, and can be subject to abuse.…”

Section: Resultsmentioning

confidence: 99%

“…Due to the significantly lower cost and labour associated with observational studies (e.g., non-randomised, cohort, and case-control studies) these often seem an appealing alternative. Compared to RCTs, observational studies produce results that have less evidential weight [ 3 , 4 , 23 – 25 ], and even when they are large-scale and well-conducted, observational studies will often greatly overestimate or underestimate potential effects, and thus fail to determine the true balance between benefits and harms from an intervention [ 3 , 4 , 23 , 26 – 29 ]. Accordingly, clinicians and investigators run large risks when they base treatment recommendations on observational evidence, especially when systematic reviews do not find an indication for the intervention at hand [ 30 – 34 ].…”

Section: Resultsmentioning

confidence: 99%

“…Roughly 50% of all initiated clinical trials fail to complete their reporting [ 50 – 52 ], and given that many clinical trials are not found in registries or detailed information on them is unavailable, this number is likely an underestimation. Moreover, of all trials reported, major risks of systematic errors (bias), design errors, and random errors (play of chance) make the clinical value of the results highly questionable [ 17 – 23 ].…”

Section: Resultsmentioning

confidence: 99%

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Barriers to the conduct of randomised clinical trials within all disease areas

Djurisic

Rath

Gaber

et al. 2017

Trials

104

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BackgroundRandomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers.MethodsWe performed systematic literature searches and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project.ResultsThe following barriers to randomised clinical trials were identified: inadequate knowledge of clinical research and trial methodology; lack of funding; excessive monitoring; restrictive privacy law and lack of transparency; complex regulatory requirements; and inadequate infrastructures. There is a need for more pragmatic randomised clinical trials conducted with low risks of systematic and random errors, and multinational cooperation is essential.ConclusionsThe present paper presents major barriers to randomised clinical trials. It also underlines the value of using a pan-European-distributed infrastructure to help investigators overcome barriers for multi-country trials in any disease area.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-2099-9) contains supplementary material, which is available to authorized users.

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Randomize the First Patient!

Cited by 47 publications

References 6 publications

Specific barriers to the conduct of randomised clinical trials on medical devices

Specific barriers to the conduct of randomised clinical trials on medical devices

The worldwide clinical trial research response to the COVID-19 pandemic - the first 100 days

Barriers to the conduct of randomised clinical trials within all disease areas

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