A 10-year-old boy is brought to the office by his parents for a follow-up visit. The patient has sickle cell disease (SCD) and says that he has had an increase in the number of pain crises in the past 12 months. The parents ask whether their child can receive the recently approved Drug Z for the treatment of vasoocclusive crises (VOCs) in patients with SCD. The drug trials' snapshot summary for Drug Z states that its benefit was evaluated in 2 randomized, placebo-controlled trials in adults with SCD who had 4 to 8 VOCs in the 12 months before they were enrolled in the trials. The first trial (n = 61) showed that therapy with high-dose Drug Z resulted in a significantly lower rate of VOCs than placebo (45.3% lower rate; p

Question

A 10-year-old boy is brought to the office by his parents for a follow-up visit.  The patient has sickle cell disease (SCD) and says that he has had an increase in the number of pain crises in the past 12 months.  The parents ask whether their child can receive the recently approved Drug Z for the treatment of vasoocclusive crises (VOCs) in patients with SCD.  The drug trials' snapshot summary for Drug Z states that its benefit was evaluated in 2 randomized, placebo-controlled trials in adults with SCD who had 4 to 8 VOCs in the 12 months before they were enrolled in the trials.  The first trial (n = 61) showed that therapy with high-dose Drug Z resulted in a significantly lower rate of VOCs than placebo (45.3% lower rate; p < 0.01).  The second trial (n = 32) showed that therapy with low-dose Drug Z resulted in a significantly lower rate of VOCs than placebo (35.8% lower rate; p = 0.01).  Which of the following conclusions can be drawn about this situation?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c10a_e5d6_8f63_572723159cad_MD0005_00 The external validity (or generalizability) of a study is the applicability of study results beyond the specific population studied. This 10-year-old boy with sickle cell disease (SCD) had an increase in the number of pain crises (ie, vasoocclusive crises [VOCs]) in the past 12 months. Although the benefit of Drug Z for the treatment of VOCs in patients with SCD was reported to be significant in 2 different randomized, placebo-controlled trials (RCTs) in patients with SCD, the study population consisted of adults (ie, patients age ≥18) who had 4 to 8 VOCs in 12 months. The patient had an increased number of pain crises in the past 12 months, but it is unclear whether he had 4 to 8 VOCs in the past 12 months (an inclusion criterion in both trials). In addition, the patient is age <18. Therefore, these study results conducted in populations that were similar to each other may not apply to this situation, which limits the ability to prescribe Drug Z to this 10-year-old patient. (Choice A) Reproducibility (reliability) refers to the extent to which a measure produces consistent results if the measurements are repeated multiple times. The fact that both RCTs showed similar results suggests the results are reproducible. However, even if they are reproducible, they may not be generalizable to this particular patient. (Choice C) Internal validity is concerned with how well results provide evidence of a causal relationship in a study; it is affected by bias (ie, due to confounding variables). In this situation, randomization improved the internal validity of each RCT by balancing the distribution of confounding variables among the groups. (Choice D) Misclassification of exposure bias occurs when the exposure is not assessed correctly, typically in observational studies in which there is no control over the exposure (eg, exposure is observed instead of controlled). In these 2 RCTs, the exposure was not likely to be misclassified because it was clearly defined by the treatment given to patients (ie, high-dose Drug Z, low-dose Drug Z, and placebo). (Choice E) Statistical power is the ability of a study to detect a significant effect (eg, improvement) when that effect exists. Both RCTs reported significant reductions in the rate of pain crises; therefore, they had sufficient statistical power. Educational objective: The external validity (or generalizability) of a study is the applicability of study results beyond the specific population studied. Results from a randomized, controlled trial conducted in a very specific population of patients are generalizable only to that specific subgroup of the population.

A 10-Year-Old Boy Is Brought to the Office by His