The Reproducibility of Cerebrovascular Randomized Controlled Trials

Adeeb, Nimer; Terrell, Danielle; Whipple, Stephen Garrett; Thakur, Jai Deep; Griessenauer, Christoph J.; Adeeb, Abdallah; Aslan, Asala; Mamilly, Ahmed; Mortazavi, Martin M.; Dossani, Rimal H; Guthikonda, Bharat; Ogilvy, Christopher S.; Thomas, Ajith J.; Moore, Justin M.

doi:10.1016/j.wneu.2020.04.106

Cited by 4 publications

(17 citation statements)

References 26 publications

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“…It further emphasises that an FI of 3 is low and RCTs in aSAH are fragile. Our finding is in agreement with those of Khan et al, and Adeeb et al, in cardiovascular and cerebrovascular RCTs respectively[5,7]. Taken together this suggests the problem is not restricted to a single speciality within medicine but is generic to clinical research.…”

Section: Discussionsupporting

confidence: 93%

“…The median fragility index in our systematic appraisal of randomized trials in aSAH is 3, with an interquartile range of 0 to 5. This is comparable to findings in critical care generally[4] and similar to a previous analysis of cerebrovascular trials[7], but is lower than that in cardiovascular studies, where the median fragility index was 13[5]. The fragility quotient relates the FI to the size of the trial and can be interpreted as the number of patients per 100 required to experience a different event to render the result non-significant.…”

Section: Discussionsupporting

confidence: 85%

“…Previous application of fragility analysis to the field of neurocritical care has been limited. A review of cerebrovascular studies limited by date and database showed the median fragility index (FI) of seven randomised controlled trials (RCTs) in aneurysmal subarachnoid haemorrhage (aSAH) to be 5[7]. No studies of nimodipine, the only drug demonstrated to have a neuroprotective effect in SAH[1], were included in the review.…”

Section: Introductionmentioning

confidence: 99%

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The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: a systematic review

Ramesh

Munby

Thomas

2021

Preprint

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Background Fragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomized trials in aneurysmal subarachnoid haemorrhage. Methods This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration. Results We identified 3809 records with 17 randomized trials selected for analysis. The median fragility index was 3 (inter-quartile range 0-5) and the median fragility quotient was 0.012 (IQR 0-0.034). Six of nineteen trial outcomes (31.6%) had an fragility index of 0. In seven trials (36.8%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 17.6% of trials are at low risk of bias. Conclusions Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: a systematic review

Ramesh

Munby

Thomas

2021

Preprint

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“…When reported along with the p-value, the fragility index can help clinicians understand the potential clinical utility and robustness of RCT findings. 8 Despite the concept of fragility index inclusion being relatively novel within the field of otolaryngology and head and neck oncology, retrospective analyses of the fragility index for RCTs have been conducted in other surgical specialties such as orthopaedic surgery, [9][10][11][12][13][14][15][16] neurosurgery [17][18][19][20] and urology. 21,22 Similarly, our aim is to characterise the fragility index of statistically significant outcomes from RCTs investigating both surgical and non-surgical interventions for head and neck cancer.…”

Section: Introductionmentioning

confidence: 99%

The fragility index: how robust are the outcomes of head and neck cancer randomised, controlled trials?

Suresh,

Go,

Fritz

et al. 2023

J. Laryngol. Otol.

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Background The fragility index represents the minimum number of patients required to convert an outcome from statistically significant to insignificant. This report assesses the fragility index of head and neck cancer randomised, controlled trials. Methods Studies were extracted from PubMed/Medline, Scopus, Embase and Cochrane databases. Results Overall, 123 randomised, controlled trials were included. The sample size and fragility index medians (interquartile ranges) were 103 (56–213) and 2 (0–5), respectively. The fragility index exceeded the number of patients lost to follow up in 42.3 per cent (n = 52) of studies. A higher fragility index correlated with higher sample size (r = 0.514, p < 0.001), number of events (r = 0.449, p < 0.001) and statistical significance via p-value (r = −0.367, p < 0.001). Conclusion Head and neck cancer randomised, controlled trials demonstrated low fragility index values, in which statistically significant results could be nullified by altering the outcomes of just two patients, on average. Future head and neck oncology randomised, controlled trials should report the fragility index in order to provide insight into statistical robustness.

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“…A review of cerebrovascular studies limited by date and database showed the median fragility index (FI) of seven randomised controlled trials (RCTs) in aneurysmal subarachnoid haemorrhage (aSAH) to be 5. 7 No studies of nimodipine, the only drug demonstrated to have a neuroprotective effect in SAH, were included in the review. Although the authors…”

Section: Introductionmentioning

confidence: 99%

The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: A systematic review

Ramesh,

Munby,

Thomas

2023

Journal of the Intensive Care Society

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Background: Fragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomised trials in aneurysmal subarachnoid haemorrhage. Methods: This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration. Results: We identified 4825 records with 18 randomised trials selected for analysis. The median fragility index was 2.5 (inter-quartile range 0.25–5) and the median fragility quotient was 0.015 (IQR 0.02–0.039). Five of 20 trial outcomes (25%) had a fragility index of 0. In seven trials (39.0%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 16.7% of trials are at low risk of bias. Conclusion: Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.

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The Reproducibility of Cerebrovascular Randomized Controlled Trials

Cited by 4 publications

References 26 publications

The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: a systematic review

The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: a systematic review

The fragility index: how robust are the outcomes of head and neck cancer randomised, controlled trials?

The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: A systematic review

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