journal club flushing out the evidence for neuraminidase inhibitors in the treatment of influenza n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Manish Khullar BSc.(Pharm) Sukhjinder Sidhu BSc.(Pharm) Interior Health Pharmacy Residents PowerPoint Presentation
Download Presentation
Manish Khullar BSc.(Pharm) Sukhjinder Sidhu BSc.(Pharm) Interior Health Pharmacy Residents

Loading in 2 Seconds...

play fullscreen
1 / 38

Manish Khullar BSc.(Pharm) Sukhjinder Sidhu BSc.(Pharm) Interior Health Pharmacy Residents - PowerPoint PPT Presentation


  • 223 Views
  • Uploaded on

Journal Club FLUshing Out the Evidence for Neuraminidase Inhibitors in the Treatment of InFLUenza. Manish Khullar BSc.(Pharm) Sukhjinder Sidhu BSc.(Pharm) Interior Health Pharmacy Residents Infectious Disease Rotation May 1, 2014. 2014. The Controversy. Influenza. Signs/symptoms

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Manish Khullar BSc.(Pharm) Sukhjinder Sidhu BSc.(Pharm) Interior Health Pharmacy Residents' - libby-ramos


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
journal club flushing out the evidence for neuraminidase inhibitors in the treatment of influenza
Journal ClubFLUshing Out the Evidence for Neuraminidase Inhibitors in the Treatment of InFLUenza

Manish KhullarBSc.(Pharm)

Sukhjinder Sidhu BSc.(Pharm)

Interior Health Pharmacy Residents

Infectious Disease Rotation

May 1, 2014

influenza
Influenza
  • Signs/symptoms
    • Fever
    • Sore throat
    • Rhinitis
    • Nonproductive cough
    • Myalgias
    • Malaise
  • Complications
    • Secondary infections (bacterial pneumonia, otitis media)
    • Hospitalizations
    • Death
title
Title
  • Title does not state it’s a meta-analysis or systematic review
  • Authors are Cochrane Collaboration Group
    • Can imply it’s at least a systematic review
introduction
Introduction

Rationale

  • Influenza antivirals are commonly used and stockpiled
  • Previous reviews have risk of reporting bias
  • On list of WHO essential drugs

Objectives

  • potential benefits and harms of NIs for influenza in all age groups… all clinical study reports of published and unpublished R, PC trials and regulatory comments
methods
Methods

Eligibility Criteria

  • Studies
    • NIs RCTs for prophylaxis, post-exposure prophylaxis and treatment of influenza
      • Published and unpublished trials
      • Manufacturer-funded and non-manufacturer funded clinical trials
    • No specific length of follow-up considered
    • Exclusion criteria not identified
  • THOUGHTS?
methods1
Methods

Eligibility Criteria

  • Participants
    • Previously health children and adults
    • Exposed to naturally occurring influenza with or without symptoms
    • Excluded people with illnesses with more significant effects on the immune system (i.e. malignancy or HIV infection)
methods2
Methods

Information Sources

  • Electronic databases
    • CENTRAL, MEDLINE, MEDLINE (Ovid), EMBASE, PubMed (NOT MEDLINE), DARE, NHSEED, HEED
    • January 2010 – July 2013
  • Clinical study reports
    • Extensive searches conducted
  • Regulatory information searches
    • Extensive searches conducted
methods3
Methods

Search Strategy

methods4
Methods

Study Selection

  • 2 authors reviewed title & abstracts
  • 4 authors independently read all data
    • definitely include; definitely exclude; need more information
  • 2 more authors reviewed for inclusion in Stage 1
methods5
Methods

Study Selection

  • Stage 1  assessing the reliability and completeness of trial data
    • authors discussed face-to-face each trial with comments and other information from regulatory sources
    • decision to whether move trial to stage 2 via consensus
  • Stage 2 satisfied following criteria:
    • completeness – CONSORT-specified methods & specified results
    • internal consistency
    • external consistency
methods6
Methods

Data Collection Process

  • Utilized a modified CONSORT statement-based extraction template
    • 2 authors each searched oseltamivir and zanamivirtrials
    • Disagreements were resolved amongst each other in oseltamivir group and by a 3rd author in the zanamivir group
  • For clinical study reports, complete list of trials were sent to manufacturers asking them to check accuracy and completeness of their list
methods7
Methods

Risk of Bias in Individual Studies

  • Used Cochrane “Risk of bias” tool
  • Review author judged risk of bias
  • Bias assessed at outcome and study level
    • Studies included had high risk of bias
    • Some outcomes from studies were poorly documented/collected
methods8
Methods

Synthesis of Results

  • Chi2: test for heterogeneity
  • I2: level of statistical heterogeneity
    • Threshold for significance unknown
  • Tau2: estimate of between-study variance
  • Combining data using random-effects approach
  • WHAT SHOULD THEIR THRESHOLD BE?
methods9
Methods

Risk of Bias Across Studies

  • Included unpublished trials
methods10
Methods

Additional analyses

  • Subgroup analysis to investigate high estimates of heterogeneity
  • Meta-regression to investigate pneumonia heterogeneity
  • Sensitivity analysis
    • Fixed-effect method of Mantel and Haenszel to supplement primary analyses using random-effects method
    • Peto’s method used when sparse data and borderline sensitivity
  • WHAT ANALYSES WOULD BE BENEFICIAL?
results
Results

Study Selection

208 studies identified form various sources

123 studies excluded

19 studies awaiting classification

66 studies for which clinical study reports requested

5 trials excluded due to incompleteness

2 trials excluded as didn’t fit inclusion criteria

53 studies met eligibility

  • 46 trials included
  • 20 oseltamivir
  • 26 zanamivir
results1
Results

Risk of Bias within Studies

  • Presented selection, attrition, reporting, performance and detection bias
    • To address issue of reporting bias, they ignored published trial reports if clinical study reports and regulatory information were available
    • Random sequence generation missing in many trials
    • Blinding may have been affected in many trials
    • Placebos may have contained active substances
results2
Results
  • No analysis conducted on mortality outcome
    • Discussed deaths in the oseltamivir and zanamivir arms, but no statistical analyses completed
  • THOUGHTS?
time to first alleviation of symptoms in adult treatment itt population oseltamivir vs placebo
Time to First Alleviation of Symptoms in Adult Treatment (ITT Population)Oseltamivir vs. Placebo
time to first alleviation of symptoms in adult treatment itt population oseltamivir vs placebo1
Time to First Alleviation of Symptoms in Adult Treatment (ITT Population)Oseltamivir vs. Placebo
  • Clinically significant reduction?
  • When to use random vs. fixed effects?
results3
Results

Risk of Bias Across Studies

  • No funnel plot or Egger’s test done to rule out publication bias
    • Made every effort to minimize publication bias by including non-published trials
  • No discussion on bias across studies, only bias within studies
  • SHOULD WE BE WORRIED ABOUT PUBLICATION BIAS?
results4
Results

Additional Analysis

  • Subgroup analysis
    • Time to first alleviation of symptoms in adults by infection status
    • Pneumonia (diagnosis vs. non-diagnosis)
discussion
Discussion

Summary of Evidence

  • NIs have small, non-specific effects on reducing time to alleviation of influenza-like illness symptoms in adults
  • Treatment trials… do not settle the question of whether complications of influenza, such as pneumonia are reduced
  • Use of oseltamivir increases the risk of adverse events such as nausea, vomiting…
discussion1
Discussion

Conclusions

  • … appears to be no evidence for patients, clinicians or policy-makers to use these drugs (NIs) to prevent serious outcomes
  • Implications for future research
    • More effective preventative measures
    • Early identification of complications
limitations
Limitations
  • Did not formally assess mortality outcome
  • Effect of complications was based on unclear and potentially unreliable definitions
  • Included many trials with high risk of bias
    • Affects validity of the results
  • Authors do not summarize results in the context of observational study results that are driving standard of care in influenza treatment
  • A generalized conclusion is made without taking severity of illness into account
our conclusions
Our Conclusions
  • Population studied was broad
    • Not generalizable to specific groups
    • Doesn’t address the question of whether to give NIs in high risk patients
  • More reviews needed to draw definite conclusions about mortality and reductions in complications
  • More reviews needed in severe influenza (i.e. critical care patients)
your conclusions
Your Conclusions?

Cochrane

IDSA