Notes
Slide Show
Outline
1
Community-Based Studies of Consumer Antiseptics

FDA Nonprescription Drug Advisory Committee Meeting


  • Allison E. Aiello, PhD, MS
  • Assistant Professor of Epidemiology
  • University of Michigan-School of Public Health
  • Center for Social Epidemiology & Population Health
2
Outline

  • Literature Review


  • Methodological Issues


  • Summary and Future Research Needs
3
Overall Goal
  • Estimate the reduction in risk attributed to specific hand hygiene products:


    • Plain soap handwash
    • Antiseptic soap handwash
      • Triclosan,Triclocarban
    • Hand sanitizers
      • Alcohol-based
      • Non-alcohol based hand sanitizers
        • Benzalkonium chloride
4
Methods
  • Use of earlier systematic review articles:
    • Aiello, AE & Larson, EL. (2002) What is the evidence for a causal link between hygiene and infections? Lancet Infect Dis. Vol.2
    • Curtis, V & Cairncross, S. (2003) Effect of washing hands with soap on diarrhoea risk in the community: a systematic review. Lancet Infect Dis. Vol.3
    • Meadows, E & Le Saux, N. (2004) A systematic review of the effectiveness of antimicrobial rinse-tree hand sanitizers for prevention of illness-related absenteeism in elementary school children. BMC Pub Health.(4)50

  • PubMed database search for other articles from 1980 to 2005


    • Key word combinations: hygiene, infection, soap, washing, handwashing, community, alcohol, antibacterial, triclosan, day care, school, hand sanitizer
5
Methods Continued
  • Inclusion Criteria:


    • Outcome:
      • Culture confirmed infection, symptoms of infection, or absenteeism associated with infectious illness

    • Study Design:
      • Community based
      • Intervention or cross-over study with or without formal randomization
        • Intervention arm provided
          • Plain soap (not identified)
          • Antiseptic soap
          • Alcohol-based hand sanitizer
          • Non-alcohol hand sanitizer
6
Number of Studies Meeting Criteria
  • Soap (plain/unidentified)  N=8


  • Antiseptic Soap N=5


  • Alcohol-Based Hand Sanitizers N=9


  • Non-Alcohol-Based Hand Sanitizers N=2
7
Plain or Unidentified Soap Versus Control (N=8)
8
Plain or Unidentified Soap (N=8):
Study Methods Overview
  • Formal randomization (n=3)
    • Soap form:
      • Bars (n=8)
        • Reported plain or non-medicated soap (n=4)
        • Unknown soap type (n=4)

  • Educational component
    • Wash hands at critical points (n=7)
      • Hygiene promotion seminar (n=3)
      • Washing of dishes (n=1)
    • Follow regular routine (n=1)
9
Plain or Unidentified Soap (N=8):
Study Methods Overview

  • Outcomes:


    • Diarrhea Incidence/Risk (n=6)
      • Prevalence, Healthcare Visits
      • Culture confirmed Shigella sp.


    • Impetigo (n=2)


    • Skin and eye disease (n=1)


    • Runny nose, cough, and pneumonia (n=1)
10
Plain or Unidentified Soap (N=8):
Study Methods Overview


  • Exposure measurements
    • Measured Soap use or Hand Washing (n=6)

  • Controlled for confounding or reported balance on covariates (n=7)
11
Plain or Unidentified Soap (N=8):Results

Reduction in Diarrhea Incidence (n=6)
12

Plain or Unidentified Soap (N=8):
Results Continued
  • Other significant findings:
    • Luby, S. et al. (2005) Lancet
      • 51% reduction in cough or difficulty breathing
      • 54% reduction in coryza (runny nose)
      • 50% reduction in pneumonia
      • 34% reduction in impetigo


  • Null findings:
    • Luby, S. et al. (2002) Am J Trop Med Hyg
      • 25% reduction in total impetigo (p=0.21)
        • No prompting of change in hygiene
13

Plain or Unidentified Soap Type (N=8):
 Summary of Results

  • Reduction in incidence of diarrhea ranged from 30% to 89%
    • Median reduction: 53%
    • Similar reduction range for other outcomes
14
Plain or Unidentified Soap Type:
 Study Design Issues
  • Most studies prior to 2004 lack formal randomization


  • Not possible to mask participants or interviewers


  • Only two studies used techniques to control for clustering


  • Limited measurement on hygiene / soap use


  • Varying definitions of symptoms and reporting methods across studies


  • All studies were conducted outside of USA
    • High risk populations


  • Difficult to tease apart the effect of soap use from that of hygiene education
    • Only one study asked participants to follow regular routine
15
Plain or Unidentified Soap Type (N=8):
 Conclusions

  • Consistent reductions observed
    • regardless of varying methods and study populations

  • Plain soap in conjunction with proper hygiene is effective in reducing diarrheal illness in high risk populations
16
Antiseptic Soap Versus Plain Soap or Control (N=5)
17
Antiseptic Soap (N=5):
Study Methods Overview
  • Comparison Groups:
    • Antiseptic Soap versus Plain Soap (placebo) (n=2)
    • Antiseptic Soap versus Plain Soap (placebo) and versus Control Group (nothing) (n=3)

  • Formal randomization (n=3)
    • Soap form:
      • Bars (n=4) (1.2% triclocarban)
      • Liquid (n=1) (0.2% triclosan)

  • Educational component
    • Washing hands at critical points (n=3)
    • Follow regular routine (n=2)
18
Antiseptic Soap (N=5): Study Methods Overview

  • Outcomes:


    • Diarrhea Incidence/Risk (n=3)


    • Impetigo (n=2)


    • Pneumonia (n=1)


    • Symptoms of infection (n=2)
19
Antiseptic Soap (N=5):
Study Methods Overview
  • Measured Soap use and/or Hand Washing (n=4)
    • Masked participants and interviewers (n=4)
      • Among placebo groups only


  • Controlled for confounding or reported balance on covariates (n=5)
20

Antiseptic Soap vs. Plain Soap:
 
Reduction in Diarrhea Incidence (n=2)
21

Antiseptic Soap vs. Plain Soap:

Reduction in Incidence of Other Symptoms / Infections (n=3)
22

Antiseptic Soap versus Control Group
(No Soap Provided in Control Group)
 Reduction in Incidence of Impetigo and Diarrhea (n=3)
23
Antiseptic Soap:
Summary of Results

  • Antiseptic Soap vs. Plain Soap (n=3)
    • No statistically significant differences for all infectious symptoms


  • Antiseptic Soap vs. Control Group (no soap) (n=2)
    • Reduction in incidence of diarrhea ranged from 29% to 50%
      • Similar to reductions associated with use of plain soap
24

Antiseptic Soap:
Study Design Issues

  • Study Design Limitations
    • Possible viral or parasitic etiology for symptom definitions
    • High risk groups

  • Study Design Strengths:
    • All studies used techniques to control for clustering
    • All studies measured baseline hygiene information
      • Hygiene practices over duration of the study (n=1)
      • Product monitoring (n=2)
    • Three studies masked participants and/or interviewers
      • Use of a placebo plain soap (n=3)
    • Extensive follow-up for symptoms
25
Antiseptic Soap:
 Conclusions


  • Lack of evidence that antiseptic soaps provide a benefit beyond plain soap in community setting in US and Pakistan
    • Diarrhea
    • Impetigo
    • Other infectious symptoms

  • When compared to a control group (no provision of plain soap or hygiene education)
    • Antiseptic soap with hygiene education is an effective intervention for reducing impetigo and diarrheal illness in high risk groups
26
Alcohol-Based Hand Sanitizers (N=9)
27
Alcohol-Based Hand Sanitizer (N=9):
Study Methods Overview
  • Comparison Groups:
    • Alcohol + Education versus Control Group (nothing) (n=6)
    • Alcohol + Education versus Control Group (education) (n=2)
    • Alcohol versus Control Group (nothing) (n=1)


  • Formal randomization (n=4)
  • Cross-over (n=2)


  • Alcohol form:
      • Hand rinse  (n=1)
        • 60% isopropyl alcohol
      • Disinfectant (n=2)
        • 63% isopropyl alcohol, 70-90% ethanol and isopropanol
      • Foam
      • Instant hand sanitizer (n=5)
        • 60-62% or unknown
28
Alcohol-Based Hand Sanitizer (N=9): Study Methods Overview

  • Outcomes:


    • Gastrointestinal illness (n=3)


    • Upper respiratory illness (n=3)
      • Viral Respiratory Illnesses (n=1)


    • Symptoms of infection (n=3)
      • Absence related
29
Alcohol-Based Hand Sanitizer (N=9):
Study Methods Overview

  • Measured Alcohol use (n=3)
    • Supplies (n=3)
      • Frequency of use (n=1)
    • Total hand hygiene practices (n=1)

  • None masked participants or interviewers
    • One study collected illness data from masked parents of children in the study

  • Controlled for confounding or reported balance on covariates (n=4)
30
Alcohol-based Hand Sanitizer

Reduction in Diarrheal Illness (n=3)
31
Alcohol-based Hand Sanitizer

Reduction in Respiratory Illness (n=4)
32
Alcohol-based Hand Sanitizer

Symptoms of Infection (n=4)
33
Alcohol-based Hand Sanitizer:
Summary of Results

  • Reductions in diarrheal illness ranged from 48% to 71%
      • Similar to reductions associated with use of plain soap


  • Most Reductions in respiratory illness were not statistically significant
    • 3%-20%


  • Infectious symptoms / absence ranged from 9% to 43%
    • Variable definitions and reporting
34
Alcohol-based Hand Sanitizer:
Study Design Issues

  • Study Design Limitations
    • Unknown etiology for symptom definitions
    • Variability in definition of symptoms and reporting methods
    • Not balanced on education intervention
    • Lack consistent measurement of alcohol use and other hand hygiene practices (soap use?)
    • Difficult to employ masking
    • Only one study controlled for clustering
35
Alcohol-based Hand Sanitizer:
 Conclusions

  • Alcohol-based hand sanitizers in conjunction with hygiene education can effectively reduce diarrhea and general infectious symptoms in the community setting
    • Alcohol alone?

  • There is less evidence of effectiveness for reducing upper respiratory infections
36
Future Research Needs

  • Assess the effect of antiseptic soaps and alcohol-based hand sanitizers in culture confirmed viral and bacterial infections studies


  • Assess the benefit of alcohol-based hand sanitizers in groups with similar baseline levels of hygiene education
    • Better control of confounding factors
    • Analytical techniques that accommodate clustered data
    • Further household level studies
37
Conflicts of Interest Statement and Acknowledgements

  • Consulted for Pfizer in September


  • Thanks to Dr. Elaine L. Larson