status relative to any alternative treatment. Such studies are usually conducted with patients who need therapeutic intervention; randomly selected patients may be treated with radiation and some other form of treatment or with different types or doses of radiation. In these trials the sample size is relatively small and the follow-up time is relatively short. Therefore, most studies to assess the long-term adverse outcomes of exposure to therapeutic radiation, are, of necessity cohort studies.

Cohort Studies

Cohort studies may be retrospective or prospective. In a retrospective cohort study of a population exposed to radiation, participants are selected on the basis of existing records such as those maintained by a company or a hospital (e.g., radiation badge records). These records were made out at the time an individual was working or treated and thus may be used as the historical basis for classification as a member of the exposed cohort. In a prospective cohort study, participants are selected on the basis of current and expected future exposure to radiation, and exposure information is measured and recorded as time passes. In both types of cohort study, the members of the study population are followed in time for a period of years, and the occurrence of new disease is measured. In a retrospective cohort study, the follow-up has already occurred, while in a prospective cohort study, the follow-up extends into the future. Many studies that are initiated as retrospective cohort studies become prospective as time passes and follow-up is extended.

The information available in a retrospective cohort study is usually limited to what is available from the written record. In general, members of the cohort are not contacted directly, and information on radiation exposure and disease must come from other sources. Typically, information on exposure comes from records that indicate the nature and amount of exposure that was accumulated by a worker or by a patient. On occasion, all that is available is the fact of exposure, and the actual dose may be estimated based on knowledge of items such as the X-ray equipment used (Boice and others 1978).

Information on disease also must come from records such as medical records, insurance records, or vital statistics. Cancer mortality is readily evaluated by retrospective cohort studies, because cancer registries exist in a number of countries or states and death from cancer is fairly reliably recorded.

Most studies that have followed patients treated with therapeutic radiation are retrospective cohort studies. Series of patients are assembled from medical and radiotherapy records, and initial follow-up is done from the date of therapy until some arbitrary end of follow-up. Patients treated as long ago as the 1910s have been studied to assess the long-term effects of radiation therapy (Pettersson and others 1985; Wong and others 1997a).

The information available in a prospective cohort study is potentially much greater than that available in a retrospective cohort study. Exposure is contemporaneous and may be measured forward in time, and members of the cohort may be contacted periodically to assess the development of any new disease. Direct evaluation of both exposure and disease may be done on an individual basis, with less likelihood of missing or incomplete information due to abstracting records compiled for a different purpose.

The follow-up of survivors of the Japanese atomic bomb explosions is largely prospective, although follow-up did not begin until 1950 (Pierce and others 1996). Exposure assessment was retrospective and was not based on any actual measurement of radiation exposure to individuals. Reconstruction of the dose of radiation exposure is an important characteristic of this study, and improvements in dose estimation continue to the present with a major revision of the dosimetry published in early 2005 (DS02).

The primary advantage of a retrospective cohort study is that time is compressed. If one wishes to evaluate whether radiation causes some disease 20–40 years after exposure, a retrospective study can be completed in several years rather than in several decades. The primary disadvantage of a retrospective cohort study is that limited information is available on both radiation exposure and disease. The primary advantage of a prospective cohort study is that radiation exposure and disease can be measured directly. The primary disadvantage is that time must pass for disease to develop. This leads to delay and expense. Most studies in radiation epidemiology are retrospective cohort studies.

Case-Control Studies

Case-control studies may be prospective or retrospective. The cases are those individuals with the disease being studied. Cases in a retrospective case-control study are usually selected on the basis of existing hospital or clinic records (i.e., the cases are “prevalent”). In a prospective case-control study, the cases are “incident,” that is, they are selected at the time their disease was first diagnosed. Controls are usually nondiseased members of the general population, although they can be persons with other diseases, family members, neighbors, or others.

After the cases and controls have been identified, it is necessary to determine which members of the study population have been exposed to radiation. Usually, this information is obtained from interviewing the cases and the controls. However, if the case or control is deceased or unable to respond, exposure information may come from a relative or from another proxy.

The information available in case-control studies usually is less reliable than that collected in cohort studies. For example, consider the accuracy of dietary history for the past year versus that of a year from several decades in the past. Exposure information may be available only from interview



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