THE SIX CITIES STUDY

History of the Study. Douglas Doherty, an epidemiologist associated with the Harvard Six Cities Study, provided an overview of the research project. In 1973, the OMB requested that the National Institute of Environmental Health Sciences (NIEHS), one of the institutes of the National Institutes of Health (NIH), review the health effects of sulfur oxides and propose a longitudinal study of the health effects of fossil fuel air pollution. Two researchers at the Harvard University School of Public Health, Ben Ferris and Frank Speizer, submitted a proposal in 1974 for a study of children and adults in six cities in the midwestern and eastern United States to evaluate the effects of the anticipated degradation in air quality. The study was approved and received funding for 20 years; the Electric Power Research Institute provided additional funding after the study began. Also, the EPA provided technical assistance, information from air monitors, equipment, and limited input into the conduct of the study.

The project studied areas around the major coal-fired power plants in the Midwest and looked at the health effects of the air pollution as it was transported northeastward by prevailing winds. To achieve a range of exposures, the researchers chose the cities of Watertown, Mass.; Steubenville, Ohio; Kingston, Tenn.; St. Louis, Mo.; Topeka, Kan.; and Portage, Ind. These communities ranged from rural areas upwind of the power plants to downwind communities with more polluted air. The core studies measured air pollution in those communities and the health of a sample of the population. The Six Cities Study was not a single study but a constellation of studies tied together in their focus on these six communities. One study, for example, was a random sample of children enrolled as first graders and followed through high school graduation. Ultimately, different groups of investigators produced at least 15 identifiable data sets; new findings then fed back into new studies. During the course of the 20-year period, more than 100 publications emerged as a result of these studies.⁶

One of the studies monitored the effects of air pollution on mortality rates, using a random selection of adults aged 25 to 74 in each community, selected from census lists and city directories. Study participants took a pulmonary function test every 3 years and filled out a questionnaire, answering the same set of questions each time. The study kept track of which participants died in the interval.

Two of the goals of this study were to determine how long study participants lived and to identify predictors of survival. The study used the Social Security System and the National Death Index to determine information. The Index allowed the researchers to search through all the death certificates in the U.S. for matches with people on the Six Cities list. Although the matches were not perfect, and each name had to be validated by Social Security number, age, gender, and other factors, it saved the investigators from having to visit all the participants each year.

To validate that the people who died were in fact the same individuals as those in the studies, and to determine the cause of death, the investigators had to obtain the original death certificates and compare the information on the certificates with the original records. The study took into account several known predictors of survival: age, sex, personal habits (such as smoking), socioeconomic status, and occupation (including exposure to chemicals).

After adjusting for all known variables, the study found that people who lived in areas with higher air pollution, as determined by fine-particle concentration, had a shorter life expectancy than people living in the cleaner cities. According to Doherty, the investigators were surprised by the magnitude of this effect because the concentrations of air pollutants seemed low.⁷

Impact of the study. Since the EPA first set standards for particulate matter in 1970, several hundred epidemiological studies of the effects of air pollution have been published. During the year when the Six Cities Study was released, it was one of several (12-15) published studies that examined the effects of particulate air pollution. While none of these studies was by itself able to capture the whole “truth” about air pollution, their cumulative power persuaded the American Lung Association (ALA) to sue the EPA to tighten the 1970 particulate standards. In 1997 a federal court found in favor of the ALA and mandated that the EPA set a new standard.

Rule making as a result of the study. The EPA evaluated the results of the mortality study, approved the basic performance of the methodology and the standards of publication, and used the study's findings in setting its ambient air quality standards. Due to the strong interest in the research, the agency encouraged the researchers to allow interested scientists and agencies the opportunity to understand fully the basis of their work. The investigators understood this to mean discussions with other scientists regarding the approach, methodology, and results of the study. The EPA did not call for a release of all the underlying data. Indeed, as mentioned above, the data were encumbered by several types of confidentiality constraints. The investigators had assured the participants in the studies that their identity and their relationship to any information obtained would be kept confidential. Specific agreements were signed by each participant, the study director, and a witness. Assurances of confidentiality are typical in studies of this kind.⁸

In an experiment to discover whether confidentiality could be preserved while opening the data for public review, the study investigators attempted to disguise the identity of the study participants. They deleted as many features as possible from the questionnaires, such as the name, the state file number, the mother's maiden name, and the name of the person providing the information. However, they needed to retain a minimum set of features if other scientists were to be able to replicate the basic findings of the study. They needed the place of death, because they were investigating the possibility of a link to air pollution exposure; they needed the date of death because the study concerned survival; and they needed both the age at death and gender in order to adjust for both factors. They found that even this minimum set of features could allow for identification of research participants. For example, Dr. Dockery performed a simple test of confidentiality by using the minimal information that a male of a certain age had died on a certain day in one of his six cities. On the Internet he was easily able to find newspaper obituaries of those who had died in that city on that day. From that relatively short list of descriptions he quickly identified one of his subjects simply by the facts of age and gender, added to the place and date of death.

In addition to the confidentiality agreements with the individual study participants, the investigators had had to sign certain statements in order to obtain death certificates from the states. They had had to agree that they would (1) limit access to the records to only the members of the research staff, (2) destroy records upon the completion of the study, and (3) not release the records to other agencies, publish data so individuals could be identified, or contact family members of decedents. Furthermore, the investigators had had to sign non-disclosure agreements to obtain information from the National Death Index. Hence, although the investigators were willing to share data sets, which is a common scientific practice, they believed that to open their thousands of boxes of original records would be unethical.⁹ Nonetheless, the study was criticized on the general grounds that the public had paid for the study (through NIH funding to Harvard) and, therefore, the public had a right to all the data.

The Health Effects Institute Analysis. In an effort to accommodate public demand for access to the data so the study findings could be contested or confirmed, the investigators ultimately agreed to make an arrangement with an independent entity, the Health Effects Institute (HEI), to reanalyze the data. Funded jointly by the EPA and the automobile manufacturers, the HEI describes itself as an “unbiased source of information on the health effects of motor vehicle emissions.”¹⁰ The HEI was given the task of reanalyzing and validating the original data.

The HEI organized an open, international competition to assemble a “reanalysis team” and established a separate review committee to examine the results of the reanalysis. The review involved a sensitivity analysis using methods not available during the original analysis and an examination of new data. The HEI found the original data to be of high quality, and essentially confirmed the validity of the original findings and conclusions.

Footnotes

5

It is worth noting that the traditional understanding of publication is being stretched in the present era of electronic communication. Today, articles posted on web sites (often including extensive data), as well as conference proceedings and other unreviewed materials, are widely used by the scientific community to communicate results. Similarly, many conference proceedings are not peer reviewed. Whether, and how, such materials should be used in the setting of regulations has not been established.

6

Probably the most widely noted of these is the following: Dockery, D.W., Pope, C. A. III, Xu, X., Spengler, J.D., Ware, J.H., Fay, M.E, Ferris, B.G., Jr., and Speizer, F.E. “An association between air pollution and mortality in six U.S. cities,” New England Journal of Medicine, 1993, 329:1753-1759.

7

Although the Six Cities Study was the most visible impetus for the Shelby Amendment another large epidemiological study led by C. Arden Pope of Brigham Young University with data from the American Cancer Society (ACS) was also fundamental to the EPA's standard setting. The data used in the Pope study were actually owned by the ACS, introducing a new complexity to the call for access to data. At issue is the question of access to large databases used for research that influence federal rule making but whose collection and maintenance involve no federal funds. (See Arden C. Pope III et. al., “Particulate Air Pollution as a Predictor of Mortality in a Prospective Study of U.S. Adults,” American Journal of Respiratory Critical Care Medicine, Vol. 151:669-674, 1995.)

8

Formal protections of privacy and confidentiality are described by the Code of Federal Regulations, Title 45, Part 46, Protection of Human Subjects. For example, one of seven mandatory requirements for federally funded research on human subjects is that “When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data” (46.111-a-7). The code also requires “a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained” (46.116-a-5).

9

The study director said that he was able to find on the Internet the deaths in Watertown, Mass., for the month preceding the workshop and easily identify a 54-year-old male who was a member of the study.

10

The following description of the HEI, located in Boston, Mass., is offered on its web site: “The Health Effects Institute (HEI) is an independent, nonprofit corporation chartered in 1980 to provide high-quality, impartial, and relevant science on the health effects of pollutants from motor vehicles and from other sources in the environment. Supported jointly by the U.S. Environmental Protection Agency (EPA) and industry, HEI has funded over 170 studies and published over 100 Research Reports and several Special Reports producing important research findings on the health effects of a variety of pollutants, including carbon monoxide, methanol and aldehydes, nitrogen oxides, diesel exhaust, ozone, and most recently, particulate air pollution.” See http://www​.healtheffects​.org/pubsspecial.htm.