Placebo and blinding techniques MCQs With Answer

Placebo and blinding techniques MCQs With Answer — Introduction

This collection of MCQs is designed specifically for M.Pharm students to deepen understanding of placebo concepts and blinding methodologies in clinical research. It covers theoretical foundations, practical applications, ethical considerations, and advanced topics such as double-dummy designs, active placebos, blinding assessment metrics, and the impact of placebo responses on trial validity and sample size. Questions emphasize critical thinking about when and how to use placebos, strategies to preserve blinding, consequences of unblinding, and regulatory expectations. Use these questions to test knowledge, prepare for exams, and reinforce best practices when designing or evaluating randomized controlled trials in pharmaceutical research.

Q1. What is the primary methodological purpose of using a placebo in a randomized controlled trial?

• To provide a treatment that is pharmacologically inert and cheaper than the experimental drug
• To blind participants and control for non-specific effects, separating specific treatment effects from placebo response
• To ensure that participants receive some form of benefit rather than nothing
• To accelerate regulatory approval by showing superiority to a null treatment

Correct Answer: To blind participants and control for non-specific effects, separating specific treatment effects from placebo response

Q2. Which of the following best describes a double-dummy design?

• Both arms receive an identical active drug but at different doses
• Each participant receives two placebos to maintain blinding
• Participants in each arm receive one active treatment and a matching placebo so that administration procedures remain identical between groups
• Investigators are blinded but participants know their allocation

Correct Answer: Participants in each arm receive one active treatment and a matching placebo so that administration procedures remain identical between groups

Q3. What is an “active placebo” and when is it most appropriately used?

• A placebo containing small amounts of the active drug; used to reduce cost of trials
• A sham procedure used in surgical trials; used only when ethics committees require surgical comparators
• A placebo that mimics some side effects of the active drug to better preserve blinding, particularly when the active drug has distinctive adverse effects
• A placebo given to the control group while investigators know allocations; used in open-label trials

Correct Answer: A placebo that mimics some side effects of the active drug to better preserve blinding, particularly when the active drug has distinctive adverse effects

Q4. Which statement most accurately differentiates placebo effect from placebo response?

• Placebo effect refers to spontaneous disease course; placebo response is the psychological benefit
• Placebo effect is the change attributable to patient expectancy and context; placebo response includes placebo effect plus natural history and regression to the mean
• Placebo effect is a measurable biomarker change; placebo response is only subjective improvement
• They are synonymous and interchangeable in clinical trial reporting

Correct Answer: Placebo effect is the change attributable to patient expectancy and context; placebo response includes placebo effect plus natural history and regression to the mean

Q5. Which blinding level is described when participants, investigators, outcome assessors, and data analysts are unaware of allocation?

• Single-blind
• Double-blind
• Triple-blind
• Open-label

Correct Answer: Triple-blind

Q6. Which method is most appropriate to assess whether blinding has been successful in a trial?

• Compare baseline characteristics between groups
• Ask participants and investigators to guess allocation and compute a blinding index such as Bang’s blinding index
• Measure objective biomarkers only, as they are unaffected by blinding
• Perform an interim analysis of efficacy outcomes

Correct Answer: Ask participants and investigators to guess allocation and compute a blinding index such as Bang’s blinding index

Q7. Which ethical consideration is most relevant when using placebo controls in trials where effective standard therapy exists?

• Placebos are always acceptable if participants consent
• Use of placebo may be unethical if it withholds established effective therapy leading to harm; active-controlled or add-on designs should be considered
• Ethics only requires financial compensation for placebo recipients
• It is ethical because placebo increases internal validity irrespective of available treatment

Correct Answer: Use of placebo may be unethical if it withholds established effective therapy leading to harm; active-controlled or add-on designs should be considered

Q8. In a crossover trial with a placebo, which feature is essential to minimize carryover effects?

• Shorten treatment periods to reduce exposure
• Exclude all participants with prior exposure to similar drugs
• Include an adequate washout period between treatment periods to allow effects of the first period to dissipate
• Use open-label periods between blinded phases

Correct Answer: Include an adequate washout period between treatment periods to allow effects of the first period to dissipate

Q9. Which of the following best explains observer-expectancy bias?

• Participants expect benefit and report improved outcomes
• Investigators unconsciously influence outcome assessment in accordance with their expectations, potentially biasing subjective endpoints
• Randomization imbalances lead to biased estimates
• Placebo causes physiological changes that mimic treatment effects

Correct Answer: Investigators unconsciously influence outcome assessment in accordance with their expectations, potentially biasing subjective endpoints

Q10. How does a high placebo response rate affect statistical power and sample size requirements?

• High placebo response reduces variability and therefore reduces required sample size
• High placebo response increases the observed effect size and increases power
• High placebo response reduces the difference between active and control arms, thereby reducing power and requiring larger sample sizes to detect a given treatment effect
• Placebo response has no bearing on sample size calculations

Correct Answer: High placebo response reduces the difference between active and control arms, thereby reducing power and requiring larger sample sizes to detect a given treatment effect

Q11. What is allocation concealment and why is it distinct from blinding?

• Allocation concealment prevents selection bias at randomization by hiding upcoming assignments; blinding prevents post-randomization performance and assessment bias
• Allocation concealment is the same as blinding both participants and investigators
• Allocation concealment only refers to hiding treatment labels on drug packaging
• They are unrelated concepts and used in different study types

Correct Answer: Allocation concealment prevents selection bias at randomization by hiding upcoming assignments; blinding prevents post-randomization performance and assessment bias

Q12. Which scenario best illustrates a nocebo effect?

• A participant receiving active drug reports improvement in pain
• A participant informed about possible nausea experiences nausea after receiving an inert placebo
• An investigator intentionally unblinds and changes outcome reporting
• A subject experiences side effects due to drug-drug interaction

Correct Answer: A participant informed about possible nausea experiences nausea after receiving an inert placebo

Q13. When is it scientifically justified to use a placebo-controlled trial rather than an active-controlled trial?

• When an effective standard therapy exists but sponsor prefers simpler design
• When no proven effective therapy exists, or when withholding treatment poses no serious risk and placebo control provides a clearer estimate of absolute efficacy
• When regulators always demand placebo evidence regardless of ethics
• Only when the experimental drug is expected to be inferior to standard care

Correct Answer: When no proven effective therapy exists, or when withholding treatment poses no serious risk and placebo control provides a clearer estimate of absolute efficacy

Q14. Which practical measure helps maintain blinding when the active drug produces distinctive side effects?

• Exclude patients likely to experience side effects
• Use an active placebo that mimics some non-serious adverse effects or use double-dummy approach
• Reveal allocation to the safety monitoring board only
• Switch to open-label design to avoid misleading participants

Correct Answer: Use an active placebo that mimics some non-serious adverse effects or use double-dummy approach

Q15. Which regulatory guidance often informs ethical use of placebos in clinical trials?

• Good Laboratory Practice (GLP)
• ICH E10 on Choice of Control Group in Clinical Trials and Declaration of Helsinki
• Guidelines on Good Manufacturing Practice (GMP)
• WHO Essential Medicines List

Correct Answer: ICH E10 on Choice of Control Group in Clinical Trials and Declaration of Helsinki

Q16. What is the likely impact on effect size estimates when unblinding occurs and assessors know treatment allocation?

• Effect size estimates remain unbiased because randomization still holds
• Effect size estimates are more likely to be biased away from the null, especially for subjective outcomes
• Effect size estimates are biased towards the null only
• Unblinding only affects safety data and not efficacy estimates

Correct Answer: Effect size estimates are more likely to be biased away from the null, especially for subjective outcomes

Q17. In trials assessing objective endpoints (e.g., mortality), what is the role of blinding?

• Blinding is unnecessary and never recommended for objective endpoints
• Blinding may be less critical but still valuable to reduce differential co-interventions and ascertainment bias
• Blinding only matters for pharmacokinetic substudies
• Objective endpoints always require participant blinding but not assessor blinding

Correct Answer: Blinding may be less critical but still valuable to reduce differential co-interventions and ascertainment bias

Q18. Which statistical or reporting practice helps readers interpret trials where blinding may have failed?

• Omit any mention of blinding to avoid confusion
• Report blinding procedures, present blinding assessment results, and perform sensitivity analyses excluding unblinded assessments if possible
• Only present per-protocol analyses
• Report only those outcomes that favor the active drug

Correct Answer: Report blinding procedures, present blinding assessment results, and perform sensitivity analyses excluding unblinded assessments if possible

Q19. Which of the following best describes a sham control in surgical trials?

• A placebo pill given after surgery
• A procedure that mimics the surgical intervention without performing its critical therapeutic component, used to control for placebo and procedural effects
• An enhanced informed consent process for the control group
• A historical control group from previous non-randomized studies

Correct Answer: A procedure that mimics the surgical intervention without performing its critical therapeutic component, used to control for placebo and procedural effects

Q20. Which approach can reduce expectancy bias when trial participants receive different dosing schedules or observable differences between treatments?

• Use of open-label randomization so participants know their treatment
• Implement matching placebos, identical packaging, and double-dummy techniques to standardize appearance and administration
• Reduce the follow-up duration to minimize behavior changes
• Avoid collecting subjective patient-reported outcomes

Correct Answer: Implement matching placebos, identical packaging, and double-dummy techniques to standardize appearance and administration

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