investigators’ attitudes and expectations for study outcomes. In a study of the anthrax vaccine by Brachman and colleagues (1962), workers in four goat hair processing mills were randomized to receive the vaccine or a placebo and then followed to assess the vaccine’s safety and efficacy (see Chapter 7).
The value of randomized controlled trials has been so convincingly demonstrated that they are required for ensuring the safety and efficacy of all new medications introduced into the market in the United States (FDA, 1998). Estimates are that 300,000 randomized controlled trials have been carried out over the past 50 years (Randal, 1999). The main drawbacks of randomized controlled trials are their expense, the time needed for completion, and the common practice of systematically excluding many groups of patients so that the results apply to only a small fraction of potentially eligible patients.
Experimental studies are most often performed for therapeutic agents, where the only expected result is a good outcome or no effect for the subject; rarely are adverse health effects expected. Ethical considerations limit experimental studies of toxic compounds and adverse health outcomes, and guidelines for informed consent and protection of human subjects are strictly implemented (NIH, 1991).
A case report is generally a detailed description of a patient’s illness reported by a clinician who may suspect that the illness is the result of exposure to a specific biological or chemical agent. A case series refers to a group of patients with the same or similar disease who experienced identical or similar exposures to a specific agent. Neither case reports nor case series are formal epidemiologic studies, but both are means for generating hypotheses about exposure and disease relationships. For Gulf War veterans, registry programs established by the VA and the Department of Defense (DoD) represent a type of voluntary case series. Any veteran may come forward to receive a clinical examination and a referral for treatment (see Chapter 2). Through documentation of veterans’ symptoms and diagnoses, these registries have been valuable in generating hypotheses, yet they are not designed for hypothesis testing or for establishing the prevalence of disease or specific exposures among Gulf War veterans.
The value of case reports and case series is that they can document possible associations between an environmental exposure and a particular health outcome. In some situations, they may be useful in suggesting causal relationships if the disease is rare and has a close temporal relationship to the exposure (Kramer and Lane, 1992). However, case reports and case series do not have control groups. Because case series are not population based, many cases caused by an exposure go unreported, and the prevalence of cases may be lower than in the population at large. Further, the cases may not have been caused by exposure to the specific agent (false-positive results).