All practice questions

A hospital's Pharmacy and Therapeutics committee is evaluating a proposal to add a novel anticoagulant, *Thrombostat*, to the formulary for stroke prevention in patients with nonvalvular atrial fibrillation. The committee reviews the primary outcome data from the pivotal, double-blind, randomized controlled trial.

The trial enrolled $8000$ patients, who were randomized in a $1:1$ ratio to receive either *Thrombostat* or standard-of-care warfarin. Over a 2-year follow-up period, the incidence of the primary endpoint (ischemic stroke) was recorded as follows:

Based on these study results, what is the number needed to treat (NNT) with *Thrombostat* instead of warfarin to prevent one ischemic stroke over 2 years?

A medical researcher is evaluating the relationship between the class of oral antidiabetic medication prescribed and the incidence of major adverse cardiovascular events (MACE) in a retrospective cohort of 1,250 patients with type 2 diabetes. The medication classes are categorized as SGLT2 inhibitors ($n = 450$), GLP-1 receptor agonists ($n = 600$), and DPP-4 inhibitors ($n = 200$). The cardiovascular outcomes over the study period are classified into three mutually exclusive categories: myocardial infarction ($n = 150$), ischemic stroke ($n = 100$), and no MACE ($n = 1,000$).

The researcher plans to use a Pearson chi-square test to determine if the choice of medication is independent of cardiovascular outcomes. A key assumption of this test is that no more than 20% of the expected cell frequencies are less than 5.

Under the null hypothesis of no association, what is the expected count of patients who were prescribed a GLP-1 receptor agonist and subsequently experienced a myocardial infarction? (Enter your answer as a whole number).

A research team is investigating the relationship between preoperative smoking status and the incidence of post-operative respiratory complications in patients undergoing elective abdominal surgery. The researchers categorize $500$ patients into three groups: current smokers ($n=100$), former smokers ($n=150$), and never smokers ($n=250$). During the $30$-day post-operative period, the following number of patients developed respiratory complications:

- Current smokers: $15$
- Former smokers: $10$
- Never smokers: $5$

The researchers plan to perform a Chi-square test of independence to analyze this categorical data. Assuming the null hypothesis of no association is true, what is the expected count of current smokers who develop post-operative respiratory complications?

A hospital's infection control committee is evaluating the efficacy of a novel chlorhexidine bathing protocol for reducing methicillin-resistant Staphylococcus aureus (MRSA) colonization. The study enrolls a cohort of 150 patients undergoing long-term hemodialysis. At baseline, each patient undergoes a nasal swab and is categorized as either MRSA-positive or MRSA-negative. The entire cohort then follows the novel bathing protocol for six months. At the conclusion of the trial, the exact same 150 patients are swabbed again and categorized as MRSA-positive or MRSA-negative. The researchers aim to determine if there is a statistically significant change in the proportion of patients colonized with MRSA following the six-month intervention. Which of the following is the most appropriate statistical test to analyze these study results?

A hospital epidemiology team is investigating a localized cluster of carbapenem-resistant *Acinetobacter baumannii* (CRAB) infections in an intensive care unit. An independent case-control study is designed to evaluate whether prior exposure to a specific shared diagnostic equipment cart is associated with the infection. The study includes 8 patients with CRAB (cases) and 12 patients without CRAB (controls) who were in the unit during the same period. Among the 8 cases, 6 were exposed to the equipment cart. Among the 12 controls, 3 were exposed to the equipment cart. The researchers wish to determine if there is a statistically significant association between equipment exposure and CRAB infection. Which of the following is the most appropriate statistical test to analyze these study data?

Investigators at a regional academic medical center are exploring the association between a newly marketed combined oral contraceptive and the incidence of venous thromboembolism. Initial analysis of the cohort yields a crude relative risk of 2.1 for venous thromboembolism among contraceptive users compared to non-users. The research team subsequently stratifies the participants based on the presence of the prothrombin G20210A mutation. In the stratum of participants without the mutation, the relative risk is 1.1. In the stratum of participants with the mutation, the relative risk is 6.4. Based on these statistical findings, which of the following conclusions and subsequent analytical steps are appropriate? (Select two that apply)

A medical education committee is reviewing several published clinical studies to teach residents how to critically appraise medical literature. Match each specific study finding or methodological characteristic described below to the most appropriate epidemiological or statistical concept.

A gastroenterology research group is conducting a randomized controlled trial to evaluate a new monoclonal antibody against standard therapy for moderate-to-severe Crohn's disease. Four hundred patients are randomized equally into two independent treatment arms. The primary endpoint compares the proportion of patients achieving clinical remission at week 12, categorized as either 'achieved' or 'not achieved', between the two groups. A secondary endpoint compares the absolute reduction in the Crohn's Disease Activity Index (CDAI), a continuous numerical score, between the two treatment groups. Preliminary data analysis reveals that the CDAI reduction scores in both treatment arms are highly skewed and significantly violate the assumption of normality.

Which of the following statistical tests are appropriate for analyzing the endpoints in this study? (Select all that apply)

A research team conducts a retrospective cohort study to evaluate the risk of acute kidney injury associated with a novel immunosuppressant in lung transplant recipients. The primary analysis yields a crude relative risk ($RR$) of $2.8$ ($95\% \text{ CI}: 1.9 - 4.1$) for acute kidney injury in patients receiving the novel agent compared to those on standard therapy. Concerned about baseline patient differences, the investigators perform a stratified analysis based on the presence or absence of pre-existing systemic hypertension. The stratum-specific relative risk is $1.1$ ($95\% \text{ CI}: 0.7 - 1.6$) in patients with pre-existing hypertension and $1.2$ ($95\% \text{ CI}: 0.8 - 1.7$) in patients without pre-existing hypertension.

Which of the following is the most accurate conclusion regarding the role of pre-existing hypertension in this study?

To optimize blood pressure control in patients with treatment-resistant hypertension, researchers design a prospective clinical trial comparing three distinct therapeutic regimens. The study enrolls 180 participants who are randomly assigned in equal proportions to receive either spironolactone, bisoprolol, or doxazosin as add-on therapy. The primary outcome measured is the absolute reduction in systolic blood pressure (in mm Hg) from baseline to the 6-month follow-up visit. The investigators verify that the reductions in blood pressure follow a normal distribution within all three treatment arms. Which of the following is the most appropriate statistical test to evaluate whether a significant difference exists in the mean systolic blood pressure reduction among the three medication groups?

Evaluate the following clinical research scenarios and match each to the specific epidemiological phenomenon or bias it most accurately represents.

Rheumatology researchers are designing a multicenter observational study to evaluate the cardiovascular safety profile of Janus kinase (JAK) inhibitors versus conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The primary outcome is the incidence of major adverse cardiovascular events (MACE). During the planning phase, the team notes a critical challenge: physicians intentionally avoid prescribing JAK inhibitors to patients with pre-existing cardiovascular risk factors. Because these same risk factors independently increase the likelihood of developing MACE, this dynamic threatens the internal validity of the study.

To effectively mitigate this threat and isolate the true association between the pharmacological therapies and MACE, which of the following strategies are appropriate to implement? (Select all that apply)

A hospital research committee is reviewing several proposed clinical trial protocols. Match each proposed clinical study design with the most appropriate statistical test to analyze its primary data.

Investigators are conducting a prospective cohort study to evaluate the association between a new sodium-glucose cotransporter-2 (SGLT2) inhibitor and the incidence of ischemic stroke in patients with type 2 diabetes. Initial analysis reveals a crude Relative Risk (RR) of $0.75$ ($95\%$ CI: $0.61 - 0.92$, $p = 0.01$) for stroke in the SGLT2 inhibitor group compared to patients on standard sulfonylurea therapy. The investigators suspect that concurrent use of antiplatelet therapy might influence the results, so they perform a stratified analysis based on baseline antiplatelet use:

- Stratum 1 (Concurrent antiplatelet use): RR = $0.45$ ($95\%$ CI: $0.32 - 0.60$)
- Stratum 2 (No concurrent antiplatelet use): RR = $1.05$ ($95\%$ CI: $0.88 - 1.25$)

Based on these statistical findings, which of the following is the most appropriate approach for the investigators to present their final data?

A team of neurologists is conducting a randomized, double-blind crossover trial to compare the efficacy of two disease-modifying therapies (Drug X and Drug Y) in patients with relapsing-remitting multiple sclerosis. Fifty patients are enrolled and randomized to receive either Drug X or Drug Y for 12 months. After a 3-month washout period, the patients are switched to the alternative therapy for another 12 months. The primary outcome measure is the total volume of T2-hyperintense white matter lesions, measured in cubic millimeters ($mm^3$) via brain magnetic resonance imaging (MRI) at the end of each 12-month treatment period. Preliminary data analysis confirms that the lesion volume measurements follow a normal distribution. Which of the following statistical tests is the most appropriate to compare the primary outcome between the two treatment periods?

A hospital therapeutics committee is reviewing several drug advertisements and recent clinical trial publications to update the institutional formulary. They must critically appraise the methodology and promotional claims to avoid adopting flawed or misleading evidence. Match each study excerpt or promotional claim with the specific methodological flaw, bias, or interpretative error it most clearly demonstrates.

A multicenter clinical trial is designed to evaluate the efficacy of newly formulated lipid-lowering regimens in patients with familial hypercholesterolemia. The study randomizes 360 patients equally into 6 distinct treatment arms: high-intensity statin monotherapy, statin plus ezetimibe, statin plus a PCSK9 inhibitor, statin plus bempedoic acid, PCSK9 inhibitor monotherapy, and a placebo group.

After 12 weeks, an initial one-way analysis of variance (ANOVA) reveals a statistically significant difference in the mean percentage reduction of LDL cholesterol across the groups ($p = 0.004$). The investigators plan to conduct post-hoc pairwise comparisons using independent $t$-tests to identify which specific groups differ from one another. To control the family-wise Type I error rate at $\alpha = 0.05$, they apply a Bonferroni correction by dividing the overall $\alpha$ by the total number of unique pairwise comparisons.

How many unique pairwise comparisons can be made among the treatment arms in this study?

An internal medicine residency program is holding an evidence-based medicine journal club. The residents are reviewing methodology excerpts from five recent clinical trials to evaluate their validity, potential biases, and clinical applicability. Match each trial methodology excerpt to the corresponding epidemiological or statistical concept it best describes.

A surgical researcher is evaluating a novel topical biologic dressing against standard petrolatum gauze for the healing of chronic diabetic foot ulcers. Twenty-four patients with comparable baseline ulcer characteristics are randomly assigned in a 1:1 ratio to one of the two treatment protocols. The primary outcome measured is the absolute reduction in ulcer surface area ($cm^2$) at 8 weeks. Statistical evaluation of the collected data indicates that the surface area reduction values are heavily right-skewed and do not follow a normal distribution. Which of the following statistical tests is most appropriate to determine if there is a statistically significant difference in the primary outcome between the two study groups?

A research group utilizes a national pharmacoepidemiology database to evaluate the risk of tendon rupture associated with a novel fluoroquinolone antibiotic compared to traditional therapeutic options. The preliminary unadjusted analysis reveals an incidence rate ratio (IRR) of 1.7 (95% CI: 1.2-2.4) for tendon rupture in patients receiving the novel fluoroquinolone.

To explore the potential influence of concurrent systemic corticosteroid therapy, the analysts divide the study population into two distinct subgroups based on active corticosteroid prescriptions.
- In the corticosteroid-exposed subgroup, the IRR for tendon rupture is 3.5 (95% CI: 2.1-5.8).
- In the unexposed subgroup, the IRR is 1.0 (95% CI: 0.7-1.4).

Based on this analysis, which of the following best categorizes the epidemiological phenomenon demonstrated by concurrent corticosteroid use, and what is the most appropriate reporting action?