Preclinical Phase of Disease

The preclinical phase of a disease is the period of time during the natural course of a disease where symptoms are not yet apparent, but the disease is biologically present. The concept of a preclinical phase of a disease is most widely referred to in the topic of screening.

Every disease has a natural history that represents the process of the disease in the absence of an intervention. The preclinical phase is one component of this natural history. It begins at the biologic onset of disease and ends when an individual begins experiencing disease-related symptoms. Thus, this phase is when the disease is present but the individual is asymptomatic. When symptoms appear, the preclinical phase ends, and the clinical phase of the disease begins. The length [Page 834]of the preclinical phase varies for different diseases and between individuals and depends on how quickly the disease progresses. For example, the preclinical phase of many cancers may be quite long, sometimes several years. Many neurodegenerative diseases such as Alzheimer's disease and Creutzfeldt-Jakob disease also have a long preclinical phase.

The preclinical phase of disease can be divided into the nondetectable component and the detectable preclinical phase (DPCP). The former represents the phase that is not yet detectable by screening methods, whereas the latter represents the time window when screening methods can detect the presence of asymptomatic disease. Diseases must have a DPCP to be a candidate for screening.

One of the aims of screening is to detect disease at an early stage so that an intervention can be implemented early and prevent future morbidity and mortality. However, for this to be achieved, the disease in question must have a DPCP. Although there are several criteria for screening, this is a key one of several criteria that indicate whether a screening program could be useful in combating a particular disease. For a screening test to be successful, the disease in question should have a relatively long DPCP with a relatively high prevalence in the population. If it does not, the individuals will pass through to the clinical phase of disease so quickly that the presence of disease will already have been detected by the presence of symptoms, and a screening test will no longer be of use. For example, colorectal cancer has a relatively long DPCP and thus is an ideal candidate for screening by colonoscopy. This is in contrast to other more aggressive tumors that have a very short DPCP, and this screening is not as effective.

For screening to be effective, the DPCP must contain a critical point where intervention is more effective if started at this earlier point than after clinical symptoms appear. Without this early critical point of intervention during the DPCP, screening is not of benefit as early intervention will not make a difference in the progression of disease.