Role of biostatistics in product development and FDA submissions MCQs With Answer

Biostatistics is essential in product development and FDA submissions, providing rigorous methods to design studies, analyze results, and support regulatory decisions. For B. Pharm students, mastering sample size calculation, power analysis, hypothesis testing, confidence intervals, and a clear statistical analysis plan is critical to demonstrate safety, efficacy, and bioequivalence. Biostatistics also informs adaptive designs, interim analyses, multiplicity control, handling missing data, PK/PD modeling, and preparing e-submissions (SDTM/ADaM) to meet FDA and ICH E9 expectations. Understanding data integrity, CMC comparability, and statistical reviewer requirements strengthens dossiers and labeling claims. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What is the primary role of biostatistics in FDA submissions for a new drug application?

• To prepare clinical trial manufacturing schedules
• To design studies, analyze data, and provide quantitative evidence of safety and efficacy
• To write marketing and promotional materials
• To handle drug packaging and distribution logistics

Correct Answer: To design studies, analyze data, and provide quantitative evidence of safety and efficacy

Q2. Which document specifies analysis methods, endpoints, populations, and handling of missing data before unblinding?

• Case Report Form (CRF)
• Investigator’s Brochure
• Statistical Analysis Plan (SAP)
• Clinical Study Report (CSR)

Correct Answer: Statistical Analysis Plan (SAP)

Q3. ICH E9 provides guidance primarily on which statistical topic important for regulatory submissions?

• Good Manufacturing Practices (GMP)
• Statistical principles for clinical trials including estimands and analysis
• Labeling language for advertisements
• Pharmacovigilance reporting timelines

Correct Answer: Statistical principles for clinical trials including estimands and analysis

Q4. Controlling the Type I error rate in confirmatory trials ensures which of the following?

• Minimizing the chance of missing a true effect
• Maximizing the sample size
• Keeping the probability of falsely declaring efficacy below a pre-specified level
• Ensuring the study is double-blinded

Correct Answer: Keeping the probability of falsely declaring efficacy below a pre-specified level

Q5. Which combination most directly determines the sample size for a superiority clinical trial?

• Alpha level, desired power, expected effect size, and variability
• Number of study sites and advertising budget
• Investigator experience and patient satisfaction
• GMP certification and batch release frequency

Correct Answer: Alpha level, desired power, expected effect size, and variability

Q6. In a noninferiority trial, selecting the noninferiority margin is important because it:

• Defines the minimum efficacy the new treatment must exceed compared to placebo
• Specifies how much worse the new treatment can be compared to active control while remaining acceptable
• Determines blinding procedures
• Sets the manufacturing release specifications

Correct Answer: Specifies how much worse the new treatment can be compared to active control while remaining acceptable

Q7. Equivalence trials typically require what statistical approach?

• Testing a single one-sided hypothesis
• Demonstrating the treatment difference falls within pre-specified upper and lower margins (two-sided)
• Comparing enrollment rates across sites
• Analyzing only per-protocol population without ITT

Correct Answer: Demonstrating the treatment difference falls within pre-specified upper and lower margins (two-sided)

Q8. For bioequivalence studies, FDA commonly uses which acceptance criterion for AUC and Cmax ratios?

• 90% confidence interval for the ratio within 80–125%
• 95% confidence interval within 70–130%
• Point estimate within 95–105% only
• P-value less than 0.01

Correct Answer: 90% confidence interval for the ratio within 80–125%

Q9. Which analysis population preserves randomization and is usually primary for regulatory efficacy assessment?

• Per-protocol population
• Safety population
• Intent-to-treat (ITT) population
• Pharmacokinetic population

Correct Answer: Intent-to-treat (ITT) population

Q10. When multiple primary endpoints are tested, what must be addressed to maintain overall Type I error?

• Multiplicity adjustment or hierarchical testing strategy
• Increase the sample size proportionally
• Exclude secondary outcomes from the protocol
• Report only the most favorable endpoint

Correct Answer: Multiplicity adjustment or hierarchical testing strategy

Q11. What is an alpha spending function used for in interim analyses?

• To allocate the total Type I error across interim looks and the final analysis
• To determine sample handling procedures in the lab
• To schedule monitoring visits
• To set the safety reporting interval

Correct Answer: To allocate the total Type I error across interim looks and the final analysis

Q12. Which feature characterizes an adaptive clinical trial design?

• No statistical changes allowed after trial start
• Pre-planned modifications (e.g., sample size, dose) based on interim data while controlling error rates
• Open-label design only
• Use of historical controls exclusively

Correct Answer: Pre-planned modifications (e.g., sample size, dose) based on interim data while controlling error rates

Q13. Regulatory agencies’ acceptance of Bayesian methods depends largely on:

• Whether the study uses more than 100 subjects
• Transparent prior specification, sensitivity analyses, and control of error rates
• Using only noninformative priors
• Replacing the SAP with Bayesian code only

Correct Answer: Transparent prior specification, sensitivity analyses, and control of error rates

Q14. In FDA e-submissions, SDTM and ADaM datasets are required because they:

• Provide raw laboratory values only
• Standardize clinical data (SDTM) and analysis-ready datasets (ADaM) for review and reproducibility
• Replace the need for a CSR
• Are used only for nonclinical studies

Correct Answer: Standardize clinical data (SDTM) and analysis-ready datasets (ADaM) for review and reproducibility

Q15. Which statistical method is commonly used for early safety signal detection across multiple adverse events?

• Survival analysis only
• Data mining approaches and sequential monitoring (e.g., disproportionality, sequential probability ratio tests)
• ANOVA without adjustment
• Bioequivalence testing

Correct Answer: Data mining approaches and sequential monitoring (e.g., disproportionality, sequential probability ratio tests)

Q16. Which approach is recommended in regulatory submissions for handling missing primary endpoint data?

• Ignore missing data and analyze completers only
• Prespecify methods (e.g., multiple imputation, mixed models) and perform sensitivity analyses
• Replace missing values with zeros without justification
• Remove affected sites from analysis

Correct Answer: Prespecify methods (e.g., multiple imputation, mixed models) and perform sensitivity analyses

Q17. Statistical evidence used to support labeling claims must be:

• Based on post-hoc exploratory analyses only
• Robust, pre-specified, and clinically interpretable with appropriate statistical significance
• Derived from pooled marketing data
• Confirmed solely by investigator opinion

Correct Answer: Robust, pre-specified, and clinically interpretable with appropriate statistical significance

Q18. Sample size re-estimation during a trial can be:

• An unplanned change that requires no documentation
• Planned (blinded or unblinded) with procedures defined in the protocol to control Type I error
• Done by changing endpoints mid-trial
• Performed by increasing alpha to reduce required subjects

Correct Answer: Planned (blinded or unblinded) with procedures defined in the protocol to control Type I error

Q19. What do FDA statistical reviewers commonly assess when reviewing clinical trial data?

• Only the manufacturing batch records
• Study design, conduct, statistical methods, data quality, and interpretation of results
• Investigator travel expenses
• Marketing strategy

Correct Answer: Study design, conduct, statistical methods, data quality, and interpretation of results

Q20. Use of historical controls is acceptable when:

• Randomized concurrent controls are infeasible and strong justification plus careful adjustment are provided
• There are no inclusion/exclusion criteria
• It helps reduce reporting timelines irrespective of bias
• It replaces the need for statistical analyses

Correct Answer: Randomized concurrent controls are infeasible and strong justification plus careful adjustment are provided

Q21. A surrogate endpoint used for regulatory approval must be:

• Easier to measure than clinical outcomes with no validation required
• Validated to reliably predict clinical benefit or be reasonably likely to predict benefit with supportive evidence
• Only a biomarker measured in a subset of subjects
• Chosen after the trial ends

Correct Answer: Validated to reliably predict clinical benefit or be reasonably likely to predict benefit with supportive evidence

Q22. In PK analysis, which metrics are primary measures of exposure used in bioequivalence?

• Heart rate and blood pressure
• AUC (area under the curve) and Cmax (maximum concentration)
• Time to event and hazard ratio
• Mean and median survival

Correct Answer: AUC (area under the curve) and Cmax (maximum concentration)

Q23. Statistical process control in manufacturing supports regulatory submissions by:

• Documenting advertising claims
• Monitoring critical quality attributes and ensuring consistent batch-to-batch product quality using control charts and capability metrics
• Replacing stability studies
• Eliminating the need for validation

Correct Answer: Monitoring critical quality attributes and ensuring consistent batch-to-batch product quality using control charts and capability metrics

Q24. Choosing an equivalence margin should be based on:

• Clinical judgment, historical efficacy of control, and regulatory guidance
• The smallest detectable difference by the lab instrument
• Investor expectations
• Arbitrary round numbers

Correct Answer: Clinical judgment, historical efficacy of control, and regulatory guidance

Q25. Subgroup analyses in regulatory submissions should be:

• Heavily relied upon for primary approval claims
• Pre-specified, limited in number, and interpreted cautiously with multiplicity control
• Performed after seeing the overall result to find favorable groups
• Excluded from the SAP

Correct Answer: Pre-specified, limited in number, and interpreted cautiously with multiplicity control

Q26. Why is data integrity important for statistical analyses in FDA submissions?

• It ensures analyses reflect reliable, complete, and auditable source data for credible regulatory conclusions
• It reduces the need for informed consent
• It accelerates site recruitment
• It allows removal of outliers without documentation

Correct Answer: It ensures analyses reflect reliable, complete, and auditable source data for credible regulatory conclusions

Q27. When sample sizes are small and data distribution is uncertain, which tests are often preferred?

• Parametric tests without checking assumptions
• Nonparametric tests that do not assume normality
• Analyses that ignore variability
• Only graphical summaries

Correct Answer: Nonparametric tests that do not assume normality

Q28. Randomization and blinding primarily protect a trial from which biases?

• Selection and assessment biases
• Manufacturing defects
• Data entry delays
• Stability failures

Correct Answer: Selection and assessment biases

Q29. A planned futility interim analysis aims to:

• Stop the trial early if there is little chance of demonstrating the treatment effect, conserving resources
• Increase the Type I error rate intentionally
• Guarantee trial success
• Determine marketing strategy

Correct Answer: Stop the trial early if there is little chance of demonstrating the treatment effect, conserving resources

Q30. The role of the statistician in cross-disciplinary regulatory teams includes:

• Only preparing figures for presentations
• Designing studies, advising on estimands, ensuring appropriate analyses, interpreting results, and responding to regulatory queries
• Handling only data entry tasks
• Deciding final labeling text without clinical input

Correct Answer: Designing studies, advising on estimands, ensuring appropriate analyses, interpreting results, and responding to regulatory queries

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com