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
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1
Community-Based Studies of Consumer Antiseptics
FDA Nonprescription Drug Advisory Committee Meeting
Allison E. Aiello, PhD, MSAssistant Professor of Epidemiology
University of Michigan-School of Public HealthCenter 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)
Year Authors Title Journal 1982 Khan M. Interruption of shigellosis by hand washing Trans R Soc Trop Med Hyg
1989 Han A. & Hlaing T. Prevention of diarrhoea and dysentery by hand washing
Trans R Soc Trop Med Hyg
1991 Wilson J, et al. Hand-washing reduces diarrhoea episodes: a study in Lombok, Indonesia
Trans R Soc Trop Med Hyg
1996 Shahid N, et al. Hand washing with soap reduces diarrhoea and spread of bacterial pathogens in a Bangladesh village
J Diarrhoeal Dis Res
1996 Pinfold J & Horan N Measuring the effect of a hygiene behavior intervention by indicators of behavior and diarrhea disease
Trans R Soc Trop Med Hyg
2002 Luby S, et al. The effect of antibacterial soap on impetigo incidence, Karachi, Pakistan
Am J Trop Med Hyg
2004 Luby S, et al. Effect of intensive handwashing promotion on childhood diarrhea in high-risk communities in Pakistan
JAMA
2005 Luby S, et al. Effect of handwashing on child health: a randomized controlled trial
Lancet
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
• 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)
-8
-6
-4
-2
0
2
4
6
8
10
12
1 2% R
eductio
n
10% Reduction*
6% Higher**
Larson (2004) United States, Families
Luby (2004) Pakistan, Children
*Not statistically significant
** Not statistically significant and not designed or powered to make this comparison
21
Antiseptic Soap vs. Plain Soap:
Reduction in Incidence of Other Symptoms / Infections (n=3)
No results were statistically significant
-20
-10
0
10
20
30
40
50
60
Cough Coryza Skin/Impetigo
% R
eductio
n
Larson, E.(2004)Luby, S. (2005)Luby, S. (2002)
22
Antiseptic Soap versus Control Group (No Soap Provided in Control Group)
Reduction in Incidence of Impetigo and Diarrhea (n=3)
All results statistically significant (P < 0.05)
43
29
50
0
10
20
30
40
50
60
Luby (2002) Pakistan, Children Luby (2004) Pakistan, Children Luby (2004) Pakistan, Children
% R
ed
uct
ion
Impetigo
Diarrhea
Diarrhea
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
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Year Authors Title Journal
1990 Butz A, et al. Occurrence of infectious symptoms in children in day care homes Am J Infect Control
1994 Kotch J, et al. Evaluation of an hygienic intervention in child day-care centers Pediatrics
1999 Falsey A, et al. Evaluation of a handwashing intervention to reuce respiratory illness rates in senior day-care centers
Infect Control Hosp Epidemiol
1999 Uhari M & Mottonen M
An open randomized controlled trial of infection prevention in child day-care centers
Pediatr Infect Dis
2000 Hammond B, et al. Effect of hand sanitizer use on elementary school absenteeism Am J Infect Control
2002 Guinan M, et al. The effect of a comprehensive handwashing program on absenteeism in elementary schools
Am J Infect Control
2003 White C, et al. The effect of hand hygiene on illness rate among students in university residence halls
Am J Infect Control
2004 Morton J & Schultz A
Healthy hands: use of alcohol gel as an adjunct to handwashing in elementary school children
J Sch Nurs
2005 Sandora T, et al. A randomized, controlled trial of a mulifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness trasmission in the home
Pediatrics
Alcohol-Based Hand Sanitizers (N=9)
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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
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Alcohol-Based Hand Sanitizer (N=9): Study Methods Overview
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)
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Alcohol-based Hand Sanitizer
Reduction in Diarrheal Illness (n=3)
* All P < 0.05, Statistically Significant Reduction
71
48
59
0
10
20
30
40
50
60
70
80
Butz, E (1990) US, Daycare Kotch et al, (1994) US, Daycare Sandora et al. (2005) US, Families
Author (Year) Group
% R
educt
ion
*
**
31
Alcohol-based Hand Sanitizer
Reduction in Respiratory Illness (n=4)
*P < 0.05, statistically significant
** Not statistically significant
1517
20
3
0
5
10
15
20
25
Kotch et al,(1994) US,Daycare
Falsey et al.(1999) US,
Elderly Daycare
White et al.(2001) US,University
Sandora et al.(2005) US,Families
Author (Year) Group
% R
educt
ion
*
**
** **
32
9
19.8
50
43
0
10
20
30
40
50
60
Uharti and Mottonen (1999)Finland, Daycare
Hammond et al. (2000) US,schools
Guinan et al. (2002) US, Schools Morton & Schultz et al. (2004)US, Families
Author (Year) Group
% R
educt
ion
Alcohol-based Hand Sanitizer
Symptoms of Infection (n=4)
* All P < 0.05, Statistically significant reduction
*
*
**
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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
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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
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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
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Conflicts of Interest Statement and Acknowledgements