What Constitutes Disease Natural History

A chief goal of natural history research is to understand the spectrum of the disease, the different manifestations, patterns of recognition and care. It is critical for differentiating self-limiting illnesses (e.g. acute infection) from chronic states (e.g. heart disease, cancer, diabetes, chronic respiratory illness) and distinguishing underlying disease from the exacerbations of chronic illness (e.g. multiple sclerosis, pain syndromes). There is often talk of "confounding by indication'' where our concern is determining events that may be attributable to the "indication" or disorder for which the therapy is prescribed rather than the therapy itself: disease natural history is the indication side of this dilemma.

The first rule of good epidemiology is to clearly define case and exposure criteria that enable us to designate subjects as being in one state of illness or another (pre-symptomatic, symptomatic, with disease or not with disease). Although it is easiest to consider ''disease'' as present or absent, most diseases change over time. Over the course of a lifetime a subject may move in and out of disease states across many diseases at any given point in time. The natural history of disease and interventions are consistent with the public health model of prevention and reflects the changes in an individual over time. It includes the following stages, which coincide with the public health model of prevention (Figure 8.1):

* Primary prevention—intervention during the stage of susceptibilty; intended to reduce new occurrences of disease.

* Secondary prevention—intervention during the pre-symptomatic phase; intended to delay the onset of disease or reduce its duration or severity.

* Tertiary prevention—intervention during the clinical stage; intended to reduce complications and disabilities.

The manifestations of the disease are not always stable over time and may be sporadic. These are often referred to as exacerbations, flares, or episodes, as seen with epilepsy, migraine, asthma, irritable bowel syndrome, depression, multiple sclerosis, or anxiety or when the symptoms themselves are unstable over time (Stang and Von Korff, 1995). This may also connote sporadic therapy, whether prescribed "as needed'' or self-medicated as such. To address this complexity, some authors distinguish between clinical course

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