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Thread: Principles of Pharmacotherapy

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    Default Principles of Pharmacotherapy

    The Threshold Concept

    The threshold concept explicitly considers both the likelihood of disease and the tradeoffs between the risks and benefits of tests and treatments; it uses simple principles to identify when to test and when to treat.

    When a treatment for a suspected disease is extremely effective and low in risk and the probability of disease is quite high, it may be appropriate to avoid using a risky test and give the treatment without complete confidence that the disease is present. With a less effective treatment or a risky treatment, the physician's confidence in the diagnosis must be quite high to avoid giving the risky treatment to patients who do not have the disease.

    When assessing a treatment, multiple factors must be considered, including the cure rate, the extension in life expectancy, and the alleviation of suffering. In addition, any measure of the value of a treatment must represent the net effect of both the efficacy and the risk of that therapy. The cost of a test is, of course, another factor. When a test is expensive but virtually risk-free and the disease sought has a large potential in terms of a patient's well-being, then the use of the test often is warranted even if the condition being sought is uncommon.

    The Therapeutic Threshold

    At the extremes of diagnostic certainty, the relations between the confidence in a diagnosis and a therapeutic intervention are readily apparent. If one is confident on clinical grounds that a patient has had a pulmonary embolus, one should be willing to give heparin as long as the benefits of treatment outweigh the risks. At the other extreme, if one is confident on clinical grounds that the patient has not had a pulmonary embolus, one should not, of course, given heparin.

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    At likelihoods of pulmonary embolism between definitely present and definitely absent, the decision to treat is a function of how likely one consider the probability of an embolus, the magnitude of the benefits of anticoagulation, and the magnitude of the risks of therapy. Indeed, some probability of pulmonary embolism exists between 0 and 1 at which the value of giving or withholding treatment are equivalent. This "break-even" probability is known as the threshold probability, or specifically the therapeutic threshold. At disease probabilities greater than the threshold, treatment should be given, whereas at disease probabilities lower than the threshold, treatment should be withheld. The higher the ratio between benefits and risks of treatment, the lower the likelihood of disease required to give treatment. The lower the ratio, the more certain one must be of the diagnosis before administering the treatment. If the suspicion of pulmonary embolism is only moderately high and there is no increased risk from heparin, heparin should be given, whereas even if suspicion of pulmonary embolism is moderate, heparin should be avoided when the risk of treatment also is high.

    Testing Thresholds

    A test that can help differentiate whether a disease is present reduces uncertainty: A positive result increases the probability of the disease and a negative test reduces its likelihood. Depending on the characteristics of a given treatment, the test result may make the posttest probability of disease sufficiently high or low to alter the decision in favor of administering treatment or withholding it, respectively. These principles are embodied in the concept of testing thresholds, which are benchmarks for the use of diagnostic tests. If, as noted in the preceding post, the two therapeutic choices for a patient suspected of having a given disease are withholding treatment or giving the treatment, and if treatment should be withheld when the disease is absent and given when the disease is present, then the "breakeven" probability at which the value of giving the treatment and not giving the treatment is the same as the therapeutic threshold. If, however, a diagnostic test is available that has the potential of altering the likelihood that the patient is suffering from the disease, then the clinician is faced not with two choices, but three: withholding therapy, ordering the test, and treating without testing.

    The decisions at very lower end and the very upper end of the probability scale are not affected by the existence of the test: The clinician will still withhold treatment when the disease is highly unlikely and still give the treatment when the disease is virtually certain. In both of these circumstances, the physician should not carry out the test. At intermediate probabilities of disease, however, the test result might have an influence on the choice of not treating or treating, and the optimal decision then is to administer the test. A negative test result decreases the chance that the patient has the disease and argues against giving the treatment; a positive test result increases the probability of disease and argues in favor of giving the treatment. The probability value at which the choice to give no treatment and the choice to use the test are equal in value is the test threshold for deciding between no treatment and testing, and probability value at which the choice to administer the test and the choice to give the treatment are equal in value is the treatment threshold for deciding between testing and empiric treatment.

    Testing thresholds are a function not only of factors such as the accuracy of the test (sensitivity and specificity) and the risk of the test but also of the efficacy and risks of treatment. Once the thresholds are calculated from these factors or estimated by the physician, they are interpreted as follows: When the estimated likelihood or probability of disease fallow below the no-treatment/test threshold, the optimal choice is not to give the treatment. When the disease probability exceeds the test/treatment threshold, the optimal choice is to give the treatment. When the disease probability falls between the two thresholds, the optimal choice is to carry out the test and to either treat or not treat, depending on the test result.
    Last edited by admin; Sat 3rd June '17 at 5:00pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease. Chengdu, Sichuan, China.

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