To explain these points in more detail, we use three examples: one each of a screening test, a diagnostic test, and a prognostic test. In discussing these examples, we consider both outcomes that result from the process of testing and outcomes associated with the results of testing, and those that affect the tested individual and others. We conclude with a discussion of additional considerations when the test is a genetic test.
Example of a Screening Test
Screening tests are used to detect disease in asymptomatic individuals or individuals with unrecognized symptoms.
7 Screening tests should be able to separate individuals with the disease of interest from those without, and should be employed when there is a treatment available and where early treatment improves outcomes. The US Preventive Services Task Force (USPSTF) develops recommendations for use of clinical preventive services in the United States. An EPC is sometimes tasked with preparing the supporting review of the evidence.
8,9 Other stakeholders have interest in screening tests as well, including professional organizations involved in guideline preparation for their practitioners; cases in point are recommendations made by the American College of Obstetrics and Gynecology regarding cervical cancer screening
10 and the American Cancer Society’s recommendations for early cancer detection.
11To illustrate outcomes in a systematic review of a screening test, we present the example of a systematic review about screening for bacterial vaginosis in pregnant women.
12 This systematic review was first done for the USPSTF in 2001 and was later updated. Figure depicts the analytic framework developed by the authors.
Clinical Management Effects
The authors addressed whether screening for bacterial vaginosis during pregnancy in asymptomatic women reduces adverse pregnancy outcomes. They included a review of the clinical management effects that would result from antibiotic treatment based on screening results. These included adverse effects of therapies and the beneficial effects of reduction in adverse pregnancy outcomes, such as preterm delivery. The authors might also have explicitly included an outcome that examines whether the screening leads to receipt of antibiotic treatment—whether screening leads to a change in clinical management. This would be a relevant intermediate outcome on the path between screening and the outcomes attributable to therapy.
Direct Test Effects
Appropriately, the authors of this review did not include outcomes that are a direct result of the testing process because direct test effects are unlikely in this example; a vaginal swab will not cause any injury. Similarly, the test does not confer any direct benefit either except perhaps contact with clinicians.
Emotional, Social, Cognitive, or Behavioral Effects
The authors might have also looked at the emotional, social, cognitive, or behavioral effects from the screening process or from the screening test results. It may have been appropriate to consider outcomes that are associated with screening but are not the result of antibiotic therapy. Consideration may have been given to the effects of testing positive for bacterial vaginosis, such as emotional responses to a diagnosis of infection leading to either healthier or riskier prenatal activities, or maternal worry as an outcome.
As with any measure, the systematic review team might require that the instrument used to measure emotional response be a validated and appropriate instrument.
Legal and Ethical Effect of Testing
Although specifying ethical issues in screening for bacterial vaginosis (which is not a sexually transmitted infection) may seem unnecessary, bacterial vaginosis testing may be done as part of an infectious disease screening for reportable diseases such as syphilis or HIV. Therefore, a review of the effects of testing should consider whether the test being reviewed might be administered with concurrent screening tests that could themselves raise ethical issues.
Costs of the Test
The authors of this review did not consider the costs of the test to the patient as an outcome. Widespread initiation of screening programs, such as on a population level, may have profound cost implications.
The authors of this review considered the effects of screening on the mother and on the fetus or infant. However, they might have also considered other relevant parties; these might include the mother’s partner and society, as antibiotic resistance is a conceivable outcome from widespread testing and treatment of bacterial vaginosis.
Example of a Diagnostic Test
We differentiate diagnostic tests from screening tests largely by the population being tested. Whereas a diagnostic test is applied to confirm or refute disease in a symptomatic person, a screening test is used in an asymptomatic or pre-symptomatic person. The USPSTF mostly makes recommendations about screening tests that may be used in the general population; other organizations are more concerned with ensuring safe use of diagnostic tests in patient populations. Payers are also interested in optimizing use of diagnostic tests, as many are costly.
We discuss a review that addressed the diagnostic value of 64-slice computed tomography (CT) in comparison to conventional coronary angiography.
13 Stating that their review concerned the “accuracy” of CT, the authors aimed to assess whether 64-slice CT angiography might replace some coronary angiography for diagnosis and assessment of coronary artery disease. A broader review may consider the effectiveness of CT angiography, and the investigators would consider the full range of outcomes as below.
Clinical Management Effects
Numerous clinical management effects might follow testing for coronary artery disease with CT. The authors of the review focused exclusively on detection of occluded coronary arteries and not on any downstream outcomes from identification of occluded coronary arteries. Individuals diagnosed with coronary artery disease are subjected to many clinical management changes; these include medications, recommendations for interventions such as angioplasty or bypass surgery, and recommendations for lifestyle changes; each of which has associated benefits and harms. All of these may be appropriate outcomes to include in evaluating a diagnostic test. If one test under consideration identifies more coronary artery disease than another, this will be reflected in clinical management changes and their consequences.
Other conceivable clinical management effects relate to the impact of testing on other health maintenance activities. For example, a patient might defer other necessary testing (e.g., bone densitometry) to proceed with the CT. We would expect, however, that this would also be the case in the comparison arm. Family members may be affected as well by testing; for instance, they may be called upon to assist the diagnosed patient with future appointments, which may necessitate time away from work and cause emotional stress.
Direct Test Effects
The test under consideration is a radiographic test. It confers no direct benefit itself (unlike the comparison procedure in which an intervention can be performed at the time of conventional diagnostic angiography). The testing process poses potential harms, including allergic reaction to the intravenous contrast material, renal failure from the contrast material, and radiation exposure. These are all outcomes that could be considered for inclusion. In this example, the comparison test carries comparable or greater risks.
Emotional, Social, Cognitive, or Behavioral Effects
The testing process itself is unlikely to have significant emotional consequences, as it is not an invasive test and is generally comfortable for the tested individual. The results of testing could indeed have emotional or behavioral consequences. An individual diagnosed with coronary disease might alter his or her lifestyle to reduce disease progression. On the other hand, an individual might become depressed by the results and engage in less self-care or riskier behavior. These behavioral effects are likely to affect the family members as well. However, in this example the emotional or behavioral effects are expected to be similar for both CT and conventional angiography and therefore may not be relevant for this particular review. In contrast, they would be relevant outcomes if CT angiography were being compared with no testing.
Legal and Ethical Effects of Testing
Testing could have legal consequences if the tested individual is in a profession that requires disclosure of health threats for the safety of the public; this might arise if, e.g., the tested person were an airline pilot. However again, this outcome is not expected to differ between CT and conventional angiography.
Costs of the Test
The relative costs of the two tests to the insurer and the patient, and the costs of diverting equipment away from other uses, could also be of interest to some stakeholders.
Outcomes Unique to Prognostic Tests
Prognostic tests are tests used in individuals with known disease to predict outcomes. The procedure itself may be identical to a procedure that is used as a screening test or a medical test, but the results are applied with a different purpose. Given this, additional considerations for outcomes should be included in reviews. For example, consider the use of spirometry for predicting prognosis in individuals with chronic obstructive pulmonary disease (COPD). The test is commonly used for making the diagnosis of COPD and monitoring response to treatment, but the question has been raised as to whether it might also predict survival. In 2005, the Minnesota EPC did a systematic review of this topic on behalf of the American Thoracic Society, American College of Physicians, American Academy of Family Physicians, and American Academy of Pediatrics.
14 The discussion below focuses on one of their key questions, which was whether prediction of prognosis with spirometry, with or without clinical indicators, is more accurate than prediction based on clinical indicators alone. They were interested in predicting survival free of premature death and disability.
Clinical Management Effects
The results from prognostic testing will have effects on clinical management. Although the prognoses for some diseases are minimally modifiable with current treatments, most prognostic information can be used to alter the course of treatment. In this example, spirometry may suggest a high likelihood of progressing to respiratory failure and prompt interventions to avert this (e.g., pulmonary rehabilitation efforts, changes in medication, avoidance of some exposures). Conversely, the prognostic information may be used to make decisions regarding other interventions. If the likelihood of dying of respiratory failure is high, patients and their physicians may choose to refrain from colonoscopy and other screening procedures from which the patient is unlikely to benefit. Similarly, treatments of other conditions may be of less interest if life expectancy is short.
Direct Test Effects
Spirometry has few direct test effects, although patients can have adverse reactions to testing particularly if challenged with methacholine as part of the test. In general, it is unlikely that tests used for prognosis are more or less likely to have direct test effects than tests used for other purposes.
Emotional, Social, Cognitive, or Behavioral Effects
We doubt that many emotional or cognitive effects would arise in response to the testing process. Spirometry is a noninvasive test that most patients tolerate well. Emotional effects to the results of testing are possible; emotional effects could even be more pronounced for prognostic tests than for screening or medical tests if the test yields more specific information about mortality risk than is usual from a diagnostic test. This could have a range of effects on behavior including efforts to alter prognosis, like smoking cessation. Test results with prognostic information would be expected to affect family members as well.
Legal and Ethical Effects of Testing
Results of tests that provide prognostic information could have legal outcomes, too, especially if the tested individual acts in ways that belie the information he has received (e.g., entering into a contract or relationship that he is unlikely to fulfill). In this present example, it is unlikely that the prognostic information from spirometry would actually raise these issues, but in other cases, such as a test that demonstrates widely metastatic cancer, this could be an issue. These legal and ethical effects of testing may reach beyond the tested individual and affect society if many individuals have substantial concealed information that influences their actions.
Costs of the Test
The relative costs of the test to the insurer and the patient, relative to the costs of collecting information from a history and physical examination, may all be of interest to stakeholders.
If the Test is a Genetic Test
Chapter 10 of this guide describes in detail unique issues regarding evaluation of genetic tests. With respect to relevant outcomes, we note a few considerations here. Most prominent is the effect on family members. Genetic information about the tested individual has direct bearing on family members who share genes. This may affect emotional and behavioral outcomes, and ethical outcomes, if family members feel pressured to proceed with testing to provide better information for the rest of the family. A second issue is possible impact of health insurance eligibility. Recent legislation in the United States prohibits the use of genetic test results to exclude an individual from health insurance coverage, making this less a relevant outcome than in the past. This policy varies worldwide, however, and may be a relevant consideration in some countries.
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