A study is evaluating the effect of agomelatine on postnatal depression at a mother and baby unit.
Which one of the following should be considered when assessing the internal validity of this study?
B. Internal validity is the degree to which a study establishes the cause-and-effect relationship between the treatment and the observed outcome. External validity is the degree to which the results of a study becomes applicable outside the experimental setting in which the study was conducted. In other words, external validity refers to generalizability of study results while internal validity refers to rigorousness of the research method. The benefit of agomelatine in different populations (choices A and E) refers to external validity; the cost of the drug and consistency of results obtained from different studies are related to applicability of the intervention in a clinical setting. Assessment of adherence to study protocol is one of many ways of analyzing the quality of an intervention trial.
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A new clinician-administered test for assessing suicidal risk is studied in a prison population in Canada, where a high suicide rate of 1 in 25 has been recorded.
Which of the following indicate that this test is NOT suitable for your clinical population?
C. Having a high positive predictive value, a likelihood ratio more than 10, and good interrater reliability as measured by kappa are desirable properties of an instrument. But when the same instrument is applied to a population with much lower prevalence of suicide (the studied phenomenon), the post-test probability decreases substantially. Post-test probability is a measure of positive predictive value in the target population; it depends on pretest probability, i.e. the prevalence and likelihood ratio.
A new rating scale being evaluated for anxiety has a sensitivity of 80% and specificity of 90% against the standard ICD-10 diagnosis.
The likelihood ratio of a positive result is:
D. The likelihood ratio of a positive test (LR+) is the ratio between the probability of a positive test in a person with disease and the probability of a positive test in a person without disease. It can also be expressed as:
A pharmaceutical company developed a new antidepressant ‘X’. They conducted a randomized double-blind placebo controlled trial of the drug. The study had two arms: an active medication arm and a placebo arm. Each arm had 100 subjects. Over a 4-week period, a 50% drop in Hamilton depression scale (HAMD) scores were seen in 40 subjects in the active medication arm, while a similar drop was seen only in 20 subjects in the placebo arm.
What is the number needed to treat (NNT) from this trial for the new antidepressant?
E. The NNT is the number of patients who will need the experimental treatment (X) for one additional patient to benefit compared with the control treatment. In the given trial, the response rate is characterized by a 50% drop in HAMD from baseline. Forty per cent of those taking drug X achieve this response. In contrast, this rate is 20% for the placebo. This means that 20% (40 – 20%) additional patients responded to the drug compared with placebo. In other words, if we treat another 100 patients with X, 20 extra patients will respond to X than those treated with a placebo. So we need to treat at least fi ve people in order to see a benefit in one additional patient. This value fi ve is known as the NNT. This can be calculated in another way. As you read further, you will note that 20% is the absolute benefit increase (ABI = EER – CER). And from the formula, NNT = 1/ABI, we get 1/20% = 5.
During the same placebo controlled trial described in question 4, 20% of people on X developed active suicidal ideas, while only 10% of patients on placebo developed the same side-effect.
What is the number needed to harm (NNH) associated with the suicidal ideas from the trial data?
B. NNH is similar to the NNT. NNH is the number of patients who need to take the experimental treatment for one additional patient to experience an adverse effect. In the question, 20% of participants on X experienced suicidal ideas compared with 10% on placebo. Put in other words, the drug is responsible for suicidal ideas in an extra 10% of patients. So, if 100 patients receive the drug, 10 extra patients will experience suicidal ideas. That is, for every 10 people treated, one additional patient will experience suicidal ideas. Hence the NNH is 100/10 = 10. This obviously can be calculated from the formula NNH = 1/ARI (absolute risk increase) = 1/10% = 10. It is highly unlikely that X was marketed by the company.
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