Preparing for pandemics: a systematic review of pandemic influenza clinical management guidelines

Ishmeala Rigby, Melina Michelen, Vincent Cheng, Andrew Dagens, Dania Dahmash, Samuel Lipworth, Eli Harriss, Erhui Cai, Valeria Balan, Alexandra Oti, Reena Joseph, Helen Groves, Peter Hart, Shevin Jacob, Lucille Blumberg, Peter W. Horby, Louise Sigfrid*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
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What is already known on this topic?
-Clinical management guidelines (CMGs) are evidence-based tools to facilitate clinical decision-making and access to the best available evidence-based care.
-The CMGs provided early in the COVID-19 pandemic were of limited quality and scope.
-Supportive care is the main treatment for many (re-) emerging infections, and early access to evidence-based supportive care can improve patient outcomes.

What are the new findings?
-There is limited availability of pandemic influenza CMGs globally, most were developed for upper-middle and higher-income settings.
-Many CMGs were of limited quality and were produced more than 5 years ago, many during the H1N1 pandemic and only one had been updated since then.
-There were limited, heterogeneous and at times contradictory recommendations on supportive care, and limited recommendations for different at-risk populations.
-All CMGs recommended oseltamivir, but with variations in recommendations for pregnant women. Recommendations on additional neuraminidase inhibitors were conflicting, reflecting the limited evidence-base to support recommendations.

What do the new findings imply?
-The data highlight a need to ensure mechanisms for regular updates of pandemic influenza CMGs are considered at the development stage, to ensure publicly available CMGs are up to date, providing the best available evidence-based treatment and supportive care recommendations, for different at-risk populations.
-The limited scope highlights a need for investments into trials to identify effective treatments and supportive care strategies to benefit patient care and outcomes.
-A living guideline framework with mechanisms for integrating new evidence and dissemination, with close links between researchers and guideline developers from different settings, is needed to improve the quality, inclusivity, and availability of evidence-based care recommendations.
-Further research is needed into the implementation of CMGs from development to the front line in different settings and contexts.


The COVID-19 pandemic has highlighted the importance of evidence-based clinical decision-making. Clinical management guidelines (CMGs) may help reduce morbidity and mortality by improving the quality of clinical decisions. This systematic review aims to evaluate the availability, inclusivity, and quality of pandemic influenza CMGs, to identify gaps that can be addressed to strengthen pandemic preparedness in this area.

Ovid Medline, Ovid Embase, TRIP (Turning Research Into Practice), and Guideline Central were searched systematically from January 2008 to 23rd June 2022, complemented by a grey literature search till 16th June 2022. Pandemic influenza CMGs including supportive care or empirical treatment recommendations were included. Two reviewers independently extracted data from the included studies and assessed their quality using AGREE II (Appraisal of Guidelines for Research & Evaluation). The findings are presented narratively.

Forty-eight CMGs were included. They were produced in high- (42%, 20/48), upper-middle- (40%, 19/48), and lower-middle (8%, 4/48) income countries, or by international organisations (10%, 5/48). Most CMGs (81%, 39/48) were over 5 years old. Guidelines included treatment recommendations for children (75%, 36/48), pregnant women (54%, 26/48), people with immunosuppression (33%, 16/48), and older adults (29%, 14/48). Many CMGs were of low quality (median overall score: 3 out of 7 (range 1–7). All recommended oseltamivir; recommendations for other neuraminidase inhibitors and supportive care were limited and at times contradictory. Only 56% (27/48) and 27% (13/48) addressed oxygen and fluid therapy, respectively.

Our data highlights the limited availability of up-to-date pandemic influenza CMGs globally. Of those identified, many were limited in scope and quality and several lacked recommendations for specific at-risk populations. Recommendations on supportive care, the mainstay of treatment, were limited and heterogeneous. The most recent guideline highlighted that the evidence-base to support antiviral treatment recommendations is still limited. There is an urgent need for trials into treatment and supportive care strategies including for different risk populations. New evidence should be incorporated into globally accessible guidelines, to benefit patient outcomes. A ‘living guideline’ framework is recommended and further research into guideline implementation in different resourced settings, particularly low- and middle-income countries.
Original languageEnglish
Article number425
JournalBMC Medicine
Publication statusPublished - 7 Nov 2022


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