special subjects
Economic Analyses in Clinical Decision Making
Outcome
The effectiveness of medical care is measured by change in outcome. Outcomes can be Patient oriented Process oriented Disease oriented Patient-oriented outcomescan be reduced to one of the three Ds: Death Disability Discomfort (physical or emotional) Patient-oriented outcomes are arguably the most important. Process improvements(eg, reducing the time to antibiotic administration or to operating room) orimprovements in disease manifestations(eg, shrinking tumor size, improving O2 saturation) that donotreduce mortality, disability, or discomfort at all can hardly be said to benefit the patient. For example,lidocainewas once routinely given to patients with myocardial infarction (MI) because it was known to reduce the incidence of ventricular fibrillation (improved disease outcome).Lidocainetreatment continued for many years before studies showed it did not decrease mortality (no change in patient outcome), and so the practice was stopped. Change in raw mortality is the most common way to evaluate effect on death. In more complex analysis, death and disability are often evaluated in combination as the quality-adjusted life year (QALY); treatment that results in an additional year of life at 100% of normal functioning is credited with 1 QALY; treatment that results in an additional year of life at only 75% functioning is credited with 0.75 QALY. QALY is more difficult to apply to discomfort, but some believe it can be estimated by the time tradeoff method: A person estimates how many years of discomfort would be acceptable vs a shorter period of perfect health. For example, if a person would prefer 9 years of health to 10 years of chronic pain (but would prefer the 10 years of pain to only 8 years of life), then each year of life with that particular pain is credited with 9/10=0.9 QALY. All such QALY estimates are somewhat problematic because people vary widely in risk tolerance and acceptance for various outcomes. Thenumber needed to treat(NNT) or harm is another way to quantify patient outcome; NNT is the reciprocal of the absolute change in a dichotomous outcome (death, disability). Thus, if a drug causes a 3% net decrease in mortality, 1/0.03=33.3 patients need to be treated to prevent 1 death. Thenumber needed to harmis similar. Thus, for a drug that causes leukopenia in 8% of patients, 1/0.08 or 12.5 need to be treated to harm 1 person. Phrased another way, 1 person is harmed for every 12.5 treated. The pertinence of the NNT is clearer when comparing mortality to mild adverse effects of a treatment. It becomes cloudier when comparing the reduction in a particular morbidity to a more serious adverse effect. From the perspective of the clinician, however, it can be a very useful tool in explaining the risk:benefit ratio of a treatment to the patient. Because the NNT is derived from absolute change, as opposed to relative change, it is more clinically relevant to a given patient. For example, a treatment that reduced mortality from 2% to 1% reduces relative mortality by 50% but absolute mortality by only 1%. This is easy to see when represented as an NNT of 1/0.01=100 treated to prevent one death. The relative change concept is more relevant to hypothesis testing (proof of concept that a therapy has efficacy) than to an individual patient. Even when appropriate outcome measures are used and analyzed correctly, it is critically important to note that a statistically significant outcome in a clinical study (ie, with an excellent p value) is not necessarilyclinically significantto a patient. Statistical significance is to a large extent dependent upon the sample size; with a large enough sample, a minimal difference of no clinical importance to a patient (eg, a reduction of duration of upper respiratory infection symptoms from 7 to 6.5 days) could well be statistically significant. The magnitude of difference between 2 groups in a clinical study is referred to as the effect size; as in the above example, an effect size may be small, but still highly statistically significant. 