A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago. His ECG shows ST- segment elevation in leads V1 to V4. He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed. A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel. On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient. He asks about the benefits and risks of the added therapy. Based on the research abstract, After a pharmaceutical drug is approved by the Food and Drug Administration, phase IV or post-marketing surveillance is conducted to detect fatal and serious side effects. The failure to detect such events in earlier phases of clinical testing is most likely due to which of the following?
A)Biased allocation of patients
B)Hidden confounders
C)Inadequate power
D)Measurement bias
E)Use of placebo

Question

A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago.  His ECG shows ST- segment elevation in leads V1 to V4.  He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed.  A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel.  On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient.  He asks about the benefits and risks of the added therapy.  Based on the research abstract, After a pharmaceutical drug is approved by the Food and Drug Administration, phase IV or post-marketing surveillance is conducted to detect fatal and serious side effects.  The failure to detect such events in earlier phases of clinical testing is most likely due to which of the following?
A)Biased allocation of patients
B)Hidden confounders
C)Inadequate power
D)Measurement bias
E)Use of placebo

Quizplus · Accepted Answer

Explanation: Post-marketing surveillance is the practice of monitoring the safety of medications or devices after they have been released on the market. The power of a study reflects its ability to detect a difference between groups, if such a difference exists. Power depends on sample size. Randomized clinical trials are efficacy trials by design and may not have adequate power to look at adverse effects, especially rare adverse effects. There may be too few participants (small sample size) to detect rare adverse effects; follow-up times are often short; and in some populations, comorbidities and additional drug interactions may not be adequately represented in earlier phases of clinical testing. The true safety profile of any medication is often understood only after the medication has been on the market for a period of time and has been used by a large number of patients. (Choices A and B) Randomized clinical trials often list baseline characteristics of patients in treatment and control arms. If successful randomization has occurred, these characteristics should be similar. Successful randomization also minimizes confounding variables, including unmeasured ones. (Choice D) Measurement bias occurs from poor data collection with inaccurate results, which often is not the case in randomized clinical trials for medication approval by the Food and Drug Administration. (Choice E) Placebos are given as control treatments, and they are often inert tablets, sham surgeries, and other procedures based on providing false information. The use of placebos allows researchers to isolate the efficacy and adverse effects of the study medication. Educational objective: Post-marketing surveillance is the practice of monitoring the safety of medications or devices after they have been released on the market. This is due to the fact that clinical trials often have short follow-up times, underrepresented populations, and too few participants to detect rare and serious side effects. References: Some concerns about adverse event reporting in randomized clinical trials. (http://www.ncbi.nlm.nih.gov/pubmed/18537786)

A 62-Year-Old Man with a History of Dyslipidemia and Type