Health Protection and Influenza Research

PRIDE Study: Post-pandemic Review of anti-Influenza Drug Effectiveness

Aims

Accumulating epidemiological studies indicate that early treatment with antiviral drugs may have reduced the likelihood of hospitalisation, severe outcomes and death. However, these studies are often too small and lack statistical power to produce conclusive findings.

Therefore this study aims to combine and analyse data from many observational studies (case series, case-control and cohort studies) and randomised control trials to provide a reliable assessment of the impact of antiviral use on public health outcomes for the 2009/10 A(H1N1)pdm09 influenza pandemic.

It is hoped that the findings from this study will inform future public health policy for pandemic deployment of antivirals and elucidate the advantages gained during 2009-10.  

pride-study

A patient-level global meta-analysis on the effectiveness of antiviral use on outcomes of public health importance during the 2009/10 A(H1N1)pdm09 influenza pandemic.

 

 

Frequently asked questions

What is the PRIDE Study research collaboration?

We invited institutions worldwide to contribute
data that would allow us to investigate the impact of antiviral (neuraminidase inhibitor) use on patient outcomes (severe illness, complications and mortality) of A(H1N1)pdm09 pandemic influenza virus infection. 

We have received 81 datasets from 38 countries
with a total sample size of 170,858 influenza patients. We have so far completed and published the IPD meta-analyses investigating the association between neuraminidase inhibitor antivirals and A(H1N1)pdm09-related mortality
(published in The Lancet Respiratory Medicine), and A(H1N1)pdm09-related pneumonia (published in Influenza and Other Respiratory Viruses).

The article along with the  commentary can be found on The Lancet Respiratory Medicine’s website.

View a  word-processed copy of the published manuscript.

The article reporting findings from the IPD
meta-analysis investigating the association between neuraminidase inhibitor antivirals and
A(H1N1)pdm09-related pneumonia can be found
on Influenza and Other Respiratory Viruses’ website.

 

Can I view the protocol?

The study protocol was registered with the PROSPERO register of systematic reviews (registration number: CRD42011001273).

 
 

Who owns the PRIDE Study data?

Although the PRIDE study pooled dataset is being held securely within The University of Nottingham for the purpose of standardisation and analysis, it is the property of individual research groups and as such data will not be disclosed to any third party.

Once we have published all the findings of the IPD analysis, all PRIDE study collaborators will discuss whether they would be happy to allow other researchers (both within and outside the collaboration) to validate our findings on request and under a data sharing agreement.

Please bear in mind that all PRIDE collaborators will need to agree for sharing of the anonymised pooled dataset to take place for the sole purpose of verifying the analyses conducted in Nottingham (not for the purposes of secondary research); and this will be subject to approval from individual institutional review boards.

Once all analyses related to the effectiveness of antivirals have been completed, all PRIDE collaborators will be invited to discuss whether they would be happy to allow the cnsortium to undertake secondary analyses (for example, exploring the effectiveness of antibiotics and corticosteroids).

 

Will findings from this study be published in a peer-reviewed journal?

We intend to publish all results from this study in peer-reviewed journals. The responsibility for data analysis and preparation of manuscripts lies with the Health Protection and Influenza Research Group at the University of Nottingham.

Draft manuscripts and appropriate supplementary material have been/will always be circulated widely to all authors (including data contributors) for comment/agreement before submission to a peer reviewed journal. Authorship for contributors of individual datasets will be as part of the PRIDE study consortium.

Two investigators from each participating institution are included within the PRIDE study consortium as authors on any publication arising from the consortium. With regard to individual named authorship, ultimately we have to adhere to the rulings and adjudications of individual journals.

We have already conducted a systematic review of published studies on this topic, which has been published in the Journal of Infectious Diseases. Our key finding was that early antiviral use was associated with a significant reduction in mortality compared to late or no antiviral use.

doi:10.1093/infdis/jis726

Our primary analysis based an Individual Participant Data (IPD) pooled approach also found that NAI treatment was associated with a reduction in mortality in adult patients hospitalised with influenza A(H1N1)pdm09.

doi:10.1016/S2213-2600(14)70041-4

Our second manuscript using the same IPD approach found that early NAI treatment of patients hospitalised with A (H1N1)pdm09 virus infection did not reduce the likelihood of influenza-related pneumonia (IRP), when compared to no treatment. However, in patients who developed IRP, early NAI treatment, when compared to later NAI treatment, reduced the likelihood of mortality and needing ventilatory support.

doi: 10.1111/irv.12363

Our third manuscript using the same IPD approach found that in a population with confirmed or suspected A(H1N1)pdm09 and at high risk of hospitalisation, outpatient or community-based NAI treatment significantly reduced the likelihood of requiring hospital admission.

doi: 10.1093/cid/cix127

 
 

What protocol will be followed when ascribing order of authorship on any publications based on this work?

Due to the potentially large number of willing collaborators (so far we have about 60 interested groups), the study's authorship will be presented as follows: Muthuri, Leonardi-Bee, Venkatesan, Van-Tam, Myles on behalf of the PRIDE study group and name all authors in the PRIDE Study group either as a footnote or before acknowledgments (following journal protocols). This is in keeping with the existing practice for large collaborative meta-analysis and IPD analysis projects.

 

Will the pooled anonymised dataset be made available to other researchers within the collaboration for validation?

Analysis plans, results and draft manuscripts have been and will be shared with all PRIDE consortium members but at this stage only the Health Protection and Influenza Research Group, University of Nottingham have access to the pooled anonymised dataset.

Ideally, in the spirit of transparency, we would have a publicly accessible pooled dataset so that other researchers can validate our analyses. In reality though, we may not be given permission by individual research groups within the PRIDE consortium or their local ethics boards to share this data even in a pooled format.

We will revisit this discussion with all our collaborators once we have completed all our planned analyses

 

Who is funding this project?

The study is taking place through an unrestricted educational grant funding from F. Hoffmann-La Roche but is being undertaken fully independently of the company, which has had/will have: no input to the project design; no access to any of the data; no role in analysis or data interpretation; no preview of the study results; and no opportunity to preview or comment on any manuscripts arising from the work.

View the ROCHE contract/letter of clarification 

 

Can I still contribute my data towards the PRIDE study?

We are no longer actively recruiting new collaborators for the PRIDE study.

 

Findings

Findings from IPD meta-analysis investigating the association between neuraminidase inhibitors treatment and mortality have now been published:

Preliminary findings on pneumonia and length of stay as presented at the Fifth European Scientific Working Group on Influenza (ESWI) Conference, Riga, 17th September 2015.

Findings from IPD meta-analysis investigating
the association between neuraminidase inhibitors treatment and A(H1N1)pdm09-related
pneumonia have now been published. Read the article on the Influenza and Other Respiratory Viruses’ website.

Findings from a collaborative project, led by researchers at the University of Warwick, looking at neuraminidase inhibitor stockpiling decisions for pandemic influenza have now been published. Read the article on the F1000 publishing platform’s website.

Findings from IPD meta-analysis investigating the impact of outpatient neuraminidase inhibitor treatment in patients infected With influenza A (H1N1) pdm09 at high risk of hospitalisation have now been published. Read the article on the Clinical Infectious Diseases’ website.

 

 

Meet the team

Professor Jonathan Nguyen van-Tam
Chair of the Health Protection and Influenza Research Group
 

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Prof. Van-Tam is a widely recognised national and international expert on influenza and advises multiple governments and the WHO and European Centre for Disease Prevention and Control. He is providing overall strategic leadership of the PRIDE study group.

Dr Puja Myles
Associate Professor of Health Protection and Epidemiology at the University of Nottingham
 

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Dr Myles’s main area of expertise is infectious disease epidemiology, particularly epidemiology influenza and pneumonia. She is the principal investigator of the PRIDE research consortium. In April 2017 Dr. Myles moved on to her current role at the Medicines and Healthcare products Regulatory Agency (MHRA). She continues to offer critical intellectual input to the PRIDE study.

joleonardibee
Dr Jo Leonardi-Bee
Associate Professor in Medical Statistics
 

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Dr Leonardi-Bee's main areas of research are the applications of systematic reviews and meta-analysis in the epidemiological studies. She is currently involved in a number of trials and projects in the areas of tobacco control, dermatology and is the methodological lead in the PRIDE study group.
stellamuthuri
Dr Stella Muthuri
Postdoctoral Researcher in Epidemiology
 

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Dr Muthuri was involved in the data collation, data cleaning, analyses and the general day-to-day running of the PRIDE study from its inception until March 2015. She has now moved on to a postdoctoral post at University College London. Dr Muthuri continues to be a part of PRIDE research consortium offering important intellectual content to subsequent manuscripts arising from the PRIDE research collaboration.

SudhirVenkatesan
Dr Sudhir Venkatesan
Research Associate

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Dr Venkatesan obtained a Master’s degree in Public Health from the University of Nottingham in 2011 and is currently pursuing PhD in computational epidemiology from the same university. Until Dr Muthuri’s departure in March 2015, Dr Venkatesan assisted her with the data standardisation and analysis on the PRIDE study, and has since taken over the day-to-day running of the project.

 

 

Contact

Dr Sudhir Venkatesan
Division of Epidemiology and Public Health
University of Nottingham
Clinical Sciences Building
City Hospital
Hucknall Road
Nottingham, NG5 1PB 

telephone: +44 (0)115 823 1718
email: sudhir.venkatesan@nottingham.ac.uk  
 

 

Health Protection and Influenza Research

Division of Epidemiology and Public Health
Nottingham City Hospital
The University of Nottingham
Hucknall Road, Nottingham, NG5 1PB


telephone: +44 (0)115 823 0276
email:Jonathan.Van-Tam@nottingham.ac.uk