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. 2019 Dec;104(12):1167-1173.
doi: 10.1136/archdischild-2019-317399. Epub 2019 Sep 19.

Development of a neonatal adverse event severity scale through a Delphi consensus approach

Thomas Salaets  1 , Mark A Turner  2 , Mary Short  3 , Robert M Ward  4 , Isamu Hokuto  5 , Ronald L Ariagno  6 , Agnes Klein  7 , Sandra Beauman  8 , Kelly Wade  9 , Merran Thomson  10 , Eve Roberts  2 , Judy Harrison  11 , Theresa Quinn  12 , Gerri Baer  13 , Jonathan Davis  14   15 , Karel Allegaert  16   17 ; International Neonatal Consortium
Affiliations

Development of a neonatal adverse event severity scale through a Delphi consensus approach

Thomas Salaets et al. Arch Dis Child. 2019 Dec.

Abstract

Background: Assessment of the seriousness, expectedness and causality are necessary for any adverse event (AE) in a clinical trial. In addition, assessing AE severity helps determine the importance of the AE in the clinical setting. Standardisation of AE severity criteria could make safety information more reliable and comparable across trials. Although standardised AE severity scales have been developed in other research fields, they are not suitable for use in neonates. The development of an AE severity scale to facilitate the conduct and interpretation of neonatal clinical trials is therefore urgently needed.

Methods: A stepwise consensus process was undertaken within the International Neonatal Consortium (INC) with input from all relevant stakeholders. The consensus process included several rounds of surveys (based on a Delphi approach), face-to-face meetings and a pilot validation.

Results: Neonatal AE severity was classified by five grades (mild, moderate, severe, life threatening or death). AE severity in neonates was defined by the effect of the AE on age appropriate behaviour, basal physiological functions and care changes in response to the AE. Pilot validation of the generic criteria revealed κ=0.23 and guided further refinement. This generic scale was applied to 35 typical and common neonatal AEs resulting in the INC neonatal AE severity scale (NAESS) V.1.0, which is now publicly available.

Discussion: The INC NAESS is an ongoing effort that will be continuously updated. Future perspectives include further validation and the development of a training module for users.

Keywords: adverse event; drug safety; neonate; severity grading.

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Conflict of interest statement

Competing interests: One coauthor is an employee of a pharmaceutical company, as noted in the list of affiliations. MT has performed paid consultancy work for Chiesi Farmaceutici S.p.A, Italy. No products are discussed in this article. The consortium aims to improve methods that can be applied to evaluating the safety and effectiveness of any medical product for neonates and is consequently drug agnostic.

Figures

Figure 1
Figure 1
This figure summarises aspects of AEs that should be considered to account for safety reporting. It visualises responsibilities of the different actors and the currently available criteria and guidance. The figure is not intended to illustrate sequential activities. *Causality assessment relies on regulatory guidance; however, algorithms (eg, Du et al 6) have been developed for a neonatal population. AE, adverse event; DMSB, Data Safety Monitoring Boards; SAE, serious adverse event; ADR, adverse drug reaction; RSI, reference safety information; IRB, institutional review board; SUSAR, suspected unexpected serious adverse drug reaction.
Figure 2
Figure 2
This figure gives an overview of the development process of the NAESS. Stakeholder involvement is indicated by C (clinicians), I (industry), N (nursing representatives), P (parent representatives) and R (regulatory authority employees). AE, adverse event; INC, International Neonatal Consortium; NCI-EVS, National Cancer Institute—Enterprise Vocabulary Services; MedDRA, Medical Dictionary for Regulatory Activities; NAESS, neonatal AE severity scale.
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