# Presentation: 566737

## 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

## Outline

- Literature Review
- Methodological Issues
- Summary and Future Research Needs

## 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

## 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

## 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

## 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

## 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 |

## 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)

## 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)

## 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)

## Plain or Unidentified Soap (N=8):ResultsReduction in Diarrhea Incidence (n=6)

-  All Results Statistically Significant (P < 0.05)

## 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

## 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

## 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

## 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

## Antiseptic Soap Versus Plain Soap or Control (N=5)

| Year | Author | Title | Journal  |
| --- | --- | --- | --- |
| 2002 | Luby S, et al. | The effect of antibacterial soap on impetigo incidence, Karachi, Pakistan | Am J Trop Med Hyg |
| 2004 | Larson E, et al.  | Effect of antibacterial home cleaning and handwashing products on infectious disease symptoms | Ann Intern Med |
| 2004 | Luby S, et al.  | Delayed effectiveness of home-based interventions in reducing childhood diarrhea, Karachi, Pakistan | Am J Trop Med Hyg 
 |
| 2005 | 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 |

**Antiseptic Soap Versus Plain Soap or Control (N=5)**

## 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)

## Antiseptic Soap (N=5): Study Methods Overview

- Outcomes:
- Diarrhea Incidence/Risk (n=3)
- Impetigo (n=2)
- Pneumonia (n=1)
- Symptoms of infection (n=2)

## 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)

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

- 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

## Antiseptic Soap vs. Plain Soap:Reduction in Incidence of Other Symptoms / Infections (n=3)

- No results were statistically significant

## 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)

## 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

## 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

## 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

## Alcohol-Based Hand Sanitizers (N=9)

| 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)**

## 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

## 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

## 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)

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

- * All P < 0.05, Statistically Significant Reduction

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

- *P < 0.05, statistically significant
- ** Not statistically significant

## Alcohol-based Hand Sanitizer Symptoms of Infection (n=4)

- Alcohol-based Hand Sanitizer Symptoms of Infection (n=4)

- * All P < 0.05, Statistically significant reduction

- *

- *

- *

- *

## 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

## 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

## 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

## 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

## Conflicts of Interest Statement and Acknowledgements

- Consulted for Pfizer in September
- Thanks to Dr. Elaine L. Larson