Meta-analyses and systematic reviews US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Meta-analyses and systematic reviews. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Meta-analyses and systematic reviews US Medical PG Question 1: A surgeon is interested in studying how different surgical techniques impact the healing of tendon injuries. In particular, he will compare 3 different types of suture repairs biomechanically in order to determine the maximum load before failure of the tendon 2 weeks after repair. He collects data on maximum load for 90 different repaired tendons from an animal model. Thirty tendons were repaired using each of the different suture techniques. Which of the following statistical measures is most appropriate for analyzing the results of this study?
- A. Chi-squared
- B. Wilcoxon rank sum
- C. Pearson r coefficient
- D. Student t-test
- E. ANOVA (Correct Answer)
Meta-analyses and systematic reviews Explanation: ***ANOVA***
- **ANOVA (Analysis of Variance)** is appropriate here because it compares the means of **three or more independent groups** (the three different suture techniques) on a continuous dependent variable (maximum load before failure).
- The study has three distinct repair techniques, each with 30 tendons, making ANOVA suitable for determining if there are statistically significant differences among their mean failure loads.
*Chi-squared*
- The **Chi-squared test** is used for analyzing **categorical data** (frequencies or proportions) to determine if there is an association between two nominal variables.
- This study involves quantitative measurement (maximum load), not categorical data, making Chi-squared inappropriate.
*Wilcoxon rank sum*
- The **Wilcoxon rank sum test** (also known as Mann-Whitney U test) is a **non-parametric test** used to compare two independent groups when the data is not normally distributed or is ordinal.
- While the study has independent groups, it involves three groups, and the dependent variable is continuous, making ANOVA a more powerful and appropriate choice assuming normal distribution.
*Pearson r coefficient*
- The **Pearson r coefficient** measures the **strength and direction of a linear relationship between two continuous variables**.
- This study aims to compare means across different groups, not to determine the correlation between two continuous variables.
*Student t-test*
- The **Student t-test** is used to compare the means of **exactly two groups** (either independent or paired) on a continuous dependent variable.
- This study involves comparing three different suture techniques, not just two, making the t-test unsuitable.
Meta-analyses and systematic reviews US Medical PG Question 2: A pharmaceutical company conducts a randomized clinical trial to demonstrate that their new anticoagulant drug, Aclotsaban, prevents more thrombotic events following total knee arthroplasty than the current standard of care. A significant number of patients are lost to follow-up, and many fail to complete treatment according to the study arm to which they were assigned. Despite these protocol deviations, the results for the patients who completed the course of Aclotsaban are encouraging. Which of the following analytical approaches is most appropriate for the primary analysis to establish the efficacy of Aclotsaban?
- A. Intention-to-treat analysis (Correct Answer)
- B. Sub-group analysis
- C. Per-protocol analysis
- D. As-treated analysis
- E. Non-inferiority analysis
Meta-analyses and systematic reviews Explanation: ***Intention-to-treat analysis***
- **Intention-to-treat (ITT) analysis** is the gold standard for the **primary analysis in superiority trials** and includes all patients in the groups to which they were originally randomized, regardless of protocol deviations, loss to follow-up, or treatment discontinuation.
- ITT preserves **randomization balance**, prevents bias from selective dropout (patients may drop out due to adverse effects or lack of efficacy), and provides a **conservative, realistic estimate** of treatment effect in actual clinical practice.
- For **regulatory approval and establishing efficacy**, ITT is the most appropriate primary analysis method even when dropout rates are high, as it maintains the integrity of the randomized comparison.
*Per-protocol analysis*
- **Per-protocol analysis** includes only patients who completed the study exactly as planned without protocol deviations.
- While the encouraging results in completers are noted, per-protocol analysis can **introduce significant bias** by excluding patients who dropped out due to adverse events or lack of efficacy, potentially **overestimating treatment benefit**.
- Per-protocol is typically used as a **secondary/supportive analysis**, not the primary method for establishing superiority.
*As-treated analysis*
- **As-treated analysis** categorizes patients according to the treatment they actually received rather than their randomized assignment.
- This violates the principle of randomization and can introduce **confounding bias**, as actual treatment received may be influenced by prognostic factors.
*Sub-group analysis*
- **Sub-group analysis** evaluates treatment effects within specific patient subsets.
- This is **hypothesis-generating** rather than confirmatory and increases the risk of false-positive findings (multiple comparisons problem) unless pre-specified in the protocol.
*Non-inferiority analysis*
- **Non-inferiority analysis** tests whether a new treatment is not worse than control by more than a pre-specified margin.
- The goal here is to demonstrate **superiority** (better than standard care), not non-inferiority, making this approach inappropriate.
Meta-analyses and systematic reviews US Medical PG Question 3: A research group wants to assess the safety and toxicity profile of a new drug. A clinical trial is conducted with 20 volunteers to estimate the maximum tolerated dose and monitor the apparent toxicity of the drug. The study design is best described as which of the following phases of a clinical trial?
- A. Phase 0
- B. Phase III
- C. Phase V
- D. Phase II
- E. Phase I (Correct Answer)
Meta-analyses and systematic reviews Explanation: ***Phase I***
- **Phase I clinical trials** involve a small group of healthy volunteers (typically 20-100) to primarily assess **drug safety**, determine a safe dosage range, and identify side effects.
- The main goal is to establish the **maximum tolerated dose (MTD)** and evaluate the drug's pharmacokinetic and pharmacodynamic profiles.
*Phase 0*
- **Phase 0 trials** are exploratory studies conducted in a very small number of subjects (10-15) to gather preliminary data on a drug's **pharmacodynamics and pharmacokinetics** in humans.
- They involve microdoses, not intended to have therapeutic effects, and thus cannot determine toxicity or MTD.
*Phase III*
- **Phase III trials** are large-scale studies involving hundreds to thousands of patients to confirm the drug's **efficacy**, monitor side effects, compare it to standard treatments, and collect information that will allow the drug to be used safely.
- These trials are conducted after safety and initial efficacy have been established in earlier phases.
*Phase V*
- "Phase V" is not a standard, recognized phase in the traditional clinical trial classification (Phase 0, I, II, III, IV).
- This term might be used in some non-standard research contexts or for post-marketing studies that go beyond Phase IV surveillance, but it is not a formal phase for initial drug development.
*Phase II*
- **Phase II trials** involve several hundred patients with the condition the drug is intended to treat, focusing on **drug efficacy** and further evaluating safety.
- While safety is still monitored, the primary objective shifts to determining if the drug works for its intended purpose and at what dose.
Meta-analyses and systematic reviews US Medical PG Question 4: An academic medical center in the United States is approached by a pharmaceutical company to run a small clinical trial to test the effectiveness of its new drug, compound X. The company wants to know if the measured hemoglobin a1c (Hba1c) of patients with type 2 diabetes receiving metformin and compound X would be lower than that of control subjects receiving only metformin. After a year of study and data analysis, researchers conclude that the control and treatment groups did not differ significantly in their Hba1c levels.
However, parallel clinical trials in several other countries found that compound X led to a significant decrease in Hba1c. Interested in the discrepancy between these findings, the company funded a larger study in the United States, which confirmed that compound X decreased Hba1c levels. After compound X was approved by the FDA, and after several years of use in the general population, outcomes data confirmed that it effectively lowered Hba1c levels and increased overall survival. What term best describes the discrepant findings in the initial clinical trial run by institution A?
- A. Type I error
- B. Hawthorne effect
- C. Type II error (Correct Answer)
- D. Publication bias
- E. Confirmation bias
Meta-analyses and systematic reviews Explanation: ***Type II error***
- A **Type II error** occurs when a study fails to **reject a false null hypothesis**, meaning it concludes there is no significant difference or effect when one actually exists.
- In this case, the initial US trial incorrectly concluded that Compound X had no significant effect on HbA1c, while subsequent larger studies and real-world data proved it did.
*Type I error*
- A **Type I error** (alpha error) occurs when a study incorrectly **rejects a true null hypothesis**, concluding there is a significant difference or effect when there isn't.
- This scenario describes the opposite: the initial study failed to find an effect that genuinely existed, indicating a Type II error, not a Type I error.
*Hawthorne effect*
- The **Hawthorne effect** is a type of reactivity in which individuals modify an aspect of their behavior in response to their awareness of being observed.
- This effect does not explain the initial trial's failure to detect a real drug effect; rather, it relates to participants changing behavior due to study participation itself.
*Publication bias*
- **Publication bias** occurs when studies with positive or statistically significant results are more likely to be published than those with negative or non-significant results.
- While relevant to the literature as a whole, it doesn't explain the discrepancy in findings within a single drug's development where a real effect was initially missed.
*Confirmation bias*
- **Confirmation bias** is the tendency to search for, interpret, favor, and recall information in a way that confirms one's preexisting beliefs or hypotheses.
- This bias would likely lead researchers to *find* an effect if they expected one, or to disregard data that contradicts their beliefs, which is not what happened in the initial trial.
Meta-analyses and systematic reviews US Medical PG Question 5: A 65-year-old man is admitted to the hospital because of a 1-month history of fatigue, intermittent fever, and weakness. Results from a peripheral blood smear taken during his evaluation are indicative of possible acute myeloid leukemia. Bone marrow aspiration and subsequent cytogenetic studies confirm the diagnosis. The physician sets aside an appointed time-slot and arranges a meeting in a quiet office to inform him about the diagnosis and discuss his options. He has been encouraged to bring someone along to the appointment if he wanted. He comes to your office at the appointed time with his daughter. He appears relaxed, with a full range of affect. Which of the following is the most appropriate opening statement in this situation?
- A. Your lab reports show that you have an acute myeloid leukemia
- B. What is your understanding of the reasons we did bone marrow aspiration and cytogenetic studies? (Correct Answer)
- C. You must be curious and maybe even anxious about the results of your tests.
- D. I may need to refer you to a blood cancer specialist because of your diagnosis. You may need chemotherapy or radiotherapy, which we are not equipped for.
- E. Would you like to know all the details of your diagnosis, or would you prefer I just explain to you what our options are?
Meta-analyses and systematic reviews Explanation: ***"What is your understanding of the reasons we did bone marrow aspiration and cytogenetic studies?"***
- This **open-ended question** allows the patient to express their current knowledge and perceptions, which helps the physician tailor the discussion.
- It establishes a **patient-centered approach**, respecting the patient's existing understanding and preparing them for further information.
*"You must be curious and maybe even anxious about the results of your tests."*
- While empathic, this statement makes an **assumption about the patient's feelings** rather than inviting them to share their own.
- It is often better to ask directly or use more open-ended questions that allow the patient to express their true emotions, especially given their **relaxed demeanor**.
*"I may need to refer you to a blood cancer specialist because of your diagnosis. You may need chemotherapy or radiotherapy, which we are not equipped for.”"*
- This statement immediately introduces **overwhelming and potentially alarming information** (referral, chemotherapy, radiotherapy) without first establishing the diagnosis or assessing the patient's readiness to receive it.
- It prematurely jumps to treatment and logistics, potentially causing **unnecessary distress** before the patient has processed the core diagnosis.
*"Would you like to know all the details of your diagnosis, or would you prefer I just explain to you what our options are?""*
- While it attempts to assess the patient's preference for information, this question is a **closed-ended "either/or" choice** that might limit the patient's ability to express nuanced needs.
- It also prematurely introduces the idea of "options" without first explaining the diagnosis in an understandable context.
*"Your lab reports show that you have an acute myeloid leukemia"*
- This is a **direct and blunt delivery of a serious diagnosis** without any preparatory context or assessment of the patient's existing knowledge or emotional state.
- Delivering such news abruptly can be shocking and overwhelming, potentially **hindering effective communication** and rapport building.
Meta-analyses and systematic reviews US Medical PG Question 6: A research team has data from three completed studies on statin use and Alzheimer's disease: Study A (case-control, OR=0.6, n=500), Study B (retrospective cohort, RR=0.7, n=10,000), and Study C (RCT with cognitive decline as secondary endpoint, RR=0.9, n=2,000). The case-control study used prevalent cases, the cohort study had significant loss to follow-up in the unexposed group, and the RCT was underpowered for cognitive outcomes. Synthesize the evidence to determine the most reliable conclusion about the association.
- A. The RCT provides the strongest evidence despite being underpowered
- B. The retrospective cohort study offers the best balance of validity and precision (Correct Answer)
- C. Case-control study is most reliable due to efficient rare outcome assessment
- D. Evidence is contradictory and no conclusion can be drawn
- E. Meta-analysis of all three studies provides the most accurate estimate
Meta-analyses and systematic reviews Explanation: ***The retrospective cohort study offers the best balance of validity and precision***
- Despite **differential loss to follow-up** in the unexposed, the very large **sample size (n=10,000)** provides high **statistical power** and precision compared to the other studies.
- Cohort studies establish a **temporal sequence** (statin use before disease onset), which is superior to cross-sectional or prevalent case-control designs for causal inference.
*The RCT provides the strongest evidence despite being underpowered*
- While **Randomized Controlled Trials (RCTs)** are higher in the evidence hierarchy, an **underpowered** study lacks the precision to detect a true effect, increasing the risk of a **Type II error**.
- Since cognitive decline was only a **secondary endpoint**, the study may not have been designed or followed long enough to assess Alzheimer's disease progression accurately.
*Case-control study is most reliable due to efficient rare outcome assessment*
- The use of **prevalent cases** instead of incident cases introduces **Neyman bias (survival bias)**, as it only includes patients who survived long enough to be studied.
- Case-control studies are prone to **recall bias** and cannot definitively prove that statin use preceded the onset of cognitive decline.
*Evidence is contradictory and no conclusion can be drawn*
- While the results vary, researchers can still synthesize evidence by weighing studies based on their **methodological quality**, **sample size**, and **bias profile**.
- A conclusion can be drawn by acknowledging the **conservative estimate** (bias toward the null) in the cohort study which still suggested a protective effect.
*Meta-analysis of all three studies provides the most accurate estimate*
- **Meta-analysis** of studies with fundamentally different designs (RCT, Cohort, Case-Control) and significant **methodological limitations** can lead to inaccurate pooled results ("garbage in, garbage out").
- Combining studies with different measures of association (OR vs RR) and distinct biases like **survival bias** and **differential attrition** increases **heterogeneity**.
Meta-analyses and systematic reviews US Medical PG Question 7: A public health department needs to determine whether a cluster of birth defects in a county is associated with industrial pollution. They have limited resources, the suspected exposure occurred 3-5 years ago, and the outcome is rare (15 cases identified). Multiple potential confounders exist including maternal age, socioeconomic status, and prenatal care access. The community demands rapid answers. Evaluate the most appropriate initial study design considering feasibility, ethics, and scientific validity.
- A. Prospective cohort study of pregnant women with exposure monitoring
- B. Randomized controlled trial comparing exposed and unexposed areas
- C. Case-control study with multiple control groups and confounder adjustment (Correct Answer)
- D. Ecologic study comparing county-level pollution and birth defect rates
- E. Cross-sectional survey of current pollution levels and birth outcomes
Meta-analyses and systematic reviews Explanation: ***Case-control study with multiple control groups and confounder adjustment***
- A **case-control study** is the gold standard for investigating **rare outcomes** (only 15 cases identified) because it identifies subjects based on disease status rather than waiting for it to develop.
- This design is highly efficient for **retrospective exposures** that occurred years ago, allows for **rapid results** with limited resources, and can adjust for multiple **confounders** like maternal age and SES through statistical modeling.
*Prospective cohort study of pregnant women with exposure monitoring*
- This design is inappropriate for **rare outcomes** because it would require an massive sample size and many years of follow-up before seeing enough cases to be statistically significant.
- It cannot address a **past exposure** (3-5 years ago) as it follows subjects forward in time from the point of current exposure.
*Randomized controlled trial comparing exposed and unexposed areas*
- It is fundamentally **unethical** to intentionally expose human populations to potentially harmful industrial pollutants in an experimental setting.
- RCTs are used for **interventions** (like new drugs) rather than investigating the etiology of environmental health hazards.
*Ecologic study comparing county-level pollution and birth defect rates*
- This design is prone to the **ecologic fallacy**, where associations found at the population level may not hold true for individuals within that population.
- It cannot adjust for **individual-level confounders** such as personal prenatal care access or specific maternal age, making the results scientifically weaker for the community's needs.
*Cross-sectional survey of current pollution levels and birth outcomes*
- This design suffers from **temporal ambiguity**, as it measures exposure and outcome simultaneously, failing to confirm that pollution Exposure preceded the birth defects.
- Current pollution levels may not accurately reflect the **historical exposure** that occurred during the critical window of embryogenesis 3-5 years ago.
Meta-analyses and systematic reviews US Medical PG Question 8: A pharmaceutical company wants to evaluate a new anticoagulant's effectiveness in preventing stroke in atrial fibrillation patients. They have limited funding and need results within 2 years. The drug has promising phase 2 data. Concurrent medications and comorbidities vary widely in the target population. The company must choose between a pragmatic trial in 50 community hospitals or an explanatory trial at 3 academic centers with strict protocols. Evaluate which design best serves both scientific and practical objectives.
- A. Cluster randomized trial across academic and community sites
- B. Explanatory trial provides definitive efficacy data with maximum internal validity
- C. Pragmatic trial in community settings with broad inclusion criteria (Correct Answer)
- D. Sequential design starting with explanatory trial then pragmatic trial
- E. Adaptive trial design with interim efficacy monitoring
Meta-analyses and systematic reviews Explanation: ***Pragmatic trial in community settings with broad inclusion criteria***
- A **pragmatic trial** evaluates **effectiveness** in real-world clinical practice, making it ideal for a target population with diverse comorbidities and concurrent medications.
- It offers higher **external validity** (generalizability) and is often more feasible and cost-effective within a short timeline compared to highly controlled designs.
*Cluster randomized trial across academic and community sites*
- While it group-randomizes sites, this design is more complex to coordinate and may not be necessary if the goal is individual-level **stroke prevention** results.
- It does not specifically address the need for **broad inclusion criteria** or the limited budget as effectively as a standard pragmatic design.
*Explanatory trial provides definitive efficacy data with maximum internal validity*
- **Explanatory trials** test **efficacy** under ideal, highly controlled conditions, which may not reflect the actual benefit in the general population with comorbidities.
- Strict protocols at only 3 centers lead to low **generalizability** and slower recruitment, potentially exceeding the 2-year deadline.
*Sequential design starting with explanatory trial then pragmatic trial*
- A **sequential design** would require significantly more time and **funding** than the current two-year budget constraints allow.
- Since the drug already has promising **Phase 2 data**, moving directly to an effectiveness-focused pragmatic trial is a more strategic use of resources.
*Adaptive trial design with interim efficacy monitoring*
- **Adaptive designs** allow for modifications based on interim data but are statistically complex and often more **expensive** to manage.
- While scientifically rigorous, it does not prioritize the need for **real-world effectiveness** data in community settings requested by the scenario.
Meta-analyses and systematic reviews US Medical PG Question 9: A randomized controlled trial of a new diabetes medication shows significant reduction in HbA1c levels (p<0.001). However, 40% of participants in the treatment group and 15% in the placebo group dropped out before study completion, primarily due to gastrointestinal side effects in the treatment group. The analysis includes only participants who completed the study. Analyze the impact on study conclusions.
- A. Hawthorne effect has contaminated both study arms equally
- B. Regression to the mean explains the observed treatment effect
- C. Intention-to-treat analysis has been violated, likely overestimating treatment benefit (Correct Answer)
- D. Per-protocol analysis provides the most accurate efficacy estimate
- E. Selection bias from randomization failure invalidates the results
Meta-analyses and systematic reviews Explanation: ***Intention-to-treat analysis has been violated, likely overestimating treatment benefit***
- By including only participants who completed the study, the researchers performed a **per-protocol analysis**, which ignores **attrition bias** caused by the high dropout rate in the treatment arm.
- **Intention-to-treat (ITT)** analysis is designed to prevent such bias by analyzing participants based on their original group assignment, regardless of completion or compliance.
*Hawthorne effect has contaminated both study arms equally*
- The **Hawthorne effect** refers to subjects changing their behavior because they know they are being observed, not loss of participants due to side effects.
- This effect would typically affect the **observation process** rather than causing differential dropout rates between treatment and placebo groups.
*Regression to the mean explains the observed treatment effect*
- **Regression to the mean** is a statistical phenomenon where extreme initial measurements naturally move toward the average upon repeated testing.
- While it can influence longitudinal studies, it does not account for the **differential attrition** and side-effect profile described in this trial.
*Per-protocol analysis provides the most accurate efficacy estimate*
- **Per-protocol analysis** often leads to an optimistic or **overestimated efficacy** because it only evaluates the "healthiest" or most compliant patients who tolerated the drug.
- It fails to reflect **real-world effectiveness**, as it disregards the significance of treatment-limiting side effects (like the GI issues seen here).
*Selection bias from randomization failure invalidates the results*
- **Selection bias** usually occurs at the recruitment or **assignment phase**, whereas this scenario describes **attrition bias** occurring after the study has begun.
- Initial **randomization** may have been successful, but the failure to account for dropouts at the analysis stage is what introduces the bias.
Meta-analyses and systematic reviews US Medical PG Question 10: A study follows 5,000 healthcare workers from 1995 to 2015, tracking their exposure to bloodborne pathogens and development of chronic infections. The researchers use employment records to determine exposure history rather than relying on participant recall. In 2010, the hospital implemented a new electronic medical record system that improved documentation of needle-stick injuries. Analyze how this change affects the validity of the exposure assessment.
- A. Introduces surveillance bias affecting the exposure-outcome relationship (Correct Answer)
- B. Creates selection bias by preferentially identifying exposed individuals
- C. Represents non-differential misclassification reducing study power
- D. Introduces lead-time bias affecting survival analysis
- E. Creates volunteer bias affecting external validity
Meta-analyses and systematic reviews Explanation: ***Introduces surveillance bias affecting the exposure-outcome relationship***
- The shift to an **electronic medical record system** in 2010 leads to more intensive or accurate monitoring of exposure (needle-sticks) specifically in the later period, creating **surveillance bias**.
- This reflects **differential measurement** of exposure over time, which can artifactually distort the association between bloodborne pathogens and infection rates during different intervals of the study.
*Creates selection bias by preferentially identifying exposed individuals*
- **Selection bias** occurs during the enrollment phase of a study when participants are selected based on factors related to both exposure and outcome.
- This scenario describes a change in **information gathering** and documentation after the cohort has already been established and followed, not a flaw in the initial selection.
*Represents non-differential misclassification reducing study power*
- **Non-differential misclassification** occurs when the degree of error in recording exposure is the same across all groups, usually biasing results toward the **null hypothesis**.
- In this study, the systematic improvement in documentation mid-study creates a **differential** change in data quality over time rather than a random, uniform error.
*Introduces lead-time bias affecting survival analysis*
- **Lead-time bias** is a phenomenon where early detection (e.g., through screening) makes it appear as though survival time has increased, even if the actual disease course is unchanged.
- The scenario focuses on the **documentation of exposure** (needle-sticks), not the early detection of the chronic infection outcome or its impact on survival duration.
*Creates volunteer bias affecting external validity*
- **Volunteer bias** occurs when individuals who choose to participate in a study have different characteristics than those who do not, affecting **generalizability**.
- Since the researchers are using **employment records** of a defined cohort rather than self-selection by the workers, volunteer bias is not the primary issue here.
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