# Presentation: 246648

## Disposition of the 
Air Force Health Study
Michael A. Stoto, PhD

Institute of Medicine
April 14, 2005

- Air Force Health Study
- Michael A. Stoto, PhD
- Institute of Medicine
- April 14, 2005

**Notes:**
Good afternoon.  I am pleased to be here today to present an overview and update of the Air Force Health Study.

## Disclaimers

- I chair the official advisory committee in my personal capacity
- Not a RAND project
- Some information from AFHS
- Opinions are my own, based on following the study closely for a decade
- Not Air Force, RHAC, RAND, or NAS/IOM

## Outline

- AFHS as a national resource to study
- Agent Orange and Vietnam herbicides
- Dioxin
- Veterans’ and occupational health issues
- Aging
- Chronic disease risks
- Other environmental health issues
- Disposition options and issues

## Congressional and Presidential mandate
To conduct a 20-year prospective epidemiological study of herbicide exposure and health, mortality, and reproductive outcomes in veterans of Operation Ranch Hand

- To conduct a 20-year prospective epidemiological study of herbicide exposure and health, mortality, and reproductive outcomes in veterans of Operation Ranch Hand

- AFHS Purpose

**Notes:**
The details of study design and subject selection are published.  The study seeks to determine whether veterans of Operation Ranch Hand have experienced adverse health and whether those health effects, if they exist, can be attributed to exposure to herbicides or their dioxin contaminant.  Ranch Hand veterans were exposed to herbicides during flight operations and maintenance of the aircraft and herbicide spray equipment.  The study compares the health, mortality experience, and reproductive outcomes of Ranch Hand veterans with a comparison group of other Air Force veterans who served in SEA during the same period (1962 to 1971) that the Ranch Hand unit was active and who were not involved with spraying herbicides.  Comparison veterans were matched to Ranch Hand veterans on date of birth, race (Black, non-black) and military occupation (officer pilot, officer navigator, nonflying officer, enlisted flyer, enlisted ground crew). 

## Study Design

- Index group: Ranch Hand veterans (N=1,208)
- Control population: Air Force veterans of Southeast Asia (N=19,080)
- Examined controls matched on age, race, military occupation (N=1,668)

**Notes:**
Ranch Hand veterans were exposed to herbicides during flight operations and maintenance of the aircraft and herbicide spray equipment.  The study compares the health, mortality experience, and reproductive outcomes of Ranch Hand veterans with a comparison group of other Air Force veterans who served in SEA during the same period (1962 to 1971) that the Ranch Hand unit was active and who were not involved with spraying herbicides.  Comparison veterans were matched to Ranch Hand veterans on date of birth, race (Black, non-black) and military occupation (officer pilot, officer navigator, nonflying officer, enlisted flyer, enlisted ground crew).  The entire population of Comparison veterans (N=19,080) is used in mortality studies.  A subset of matched Comparisons was invited with the Ranch Hand veterans to participate in the periodic physical examinations (N=1,668).  Non-compliant Comparisons were replaced by a health-matched Comparison in the same matched set following an algorithm prescribed in the protocol.

## Study Design (Continued)

- Multiple endpoints
- Mortality, morbidity, reproductive outcomes
- Repeated physical examinations, interviews and mortality assessments, plus
- Biological samples
- Medical records
- Military and civilian employment history
- Herbicide and dioxin exposure based on military records, military occupation, serum dioxin measurement

**Notes:**
During protocol development, study investigators and reviewers recognized the limitations of existing records to provide an exposure index for each Ranch Hand veteran.  Military spray records were used initially to compute an approximate index.  Subsequently, in 1986, collaboration began with the Centers for Disease Control and Prevention to measure dioxin in serum.  This measure was later incorporated into the study and served as a basis for several exposure indices.  The study includes multiple endpoints and data is collected through repeated physical examinations, in-person interviews, and mortality assessments.

## Morbidity Endpoints

- General Health
- Cancer
- Neurological
- Psychological
- Gastrointestinal
- Dermatological

- Endocrinological
- Immunological
- Pulmonary
- Cardiovascular
- Renal

**Notes:**
Over two hundred measures of health are included in the study.  These are analyzed in our reports under chapter headings shown here.  The measures were derived from the Agent Orange Registry, a database of conditions reported by Vietnam veterans as being related to their exposure to herbicides during the war.

## Study Schedule

**       **1960         1970        1980          1990         2000       2010

- Protocol Development

- Physical Examination

- Exposure period

**Notes:**
This slide depicts the period of exposure, between 1961 and 1971, the protocol development between 1976 and 1978, and physical examinations in 1982, 1985, 1987, 1992, 1997, and 2002. The first examination was conducted at Kelsey Seybold Clinic in Houston, Texas, and all subsequent examinations were conducted by Scripps Clinic in La Jolla, California.   Examination content was specified in the protocol, and was periodically reviewed by the Institutional Review Boards at the participating facilities.  Participation was voluntary and informed consent was given at the examination sites.  

##   Median serum dioxin levels in selected populations

-  Serum dioxin (ppt)

-   Median serum dioxin levels in selected populations

- 157

- 4540

- 16,600

- 355

- 0

- 20

- 40

- 60

- 80

- 100

- 1000

- 10,000

**Notes:**
This slide depicts the relative position of Air Force Health Study dioxin levels compared to other studies.  The Ranch Hand initial dose, about 4000 ppt is about 10% of the maximum dose received by victims of the Seveso accident.  The bars give the mean dioxin level in 1987 in study participants.  The Seveso bars give dioxin levels measured within 3 years after the accident.  Members of the CDC Agent Orange Vietnam Study had background levels similar to Air Force Health Study Comparison veterans.

## Numbers of Veterans Physically Examined 

| Year | Ranch Hand | Comparison | Total |
| --- | --- | --- | --- |
| 1982
1985
1987
1992
1997
2002  | 1,045
1,016
995
952
869
777  | 1,224
1,293
1,299
1,281
1,252
1,174  | 2,269
2,309
2,294
2,233
2,121
1,951  |

**Notes:**
Most participants (95.8%) consented to other Agent Orange (AO) or health research.  The consent patterns were similar between groups.

## Study Materials

**Notes:**
Most participants (95.8%) consented to other Agent Orange (AO) or health research.  The consent patterns were similar between groups.

## Knowledgeable Staff

## Research Results

## Study Disposition

- Veterans Benefits Act of 2003 (PL108-183): NAS study to address (among others)
- Potential value of extending the study
- Scientific merit of retaining and maintaining medical records, specimens, other data
- Obstacles to  retaining materials
- Advisability and cost of making specimens available to independent researchers

## Extending the Study

- Due to age and number of remaining participants, value of extending the study to do more physical examinations is not clear
- Consider
- Value of completing research in progress
- Monitoring mortality

**Notes:**
During protocol development, study investigators and reviewers recognized the limitations of existing records to provide an exposure index for each Ranch Hand veteran.  Military spray records were used initially to compute an approximate index.  Subsequently, in 1986, collaboration began with the Centers for Disease Control and Prevention to measure dioxin in serum.  This measure was later incorporated into the study and served as a basis for several exposure indices.  The study includes multiple endpoints and data is collected through repeated physical examinations, in-person interviews, and mortality assessments.

## Retaining and Maintaining Materials

- Not the original goal, but the result is a
- Longitudinal study of males with very detailed information on a variety of occupational and other health risks and outcomes
- Clear value of retaining and maintaining materials to study
- Health effects of herbicides/dioxin in veterans
- Other aspects of military health and environmental and occupational exposures
- Chronic disease risks
- Normal aging

**Notes:**
During protocol development, study investigators and reviewers recognized the limitations of existing records to provide an exposure index for each Ranch Hand veteran.  Military spray records were used initially to compute an approximate index.  Subsequently, in 1986, collaboration began with the Centers for Disease Control and Prevention to measure dioxin in serum.  This measure was later incorporated into the study and served as a basis for several exposure indices.  The study includes multiple endpoints and data is collected through repeated physical examinations, in-person interviews, and mortality assessments.

## Consent to Use Records and Materials

| 
Response | Comparison
N (%) | Ranch Hand
N (%) | Total
N (%) |
| --- | --- | --- | --- |
| AO & Health
AO only
Do not use
Other

Total | 1,138 (96.9)
23 (2.0)
11 (0.9)
2 (0.2)

1,174 | 731 (94.1)
32 (4.1)
11 (1.4)
3 (0.4)

777 | 1,869 (95.8)
55 (2.8)
22 (1.1)
5 (0.3)

1,951 |

**Notes:**
Most participants (95.8%) consented to other Agent Orange (AO) or health research.  The consent patterns were similar between groups.

## Making Data and Materials Available to Researchers

- Separately consider
- A. Logistics and costs of maintenance of materials
- B. Costs of further research using these materials
- If data and material were available to researchers, NIH and other research funders could support research using it through established programs