Chapter 078. Prevention and Early Detection of Cancer (Part 7)

Potential Biases of Screening Tests The common biases of screening are lead time, length-biased sampling, and selection. These biases can make a screening test seem beneficial when actually it is not (or even causes net harm). Whether beneficial or not, screening can create the false impression of an epidemic by increasing the number of cancers diagnosed. It can also produce a shift in proportion of patients diagnosed at an early stage that improves survival statistics without reducing mortality (i.e., the number of deaths from a given cancer relative to the number of those at risk for the cancer). In...
Nội dung trích xuất từ tài liệu:
Chapter 078. Prevention and Early Detection of Cancer (Part 7) Chapter 078. Prevention and Early Detection of Cancer (Part 7) Potential Biases of Screening Tests The common biases of screening are lead time, length-biased sampling, andselection. These biases can make a screening test seem beneficial when actually itis not (or even causes net harm). Whether beneficial or not, screening can createthe false impression of an epidemic by increasing the number of cancersdiagnosed. It can also produce a shift in proportion of patients diagnosed at anearly stage that improves survival statistics without reducing mortality (i.e., thenumber of deaths from a given cancer relative to the number of those at risk forthe cancer). In such a case, the apparent duration of survival (measured from dateof diagnosis) increases without lives being saved or life expectancy changed. Lead-time bias occurs when a test does not influence the natural history ofthe disease; the patient is merely diagnosed at an earlier date. When lead-time biasoccurs, survival appears increased, but life is not really prolonged. The screeningtest only prolongs the time the subject is aware of the disease and spends as apatient. Length-biased sampling occurs when slow-growing, less aggressive cancersare detected during screening. Cancers diagnosed due to the onset of symptomsbetween scheduled screenings are on average more aggressive, and treatmentoutcomes are not as favorable. An extreme form of length bias sampling is termedoverdiagnosis, the detection of pseudo disease. The reservoir of someundetected slow-growing tumors is large. Many of these tumors fulfill thehistologic criteria of cancer but will never become clinically significant or causedeath. This problem is compounded by the fact that the most common cancersappear most frequently at ages when competing causes of death are more frequent. Selection bias must be considered in assessing the results of any screeningeffort. The population most likely to seek screening may differ from the generalpopulation to which the screening test might be applied. The individuals screenedmay have volunteered because of a particular risk factor not found in the generalpopulation, such as a strong family history. In general, volunteers for studies aremore health conscious and likely to have a better prognosis or lower mortality rate,irrespective of the screening result. This is termed the healthy volunteer effect. Potential Drawbacks of Screening Risks associated with screening include harm caused by the screeningintervention itself, harm due to the further investigation of persons with positivetests (both true and false positives), and harm from the treatment of persons with atrue-positive result, even if life is extended by treatment. The diagnosis andtreatment of cancers that would never have caused medical problems can lead tothe harm of unnecessary treatment and give patients the anxiety of a cancerdiagnosis. The psychosocial impact of cancer screening can also be substantialwhen applied to the entire population. Assessment of Screening Tests Good clinical trial design can offset some biases of screening anddemonstrate the relative risks and benefits of a screening test. A randomized,controlled screening trial with cause-specific mortality as the endpoint providesthe strongest support for a screening intervention. Overall survival should also bereported to detect an adverse effect of screening and treatment on other diseaseoutcomes (e.g., cardiovascular disease). In a randomized trial, two like populationsare randomly established. One is given the medical standard of care (which maybe no screening at all) and the other receives the screening intervention beingassessed. The two populations are compared over time. Efficacy for the populationstudied is established when the group receiving the screening test has a bettercause-specific mortality rate than the control group. Studies showing a reductionin the incidence of advanced-stage disease, an improved survival, or a stage shiftare weaker (and possibly misleading) evidence of benefit. These latter criteria arenecessary but not sufficient to establish the value of a screening test. Although a randomized, controlled screening trial provides the strongestevidence to support a screening test, it is not perfect. Unless the trial is population-based, it does not remove the question of generalizability to the target population.Screening trials generally involve thousands of persons and last for years. Lessdefinitive study designs are therefore often used to estimate the effectiveness ofscreening practices. After a randomized controlled clinical trial, in descendingorder o ...