Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

Sigfrid, Louise; Maskell, Katherine; Bannister, Peter; Ismail, Sharif; Collinson, Shelui; Regmi, Sadie; Blackmore, Claire; Harriss, Eli; Longuere, Kajsa Stina; Gobat, Nina; Horby, Peter; Clarke, Mike; Carson, Gail

doi:10.1186/s12916-020-01624-8

Cited by 39 publications

(48 citation statements)

References 75 publications

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“…Lastly, on-going research concerning longer term sequelae and underlying biology is necessary ( 34 – 36 ), especially since the H1N1 pandemic was followed by a wave of encephalitis lethargica that put a considerable strain on health services ( 37 ).…”

Section: Moving Forwardmentioning

confidence: 99%

“…In order to become more proficient and expedient at addressing viral outbreaks we must learn from current events; what has been done well in addition to shortcomings ( 36 ). Rapid and early identification of novel zoonoses or mutations is vital to limit spread; containment alone however may prove difficult, as demonstrated by SARS-CoV-2.…”

Section: Future Pandemicsmentioning

confidence: 99%

“…Rapid and early identification of novel zoonoses or mutations is vital to limit spread; containment alone however may prove difficult, as demonstrated by SARS-CoV-2. Once a new threat has reached pandemic proportions, emphasis should turn toward international collaborative efforts of identification, classification, and knowledge sharing, especially with neurological complications where caseloads may be smaller ( 36 , 38 ).…”

Section: Future Pandemicsmentioning

confidence: 99%

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Encephalitis in a Pandemic

Walton

Thakur

Venkatesan³

et al. 2021

Front. Neurol.

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Section: Moving Forwardmentioning

confidence: 99%

Section: Future Pandemicsmentioning

confidence: 99%

Section: Future Pandemicsmentioning

confidence: 99%

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Encephalitis in a Pandemic

Walton

Thakur

Venkatesan³

et al. 2021

Front. Neurol.

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“…Emerging epidemics represent a substantial challenge to human health worldwide [1][2][3][4]. When cases are clustered in specific locations, two key questions arise: (i) will exported cases lead to local outbreaks in new locations?…”

Section: Introductionmentioning

confidence: 99%

Interventions targeting non-symptomatic cases can be important to prevent local outbreaks: SARS-CoV-2 as a case study

Lovell-Read

Funk

Obolski

et al. 2021

J. R. Soc. Interface.

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During infectious disease epidemics, an important question is whether cases travelling to new locations will trigger local outbreaks. The risk of this occurring depends on the transmissibility of the pathogen, the susceptibility of the host population and, crucially, the effectiveness of surveillance in detecting cases and preventing onward spread. For many pathogens, transmission from pre-symptomatic and/or asymptomatic (together referred to as non-symptomatic) infectious hosts can occur, making effective surveillance challenging. Here, by using SARS-CoV-2 as a case study, we show how the risk of local outbreaks can be assessed when non-symptomatic transmission can occur. We construct a branching process model that includes non-symptomatic transmission and explore the effects of interventions targeting non-symptomatic or symptomatic hosts when surveillance resources are limited. We consider whether the greatest reductions in local outbreak risks are achieved by increasing surveillance and control targeting non-symptomatic or symptomatic cases, or a combination of both. We find that seeking to increase surveillance of symptomatic hosts alone is typically not the optimal strategy for reducing outbreak risks. Adopting a strategy that combines an enhancement of surveillance of symptomatic cases with efforts to find and isolate non-symptomatic infected hosts leads to the largest reduction in the probability that imported cases will initiate a local outbreak.

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“…Recently, a scoping review evaluated political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges associated with clinical research in the context of emergency epidemics [ 5 ]. The authors highlighted the challenges associated with the planning, conduct and dissemination of clinical research responses during an epidemic.…”

Section: Introductionmentioning

confidence: 99%

Evaluation by simulation of clinical trial designs for evaluation of treatment during a viral haemorrhagic fever outbreak

Manchon

Belhadi

Laouénan

2021

BMC Med Res Methodol

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Background Viral haemorrhagic fevers are characterized by irregular outbreaks with high mortality rate. Difficulties arise when implementing therapeutic trials in this context. The outbreak duration is hard to predict and can be short compared to delays of trial launch and number of subject needed (NSN) recruitment. Our objectives were to compare, using clinical trial simulation, different trial designs for experimental treatment evaluation in various outbreak scenarios. Methods Four type of designs were compared: fixed or group-sequential, each being single- or two-arm. The primary outcome was 14-day survival rate. For single-arm designs, results were compared to a pre-trial historical survival rate pH. Treatments efficacy was evaluated by one-sided tests of proportion (fixed designs) and Whitehead triangular tests (group-sequential designs) with type-I-error = 0.025. Both survival rates in the control arm pC and survival rate differences Δ (including 0) varied. Three specific cases were considered: “standard” (fixed pC, reaching NSN for fixed designs and maximum sample size NMax for group-sequential designs); “changing with time” (increased pC over time); “stopping of recruitment” (epidemic ends). We calculated the proportion of simulated trials showing treatment efficacy, with K = 93,639 simulated trials to get a type-I-error PI95% of [0.024;0.026]. Results Under H0 (Δ = 0), for the “standard” case, the type-I-error was maintained regardless of trial designs. For “changing with time” case, when pC > pH, type-I-error was inflated, and when pC < pH it decreased. Wrong conclusions were more often observed for single-arm designs due to an increase of Δ over time. Under H1 (Δ = + 0.2), for the “standard” case, the power was similar between single- and two-arm designs when pC = pH. For “stopping of recruitment” case, single-arm performed better than two-arm designs, and fixed designs reported higher power than group-sequential designs. A web R-Shiny application was developed. Conclusions At an outbreak beginning, group-sequential two-arm trials should be preferred, as the infected cases number increases allowing to conduct a strong randomized control trial. Group-sequential designs allow early termination of trials in cases of harmful experimental treatment. After the epidemic peak, fixed single-arm design should be preferred, as the cases number decreases but this assumes a high level of confidence on the pre-trial historical survival rate.

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Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

Cited by 39 publications

References 75 publications

Encephalitis in a Pandemic

Encephalitis in a Pandemic

Interventions targeting non-symptomatic cases can be important to prevent local outbreaks: SARS-CoV-2 as a case study

Evaluation by simulation of clinical trial designs for evaluation of treatment during a viral haemorrhagic fever outbreak

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